The User’s Guide to Amivantamab

Abstract

Targeted therapies have revolutionized treatment of non-small-cell lung cancer (NSCLC); however, epidermal growth factor receptor (EGFR) exon20ins mutations are resistant to tyrosine kinase inhibitors. Amivantamab utilizes multiple mechanisms of action to bypass the altered binding site conformation and recruits immune cells for anti-cancer activity. Amivantamab is approved in the frontline setting of EGFR exon20ins-mutated NSCLC in combination with carboplatin plus pemetrexed. Single-agent amivantamab is approved in second line or later for EGFR exon20ins. Furthermore, amivantamab with lazertinib for first line as well as amivantamab in combination with carboplatin and pemetrexed for second line after osimertinib have both been approved in the treatment of NSCLC harboring EGFR-sensitizing mutations. Now with multiple indications, we must learn how to manage the unique side effects of amivantamab to maximize treatment benefit for the patients. Side effects of amivantamab can be associated with inhibition of the EGFR and/or mesenchymal epithelial transcription factor (MET) signaling pathways. This work reviews the mechanism of action, pharmacology, clinical trial data, and covers management of toxicities. This guide is designed as a practical reference tool for clinicians, pharmacists, and basic science researchers.

Key Points

Amivantamab monotherapy or in combination with carboplatin + pemetrexed is standard of care for non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon20ins mutations.

Amivantamab with lazertinib and amivantamab with chemotherapy is also standard of care for NSCLC patients with sensitizing EGFR mutations.

Amivantamab is dosed based on weight. Dosing schedule varies for monotherapy, combination therapy, and the subcutaneous route of administration.

Amivantamab is manegeable and the most common side effects include skin and nail changes as well as infusion-related reactions. Potentially serious side effects include venous thromboembolism.

Introduction

Lung cancer remains the leading cause of cancer-related death worldwide. The epidermal growth factor receptor (EGFR) gene is mutated in 10–15% of lung adenocarcinomas and mutations are more common in never smokers [1, 2]. EGFR exon 20 insertion gene mutations (exon20ins) account for 4–10% of EGFR gene mutations and are resistant to traditional EGFR tyrosine kinase inhibitors (TKIs) due to altered conformation at the kinase-active site. Treatment of EGFR exon20ins with platinum-based chemotherapy yields an objective response rate of 23–29% with a median progression-free survival (PFS) up to 6.9 months [3]. Over 100 unique exon20ins mutations have been identified, yet they are often underdetected and associated with a worse prognosis than classic sensitizing mutations of EGFR L858R and exon 19 deletion mutations [4–7].

EGFR gene and mesenchymal epithelial transcription factor (MET) gene are both highly expressed on non-small-cell lung cancer (NSCLC) tumors but rarely simultaneously expressed on healthy cells [8–11]. EGFR and MET genes promote oncogenic signaling and remodeling of the tumor microenvironment [12–14]. Interaction between EGFR and MET signaling is well documented and each can compensate when the other is inhibited [15]. Alterations in the EGFR and/or MET signaling pathway are the most common mechanisms of resistance to EGFR TKIs [16–19].

Amivantamab (Rybrevant, Janssen Biotech, Inc) was designed to concomitantly inhibit both EGFR and MET to improve clinical outcomes and reduce MET and/or EGFR resistance. As defined in preclinical studies amivantamab utilizes multiple mechanisms of action to bypass the altered binding site conformation and recruits immune cells for anti-cancer activity. In May 2021 amivantamab was granted its first Federal Drug Administration (FDA) approval based on the CHRYSALIS study, and has since been approved in the front-line setting when combined with platinum-based chemotherapy based on the PAPPILLION trial.

Furthermore, amivantamab with lazertinib for first line as well as amivantamab in combination with carboplatin and pemetrexed for second line after osimertinib have been both approved in the treatment of NSCLC harboring EGFR-sensitizing mutations.

Here we review the mechanism of action, pharmacology, and clinical data of amivantamab. We also discuss most common toxicities and recommended management.

