Amivantamab Plus Chemotherapy vs Chemotherapy as First-line Treatment in EGFR Exon 20 Insertion–Mutated Advanced NSCLC: Primary Results From PAPILLON, a Randomized Phase 3 Global Study

Background

• Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell–directing activity.
• Ami combined with carboplatin/pemetrexed (ami-chemo) demonstrated safety and antitumor activity in the phase 1 CHRYSALIS study.
• PAPILLON (NCT04538664) evaluated ami-chemo vs chemo in first-line EGFR Ex20ins advanced NSCLC.

Methods

• Treatment-naïve pts were randomized 1:1 to ami-chemo or chemo.
• The primary endpoint was progression-free survival (PFS) by blinded independent central review.
• Secondary endpoints included objective response rate (ORR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety.
• Crossover to ami monotherapy was allowed for the chemo arm upon progression.

Results

• Overall, 308 pts were randomized (ami-chemo, 153; chemo, 155); median age was 61/62 years, 56/60% female, 64/59% Asian, and 23/23% with history of brain metastases for ami-chemo/chemo, respectively.
• At median follow-up of 14.9 months, the median PFS was 11.4 months (95% CI, 9.8–13.7) for ami-chemo vs 6.7 months (95% CI, 5.6–7.3) for chemo (hazard ratio [HR], 0.40; 95% CI, 0.30–0.53; P<0.001).
• The 18-month PFS rate was 31% for ami-chemo vs 3% for chemo.
• PFS benefit of ami-chemo was consistent across subgroups.
• ORR was 73% (95% CI, 65–80) for ami-chemo vs 47% (95% CI, 39–56) for chemo (odds ratio, 2.97; 95% CI, 1.84–4.79; P<0.001).
• Median PFS2 was not estimable for ami-chemo vs 17.2 months for chemo (HR, 0.49; 95% CI, 0.32–0.76; P=0.001).
• Interim OS analysis (33% maturity) showed a favorable trend for ami-chemo vs chemo (HR, 0.67; 95% CI, 0.42–1.09; P=0.106), despite 66%, of chemo-randomized pts whose disease had progressed, receiving second-line ami.
• The most common TEAEs (≥40%) for ami-chemo were neutropenia, paronychia, rash, anemia, infusion-related reactions, and hypoalbuminemia; no new safety signals.
• Discontinuation of ami due to treatment-related AEs was 7%.

Conclusions

• Among pts with EGFR Ex20ins advanced NSCLC, ami-chemo achieved superior PFS vs chemo.
• Safety profile was consistent with that of each individual agent.
• PAPILLON establishes ami-chemo as the new first-line standard of care in EGFR Ex20ins advanced NSCLC.

Girard N, Park K, Tang K et al. LBA5 Amivantamab plus chemotherapy vs chemotherapy as first-line treatment in EGFR Exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC): Primary results from PAPILLON, a randomized phase III global study. Abstract presented at ESMO Congress 2023, October 20-24, 2023.