Johnson & Johnson has announced initial results from its phase 3 PALOMA-3 study evaluating subcutaneous (SC) amivantamab combined with lazertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) or L858R mutations.
Study results showed non-inferior efficacy and pharmacokinetics for SC amivantamab combined with lazertinib compared to intravenous (IV) administration, the currently approved formulation of Rybrevant (amivantamab-vmjw). Administration time for SC amivantamab was reduced to approximately five minutes from five hours (across two days) and showed a five-fold reduction in infusion-related reactions (IRRs). These late-breaking results were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.
“The PALOMA-3 data show that subcutaneous amivantamab offers shorter infusion times and lower rates of infusion-related reactions and venous thromboembolism with pharmacokinetics and efficacy comparable to the current IV administration,” said presenting author Natasha B. Leighl, MD, MMSc, medical oncologist at the Princess Margaret Cancer Centre in Toronto, Canada. “I look forward to seeing how these findings can make a meaningful difference in clinical practice by potentially improving the treatment experience for patients with EGFR-mutated non-small cell lung cancer.”
Results showed SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary pharmacokinetic (PK) efficacy endpoints as measured by amivantamab levels in the blood (Ctrough and area under the serum concentration time curve from day 1 to 15).
At a median follow-up of seven months, the overall response rate was 30% (95% confidence interval [CI], 24–37) in the subcutaneous arm and 33% (95% CI, 26–39) for IV (relative risk, 0.92; 95% CI, 0.70-1.23; P=0.001), meeting the noninferiority criteria. SC amivantamab also demonstrated longer duration of response (DoR), progression-free survival (PFS) and significant improvement in overall survival (OS) compared to IV administration during this time. Specifically, median DoR was numerically longer for SC amivantamab combined with lazertinib compared to IV (median, 11.2 vs 8.3 months among confirmed responders) as was PFS (median, 6.1 vs 4.3 months; hazard ratio [HR], 0.84; 95% CI, 0.64–1.10; P=0.20). A pre-specified exploratory endpoint showed patients treated with SC amivantamab had significantly longer OS compared with IV (HR, 0.62; 95% CI, 0.42–0.92; nominal P=0.02). At 12 months, 65% of patients who received SC amivantamab combined with lazertinib were alive compared with 51% of those treated with the IV regimen. It is theorized that the efficacy seen with SC amivantamab may be linked to SC absorption via the lymphatic system, potentially enhancing immune-mediated activity.
Of particular note, administration time was substantially shorter for SC amivantamab (median less than approximately five minutes) compared to IV administration (up to five hours), with significantly more patients reporting convenience with the SC administration (85% with SC amivantamab vs 35% with IV administration at end of treatment; P<0.001).
The overall safety profile of SC amivantamab is consistent with the known profile of IV administration. The most common all-grade adverse events (≥ 20%) for SC amivantamab compared to IV were paronychia (54% vs 51%), hypoalbuminemia (47% vs 37%) and rash (46% vs 43%), respectively. No grade 4 or 5 IRRs were reported. The rate of IRRs for patients treated with SC amivantamab combined with lazertinib was shown to be approximately five-fold lower than that observed with the IV formulation (13% vs 66%, respectively). Prophylactic anticoagulation was used in most patients in the study and was found to be safe and effective in reducing the rate of venous thromboembolic events (VTE). Patients receiving prophylactic anticoagulation had lower rates of VTE (10%) than those without prophylaxis (21%). Furthermore, VTE incidence was lower in the SC arm compared to the IV arm (9% vs 14%, respectively) regardless of anticoagulation use. Severe bleeding risk was low and similar among patients receiving anticoagulants in the SC (2%) and IV (1%) arms.
Janssen-Cilag International NV, a Johnson & Johnson company, announced the submission of an application for the extension of the Rybrevant marketing authorization (line extension) to the European Medicines Agency (EMA) seeking approval of SC amivantamab in combination with lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R mutations and as monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy based on the PALOMA-3 data. Johnson & Johnson will submit regulatory applications seeking the approval of SC amivantamab in other markets, including the United States.
