Abstract
PURPOSE
Amivantamab, an EGFR-MET bispecific antibody with immune cell–directing activity, is approved in non–small cell lung cancer (NSCLC). Effective treatments are limited for chemorefractory metastatic colorectal cancer (mCRC).
METHODS
OrigAMI-1 (ClinicalTrials.gov identifier: NCT05379595) is a phase Ib/II study evaluating amivantamab monotherapy in chemorefractory (2-3 prior lines) mCRC. Participants had centrally confirmed RAS/BRAF/EGFR ectodomain wild-type status, without ERBB2/HER2 amplification. Participants with left-sided mCRC without (cohort A) or with (cohort B) prior anti-EGFR antibody treatment, or right-sided mCRC (cohort C) regardless of prior anti-EGFR treatment, received intravenous amivantamab 1,050 mg (1,400 mg for ≥80 kg) once every 2 weeks. The primary end point was objective response rate (ORR) per RECIST v1.1.
RESULTS
By October 31, 2024, 94 participants received amivantamab monotherapy (median follow-up, 11.9 months). The median age was 60 years, and 65% of participants were male, with a median of 2 prior lines (94%, prior bevacizumab). In left-sided cohorts, the ORR was 29% (5 of 17) in cohort A and 19% (10 of 54) in cohort B; the median duration of response (DoR) was 9.0 months and 6.1 months, and the median progression-free survival (PFS) was 5.7 months and 4.6 months, respectively. In the right-sided cohort, the ORR was 22% (10 of 23; 43% had prior anti-EGFR), the median DoR was 9.8 months, and the median PFS was 3.7 months. Most frequent treatment-related grade ≥3 adverse events (AEs) were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (4%). One participant discontinued amivantamab because of a treatment-related AE.
CONCLUSION
Amivantamab monotherapy demonstrated promising, durable antitumor activity in chemorefractory mCRC, regardless of prior anti-EGFR therapy and the primary tumor location. The amivantamab safety profile in mCRC is consistent with experience in NSCLC. Amivantamab plus chemotherapy is currently being explored in two phase III studies in first-line and second-line mCRCs.
INTRODUCTION
Colorectal cancer (CRC) accounted for approximately 10% of new cancer cases in 2020 and represents the third most common and second deadliest cancer.1 Approximately 50% of patients with metastatic colorectal cancer (mCRC) have no actionable genomic alterations within RAS/BRAF (and termed hereafter as RAS/BRAF wild-type [WT]).2 Chemotherapy alone or in combination with anti–epidermal growth factor receptor (EGFR) antibodies (for predominantly left-sided disease) or anti–vascular endothelial growth factor (VEGF) therapy (ie, bevacizumab) is the standard of care for first-line mCRC. Second-line treatment often involves changing the chemotherapy backbone and/or accompanying biologics based on the first-line treatment choice. Anti-EGFR monotherapy is often used in late-line chemorefractory settings, particularly as a rechallenge after the clearance of previously detected RAS/BRAF-mutant clones in circulating tumor DNA (ctDNA), although response rates (8%-22%) remain low.2-5
CONTEXT
Key Objective
Does amivantamab monotherapy demonstrate clinically meaningful and durable antitumor activity against chemorefractory metastatic colorectal cancer (mCRC)? OrigAMI-1 is the first study to demonstrate amivantamab activity in mCRC.
Knowledge Generated
At a median follow-up of 11.9 months, amivantamab monotherapy demonstrated meaningful antitumor activity in left- and right-sided chemorefractory mCRC (with or without prior anti-EGFR therapies). No new safety signals were identified.
Relevance (E.M. O'Reilly)
Dual-targeted therapy modulation against EGFR-MET with amivantamab in late-stage CRC provides a signal of promise in both left- and right-sided disease. The field looks forward to seeing the results of randomized trials with chemotherapy ± amivantamab in early lines of treatment for CRC.*
*Relevance section written by JCO Associate Editor Eileen M. O'Reilly, MD, FASCO.
Elevated EGFR expression, as detected by immunohistochemistry, is seen in tumor tissues of most patients with mCRC and associated with poor prognosis, disease progression, and metastatic disease.6 MET is often highly expressed or amplified in mCRC and mediates resistance to anti-EGFR therapies7; however, MET inhibitors are not approved for mCRC treatment.
Amivantamab is an IgG1-based EGFR and MET bispecific antibody with a triple mechanism of action: first, inhibition of EGFR; second, inhibition of MET; and third, immune cell–directing activity.8-10 In a preclinical study using non–small cell lung cancer (NSCLC) cell lines, amivantamab induced antibody-dependent cellular cytotoxicity to a greater extent than cetuximab.9 Amivantamab is approved in the United States, the European Union, China, Japan, and other countries for use alone or in combination with lazertinib or carboplatin plus pemetrexed across a variety of treatment settings in EGFR-mutant advanced NSCLC.11-14 Dual inhibition of EGFR and MET was hypothesized to improve outcomes and address the unmet need for more efficacious treatment options in chemorefractory mCRC.
Here, we present the results of the OrigAMI-1 study, which evaluated the efficacy and safety of amivantamab monotherapy in participants with chemorefractory mCRC.
METHODS
Study Design and Participants
OrigAMI-1 (ClinicalTrials.gov identifier: NCT05379595) is a global, multicenter, open-label, phase Ib/II study of amivantamab monotherapy or amivantamab in combination with chemotherapy in participants with advanced or metastatic CRC. The full trial Protocol (online only) is provided online. This analysis presents results from participants who received amivantamab monotherapy (Fig 1). Eligible participants were 18 years and older with previously diagnosed unresectable/metastatic CRC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate organ and bone marrow function. Participants must have received ≥2 but not more than 3 prior lines of systemic therapy for metastatic disease and must have previously received or been intolerant to fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and an anti-VEGF treatment. Cohorts A and B included participants with left-sided mCRC (including the splenic flexure, descending colon, sigmoid colon, or rectum) without or with prior exposure to anti-EGFR monoclonal antibodies, respectively. Cohort C included participants with right-sided mCRC (including the cecum, the ascending colon, or the transverse colon), irrespective of prior anti-EGFR treatment. Participants were required to submit a tumor biopsy sample at screening, taken after progression on the most recent therapy, and have had a tumor previously characterized as having WT KRAS, NRAS, and BRAF, without evidence of ERBB2/HER2 amplification by central ctDNA testing at screening. Participants with EGFR ectodomain mutations by central ctDNA testing at screening and BRAF V600 missense mutations were excluded. Additional details are given in the Data Supplement (online only).
FIG 1.
OrigAMI-1 study design. aParticipants must have received standard-of-care fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and anti-VEGF therapy, with or without an anti-EGFR therapy. bMaximum of one prior line in the metastatic setting. 2L, second-line; AE, adverse event; CBR, clinical benefit rate; CRC, colorectal cancer; DL0, dose level 0 (amivantamab 1,050 mg IV or 1,400 mg IV if ≥80 kg once every 2 weeks); DoR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EGFR, epidermal growth factor receptor; FOLFIRI, leucovorin calcium, 5-fluorouracil, irinotecan; IV, intravenous; mCRC, metastatic colorectal cancer; mFOLFOX6, modified FOLFOX-6 regimen (leucovorin calcium, 5-fluorouracil, oxaliplatin); ORR, objective response rate; PFS, progression-free survival; RP2D, recommended phase II dose; VEGF, vascular endothelial growth factor; WT, wild-type.
Trial Oversight
The trial was conducted in accordance with the provisions of the Declaration of Helsinki, Good Clinical Practice guidelines (as defined by the International Council for Harmonisation), and applicable regulatory and country-/territory-specific requirements. The protocol was approved by the local institutional review boards and independent ethics committees of the participating centers. Participants provided written informed consent prior to study participation.
Study Treatment
Amivantamab was administered intravenously once weekly during Cycle (C) 1 at the recommended phase II dose (RP2D) of 1,050 mg (1,400 mg for ≥80 kg body weight), with the first dose split between 2 days (350 mg once on C1 Day [D] 1, the remainder once on C1D2), and then given once every 2 weeks in subsequent cycles. Treatment continued until disease progression per RECIST version 1.1, the investigator identified unacceptable toxicity, the participant withdrew consent, or the participant died.
End Points and Assessments
The primary end point was objective response rate (ORR) per RECIST version 1.1 as determined by the investigator. Secondary end points included duration of response (DoR), clinical benefit rate (CBR; defined as complete response [CR], partial response [PR], or stable disease [SD] lasting ≥11 weeks), progression-free survival (PFS) per RECIST version 1.1 as determined by the investigator, and incidence of adverse events (AEs). Biomarkers were analyzed as an exploratory end point.
Biomarker Analysis
Blood sample collection, ctDNA testing, whole-transcriptome RNA sequencing, and gene expression analysis methods are given in the Data Supplement. If clinically feasible, tumor biopsies were obtained at C3D1 and at the time of progression; tumor biopsy at baseline (screening) was mandatory. Median mRNA levels for amphiregulin (AREG) and epiregulin (EREG) were used to define the thresholds for high versus low expression groups as biomarkers of anti-EGFR treatment efficacy in mCRC.15,16
Statistical Analysis
The sample size was based on the null hypothesis that the ORR was ≤10% and the alternative hypothesis that the ORR was >25% for each cohort. With a two-sided α of 5% and a power of 80%, it was estimated that approximately 50 response-evaluable participants were needed per cohort. The Bayesian Optimal Phase II (BOP2) design was used to determine the decision at each interim and at the final data review. If there were >9 responders of the 50 response-evaluable participants, the null hypothesis was rejected to claim statistical significance.