Structure

Amivantamab is a fully human monoclonal antibody with bispecific binding generated using Genmab’s DuoBody technology. The drug consists of two arms, one binds the extracellular domain of EGFR to block binding with its ligand epidermal growth factor (EGF) while the other blocks hepatocyte growth factor (HGF) from binding to the MET receptor. It was designed with low levels of fucose in the Fc region to enhance antibody binding to immune effector cells and promote antitumor immune cell activity [20–22].

Pharmacodynamics and Pharmacokinetics

Preclinical studies found that amivantamab blocked ligand-induced receptor phosphorylation more potently than the combination of monovalent antibodies against EGFR and MET [8]. Amivantamab binds the extracellular domain of EGFR with KD of 1.4 nanomolar/L and extracellular domain of the MET gene with KD of 40 picomolar/L [20].

Exposure increased proportionally with each administered amivantamab dose ranging from 350 mg to 1,750 mg. Steady state was achieved by the ninth infusion [23]. The half-life of amivantamab is 11.3 (± 4.53) days. The mean volume of distribution was 5.13 L.

Amivantamab distribution and clearance are increased in patients with a body weight of 80 kg or greater. As a result, amivantamab exposure is 30–40% lower in patients weighing at least 80 kg.

There was no meaningful effect of creatinine clearance or mild hepatic impairment on the exposure of amivantamab. There are no recommended dose adjustments in the setting of renal or hepatic impairment [24]. While not specific to amivantamab, prior to starting systemic anticancer therapy, patients should be screened for hepatitis B surface antigen, hepatitis B core antibody, and hepatitis B surface antibody, based on ASCO 2020 recommendations [25].

Clinical Data

In the phase I, open-label CHRYSALIS trial (NCT02609776), 81 patients with EGFR exon20ins who had progressed on prior platinum-based chemotherapy were treated with amivantamab. The primary endpoint was objective response (ORR) by blinded independent central review (BICR). The dose-escalation and dose-expansion study reported an ORR of 40% (95% confidence interval (CI) 29–51) with median duration of response (DOR) of 11.1 months (95% CI 6.9–not reached) [23]. The median progression-free survival (PFS) was 8.3 months (95% CI 6.5–10.9). This led to the US Food and Drug Administration (FDA) approval of amivantamab in EGFR exon20ins post platinum chemotherapy. Additional arms of the CHRYSALIS trial explored amivantamab monotherapy and in combination with lazertinib or chemotherapy.

PAPILLON (NCT04538664) is a phase III randomized trial that assigned NSCLC EGFR exon20ins participants to receive amivantamab plus chemotherapy or chemotherapy alone in the front-line setting [24]. The primary endpoint was PFS by BICR. PFS was significantly longer in the amivantamab plus chemotherapy arm than with chemotherapy alone (11.4 months vs. 6.7 months, 95% CI 0.3–0.53). This led to the FDA approval of amivantamab combined with chemotherapy for first-line treatment of patients with EGFR exon20ins.

MARIPOSA (NCT04487080) is a phase III clinical trial comparing amivantamab plus lazertinib versus lazertinib monotherapy or osimertinib monotherapy in the first-line setting. The primary endpoint was PFS by BICR. ORR was 86% (95% CI 83–89) with amivantamab plus lazertinib versus 85% (95% CI 81–88%) with osimertinib. The median PFS was longer with amivantamab plus lazertinib compared to osimertinib (23.7 months, 95% CI 19.1–27.7 vs. 16.6 months, 95% CI 14.8–18.5). Interim analysis showed a favorable trend toward OS benefit in amivantamab plus lazertinib (hazard ration (HR) 0.77; 95% CI 0.61–0.96) [26].

