ASCO 2024: SC vs. IV amivantamab with lazertinib in EGFR-mutated, advanced NSCLC

The phase 2 PALOMA-2 study evaluated subcutaneous amivantamab combined with lazertinib (SC ami + laz) vs. IV ami + laz in patients with advanced NSCLC with EGFR exon 19 deletion or L858R mutations. Investigators found a comparable response rate, shorter treatment times, and lower rates of infusion-related reactions in patients treated with SC ami + laz compared with the IV formulation.

• In total, 418 patients were randomized (SC, n = 206; IV, n = 212); 416 received ≥1 dose. Overall, median age was 61 years, 67% were female, 61% Asian, with a median of 2 prior lines. Co-primary pharmacokinetic noninferiority endpoints were trough concentration on cycle 2/day 1 or cycle 4/day 1 and cycle 2 area under the curve (AUC). Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS).
• At a median follow-up of 7 months, PALOMA-3 met both co-primary endpoints.
• ORR was 30.1% in the SC arm and 32.5% for IV (relative risk, 0.92; P= 0.001), meeting noninferiority criteria.
• Median duration of response (DoR) was longer for SC ami+laz vs. IV (median, 11.2 vs. 8.3 months among confirmed responders).
• A favorable PFS trend was observed for SC ami+laz over IV (median, 6.1 vs. 4.3 months). Overall survival was notably longer for SC ami+laz vs. IV. At 12 months, 65% were alive in the SC arm vs. 51% for IV. Infusion-related reactions were ~5-fold lower in the SC arm.
• Overall, 81% received prophylactic anticoagulants, with VTE reported by 9% in the SC arm vs. 14% for IV. Across both arms, VTE incidence was 10% for patients who received prophylactic anticoagulants vs. 21% for patients who didn't. Severe bleeding risk was low among all patients receiving anticoagulants (1% grade ≥3).

Source:

Leighl, N., et al. Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. Abstract #LBA8505. Presented at: 2024 ASCO Annual Meeting; May 31 – June 4. Chicago, IL. https://meetings.asco.org/abstracts-presentations/232405