Methods describing the futility analysis for cohort enrollment are given in the Data Supplement. Enrollment in cohort A was closed at the interim analysis by the sponsor because of strategic decisions (eg, investigation of amivantamab plus chemotherapy in two phase III registrational trials) after the RP2D was deemed safe, and cohort C was closed at the interim analysis for futility at the interim analysis. All data reported here are from a clinical cutoff (CCO) of October 31, 2024.
RESULTS
As of October 31, 2024, 94 participants received amivantamab monotherapy (cohort A: 17, cohort B: 54, cohort C: 23). Baseline demographic and disease characteristics are listed in Table 1. The median age was 60 years (range, 34-80), 65% of participants were male, 65% were Asian, and the median number of prior lines of therapy in the metastatic setting was 2 (range, 2-3), with 94% of participants receiving prior bevacizumab. In cohort B, 27 of 54 (50%) participants responded to prior anti-EGFR treatment in any line (Data Supplement, Table S1). In cohort C, 10 of 23 (43%) participants had received prior anti-EGFR treatment, and 2 of 10 (20%) participants responded to prior anti-EGFR treatment. The median time from metastatic disease diagnosis to first dose of amivantamab was 27 months (range, 3-109).
TABLE 1.
Demographic and Clinical Characteristics of Patients at Baselinea
| Characteristic | Cohort A L-Sided, Without Prior EGFRi (n = 17) |
Cohort B L-Sided, With Prior EGFRi (n = 54) |
Cohort C R-Sided, With or Without Prior EGFRi (n = 23) |
|---|---|---|---|
| Age, years | |||
| Median (range) | 63 (45-80) | 60.5 (36-79) | 60 (34-79) |
| Category, No. (%) | |||
| <65 | 9 (53) | 33 (61) | 16 (70) |
| ≥65 to <75 | 7 (41) | 16 (30) | 3 (13) |
| ≥75 | 1 (6) | 5 (9) | 4 (17) |
| Sex, No. (%) | |||
| Female | 5 (29) | 18 (33) | 10 (43) |
| Male | 12 (71) | 36 (67) | 13 (57) |
| Race, No. (%) | |||
| Asian | 14 (82) | 34 (63) | 13 (57) |
| White | 2 (12) | 19 (35) | 6 (26) |
| Black or African American | 1 (6) | 1 (2) | 1 (4) |
| American Indian or Alaska Native | 0 | 0 | 1 (4) |
| Multiple/not reported | 0 | 0 | 2 (9) |
| Body weight, kg | |||
| Median (range) | 67 (48-91) | 69 (44-115) | 67 (44-120) |
| Category, No. (%) | |||
| <80 | 13 (76) | 44 (81) | 16 (70) |
| ≥80 | 4 (24) | 10 (19) | 7 (30) |
| Eastern Cooperative Oncology Group performance status, No. (%) | |||
| 0 | 11 (65) | 26 (48) | 9 (39) |
| 1 | 6 (35) | 28 (52) | 14 (61) |
| History of alcohol use, No. (%) | |||
| No | 6 (35) | 33 (61) | 14 (61) |
| Yes | 11 (65) | 21 (39) | 9 (39) |
| Time from metastatic diagnosis to first dose, months, median (range) | 30 (4-109) | 27 (3-87) | 26 (12-68) |
| No. of prior lines of therapy, median (range) | 2 (2-3) | 2 (2-3) | 2 (2-3) |
| No. of prior lines of therapy in the metastatic settingb | |||
| Median (range) | 2 (2-3) | 2 (2-3) | 2 (1-3)b |
| 2, No. (%) | 10 (59) | 30 (56) | 13 (57) |
| 3, No. (%) | 7 (41) | 24 (44) | 9 (39) |
| Location of primary disease, No. (%) | |||
| Right sidec | 0 | 0 | 23 (100) |
| Left sided | 13 (76) | 30 (56) | 0 |
| Extraperitoneal rectum | 4 (24) | 24 (44) | 0 |
| Presence of liver metastases, No. (%) | 13 (76) | 39 (72) | 18 (78) |
| Presence of peritoneum metastases, No. (%) | 0 | 11 (20) | 8 (35) |
Abbreviations: CRC, colorectal cancer; EGFRi, epidermal growth factor receptor inhibitor.
Left-sided CRC was defined as a primary tumor that arose from the splenic flexure, descending colon, sigmoid colon, or rectum; right-sided CRC was defined as a primary tumor that arose from the cecum, ascending colon, or transverse colon.
One participant incorrectly received a higher dose of amivantamab in cohort A but was later changed to cohort C despite receiving only one prior line of therapy in the metastatic setting.
Right-sided primary disease includes participants with primary tumors located in the ascending colon (cohort C, 39%), hepatic flexure (cohort C, 30%), or transverse colon (cohort C, 30%).
Left-sided primary disease includes participants with primary tumors located in the descending colon (cohort A, 6%; cohort B, 4%), retrosigmoid junction (cohort A, 12%; cohort B, 7%), or sigmoid colon (cohort A, 59%; cohort B, 44%).
Efficacy
Cohort A: Participants With Left-Sided mCRC Without Prior Anti-EGFR Exposure
At a median follow-up of 16.0 months (range, 2.3-22.3), the median duration of treatment was 6.9 months (range, 1.0-12.1). The investigator-assessed ORR was 29% (95% CI, 10 to 56). PR was observed in 5 (29%) participants, SD in 10 (59%) participants, and progressive disease (PD) in 2 (12%) participants (Fig 2A and Table 2). The median DoR was 9.0 months (95% CI, 7.3 to not estimable [NE]; Data Supplement, Fig S1A), the CBR was 71% (95% CI, 44 to 90), and the median PFS was 5.7 months (95% CI, 3.6 to 7.4). The Data Supplement (Table S2) shows overall survival (OS). No participants were still receiving amivantamab as of the CCO.
FIG 2.
Antitumor activity of amivantamab monotherapy in participants with left-sided mCRC (A) without or (B) with prior anti-EGFR exposure or (C) with right-sided mCRC. Data present the response-evaluable set, which includes patients who received ≥1 dose of the study drug, had ≥1 postbaseline efficacy disease assessment on or after 7 weeks, and did not discontinue treatment before that. CR, complete response; EGFR, epidermal growth factor receptor; mCRC, metastatic colorectal cancer; NE, not evaluable or unknown; PD, progressive disease; PR, partial response; SD, stable disease; SoD, sum of diameters.
TABLE 2.
Summary of Efficacy Outcomes
| End Point | Cohort A L-Sided, Without Prior EGFRi (n = 17) |
Cohort B L-Sided, With Prior EGFRi (n = 54) |
Cohort C R-Sided, With or Without Prior EGFRi (n = 23) |
|---|---|---|---|
| Follow-up, months, median (range) | 16.0 (2.3-22.3) | 13.7 (0.7-25.2) | 8.1 (0.6-20.3) |
| Objective response rate, % (95% CI) | 29 (10 to 56) | 19 (9 to 31) | 22 (8 to 44) |
| Best response, No. (%) | |||
| CR | 0 | 0 | 1 (4) |
| PR | 5 (29) | 10 (19) | 4 (17) |
| SD | 10 (59) | 29 (54) | 13 (57) |
| PD | 2 (12) | 14 (26) | 5 (22) |
| Not estimable/UNK | 0 | 1 (2) | 0 |
| DoR, months, median (95% CI) | 9.0 (7.3 to NE) | 6.1 (1.9 to 8.9) | 9.8 (3.7 to NE) |
| DoR ≥6 months, No. (%)a | 4 (80) | 5 (50) | 4 (80) |
| Clinical benefit rate, % (95% CI)b | 71 (44 to 90) | 52 (38 to 66) | 48 (27 to 69) |
| PFS, months, median (95% CI) | 5.7 (3.6 to 7.4) | 4.6 (3.5 to 5.6) | 3.7 (3.4 to 5.5) |
Abbreviations: CBR, clinical benefit rate; CR, complete response; DoR, duration of response; EGFRi, epidermal growth factor receptor inhibitor; NE, not estimable; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; UNK, unknown.
Among responders (cohort A: n = 5; cohort B: n = 10; cohort C: n = 5).
CBR is defined as the percentage of participants achieving confirmed CR, PR, or durable SD (duration of ≥11 weeks).
Cohort B: Participants With Left-Sided mCRC With Prior Anti-EGFR Exposure
At a median follow-up of 13.7 months (range, 0.7-25.2), the median duration of treatment was 5.1 months (range, 0-22.1). The investigator-assessed ORR was 19% (95% CI, 9 to 31). PR was observed in 10 (19%) participants, SD in 29 (54%) participants, and PD in 14 (26%) participants; 1 participant was not evaluable (Fig 2B and Table 2). The median DoR was 6.1 months (95% CI, 1.9 to 8.9; Data Supplement, Fig S1B), the CBR was 52% (95% CI, 38 to 66), and the median PFS was 4.6 months (95% CI, 3.5 to 5.6). Two participants were still receiving amivantamab as of the CCO.