The phase III MARIPOSA 2 study (NCT04988295) compared amivantamab plus lazertinib plus chemotherapy to amivantamab plus chemotherapy to pemetrexed and carboplatin chemotherapy alone, for patients with EGFR TKI refractory disease. The primary endpoint was PFS by BICR. Primary results found that amivantamab plus chemotherapy with or without lazertinib had improved median PFS (8.3 months amivantamab + lazertinib + chemotherapy, 6.3 months amivantamab + chemotherapy, 4.2 months chemotherapy) [27]. ORR was also higher in the amivantamab arms (63% vs. 64% vs. 36%, respectively).

In a retrospective real-world analysis of 61 patients who received amivantamab not on a clinical trial, the ORR was 45.2% [28]. The response rate was higher in patients with atypical mutations than in classical EGFR mutations, 85.7% versus 35.4%. This review also showed that amivantamab plus concurrent osimertinib or radiation was safe and feasible, although caution is advised while we await prospective studies.

A summary of study designs for trials on amivantamab is depicted in Fig. 1.

Fig. 1.

Clinical trials with Amivantamab

Intracranial Activity

The CHRYSALIS study included 33 patients with asymptomatic previously treated brain metastases. The ORR subgroup analysis for these patients was 39% (95% CI 17–64) [23].

Combined with chemotherapy in the PAPILLON trial, PFS in 35 patients with asymptomatic previously treated brain metastases was 11.4 months compared to 6.7 months with chemotherapy alone. The HR for disease progression or death was 0.63 (95% CI 0.38–1.06) and 0.33 (95% CI 0.23–0.46) for patients with and without brain metastases, respectively [24].

When combined with lazertinib, a CNS-penetrant third-generation EGFR TKI, amivantamab demonstrates an intracranial ORR of 77% in 139 patients with brain metastases enrolled in the MARIPOSA study [26].

In the MARIPOSA-2 study, which is in the second-line setting, intracranial PFS was improved with amivantamab-chemotherapy (12.5 months; n = 58) versus chemotherapy alone (8.3 months; n = 120) for an HR of 0.55 (95% CI 0.38–0.79) [27].

Taken together, these findings show that amivantamab has efficacy even in the presence of CNS disease.

Indications

Amivantamab is FDA approved in the front-line setting of EGFRex20ins-mutated NSCLC in combination with chemotherapy based on the phase III PAPILLON trial [24]. Participants received amivantamab plus platinum plus pemetrexed for four cycles followed by amivantamab plus pemetrexed maintenance until disease progression.

Amivantamab is also FDA approved as monotherapy in the second-line therapy of EGFRex20ins-mutated NSCLC based on the phase I CHRYSALIS trial [23].

Recently, amivantamab in combination with lazertinib, a third-generation EGFR TKI similar to osimertinib, was given FDA approval in August 2024 for the first-line treatment of patients with NSCLC harboring sensitizing EGFR mutations, based on the MARIPOSA study [26]. Additionally, amivantamab in combination with chemotherapy was given FDA approval in September 2024 for the subsequent-line treatment of patients with NSCLC harboring sensitizing EGFR mutations who have progressed on osimertinib based on the MARIPOSA-2 study [27].

A timeline of amivantamab approvals by indication is shown in Fig. 2.

Fig. 2.

Timeline of Amivantamab FDA approvals

Dosing

First-Line or Second-Line with Chemotherapy

The recommended doses for weeks 1–4 are 1,400 mg for patients weighing less than 80 kg or 1,750 mg for patients 80 kg or greater. The first dose is split into D1 (350 mg) and D2 (1,050 mg) or D1 (350 mg) and D2 (1,400 mg) for < 80 kg and ≥ 80 kg, respectively. The recommended doses for weeks 7 and beyond are 1,750 mg for patients < 80 kg or 2,100 mg for patients ≥ 80 kg.

Amivantamab is administered intravenously (IV) every week for 4 weeks then every 3 weeks until disease progression or toxicity. The administration of amivantamab is depicted in Fig. 3.

Fig. 3.

