Final overall survival (OS) data from the PAPILLON study showed a numerical survival advantage for amivantamab (Rybrevant) plus carboplatin-pemetrexed chemotherapy versus chemotherapy alone in first-line EGFR exon 20 insertion-mutated non-small cell lung cancer (NSCLC), although the protocol-specified analysis did not reach statistical significance. Median OS was 34.3 months with the amivantamab combination versus 27.9 months with chemotherapy, according to results presented at the Presidential Symposium of the International Association for the Study of Lung Cancer 2026 World Conference on Lung Cancer in Seoul. The final OS analysis fulfills a postmarketing commitment agreed with the FDA when the first-line combination was approved in 2024, requiring J&J to complete PAPILLON and report mature survival data to further characterize the treatment’s clinical benefit.
The final OS analysis produced a hazard ratio of 0.87 (95% CI 0.66–1.14; P=0.307). Interpretation is complicated by extensive crossover: 76% of eligible patients in the chemotherapy arm received second-line amivantamab after disease progression, likely reducing the observed difference between the randomized groups. In a prespecified crossover-adjusted analysis, the hazard ratio for death was 0.57 (95% CI 0.39–0.82; nominal P=0.003), corresponding to a 43% reduction in the modeled risk of death. That adjusted result should be interpreted separately from the protocol-specified randomized OS analysis.
Of patients assigned to amivantamab plus chemotherapy, 12% remained on first-line treatment at the clinical cutoff, compared with none in the chemotherapy arm. Progression-free survival through second disease progression (PFS2) also favored the combination, at 28.3 months versus 17.5 months (HR 0.59; P<0.0001), adding evidence that the initial treatment benefit extended beyond first progression.
The safety profile was consistent with previous PAPILLON reports, with no new signals identified. The most common treatment-related adverse events included paronychia (60%), neutropenia (60%), and rash (58%).
Amivantamab is an EGFR/MET bispecific antibody designed to inhibit signaling through both receptors and address resistance mechanisms associated with EGFR exon 20 insertion mutations. The US FDA approved amivantamab plus carboplatin-pemetrexed for first-line treatment of EGFR ex20ins-mutated advanced NSCLC in March 2024 after the primary PAPILLON analysis showed a 60% reduction in the risk of disease progression or death versus chemotherapy. A subcutaneous formulation, Rybrevant Faspro (amivantamab and hyaluronidase-lpuj), received US FDA approval in December 2025 across amivantamab indications. PAPILLON previously served as the confirmatory trial that converted Rybrevant’s original 2021 accelerated approval to traditional approval in 2024, while also establishing the amivantamab-chemotherapy combination as a first-line option.