EGFR Rechallenge Analysis in Cohort B
In cohort B, 29 participants were rechallenged with amivantamab ≤8.8 months (≤2 MD half-lives for RAS and EGFR-mutant clones17) and 25 participants rechallenged >8.8 months (>2 MD half-lives) since discontinuation of prior anti-EGFR therapy. Improved efficacy was seen in participants who had a longer interval between amivantamab rechallenge and prior anti-EGFR treatment (Data Supplement, Table S3 and Data Supplement, Fig S2). The ORR was 32% (95% CI, 14.9 to 53.5) versus 7% (95% CI, 0.8 to 22.8) among those with >8.8 months versus ≤8.8 months, respectively, since discontinuation of prior anti-EGFR treatment. Anti-EGFR treatment in the last line (Data Supplement, Table S3) and mutational analyses using baseline ctDNA were not predictive of response (Data Supplement, Fig S3). However, among participants who received anti-EGFR treatment in their last regimen, prior response to anti-EGFR treatment (ie, CR or PR) was associated with improved outcomes with amivantamab (Data Supplement, Table S1).
Cohort C: Participants With Right-Sided mCRC
At a median follow-up of 8.1 months (range, 0.6-20.3), the median duration of treatment was 3.3 months (range, 0-20.3). The investigator-assessed ORR was 22% (95% CI, 8 to 44). CR was observed in 1 (4%) participant, PR in 4 (17%) participants, SD in 13 (57%) participants, and PD in 5 (22%) participants (Fig 2C and Table 2). The median DoR was 9.8 months (95% CI, 3.7 to NE; Data Supplement, Fig S1C), the CBR was 48% (95% CI, 27 to 69), and the median PFS was 3.7 months (95% CI, 3.4 to 5.5). Three participants were still receiving amivantamab as of the CCO.
Safety
The safety profile was consistent with prior reports of amivantamab monotherapy (Table 3).18 Among all treatment-emergent adverse events (TEAEs), 50% (47 of 94) were grades 1-2, 41% (39 of 94) were grade 3, and 7% (7 of 94) were grades 4-5; TEAEs were expected because of EGFR and MET inhibition. The most common TEAEs were infusion-related reactions (54%), dermatitis acneiform (38%) and rash (31%; both being EGFR inhibitor–related), and hypoalbuminemia (31%; MET inhibitor–related). Grade ≥3 TEAEs were reported in 46 (49%) participants. Among these participants, 25 (27%) experienced grade ≥3 treatment-related AEs. The most frequent grade ≥3 treatment-related AEs were rash (7%), dermatitis acneiform (4%), and hypoalbuminemia (7%). Serious TEAEs were reported for 30 (32%) participants, 6 (6%) of which were considered related to treatment. Dose interruptions, reductions, and discontinuations because of TEAEs were seen in 41 (44%), 11 (12%), and 2 (2%) participants, respectively. Discontinuation because of a treatment-related AE (dermatitis) occurred in 1 (1%) participant.
TABLE 3.
Summary of TEAEs
| Event | N = 94, No. (%) |
|---|---|
| Any TEAE | 93 (99) |
| Grade ≥3 TEAE | 46 (49) |
| Serious TEAE | 30 (32) |
| Any TEAE leading to | |
| Dose interruption | 41 (44) |
| Dose reduction | 11 (12) |
| Discontinuation | 2 (2) |
| TEAE (≥20%) by Preferred Term | All Grade, No. (%) | Grade ≥3, No. (%) |
|---|---|---|
| Infusion-related reaction | 51 (54) | 1 (1) |
| Dermatitis acneiform | 36 (38) | 4 (4) |
| Rash | 29 (31) | 7 (7) |
| Hypoalbuminemia | 29 (31) | 7 (7) |
| Paronychia | 24 (26) | 1 (1) |
| Peripheral edema | 23 (24) | 1 (1) |
| Fatigue | 19 (20) | 2 (2) |
Abbreviation: TEAE, treatment-emergent adverse event.
Biomarker Analysis
Across all cohorts, a total of 76 participant samples passed quality control and had analyzable data. Treatment response was associated with high baseline mRNA expression of AREG and EREG, which are EGFR ligands and biomarkers of anti-EGFR treatment efficacy in mCRC15,16,19 (Data Supplement, Fig S4). In cohort A (n = 16), a trend for improved PFS was observed for participants with high (n = 8) versus low (n = 8) AREG expression (9.1 months v 4.5 months, respectively; P = .0076). A similar trend was not observed in cohorts B and C. Differentially expressed gene analyses in paired baseline and on-treatment (C3D1) samples showed significant changes in >800 genes (P < .01) across all cohorts (n = 17). Significant upregulation of dendritic cells (P < .005) and T cell–inflamed gene signatures (P < .05) with amivantamab treatment was observed in paired baseline and C3D1 tumor samples. Amivantamab also significantly increased the natural killer cell–mediated cytotoxicity and cytolytic gene signatures (both P < .05; Fig 3). Amivantamab significantly downregulated EGFR and cell cycle pathway signatures (both P < .01; Data Supplement, Fig S5). Amivantamab showed activity across a range of mutations, including those conferring resistance to anti-EGFR therapy (Data Supplement, Fig S6).
FIG 3.
Immune-related gene signature scores from paired baseline and C3D1 tumor samples: (A) Dendritic cell gene signature score,a,b (B) T cell–inflamed gene signature score,a,c (C) natural killer cell–mediated cytotoxicity gene signature score,a,d and (D) cytolytic gene signature score.a,e,f Blue lines indicate a best response of PR, and orange lines indicate a best response of SD. aSignificance of the score change was measured using the paired Wilcoxon test. bDendritic cell gene signature obtained from the BioCarta and ssGSEA databases was used to calculate the signature score. cThis 18-gene signature quantifies the T cell–inflamed microenvironment. dGene list included in the cell cycle pathway was collected from the KEGG website. Pathway scores were calculated using the ssGSEA method. eCytolytic score was defined as the mean of GZMA and PRF1. fRooney et al.31 C, cycle; CYT, cytolytic activity; D, day; PR, partial response; SD, stable disease.
DISCUSSION
In OrigAMI-1, amivantamab monotherapy elicited promising antitumor activity among participants with left-sided mCRC without prior anti-EGFR, with an ORR of 29%. Among participants with left-sided mCRC with prior anti-EGFR exposure, the ORR was 19%; however, a longer gap between prior anti-EGFR treatment and amivantamab treatment (>8.8 months) was associated with a higher ORR of 32%. Among participants with right-sided mCRC, a population historically less responsive to anti-EGFR therapies,20 amivantamab demonstrated an ORR of 22%. Responses were durable, as evidenced by median DoR for confirmed responders ranging from 6.1 to 9.8 months. The safety profile for amivantamab monotherapy in mCRC is consistent with that previously reported in NSCLC, and no new safety signals were observed.
Previous studies among patients with chemorefractory CRC (Data Supplement, Table S4) treated with anti-EGFR monotherapy have shown low response rates and poor PFS.3,5,21,22 The phase III ASPECCT study included participants with RAS WT mCRC who had disease progression or intolerance to irinotecan- and oxaliplatin-based therapy, had received a thymidylate synthase inhibitor, and had not received prior anti-EGFR therapy.5 The response rate with panitumumab was 22%, the median PFS was 4.1 months, and the median DoR was 3.8 months.5 In another study involving participants with KRAS WT CRC who previously received oxaliplatin-, irinotecan-, and fluoropyrimidine-based treatment (majority having three prior lines of therapy) and were anti-EGFR therapy–naïve, cetuximab monotherapy resulted in an ORR of 13% and a median PFS of 3.7 months.21 In a separate study involving 14 participants with right-sided RAS/BRAF WT mCRC evaluating the efficacy of anti-EGFR antibodies as monotherapy or in combination with irinotecan, participants who were treatment-naïve or received one or two prior lines of treatment did not gain clinical benefit (ORR, 0%).22 Differences in eligibility criteria, timing of the studies, and intervening changes to the clinical management of chemorefractory CRC in the aforementioned studies and OrigAMI-1 make benchmarking using previous studies problematic.
Nevertheless, results from OrigAMI-1 contribute to the clinical understanding of treatment for chemorefractory mCRC. Among participants who had a response with anti-EGFR treatment in any prior treatment line, 33% achieved a PR and 52% had SD with amivantamab. Among participants who had prior response with anti-EGFR in the last regimen, 60% achieved a PR and 40% had SD with amivantamab. These data build upon results reported in the phase II CHRONOS study that enrolled participants without RAS/BRAF or EGFR ectodomain mutations who had a CR or PR to anti-EGFR monotherapy or with chemotherapy, but had not received anti-EGFR treatment in the last regimen (by contrast, OrigAMI-1 allowed anti-EGFR therapy in any prior line).23 After panitumumab rechallenge at a median time of 11.5 months between the last anti-EGFR therapy and screening, efficacy was comparable with other chemorefractory treatments.23 Rechallenge with amivantamab in OrigAMI-1 demonstrated promising antitumor activity and prolonged PFS and OS for participants with a longer interval (>8.8 months) between prior anti-EGFR therapies compared with a shorter interval (≤8.8 months).
Biomarker analyses showed that amivantamab treatment is associated with downregulation of EGFR and cell cycle pathway signatures, which is consistent with the EGFR-MET–targeted antitumor activity of amivantamab. The immune cell–directing activity of amivantamab might have contributed to increases in cytotoxic immune cell signatures consistent with immune cell filtration into tumors. Elevated AREG and EREG baseline ligand expression correlated with response to amivantamab, which is consistent with prior findings showing that AREG and EREG expression correlates with response to anti-EGFR treatment and disease control.15,19,24,25 Moreover, these analyses provide further evidence that acquired genetic alterations in RAS, EGFR ectodomain, and MET, among others, are common mechanisms of resistance to anti-EGFR antibodies.26-28 Studies investigating the prognostic role of uncommon and rare genetic alterations using the PRESSING panel could identify additional mechanisms underlying the response to amivantamab in chemorefractory mCRC.29 Finally, amivantamab showed antitumor activity in tumors with genetic alterations across a range of mutations, including those associated with anti-EGFR antibody resistance (eg, PIK3CA alterations). These participants might not have been expected to respond to anti-EGFR treatment alone.