Chemo combination dosing

Second-Line as Single Agent and First-Line with Lazertinib

The recommended dose for patients < 80 kg is 1,050 mg split over D1 (350 mg) and D2 (700 mg) followed by 1,050 mg on D1 for weeks 2–5. Starting at week 7, amivantamab 1,050 mg is administered every 2 weeks. For patients ≥ 80 kg the first dose is 1,400 mg split over D1–2 (350 mg on D1, 1,050 mg on D2) followed by 1,400 mg on D1 of weeks 2–5. Starting at week 7, amivantamab 1,400 mg is administered every 2 weeks. This dosing regimen is depicted in Fig. 3.

The actual dosing schedule is shown in Fig. 4.

Fig. 4.

Amivantamab alone or with lazertinib dosing

Subcutaneous

The recommended dose for patients < 80 kg is 1,600 mg weekly for 4 weeks then administered every 2 weeks. For patients ≥ 80 kg is 2,240 mg weekly for 4 weeks then given every 2 weeks.

Dose modifications based on toxicities are listed in Table 1.

Table 1.

Dose modifications for amivantamab

Dose at which toxicity occurred	1st dose reduction	2nd dose reduction	3rd dose reduction
1050 mg	700 mg	350 mg	Discontinue amivantamab
1400 mg	1050 mg	700 mg
1750 mg	1400 mg	1050 mg
2100 mg	1750 mg	1400 mg

Safety Profile

The most common adverse events (AEs) in the CHRYSALIS trial were rash (86%), infusion-related reactions (IRRs) (66%), and paronychia (45%) [23]. Treatment-related dose reductions and treatment discontinuation occurred in 13% and 4%, respectively. In the PAPILLON trial the most common AEs in the amivantamab plus chemotherapy group include neutropenia (59%), paronychia (56%), and rash (54%) [24].

Other common side effects include myalgias, arthralgias, dyspnea, nausea, fatigue, edema, mucositis, constipation, and vomiting. Common side effects when amivantamab is combined with carboplatin and pemetrexed chemotherapy include rash, infections around the nail, mucositis, IRRs, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting. Amivantamab combined with lazertinib can be associated with venous thromboembolism. Common side effects for EGFR and MET inhibition are depicted in Fig. 5.

Fig. 5.

Common side effects of EGFR and MET inhibition

Management of Adverse Events

Infusion-Related Reactions

The mechanism behind amivantamab-associated IRRs is unknown as results suggest that immunoglobulin E (IgE) mediated allergic reactions, cytokine release syndrome, mast cell degranulation, tumor lysis syndrome, and complement activation do not play role [30]. Signs and symptoms of IRRs include chills, dyspnea, flushing, nausea, chest discomfort, and vomiting. The majority (90%) of IRRs occurred on cycle 1 day 1 [30]. The median time to IRR onset was 60 min. Premedication of antihistamine (diphenhydramine 25–50mg or equivalent) and antipyretics (acetaminophen 650–1,000 mg) are given for all doses while glucocorticoid is required for week 1 dose 1 (dexamethasone 20 mg IV or equivalent) and week 1 dose 2 (dexamethasone 10 mg IV or equivalent) but becomes optional for subsequent doses as the risk of IRRs substantially decreases with subsequent treatment. For salvage steroids, clinicians can consider methylprednisolone or hydrocortisone for faster onset of action. See Table 3 for recommended dose modifications for IRRs.

Table 3.

