From PALOMA-3 to PALOMA-2 Cohort 5 — SC Q4W Dosing Evidence

Dr. Nagasaka traces the evidence pathway behind subcutaneous amivantamab Q4W. She begins with PALOMA-3, a non-inferiority trial in patients previously treated with osimertinib and chemotherapy that compared intravenous amivantamab Q2W with subcutaneous amivantamab Q2W, both with lazertinib. The pharmacokinetic primary end point was met; administration time fell from hours of chair time to approximately 5 minutes, and administration-related reactions decreased from 66% to 13%, an 80% relative reduction. Venous thromboembolism rates were lower with the subcutaneous formulation (9% vs 14%), with 80% of patients receiving prophylaxis, and overall response rates were preserved (33% vs 30%).

With non-inferiority established for the route change, PALOMA-2 cohort 5 then extended the dosing interval from every 2 weeks to every 4 weeks in the first-line setting, reducing annual clinic visits from approximately 26 to 13. Dr. Nagasaka reviews the cohort 5 design — treatment-naive patients with exon 19 deletion or L858R, stable brain metastases permitted, ECOG performance status 0 or 1 — and the regimen, which included a weekly loading phase for the first 4 weeks followed by Q4W maintenance, with prophylactic anticoagulation in months 1 through 4. Among the 77 enrolled patients (median age, 63 years; 68% female; 62% Asian; 43% with baseline brain metastases), the investigator-assessed overall response rate was 82%, exceeding the prespecified threshold and consistent with the 86% by BICR observed in MARIPOSA. The confirmed clinical benefit rate was 97%, and median duration of response, progression-free survival, and overall survival were not reached at data cutoff.

In the next episode, "SC Q4W in Practice — Workflow, Dose Modifications, and Patient Conversations," Drs. Nagasaka and Goldberg discuss how this delivery innovation translates into the clinic.