OrigAMI-1 has shown safety and efficacy with amivantamab monotherapy in the third-line treatment or later setting, and further research is ongoing to evaluate amivantamab in combination with chemotherapy (infusional fluorouracil, leucovorin, and oxaliplatin [FOLFOX] and leucovorin calcium, 5-fluorouracil, irinotecan [FOLFIRI]) earlier in the treatment of mCRC to understand how timing and mutational profile shape responses to amivantamab. Combination regimens (cohorts D and E, respectively) previously showed rapid and durable antitumor activity in participants with anti-EGFR therapy–naïve first- or second-line treatment for RAS/BRAF WT mCRC.30 Based on these data, combination regimens are being further evaluated in two phase III studies. The phase III OrigAMI-2 study (ClinicalTrials.gov identifier: NCT06662786) is evaluating subcutaneous amivantamab versus cetuximab, both in combination with FOLFOX or FOLFIRI, as first-line therapy for participants with left-sided RAS/BRAF WT unresectable or metastatic CRC. The phase III OrigAMI-3 study (ClinicalTrials.gov identifier: NCT06750094) is evaluating subcutaneous amivantamab plus FOLFIRI versus cetuximab or bevacizumab plus FOLFIRI as second-line therapy for participants with recurrent RAS/BRAF WT mCRC. These ongoing studies aim to assess the role of amivantamab as a key treatment option for CRC.
This study has limitations. Enrollment in cohort A and cohort C was closed at the first interim analysis; however, the data obtained provided promising efficacy and safety information in the context of this phase Ib/II study. Cohort C was closed at the interim analysis with one response observed at that time; however, five participants responded as the data matured. This finding suggests that response to amivantamab in right-sided mCRC is delayed, which highlights the importance of long-term follow-up. The EGFR rechallenge results should be considered in the context of small sample sizes and a potential survivor bias because participants who rechallenged >8.8 months after prior anti-EGFR therapy may represent a more promising cohort compared with those who rechallenged ≤8.8 months after prior anti-EGFR therapy. OrigAMI-1 participants were a highly selected population who were enrolled based on prior molecular characterization of tumors by ctDNA testing and history of anti-EGFR treatment. Phase III studies will be important to better understand the generalizable clinical utility of amivantamab in patients with other molecular subtypes of mCRC and prior treatment regimens.
In conclusion, amivantamab monotherapy demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in left- and right-sided mCRCs, including in participants with and without prior exposure to anti-EGFR monoclonal antibodies. Amivantamab, which is being investigated using the subcutaneous formulation with an improved convenience and safety profile plus chemotherapy for earlier lines of treatment in mCRC, may be a new treatment choice for patients with chemorefractory mCRC who currently have few efficacious options.
ACKNOWLEDGMENT
The authors would like to thank all the individuals who participated in this study and their families and caregivers, the physicians and nurses who cared for them, and the staff at the clinical sites. The authors would like to acknowledge Tsai-Sheng Yang of Chang Gung Memorial Hospital and Roland E. Knoblauch and Supriya Shah of Johnson & Johnson for their contributions to the study. Medical writing assistance was provided by Claire E. Brady, PharmD, and Michael Dyle, PhD (Lumanity Communications Inc.), and funded by Johnson & Johnson.
Paul E. Oberstein
Consulting or Advisory Role: Loxo/Lilly, Ipsen, Janssen Oncology, Boehringer Ingelheim, Jazz Pharmaceuticals, Revolution Medicines
Speakers' Bureau: Ipsen, Jazz Pharmaceuticals
Research Funding: Merck (Inst), Roche/Genentech (Inst), Arcus Biosciences (Inst), Novartis (Inst), Amal Therapeutics (Inst), Revolution Medicines (Inst), Loxo/Lilly (Inst)
Expert Testimony: Merck
Open Payments Link: https://openpaymentsdata.cms.gov/physician/284735
J. Randolph Hecht
Stock and Other Ownership Interests: Rafael Pharmaceuticals, Actym Therapeutics, Trumvira, Johnson & Johnson (I)
Consulting or Advisory Role: BeiGene, MBQ Pharma, Xilio Therapeutics, Agenus, Revolution Medicines, UroGen Pharma, Xilio Therapeutics, ALX Oncology, Civala, Fog Pharmaceuticals, Merus NV, Boehringer Ingelheim, Genmab, Cardiff Oncology, Cartography, Curium Pharma
Research Funding: Amgen (Inst), Merck (Inst), Gritstone Bio (Inst), Bold Therapeutics (Inst), Tizona Therapeutics, Inc (Inst), A2 Biotherapeutics (Inst), Gilead Sciences (Inst), Exelixis (Inst), NGM Biopharmaceuticals (Inst), Tizona Therapeutics, Inc (Inst), Camurus (Inst), CG Pharmaceuticals (Inst), Crinetics Pharmaceuticals (Inst), Lyell Immunopharma (Inst), Mirati Therapeutics (Inst), Xilio Therapeutics (Inst), Revolution Medicines (Inst), Regeneron (Inst), Agenus (Inst), Neogene Therapeutics (Inst), Affini-T Therapeutics (Inst), Janssen Oncology (Inst), Seagen (Inst), Cardiff Oncology (Inst)
Travel, Accommodations, Expenses: A2 Biotherapeutics
Kanwal Raghav
Honoraria: Bayer, Eisai, Merck, Daiichi Sankyo/AstraZeneca, Seagen
Consulting or Advisory Role: Bayer, Eisai, Merck, Daiichi Sankyo/AstraZeneca, Seagen
Research Funding: Bayer (Inst), Roche/Genentech (Inst), Guardant Health (Inst), HiberCell (Inst), Merck Serono (Inst), AbbVie (Inst), Eisai (Inst), Xencor (Inst), Innovent Biologics (Inst), Janssen (Inst), UCB (Inst), Daiichi Sankyo/AstraZeneca (Inst)
Filippo Pietrantonio
Honoraria: SERVIER, Bayer, MSD Oncology, Amgen, Pierre Fabre, Bristol Myers Squibb, Merck Serono, Astellas Pharma, Takeda, Ipsen, Johnson & Johnson, Rottapharm Biotech, Seagen, AstraZeneca, Daiichi-Sankyo, BeiGene, Incyte
Consulting or Advisory Role: Amgen, SERVIER, MSD Oncology, Bayer, Merck Serono, Takeda, GSK, Rottapharm Biotech, Johnson & Johnson/Janssen, Pfizer, Astellas Pharma, Bristol Myers Squibb, BeiGene, Agenus, Gilead Sciences, Daiichi-Sankyo, Incyte, Jazz Pharmaceuticals, Pierre Fabre, AstraZeneca, Revolution Medicines
Research Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst), Incyte (Inst), Agenus (Inst), Lilly (Inst), Amgen (Inst), Rottapharm Biotech (Inst), GSK (Inst), Johnson & Johnson/Janssen (Inst), BeOne (Inst)
Travel, Accommodations, Expenses: Pierre Fabre, Merck Serono, Takeda Science Foundation, Amgen, Astellas Pharma, Johnson & Johnson/Janssen
Dirk Arnold
Employment: Asklepios Kliniken
Honoraria: Merck Serono, SERVIER, Bristol Myers Squibb, Merck Sharp and Dome, AstraZeneca, Boston Scientific, Pierre Fabre, Gilead Sciences, GSK, Janssen Oncology, Sanofi/Regeneron, Seagen, Sirtex Medical, Takeda, TERUMO, Taiho Pharmaceutical, Incyte, Pfizer, Boehringer Ingelheim, Daiichi Sankyo Europe GmbH
Consulting or Advisory Role: Oncolytics, Phanes Therapeutics
Research Funding: Oncolytics (Inst)
Travel, Accommodations, Expenses: AstraZeneca, Daiichi Sankyo Europe GmbH
Uncompensated Relationships: ESMO, ESMO Open, Deputy Editor Clin Colorectal Cancer
Victor Moreno
Employment: START
Consulting or Advisory Role: Merck, Bristol Myers Squibb, Bayer, Janssen Oncology, Roche, Basilea, Affimed Therapeutics, AstraZeneca, AbbVie, Ellipses Pharma