Management of amivantamab associated toxicities

Adverse reaction	Grade	Management
Infusion-related reactions	Grade 1–2	Interrupt infusion until symptoms resolve Resume at 50% of infusion rate If no symptoms after 30 minutes, rate may be escalated Corticosteroid premedication for future doses
	Grade 3	Interrupt infusion until symptoms resolve Resume at 50% of infusion rate If no symptoms after 30 minutes, rate may be escalated Corticosteroid premedication for future doses
	Grade 4	Permanently discontinue amivantamab
Interstitial Lung Disease	Any Grade	Permanently discontinue amivantamab
Dermatitis Acneiform, Pruritus, Dry Skin	Tips for prophylaxis	Use mild soaps, fragrance-free moisturizers/alcohol free emollient cream, urea-based products. Avoid irritants or sun exposure (limiting sun exposure, using sunscreen, hat, and long sleeves). Avoid washing skin/scalp with hot water. Consider prophylactic doxycycline, 100 mg BID or minocycline 100 mg qD for the first 3 months.
	Grade 1	Supportive care Face: 2.5% hydrocortisone BID Torso: 0.1% triamcinolone BID Scalp: clobetasol solution
	Grade 2	If rash persists ≥ 2 weeks consider dose reduction
	Grade 3	Hold amivantamab Supportive Care Upon recovery to Grade ≤ 2 resume amivantamab at reduced dose If rash persists ≥ 2 weeks permanently discontinue amivantamab
	Grade 4 or bullous conditions	Permanently discontinue amivantamab
Other Adverse Reactions	Grade 3	Hold amivantamab until recovery to Grade ≤ 1 If recovery ≤ 1 week resume same dose If recovery 1-4 weeks resume at reduced dose If recovery >4 weeks permanently discontinue amivantamab
	Grade 4	Hold amivantamab until recovery to Grade ≤ 1 If recovery ≤ 4 weeks resume at reduced dose If recovery >4 weeks permanently discontinue amivantamab

The phase II SKIPPirr study was designed to prevent IRRs secondary to IV amivantamab use. Prophylactic regimens in different study arms included: (1) dexamethasone 4 mg twice daily (BID) day-1; (2) dexamethasone 8 mg BID day-2, day-1, and 1 h prior to infusion; (3) montelukast 10 mg days-4 to -1 and prior to infusion; (4) methotrexate 25 mg days-7 to -3 [31]. Only the oral dexamethasone 8 mg BID day-2, day-1, and once prior to infusion arm proceeded to the expansion stage. This regimen decreased amivantamab IRRs threefold from 67.4% to 22.5%. No new safety signals were reported.

To counteract on the AEs such as IRRs and for patient convenience, the subcutaneous (SC) formulation of amivantamab is being studied in the PALOMA trials to study the safety and efficacy of SC amivantamab. Recently, the PALOMA-3 study (NCT05388669), which compared SC versus IV amivantamab in combination with Lazertinib, was reported at ASCO 2024. The SC formulation met criteria for noninferiority for the pharmacokinetic studies as well as for ORR efficacy outcomes, which showed 30.1% (95% CI 24–37) in the SC arm and 32.5% (95% CI 26–39) in the IV cohort [32]. IRRs were fivefold lower in the SC cohort (13% vs. 66%).

Dermatologic Toxicities

Prevention and management of dermatologic toxicities includes use of mild soaps, fragrance-free moisturizers/alcohol-free emollient cream, urea-based products, avoiding irritants or sun exposure (limiting sun exposure, using sunscreen, hat, and long sleeves), and avoiding washing with hot water [33]. Prophylactic doxycycline 100 mg BID or minocycline 100 mg once daily is currently recommended, though robust data are not yet available (Cocoon study; NCT06120140), and some physicians recommend a more reactive approach. This is generally maintained for the first 3 months and then discontinued or tapered.

Acneiform eruption associated with EGFR inhibition presents within the first few weeks of initiation and peaks by weeks 4–6 [34, 35]. Paronychia, pyogenic granulomas, hair changes, and nail changes can occur later in the treatment course. These acneiform rashes are most common in the acne-prone areas of the head and upper torso, though the scalp is frequently involved as well. Spread to areas that are not acne prone may suggest a secondary bacterial component, and bacterial culture and sensitivities are recommended. Oral retinoids may be used in recalcitrant disease.

Low-potency topical corticosteroids, 2.5% hydrocortisone BID for the face and more potent steroids for the torso and scalp, 0.1% triamcinolone BID and clobetasol solution BID, respectively, may be utilized.

As the acneiform rash wanes the patient will next experience increasing xerosis; this makes daily moisturizers of utmost importance. Topical urea or lactic acid products may also be of benefit as well as continuation of topical steroids, noted above, to manage the pruritus. Antihistamines may be required for pruritus; other treatments are available and prompt consultation to dermatology may be beneficial for refractory or severe cases.

