Background
Phase 2 multicohort single-arm; advanced MET-dysregulated NSCLC (MET exon 14 skipping or MET amplification); cohorts split by prior-therapy line and molecular status. N=364 assigned. MET exon 14 skipping occurs in ~3–4% of NSCLC.
Results
Interventions and follow up: Treatment: capmatinib 400 mg PO BID continuously.
Primary endpoint: overall response (CR+PR) by independent review committee per RECIST v1.1.
mFollow up: NR.
Results: MET ex14, treatment-naive (n=28): ORR 68% (95% CI 48–84), mDOR 12.6mo.
MET ex14, 1–2 prior lines (n=69): ORR 41% (95% CI 29–53), mDOR 9.7mo.
MET amplification GCN ≥10: treatment-naive ORR 40% (95% CI 16–68); previously treated ORR 29% (95% CI 19–41).
MET amplification GCN <10: limited efficacy (ORR 7–12%).
Primary endpoint: overall response (CR+PR) by independent review committee per RECIST v1.1.
mFollow up: NR.
Results: MET ex14, treatment-naive (n=28): ORR 68% (95% CI 48–84), mDOR 12.6mo.
MET ex14, 1–2 prior lines (n=69): ORR 41% (95% CI 29–53), mDOR 9.7mo.
MET amplification GCN ≥10: treatment-naive ORR 40% (95% CI 16–68); previously treated ORR 29% (95% CI 19–41).
MET amplification GCN <10: limited efficacy (ORR 7–12%).
Adverse events
Most common (any grade): peripheral edema 51%, nausea 45% — predominantly grade 1–2.
Grade ≥3: treatment-related grade ≥3 events uncommon.
Grade ≥3: treatment-related grade ≥3 events uncommon.
Conclusions
Capmatinib showed substantial activity in MET exon 14-skipping NSCLC, greatest in treatment-naive patients; MET-amplified activity tracked with gene copy number. Acceptable, mostly low-grade toxicity.
Key Limitations
Single-arm cohorts, no comparator, ORR surrogate, no OS comparison; modest cohort sizes; lower efficacy in pretreated patients argues for early testing and first-line use.
Clinical Context
Supported FDA accelerated approval of capmatinib (May 2020) for MET exon 14-skipping metastatic NSCLC (later converted to regular approval); a preferred MET inhibitor in this setting alongside tepotinib.