Speakers' Bureau: Bayer, Pierre Fabre
Research Funding: AbbVie (Inst), ACEA Biosciences (Inst), Adaptimmune (Inst), Amgen (Inst), AstraZeneca (Inst), Bayer (Inst), BeiGene (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), Celgene (Inst), Eisai (Inst), E-therapeutics (Inst), GSK (Inst), Janssen (Inst), Menarini (Inst), Merck (Inst), Nanobiotix (Inst), Novartis (Inst), Pfizer (Inst), PharmaMar (Inst), PsiOxus Therapeutics (Inst), Puma Biotechnology (Inst), Regeneron (Inst), RigonTEC (Inst), Roche (Inst), Sanofi (Inst), Sierra Oncology (Inst), Synthon (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Tesaro (Inst), Transgene (Inst), MonTa Biosciences (Inst), Revolution Medicines (Inst), ADC Therapeutics (Inst), Ascendis Pharma (Inst), Bicycle Therapeutics (Inst), Bioinvent (Inst), Biomea Fusion (Inst), C4 Therapeutics (Inst), Constellation Pharmaceuticals (Inst), Crescendo Bioscience (Inst), Cullinan Oncology (Inst), F-Star Biotechnology (Inst), Genmab (Inst), Gray Wolf Therapeutics (Inst), Hemavant (Inst), HiFiBiO Therapeutics (Inst), Kinnate Biopharma (Inst)
Expert Testimony: Medscape/Bayer, Nanobiotix
Travel, Accommodations, Expenses: Sanofi/Regeneron
Other Relationship: Bristol Myers Squibb
Eric Van Cutsem
Consulting or Advisory Role: Bayer, Lilly, SERVIER, Bristol Myers Squibb, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Daiichi Sankyo, Pierre Fabre, Taiho Pharmaceutical, Astellas Pharma, GSK, Nordic Group, Pfizer, Takeda, ALX Oncology, AbbVie, BeiGene, Boehringer Ingelheim, Ipsen, Agenus, Amgen, Arcus Biosciences, ElmediX, Cantargia AB, Fosum, Galapagos NV, Novocure, Sanofi, Trishula Therapeutics, Biond Biologics, Cardiff Oncology, Corcept Therapeutics, CytomX Therapeutics, Fortvita, Gilead Sciences, Glenmark, Incyte, Jazz Pharmaceuticals, Johnson & Johnson/Janssen, Merus, Oncoshot, Oxford BioTherapeutics, Zuellig Pharma, Zymeworks
Rozita Abdul Malik
Research Funding: Novartis (Inst), Roche (Malaysia) Sdn Bhd (Inst), Janssen Research & Development (Inst), Merck Sharp & Dohme (Malaysia) Sdn Bhd (Inst), AstraZeneca (Inst)
Myung Ah Lee
Honoraria: Takeda, Merck
Consulting or Advisory Role: Green Cross, Onconic Therapeutics, Handok
Harvey Yu-Li Su
Honoraria: Pfizer, Takeda, Merck KGaA, Amgen, Boehringer Ingelheim, Johnson & Johnson/Janssen, Novartis, Fresenius Kabi, Bayer
Consulting or Advisory Role: MSD Oncology, Merck Serono, AstraZeneca, Astellas Pharma, Boehringer Ingelheim
Speakers' Bureau: Merck KGaA, Pfizer
Travel, Accommodations, Expenses: Merck KGaA, Takeda
Jeeyun Lee
Consulting or Advisory Role: AstraZeneca, Trutino Biosciences, Amgen, Daichi Sankyo, Immunoncia, Bristol Myers Squibb, AbbVie, Samsung Bioepis (Inst), Samsung Biologics (Inst), Samsung Electronics (Inst)
Research Funding: AstraZeneca, Merck Sharp & Dohme, Samsung Biopeis
Sreenivasa Chandana
Leadership: The Cancer & Hematology Centers
Consulting or Advisory Role: IPSEN, AstraZeneca, Novocure
Speakers' Bureau: Natera
Research Funding: AbbVie (Inst), Merck (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Exact Sciences (Inst), Zymeworks (Inst), AstraZeneca (Inst), Mirati Therapeutics (Inst), Elevation Oncology (Inst), Adcentrx Therapeutics (Inst), Amgen (Inst), Cardiff Oncology (Inst), Dicephera Pharmaceuticals, Inc (Inst), Genentech/Roche (Inst), IDEAYA Biosciences (Inst), IgM Biosciences (Inst), Incyte (Inst), Ipsen (Inst), Novocure (Inst), Qualigen Therapeutics (Inst), Janssen (Inst), BioNTech SE (Inst), Corcept Therapeutics (Inst), Arvinas (Inst), Chugai Pharma (Inst), Halda Therapeutics (Inst), IDEAYA Biosciences (Inst), Johnson & Johnson/Janssen (Inst), Monte Rosa Therapeutics (Inst), Rondo Therapeutics (Inst), Tizona Therapeutics, Inc (Inst), Exelixis (Inst), Medlink (Inst)
Marcia Cruz-Correa
Employment: Pan American Center for Oncology Trials
Stock and Other Ownership Interests: Pan American Center for Oncology Trials
Consulting or Advisory Role: BeOne Pharmaceutical
Research Funding: Janssen (Inst), Merck (Inst), BeiGene (Inst), Bristol Myers Squibb/Celgene (Inst), Pfizer (Inst), Genentech/Roche (Inst), AbbVie (Inst), GENFIT (Inst), VMO (Inst), HUYA Bioscience International (Inst), Incyte Japan (Inst), Astellas Pharma (Inst), Boehringer Ingelheim (Inst)
Eric Xueyu Chen
Honoraria: Eisai, Merck, Roche, GSK, Takeda, Daiichi Sankyo/AstraZeneca, Bristol Myers Squibb, AbbVie, Amgen, Incyte
Research Funding: AstraZeneca/MedImmune (Inst), Bristol Myers Squibb (Inst), Mirati Therapeutics (Inst), Roche Canada (Inst), 1Globe Health Institute (Inst), Repare Therapeutics (Inst), GSK (Inst), Janssen Oncology (Inst), Pfizer, BNT (Inst), Ono Pharmaceutical (Inst), Nouscom (Inst)
Elena Elez
Honoraria: Bristol Myers Squibb, SERVIER, Amgen, Merck Serono, Merck, Novartis, Takeda, Pfizer, Bayer, Boehringer Ingelheim, Cure Teq AG, Roche, Janssen, Lilly, Medscape, MSD, Pierre Fabre, Repare Therapeutics, RIN Institute Inc, Agenus, GSK, Nordic Group BV, Johnson & Johnson, Rottapharm Biotech, Sanofi, Seagan
Consulting or Advisory Role: Amgen, Merck Serono, Sanofi, SERVIER, Bayer, Bristol Myers Squibb, Pierre Fabre, MSD, Boehringer Ingelheim, Cure Teq AG, Roche, Janssen, Novartis, Pfizer, Repare Therapeutics Inc, RIN Institute Inc, Takeda, Merck, Agenus, GSK, Johnson & Johnson, Nordic Group BV, Rottapharm Biotech, Lilly, Medscape, Seagan (Inst)
Speakers' Bureau: Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cure Teq AG, GSK, Roche, Janssen, Johnson & Johnson, Lilly, Medscape, Merck Serono, MSD, Nordic Group BV, Novartis, Merck, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Rottapharm Biotech, Sanofi, SERVIER, Takeda, Agenus, Seagan (Inst)
Research Funding: 1Globe Health Institute (Inst), Agenus (Inst), Amgen (Inst), Artios (Inst), AstraZeneca (Inst), Biontech Rna Pharmaceuticals Gmbh (Inst), Biontech Small Molecules Gmbh (Inst), Bristol Myers Squibb International Corporation (Bms) (Inst), Exelixis (Inst), Roche (Inst), Fédération Francophone De Cancérologie Digestive (Inst), GSK (Inst), Grupo de Tratamiento de los Tumores Digestivos (TTD) (Inst), Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD) (Inst), Istituto Fondazione AIRC di Oncologia Molecolare (IFOM) (Inst), INCLIVA Instituto de Investigación Sanitaria (Inst), InhibRx (Inst), Janssen Research & Development (Inst), Janssen-Cilag SA (Inst), Merck (Inst), Merck, Sharp & Dohme de España SA (Inst), Msd Regional Business Support Center Gmbh (Inst), Nouscom (Inst), Pfizer (Inst), Roche (Inst), Seagen (Inst), Cancer Research UK (Inst), Fundación CRIS Contra el Cáncer (Inst), Instituto de Salud Carlos III (ISCIII) (Inst)
Travel, Accommodations, Expenses: Merck Serono, Sanofi, Amgen, SERVIER, Bristol Myers Squibb, Bayer, Boehringer Ingelheim, Cure Teq AG, Janssen, Lilly, Medscape, MSD, Novartis, Merck, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute Inc, Seagan, Takeda, Agenus, GSK, Johnson & Johnson, Nordic Group BV, Rottapharm Biotech, Roche
Chia-Chi Lin
Honoraria: Novartis, Roche, Daiichi Sankyo, Novartis, Lilly
Consulting or Advisory Role: Novartis, Boehringer Ingelheim, Blueprint Medicines, Daiichi Sankyo, AbbVie, PharmaEngine, Bristol Myers Squibb, Bayer, IMPAC Medical Systems, Anbogen Therapeutics