Next, the patient may note increasing inflammation around the nails of the hands and feet. Chlorohexidine 4% topical solution can be applied for prophylaxis. Medications that may be helpful for decreasing inflammation include potent topical steroids and mupirocin BID. Acetic acid soaks (50% acetic acid 50% water) may help prevent secondary infection. It is not unusual for this inflammation to progress to excessive granulation tissue, often referred to as pyogenic granulomas (PGs). Although PGs are initially sterile, they can easily become infected, and daily acetic acid soaks should be maintained. The presence of suppuration warrants a bacterial culture and treatment with either topical mupirocin or oral antibiotics. Should the inflammation progress to excess granulation tissue a topical beta blocker (e.g., timolol gel) may be of benefit. Frequent visits for silver nitrate application may also be beneficial.

While the ongoing Cocoon study (NCT06120140) will provide us with prospective clinical trial-based data on how enhanced dermatologic management (prophylactic oral and topical antibiotics, paronychia prophylaxis and skin moisturization) may benefit patients compared to the standard dermatologic approach, which is often more reactive, until we have such data, we hope that the strategies outlined in this paper would be of clinical value to providers.

Peripheral Edema

Edema can be managed with compression stockings, specific exercises, massage, and limb elevation. For resistant or severe edema, diuretics can be used. Patients are often started at furosemide 20–40 mg daily as needed and titrated as needed.

Venous Thromboembolism

Providers should have a low threshold to order deep vein thrombosis ultrasound for any patient with calf tenderness, calf erythema, or unilateral leg swelling. A CT angiography should be considered for patients with chest pain, dyspnea, shortness of breath, tachycardia, or palpitations. Patients confirmed to have pulmonary embolism should have additional testing with echocardiogram, troponin, and brain natriuretic peptide to rule out right heart strain. Patients can be treated with anticoagulation such as apixaban 10 mg BID for 1 week followed by 5 mg BID.

For patients being treated with concomitant amivantamab and lazertinib, prophylactic dosing of anticoagulation (e.g., apixaban 2.5 mg BID) is recommended, if not contraindicated, for the first 4 months of treatment. After 4 months, the prophylactic anticoagulation may be continued or discontinued based on physician discretion.

Recommended premedication regimens are listed in Table 2. Management of common toxicities associated with amivantamab are outlined in Table 3.

Table 2.

Premedication recommendations for amivantamab

Medication	Dose	Route	Dosing window prior to administration	Frequency
Antihistamine	Diphenhydramine 25–50 mg	Intravenous	15–30 mins	All doses
		Oral	30–60 mins
Antipyretic	Acetaminophen 650–1000 mg	Intravenous	15–30 mins	All doses
		Oral	30–60 mins
Glucocorticoid	Dexamethasone	8mg PO 10mg IV	D-2 PO BID, D-1 PO BID, PO once prior to 10mg IV	Week 1, Day 1
	Dexamethasone 10 mg			Week 1, Day 2 Optional for subsequent doses

Discussion

As a result of the phase I CHRYSALIS findings, amivantamab was given accelerated approval by the FDA in May 2021 as the first targeted therapy for use in advanced or metastatic EGFR exon20ins upon progression on or after platinum-based chemotherapy. Furthermore, in March 2024, the FDA granted approval of amivantamab with chemotherapy for the first-line treatment of advanced or metastatic EGFR exon20ins and also granted traditional approval for amivantamab in the post platinum chemotherapy setting for exon20ins, followed by front-line use of amivantamab in combination with lazertinib for EGFR-sensitizing mutations in August 2024 and the subsequent use of amivantamab in combination with chemotherapy for EGFR-sensitizing mutations post progression on osimertinib, which was the latest FDA approval for amivantamab, recently witnessed in September 2024.

