Table 3. Clinical utility of F1CDx in each efficacy analysis population.
| Therapy (References) | Clinical Trials | Biomarker | Disease Indication | Concordance to Local CTAs | Clinical Efficacy | ||||
|---|---|---|---|---|---|---|---|---|---|
| PPA, % (95% CI) | NPA, % (95% CI) | Detailed Data | Clinical Endpoints | F1CDx Results | CTA Results | ||||
| larotrectiniba,b,c ([48, 74] [75]) |
LOXO-TRK-14001 (Bayer 20288, NCT02122913) LOXO-TRK-15002 (Bayer 20289, NAVIGATE, NCT02576431) LOXO-TRK—15003 (Bayer 20290, SCOUT, NCT02637687) |
Gene fusions in NTRK1, NTRK2, and NTRK3 | Solid tumors | 84.1 (69.9, 93.4) |
100.0 (98.4, 100.0) |
Tables S23 and S24 in S1 Appendix | ORR, % (n/N) (95% CI) |
77 (20/26) (56, 91) N = 26 |
75 (41/55) (61, 85) N = 55 |
| DOR, range (months) % with duration ≥6 months % with duration ≥9 months % with duration ≥12 months |
1.6, 20.3 80.0 65.0 25.0 |
1.6, 33.2 73.2 63.4 39.0 |
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| capmatinibd,e ([77–79] [80]) |
GEOMETRY-mono 1 trial [79] | MET SNVs and INDELs that lead to exon 14 skipping | NSCLC | 98.6f (92.6, 100.0) |
100.0f (97.1, 100.0) |
Table S25 in S1 Appendix | Cohort 4: ORRg, % (n/N) (95% CI) | 44.2 (23/52) (30.5, 58.7) N = 52 |
40.6 (28/69) (28.9, 53.1) N = 69 |
| Cohort 5b: ORRg, % (n/N) (95% CI) | 70.0 (14/20) (45.7, 88.1) N = 20 |
67.9 (19/28) (47.6, 84.1) N = 28 |
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| Cohort 4: Median DORg, months (95% CI) Patients with DOR >12 months, % |
9.72 (4.27, 12.98) 34.8 N = 23 |
9.7 (5.5, 13.0) 32 N = 28 |
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| Cohort 5b: Median DORg, months (95% CI) Patients with DOR >12 months, % |
12.58 (5.55, 25.33) 50.0 |
12.6 (5.5, 25.3) 47 |
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| pemigatinib [89] [90] | FIGHT-202 | FGFR2 fusions and select rearrangements | CCA | 100.0 h (95.70, 100.00) |
100.0 h (96.27, 100.00) |
Table S26 in S1 Appendix | ORRi, % (95% CI) |
37.50 (26.92, 49.04) N = 80 |
35.51 (26.50, 45.35) N = 107 |
| infigratinib [45] | CBGJ398X2204 (NCT02150967) | FGFR2 fusions and select rearrangements | CCA | 96.7 (88.6, 99.1) | 100.0 (96.4, 100.0) | Table S27 in S1 Appendix | ORRi, % (95% CI) |
28.07 (17.22, 38.92) N = 67 |
23.15 (16.20, 31.94) N = 108 |
| alpelisib + fulvestrant [81, 82] | SOLAR-1 clinical trial | PIK3CA alterations (PIK3CA C420R, E542K, E545A, E545D [1635G>T only], E545G, E545K, Q546E, Q546R, H1047L, H1047R, and H1047Y) | Breast cancer | 93.8 (87.7, 97.5) j |
98.8 (95.6, 99.8) j |
Table S28 in S1 Appendix | PFSk, months, HR (95% CI) CTA1j |
11.2 0.52 (0.29, 0.93) N = 56 |
11.0l 0.65 (0.50, 0.85) N = 169 |
| 91.6 (87.1, 95.0) j |
98.8 (95.7, 99.9) j |
PFSk, months, HRe (95% CI) CTA2j |
10.9 0.35 (0.16, 0.77) N = 42 |
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BICR = blinded independent central review; CCA = cholangiocarcinoma; CI = confidence interval; CTA = clinical trial assay; DOR = duration or response; F1CDx = FoundationOne®CDx; FISH = fluorescence in situ hybridization; HR = hazard ratio; NPA = negative percent agreement; NR = not reported; NSCLC = non-small cell lung cancer
PFS = Progression Free Survival; PCR = polymerase chain reaction; PPA = positive percent agreement; RECIST = Response Evaluation Criteria in Solid Tumors; RT-PCR = reverse transcriptase-polymerase chain reaction.
a PPA and NPA results exclude the F1CDx invalid results. Including the F1CDx invalid results, the PPA was 82.2% (95% CI: 67.9, 92.0) and the NPA was 98.3% (95% CI: 95.6, 99.5).
b ORR was assessed by an independent review committee using RECIST v1.1 [71].
c Local CTAs included DNA NGS, RNA NGS, FISH, and RT-PCR methods, with the majority (92%) of the clinical trial patients with known NTRK fusion status enrolled with NGS methods.
d Using an RT-PCR CTA, Cohort 4 enrolled 69 patients with MET exon 14 skipping alterations and one or two prior lines of therapy, while Cohort 5b enrolled 28 patients with MET exon 14 skipping alterations who were treatment naïve. F1CDx was used to analyze samples retrospectively from patients enrolled in the GEOMETRY-mono 1 trial.
e The results exclude the F1CDx invalid results. Including the F1CDx invalid results, the PPA was 92.3% (95% CI: 84.0, 97.1) and the NPA was 99.2% (95% CI: 95.7, 100.0).
f The concordance reported is for the combined cohorts (Cohort 4 and Cohort 5b).
g Cohort 4: previously treated patients; Cohort 5b: treatment-naïve patients. ORR as assessed by BICR according to RECIST v1.1. DOR is based on the data reported in the capmatinib USPI.
h The enrollment assay was the FoundationOne assay, an earlier version of the F1CDx assay.
i ORR per central review per RECIST v1.1. Note that ORR is objective response rate for pemigatinib and overall response rate for infigratinib.
j CTA1 = PCR-based PIK3CA hot-spot test; CTA2 = PCR-based PIK3CA hot-spot test. The results shown exclude the F1CDx invalid results. Including the F1CDx invalid results, the CTA1 PPA was 93.0% (95% CI: 86.6%, 96.9%) and the CTA1 NPA was 95.8% (95% CI: 91.5%, 98.3%). Including the F1CDx invalid results, the CTA2 PPA was 90.4% (95% CI: 85.7%, 93.9%) and the CTA2 NPA was 97.0% (95% CI: 93.2%, 99.0%).
k PFS by investigator assessment in patients with PIK3CA alteration-positive tumors. The HR shown here for both the F1CDx results and the CTA results is for alpelisib + fulvestrant for risk of disease progression or death compared to placebo in the PIK3CA alteration-positive population.
l The CTA results report the combined efficacy of both CTA1- and CTA2-enrolled patients.