Travel, Accommodations, Expenses: Lilly, Daiichi Sankyo, BeiGene, IMPAC Medical Systems
Carlos Lopez
Honoraria: Roche, Merck, Eisai, Ipsen, AstraZeneca, SERVIER, Bristol Myers Squibb, MSD Oncology, Advanced Accelerator Applications, GSK
Consulting or Advisory Role: Amgen, Roche, Merck, SERVIER, Ipsen, Bayer, Eisai, AstraZeneca, Takeda
Research Funding: Amgen, Roche, Merck, Merck Sharp & Dohme, AstraZeneca Spain, Ipsen, Eisai, Bristol Myers Squibb, GSK
Travel, Accommodations, Expenses: Roche, Merck, SERVIER, Amgen, Ipsen, Advanced Accelerator Applications
Hans Prenen
Honoraria: Amgen, AstraZeneca, Merck
Consulting or Advisory Role: Biocartis, AstraZeneca
Susana Roselló-Keränen
Research Funding: Pfizer (Inst), Novartis (Inst), GSK (Inst), Janssen Oncology (Inst), Mirati Therapeutics (Inst), Inspirna (Inst), Roche (Inst), Nouscom (Inst)
Yu-Min Yeh
Consulting or Advisory Role: Guardant Health, Ono Pharmaceutical, Pfizer
Volker Heinemann
Stock and Other Ownership Interests: BioNTech SE
Honoraria: Roche, Amgen, Sanofi, Merck, SERVIER, Pfizer, Pierre Fabre, AstraZeneca, MSD, Seagen, Novartis, Boehringer Ingelheim, Sirtex Medical, GSK, Oncosil
Consulting or Advisory Role: Merck, Amgen, Roche, MSD, Pierre Fabre, GSK, Servier/Pfizer, AstraZeneca, Oncosil, Nordic Bioscience, Janssen, IOMX, SYSMEX, Isofol Medical, Natera, Takeda, AbbVie
Research Funding: Merck (Inst), Amgen (Inst), Roche (Inst), Servier (Inst)
Expert Testimony: Servier, Oncosil
Travel, Accommodations, Expenses: Merck, AstraZeneca, Amgen, MSD, Nordic Bioscience
Cathy Eng
Consulting or Advisory Role: Pfizer, Amgen (I), Taiho Oncology (I), AbbVie, Takeda, Merus, Agenus, EMD Serono, Revolution Medicines, Incyte, Boehringer Ingelheim, Gilead Sciences, Merck, GSK, Bristol Myers Squibb Foundation
Research Funding: Hutchison MediPharma (Inst), Merck (Inst), Gritstone Bio (Inst), Janssen Oncology (Inst), Pfizer (Inst), Sumitomo Dainippon Pharma Oncology (Inst)
Travel, Accommodations, Expenses: Takeda
Seung-Hoon Beom
Honoraria: Jeil Pharmaceutical Co, Takeda, Astellas Pharma
Consulting or Advisory Role: Amgen, Astellas Pharma, Guardant Health, Jeil Pharmaceutical Co, Ono Pharmaceutical, IMBdx
Research Funding: Roche (Inst), MSD (Inst), Bayer (Inst), Johnson & Johnson/Janssen (Inst), Takeda (Inst), Jeil Pharmaceutical Co (Inst), Merck (Inst), ST Cube (Inst), Pfizer (Inst), Amgen (Inst), Revolution Medicines (Inst), IgM Biosciences (Inst)
Sabine Tejpar
Consulting or Advisory Role: Boehringer Ingelheim, GSK, Agenus
Speakers' Bureau: Merck Serono, Sanofi, Roche, Bristol Myers Squibb, MSD
Research Funding: GSK, Bristol Myers Squibb GmbH & Co KG
Travel, Accommodations, Expenses: Sanofi, Amgen, Roche, Merck Serono, Bayer
Sanjib Chowdhury
Employment: Janssen Research & Development
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Xuesong Lyu
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Medha Kamat
Employment: Johnson & Johnson/Janssen (I)
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Joshua C. Curtin
Employment: Janssen Research & Development
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Bharvin Patel
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
John Xie
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Rianka Bhattacharya
Employment: Johnson & Johnson/Janssen
Robert W. Schnepp
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Emrullah Yilmaz
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Ryota Iwasawa
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Patents, Royalties, Other Intellectual Property: Johnson & Johnson IP
Travel, Accommodations, Expenses: Johnson & Johnson
Mahesh Daksh
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Travel, Accommodations, Expenses: Johnson & Johnson
Patricia Lorenzini
Employment: Janssen Pharmaceuticals of Johnson & Johnson
Meena Thayu
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Other Relationship: Janssen Oncology
Mahadi Baig
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Sae-Won Han
Stock and Other Ownership Interests: IMBdx
Consulting or Advisory Role: AstraZeneca, Natera, AbbVie, IMBdx
Research Funding: IMBdx (Inst), Hanmi (Inst), Loxo (Inst), Roche (Inst), Genentech (Inst), Mirati Therapeutics (Inst), Arcus Biosciences (Inst), MSD (Inst), BeyondBio (Inst), GC Pharma (Inst), Jeil Pharmaceutical Co (Inst), Janssen (Inst), Lilly (Inst), MedImmune (Inst), Seagen (Inst), Hengrui Pharmaceutical (Inst), GSK (Inst), AstraZeneca (Inst), Astellas Pharma (Inst), AbbVie (Inst), Cell Biotech (Inst), Merck KGaA (Inst), Boryung (Inst)
No other potential conflicts of interest were reported.
PRIOR PRESENTATION
Presented at the ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, January 18-20, 2024; ASCO Gastrointestinal Cancers Symposium, San Francisco, CA, January 23-25, 2025; ASCO Annual Meeting, Chicago, IL, May 30-June 3, 2025; and ESMO Gastrointestinal Cancers Congress, Barcelona, Spain, July 2-5, 2025.
SUPPORT
Supported by Janssen Research & Development, LLC, a Johnson & Johnson Company.
CLINICAL TRIAL INFORMATION
Supplementary Materials
Protocols
DATA SHARING STATEMENT
A data sharing statement provided by the authors is available with this article at DOI https://doi.org/10.1200/JCO-25-02187. The data sharing policy of Johnson & Johnson is available at https://innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.
AUTHOR CONTRIBUTIONS
Conception and design: Paul E. Oberstein, Dirk Arnold, Eric Van Cutsem, Marcia Cruz-Correa, Sanjib Chowdhury, Medha Kamat, John Xie, Rianka Bhattacharya, Robert W. Schnepp, Emrullah Yilmaz, Ryota Iwasawa, Meena Thayu, Mahadi Baig, Han Sang Kim
Provision of study materials or patients: J. Randolph Hecht, Filippo Pietrantonio, Dirk Arnold, Eric Van Cutsem, Myung Ah Lee, Marcia Cruz-Correa, Ying Yuan, Azura Ahmad, Hung-Chih Hsu, Eric Xueyu Chen, Elena Elez, Chia-Chi Lin, Hans Prenen, Susana Roselló-Keränen, Yu-Min Yeh, Volker Heinemann, Cathy Eng, Sabine Tejpar, Rianka Bhattacharya, Robert W. Schnepp, Han Sang Kim
Collection and assembly of data: Paul E. Oberstein, J. Randolph Hecht, Kanwal Raghav, Filippo Pietrantonio, Dirk Arnold, Victor Moreno, Eric Van Cutsem, Rozita Abdul Malik, Yong Sang Hong, Myung Ah Lee, Harvey Yu-Li Su, Jeeyun Lee, Sreenivasa Chandana, Marcia Cruz-Correa, Ying Yuan, Azura Ahmad, Kuan-Ming Lai, Hung-Chih Hsu, Eric Xueyu Chen, Elena Elez, Chia-Chi Lin, Carlos Lopez, Hans Prenen, Susana Roselló-Keränen, Hector Velez, Yu-Min Yeh, Volker Heinemann, Seung-Hoon Beom, Sabine Tejpar, Sanjib Chowdhury, Medha Kamat, Robert W. Schnepp, Emrullah Yilmaz, Ryota Iwasawa, Mahesh Daksh, Patricia Lorenzini, Meena Thayu, Mahadi Baig, Han Sang Kim, Sae-Won Han
Data analysis and interpretation: Paul E. Oberstein, J. Randolph Hecht, Kanwal Raghav, Filippo Pietrantonio, Dirk Arnold, Victor Moreno, Eric Van Cutsem, Myung Ah Lee, Sreenivasa Chandana, Marcia Cruz-Correa, Eric Xueyu Chen, Elena Elez, Chia-Chi Lin, Volker Heinemann, Cathy Eng, Sanjib Chowdhury, Xuesong Lyu, Joshua C. Curtin, Bharvin Patel, John Xie, Rianka Bhattacharya, Emrullah Yilmaz, Ryota Iwasawa, Mahesh Daksh, Meena Thayu, Mahadi Baig, Han Sang Kim, Sae-Won Han
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.
Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).