Amivantamab has shown clinical benefit in chemotherapy pre-treated patients (CHRYSALIS), in treatment-naïve patients (with chemotherapy for exon20ins from the PAPILLON study and with lazertinib per the MARIPOSA study for classical EGFR mutations), and after progression on osimertinib (with chemotherapy plus minus lazertinib based on the MARIPOSA 2 study for classical EGFR mutations).

Given its dual anti-EGFR and anti-MET targeting, amivantamab overcomes common resistance pathways to standard EGFR inhibitors.

As we embrace the multiple approvals, we must be cognizant of the toxicity profile of amivantamab and must learn how to manage them head-on, so that patients may receive the benefit of long-term treatment.

While IRRs are commonly linked with use of amivantamab, with the adoption of the SKIPPirr prophylaxis regimen (oral dexamethasone 8 mg BID day-2, day-1, and once prior to infusion), the rates have shown a decrease to 22.5%. Furthermore, the SC formulation appears to have even less rates of IRRs, at 13%. Also, as the IRR rates significantly decline from C1D2, these measures provide us with comfort that IRRs may not be as “big of an issue.”

However, for the long-term use of amivantamab, whether it be IV or SC, the management of skin toxicities is key. As described in depth in this paper, clinicians should advise patients to use mild soaps, fragrance-free moisturizers/alcohol-free emollient cream, and urea-based products, avoiding irritants or sun exposure (limiting sun exposure, using sunscreen, hat, and long sleeves) and avoiding washing with hot water, and also consider prophylactic doxycycline 100 mg BID or minocycline 100 mg once daily when not contraindicated. Once skin changes occur, low-potency topical corticosteroids, 2.5% hydrocortisone BID for the face and more potent steroids for the torso and scalp, 0.1% triamcinolone BID, and clobetasol solution BID, respectively, may be utilized. For nail changes, chlorohexidine 4% topical solution can be applied for prophylaxis. Medications that may be helpful for decreasing inflammation include potent topical steroids and mupirocin BID. Acetic acid soaks (50% acetic acid 50% water) may help prevent secondary infection.

Amivantamab is tolerable with a low rate of treatment discontinuation due to toxicity across multiple clinical trials. Toxicities including IRRs, skin changes, and hematologic issues (when given with chemotherapy) are often low grade and can be handled with supportive care or dose interruptions/reductions. That being said, clinicians must be sensitive towards and be “pro-active” in the supportive management of such toxicities so that patients may receive the full benefit of treatment while minimizing toxicities that may be quality-of-life altering if not managed aggressively.

Declarations

Funding

No external funding was used in the preparation of this article.

Conflict of Interest

D.B. declares that they have no conflicts of interest that might be relevant to the contents of this article. J.S. is a consultant for Janssen. S.H.I.O reports consulting fees from AnHeart Therapeutics, Pfizer, Janssen, Daiichi Sankyo, BMS, Merus and Avistone, honoraria from Dava Oncology, OncLive and Caris, is on the DSMB for Elevation Oncology and AnHeart, as well as stock/stock options from MBrace Therapeutics, BlossomHill Therapeutics, Elevation Oncology, Turning Point Therapeutics, Nuvalent, Lilly and Nuvation Bio. M.N. is on the advisory board for AstraZeneca, Daiichi Sankyo, Takeda, Novartis, EMD Serono, Janssen, Pfizer, Eli Lilly and Company, Bayer, Regeneron, BMS and Genentech; consultant for Caris Life Sciences (virtual tumor board); speaker for Blueprint Medicines, Janssen, Mirati and Takeda; and reports travel support from AnHeart Therapeutics. Reports stock/stock options from MBrace Therapeutics. Furthermore, M.N. is an Editorial Board member of Targeted Oncology. He was not involved in the selection of peer reviewers for the manuscript nor any of the subsequent editorial decisions.

Ethics Approval

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Consent for Publication

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Availability of Data and and Material

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Code Availability

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Authors’ Contributions

DB drafted the manuscript. JS drafted the manuscript and provided clinical interpretation. SHIO provided clinical interpretation and oversight. MN conceptualized the project and provided final review. All authors reviewed the final version of the manuscript.