Paul E. Oberstein
Consulting or Advisory Role: Loxo/Lilly, Ipsen, Janssen Oncology, Boehringer Ingelheim, Jazz Pharmaceuticals, Revolution Medicines
Speakers' Bureau: Ipsen, Jazz Pharmaceuticals
Research Funding: Merck (Inst), Roche/Genentech (Inst), Arcus Biosciences (Inst), Novartis (Inst), Amal Therapeutics (Inst), Revolution Medicines (Inst), Loxo/Lilly (Inst)
Expert Testimony: Merck
Open Payments Link: https://openpaymentsdata.cms.gov/physician/284735
J. Randolph Hecht
Stock and Other Ownership Interests: Rafael Pharmaceuticals, Actym Therapeutics, Trumvira, Johnson & Johnson (I)
Consulting or Advisory Role: BeiGene, MBQ Pharma, Xilio Therapeutics, Agenus, Revolution Medicines, UroGen Pharma, Xilio Therapeutics, ALX Oncology, Civala, Fog Pharmaceuticals, Merus NV, Boehringer Ingelheim, Genmab, Cardiff Oncology, Cartography, Curium Pharma
Research Funding: Amgen (Inst), Merck (Inst), Gritstone Bio (Inst), Bold Therapeutics (Inst), Tizona Therapeutics, Inc (Inst), A2 Biotherapeutics (Inst), Gilead Sciences (Inst), Exelixis (Inst), NGM Biopharmaceuticals (Inst), Tizona Therapeutics, Inc (Inst), Camurus (Inst), CG Pharmaceuticals (Inst), Crinetics Pharmaceuticals (Inst), Lyell Immunopharma (Inst), Mirati Therapeutics (Inst), Xilio Therapeutics (Inst), Revolution Medicines (Inst), Regeneron (Inst), Agenus (Inst), Neogene Therapeutics (Inst), Affini-T Therapeutics (Inst), Janssen Oncology (Inst), Seagen (Inst), Cardiff Oncology (Inst)
Travel, Accommodations, Expenses: A2 Biotherapeutics
Kanwal Raghav
Honoraria: Bayer, Eisai, Merck, Daiichi Sankyo/AstraZeneca, Seagen
Consulting or Advisory Role: Bayer, Eisai, Merck, Daiichi Sankyo/AstraZeneca, Seagen
Research Funding: Bayer (Inst), Roche/Genentech (Inst), Guardant Health (Inst), HiberCell (Inst), Merck Serono (Inst), AbbVie (Inst), Eisai (Inst), Xencor (Inst), Innovent Biologics (Inst), Janssen (Inst), UCB (Inst), Daiichi Sankyo/AstraZeneca (Inst)
Filippo Pietrantonio
Honoraria: SERVIER, Bayer, MSD Oncology, Amgen, Pierre Fabre, Bristol Myers Squibb, Merck Serono, Astellas Pharma, Takeda, Ipsen, Johnson & Johnson, Rottapharm Biotech, Seagen, AstraZeneca, Daiichi-Sankyo, BeiGene, Incyte
Consulting or Advisory Role: Amgen, SERVIER, MSD Oncology, Bayer, Merck Serono, Takeda, GSK, Rottapharm Biotech, Johnson & Johnson/Janssen, Pfizer, Astellas Pharma, Bristol Myers Squibb, BeiGene, Agenus, Gilead Sciences, Daiichi-Sankyo, Incyte, Jazz Pharmaceuticals, Pierre Fabre, AstraZeneca, Revolution Medicines
Research Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst), Incyte (Inst), Agenus (Inst), Lilly (Inst), Amgen (Inst), Rottapharm Biotech (Inst), GSK (Inst), Johnson & Johnson/Janssen (Inst), BeOne (Inst)
Travel, Accommodations, Expenses: Pierre Fabre, Merck Serono, Takeda Science Foundation, Amgen, Astellas Pharma, Johnson & Johnson/Janssen
Dirk Arnold
Employment: Asklepios Kliniken
Honoraria: Merck Serono, SERVIER, Bristol Myers Squibb, Merck Sharp and Dome, AstraZeneca, Boston Scientific, Pierre Fabre, Gilead Sciences, GSK, Janssen Oncology, Sanofi/Regeneron, Seagen, Sirtex Medical, Takeda, TERUMO, Taiho Pharmaceutical, Incyte, Pfizer, Boehringer Ingelheim, Daiichi Sankyo Europe GmbH
Consulting or Advisory Role: Oncolytics, Phanes Therapeutics
Research Funding: Oncolytics (Inst)
Travel, Accommodations, Expenses: AstraZeneca, Daiichi Sankyo Europe GmbH
Uncompensated Relationships: ESMO, ESMO Open, Deputy Editor Clin Colorectal Cancer
Victor Moreno
Employment: START
Consulting or Advisory Role: Merck, Bristol Myers Squibb, Bayer, Janssen Oncology, Roche, Basilea, Affimed Therapeutics, AstraZeneca, AbbVie, Ellipses Pharma
Speakers' Bureau: Bayer, Pierre Fabre
Research Funding: AbbVie (Inst), ACEA Biosciences (Inst), Adaptimmune (Inst), Amgen (Inst), AstraZeneca (Inst), Bayer (Inst), BeiGene (Inst), Bristol Myers Squibb (Inst), Boehringer Ingelheim (Inst), Celgene (Inst), Eisai (Inst), E-therapeutics (Inst), GSK (Inst), Janssen (Inst), Menarini (Inst), Merck (Inst), Nanobiotix (Inst), Novartis (Inst), Pfizer (Inst), PharmaMar (Inst), PsiOxus Therapeutics (Inst), Puma Biotechnology (Inst), Regeneron (Inst), RigonTEC (Inst), Roche (Inst), Sanofi (Inst), Sierra Oncology (Inst), Synthon (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst), Tesaro (Inst), Transgene (Inst), MonTa Biosciences (Inst), Revolution Medicines (Inst), ADC Therapeutics (Inst), Ascendis Pharma (Inst), Bicycle Therapeutics (Inst), Bioinvent (Inst), Biomea Fusion (Inst), C4 Therapeutics (Inst), Constellation Pharmaceuticals (Inst), Crescendo Bioscience (Inst), Cullinan Oncology (Inst), F-Star Biotechnology (Inst), Genmab (Inst), Gray Wolf Therapeutics (Inst), Hemavant (Inst), HiFiBiO Therapeutics (Inst), Kinnate Biopharma (Inst)
Expert Testimony: Medscape/Bayer, Nanobiotix
Travel, Accommodations, Expenses: Sanofi/Regeneron
Other Relationship: Bristol Myers Squibb
Eric Van Cutsem
Consulting or Advisory Role: Bayer, Lilly, SERVIER, Bristol Myers Squibb, Merck Sharp & Dohme, Merck KGaA, Novartis, AstraZeneca, Daiichi Sankyo, Pierre Fabre, Taiho Pharmaceutical, Astellas Pharma, GSK, Nordic Group, Pfizer, Takeda, ALX Oncology, AbbVie, BeiGene, Boehringer Ingelheim, Ipsen, Agenus, Amgen, Arcus Biosciences, ElmediX, Cantargia AB, Fosum, Galapagos NV, Novocure, Sanofi, Trishula Therapeutics, Biond Biologics, Cardiff Oncology, Corcept Therapeutics, CytomX Therapeutics, Fortvita, Gilead Sciences, Glenmark, Incyte, Jazz Pharmaceuticals, Johnson & Johnson/Janssen, Merus, Oncoshot, Oxford BioTherapeutics, Zuellig Pharma, Zymeworks
Rozita Abdul Malik
Research Funding: Novartis (Inst), Roche (Malaysia) Sdn Bhd (Inst), Janssen Research & Development (Inst), Merck Sharp & Dohme (Malaysia) Sdn Bhd (Inst), AstraZeneca (Inst)
Myung Ah Lee
Honoraria: Takeda, Merck
Consulting or Advisory Role: Green Cross, Onconic Therapeutics, Handok
Harvey Yu-Li Su
Honoraria: Pfizer, Takeda, Merck KGaA, Amgen, Boehringer Ingelheim, Johnson & Johnson/Janssen, Novartis, Fresenius Kabi, Bayer
Consulting or Advisory Role: MSD Oncology, Merck Serono, AstraZeneca, Astellas Pharma, Boehringer Ingelheim
Speakers' Bureau: Merck KGaA, Pfizer
Travel, Accommodations, Expenses: Merck KGaA, Takeda
Jeeyun Lee
Consulting or Advisory Role: AstraZeneca, Trutino Biosciences, Amgen, Daichi Sankyo, Immunoncia, Bristol Myers Squibb, AbbVie, Samsung Bioepis (Inst), Samsung Biologics (Inst), Samsung Electronics (Inst)
Research Funding: AstraZeneca, Merck Sharp & Dohme, Samsung Biopeis
Sreenivasa Chandana
Leadership: The Cancer & Hematology Centers
Consulting or Advisory Role: IPSEN, AstraZeneca, Novocure
Speakers' Bureau: Natera
Research Funding: AbbVie (Inst), Merck (Inst), Pfizer (Inst), Bristol Myers Squibb (Inst), Exact Sciences (Inst), Zymeworks (Inst), AstraZeneca (Inst), Mirati Therapeutics (Inst), Elevation Oncology (Inst), Adcentrx Therapeutics (Inst), Amgen (Inst), Cardiff Oncology (Inst), Dicephera Pharmaceuticals, Inc (Inst), Genentech/Roche (Inst), IDEAYA Biosciences (Inst), IgM Biosciences (Inst), Incyte (Inst), Ipsen (Inst), Novocure (Inst), Qualigen Therapeutics (Inst), Janssen (Inst), BioNTech SE (Inst), Corcept Therapeutics (Inst), Arvinas (Inst), Chugai Pharma (Inst), Halda Therapeutics (Inst), IDEAYA Biosciences (Inst), Johnson & Johnson/Janssen (Inst), Monte Rosa Therapeutics (Inst), Rondo Therapeutics (Inst), Tizona Therapeutics, Inc (Inst), Exelixis (Inst), Medlink (Inst)
Marcia Cruz-Correa
Employment: Pan American Center for Oncology Trials
Stock and Other Ownership Interests: Pan American Center for Oncology Trials
Consulting or Advisory Role: BeOne Pharmaceutical
Research Funding: Janssen (Inst), Merck (Inst), BeiGene (Inst), Bristol Myers Squibb/Celgene (Inst), Pfizer (Inst), Genentech/Roche (Inst), AbbVie (Inst), GENFIT (Inst), VMO (Inst), HUYA Bioscience International (Inst), Incyte Japan (Inst), Astellas Pharma (Inst), Boehringer Ingelheim (Inst)
Eric Xueyu Chen
Honoraria: Eisai, Merck, Roche, GSK, Takeda, Daiichi Sankyo/AstraZeneca, Bristol Myers Squibb, AbbVie, Amgen, Incyte
Research Funding: AstraZeneca/MedImmune (Inst), Bristol Myers Squibb (Inst), Mirati Therapeutics (Inst), Roche Canada (Inst), 1Globe Health Institute (Inst), Repare Therapeutics (Inst), GSK (Inst), Janssen Oncology (Inst), Pfizer, BNT (Inst), Ono Pharmaceutical (Inst), Nouscom (Inst)
Elena Elez
Honoraria: Bristol Myers Squibb, SERVIER, Amgen, Merck Serono, Merck, Novartis, Takeda, Pfizer, Bayer, Boehringer Ingelheim, Cure Teq AG, Roche, Janssen, Lilly, Medscape, MSD, Pierre Fabre, Repare Therapeutics, RIN Institute Inc, Agenus, GSK, Nordic Group BV, Johnson & Johnson, Rottapharm Biotech, Sanofi, Seagan
Consulting or Advisory Role: Amgen, Merck Serono, Sanofi, SERVIER, Bayer, Bristol Myers Squibb, Pierre Fabre, MSD, Boehringer Ingelheim, Cure Teq AG, Roche, Janssen, Novartis, Pfizer, Repare Therapeutics Inc, RIN Institute Inc, Takeda, Merck, Agenus, GSK, Johnson & Johnson, Nordic Group BV, Rottapharm Biotech, Lilly, Medscape, Seagan (Inst)
Speakers' Bureau: Amgen, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Cure Teq AG, GSK, Roche, Janssen, Johnson & Johnson, Lilly, Medscape, Merck Serono, MSD, Nordic Group BV, Novartis, Merck, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Rottapharm Biotech, Sanofi, SERVIER, Takeda, Agenus, Seagan (Inst)
Research Funding: 1Globe Health Institute (Inst), Agenus (Inst), Amgen (Inst), Artios (Inst), AstraZeneca (Inst), Biontech Rna Pharmaceuticals Gmbh (Inst), Biontech Small Molecules Gmbh (Inst), Bristol Myers Squibb International Corporation (Bms) (Inst), Exelixis (Inst), Roche (Inst), Fédération Francophone De Cancérologie Digestive (Inst), GSK (Inst), Grupo de Tratamiento de los Tumores Digestivos (TTD) (Inst), Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD) (Inst), Istituto Fondazione AIRC di Oncologia Molecolare (IFOM) (Inst), INCLIVA Instituto de Investigación Sanitaria (Inst), InhibRx (Inst), Janssen Research & Development (Inst), Janssen-Cilag SA (Inst), Merck (Inst), Merck, Sharp & Dohme de España SA (Inst), Msd Regional Business Support Center Gmbh (Inst), Nouscom (Inst), Pfizer (Inst), Roche (Inst), Seagen (Inst), Cancer Research UK (Inst), Fundación CRIS Contra el Cáncer (Inst), Instituto de Salud Carlos III (ISCIII) (Inst)
Travel, Accommodations, Expenses: Merck Serono, Sanofi, Amgen, SERVIER, Bristol Myers Squibb, Bayer, Boehringer Ingelheim, Cure Teq AG, Janssen, Lilly, Medscape, MSD, Novartis, Merck, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute Inc, Seagan, Takeda, Agenus, GSK, Johnson & Johnson, Nordic Group BV, Rottapharm Biotech, Roche
Chia-Chi Lin
Honoraria: Novartis, Roche, Daiichi Sankyo, Novartis, Lilly
Consulting or Advisory Role: Novartis, Boehringer Ingelheim, Blueprint Medicines, Daiichi Sankyo, AbbVie, PharmaEngine, Bristol Myers Squibb, Bayer, IMPAC Medical Systems, Anbogen Therapeutics
Travel, Accommodations, Expenses: Lilly, Daiichi Sankyo, BeiGene, IMPAC Medical Systems
Carlos Lopez
Honoraria: Roche, Merck, Eisai, Ipsen, AstraZeneca, SERVIER, Bristol Myers Squibb, MSD Oncology, Advanced Accelerator Applications, GSK
Consulting or Advisory Role: Amgen, Roche, Merck, SERVIER, Ipsen, Bayer, Eisai, AstraZeneca, Takeda
Research Funding: Amgen, Roche, Merck, Merck Sharp & Dohme, AstraZeneca Spain, Ipsen, Eisai, Bristol Myers Squibb, GSK
Travel, Accommodations, Expenses: Roche, Merck, SERVIER, Amgen, Ipsen, Advanced Accelerator Applications
Hans Prenen
Honoraria: Amgen, AstraZeneca, Merck
Consulting or Advisory Role: Biocartis, AstraZeneca
Susana Roselló-Keränen
Research Funding: Pfizer (Inst), Novartis (Inst), GSK (Inst), Janssen Oncology (Inst), Mirati Therapeutics (Inst), Inspirna (Inst), Roche (Inst), Nouscom (Inst)
Yu-Min Yeh
Consulting or Advisory Role: Guardant Health, Ono Pharmaceutical, Pfizer
Volker Heinemann
Stock and Other Ownership Interests: BioNTech SE
Honoraria: Roche, Amgen, Sanofi, Merck, SERVIER, Pfizer, Pierre Fabre, AstraZeneca, MSD, Seagen, Novartis, Boehringer Ingelheim, Sirtex Medical, GSK, Oncosil
Consulting or Advisory Role: Merck, Amgen, Roche, MSD, Pierre Fabre, GSK, Servier/Pfizer, AstraZeneca, Oncosil, Nordic Bioscience, Janssen, IOMX, SYSMEX, Isofol Medical, Natera, Takeda, AbbVie
Research Funding: Merck (Inst), Amgen (Inst), Roche (Inst), Servier (Inst)
Expert Testimony: Servier, Oncosil
Travel, Accommodations, Expenses: Merck, AstraZeneca, Amgen, MSD, Nordic Bioscience
Cathy Eng
Consulting or Advisory Role: Pfizer, Amgen (I), Taiho Oncology (I), AbbVie, Takeda, Merus, Agenus, EMD Serono, Revolution Medicines, Incyte, Boehringer Ingelheim, Gilead Sciences, Merck, GSK, Bristol Myers Squibb Foundation
Research Funding: Hutchison MediPharma (Inst), Merck (Inst), Gritstone Bio (Inst), Janssen Oncology (Inst), Pfizer (Inst), Sumitomo Dainippon Pharma Oncology (Inst)
Travel, Accommodations, Expenses: Takeda
Seung-Hoon Beom
Honoraria: Jeil Pharmaceutical Co, Takeda, Astellas Pharma
Consulting or Advisory Role: Amgen, Astellas Pharma, Guardant Health, Jeil Pharmaceutical Co, Ono Pharmaceutical, IMBdx
Research Funding: Roche (Inst), MSD (Inst), Bayer (Inst), Johnson & Johnson/Janssen (Inst), Takeda (Inst), Jeil Pharmaceutical Co (Inst), Merck (Inst), ST Cube (Inst), Pfizer (Inst), Amgen (Inst), Revolution Medicines (Inst), IgM Biosciences (Inst)
Sabine Tejpar
Consulting or Advisory Role: Boehringer Ingelheim, GSK, Agenus
Speakers' Bureau: Merck Serono, Sanofi, Roche, Bristol Myers Squibb, MSD
Research Funding: GSK, Bristol Myers Squibb GmbH & Co KG
Travel, Accommodations, Expenses: Sanofi, Amgen, Roche, Merck Serono, Bayer
Sanjib Chowdhury
Employment: Janssen Research & Development
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Xuesong Lyu
Employment: Johnson & Johnson/Janssen
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Medha Kamat
Employment: Johnson & Johnson/Janssen (I)
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Joshua C. Curtin
Employment: Janssen Research & Development
Stock and Other Ownership Interests: Johnson & Johnson/Janssen
Bharvin Patel
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
John Xie
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Rianka Bhattacharya
Employment: Johnson & Johnson/Janssen
Robert W. Schnepp
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Emrullah Yilmaz
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Ryota Iwasawa
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Patents, Royalties, Other Intellectual Property: Johnson & Johnson IP
Travel, Accommodations, Expenses: Johnson & Johnson
Mahesh Daksh
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Travel, Accommodations, Expenses: Johnson & Johnson
Patricia Lorenzini
Employment: Janssen Pharmaceuticals of Johnson & Johnson
Meena Thayu
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Other Relationship: Janssen Oncology
Mahadi Baig
Employment: Johnson & Johnson
Stock and Other Ownership Interests: Johnson & Johnson
Sae-Won Han
Stock and Other Ownership Interests: IMBdx
Consulting or Advisory Role: AstraZeneca, Natera, AbbVie, IMBdx
Research Funding: IMBdx (Inst), Hanmi (Inst), Loxo (Inst), Roche (Inst), Genentech (Inst), Mirati Therapeutics (Inst), Arcus Biosciences (Inst), MSD (Inst), BeyondBio (Inst), GC Pharma (Inst), Jeil Pharmaceutical Co (Inst), Janssen (Inst), Lilly (Inst), MedImmune (Inst), Seagen (Inst), Hengrui Pharmaceutical (Inst), GSK (Inst), AstraZeneca (Inst), Astellas Pharma (Inst), AbbVie (Inst), Cell Biotech (Inst), Merck KGaA (Inst), Boryung (Inst)
No other potential conflicts of interest were reported.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
A data sharing statement provided by the authors is available with this article at DOI https://doi.org/10.1200/JCO-25-02187. The data sharing policy of Johnson & Johnson is available at https://innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.