The combination of subcutaneous amivantamab-vmjw every 4 weeks plus daily oral lazertinib led to a high response rate in patients with previously untreated EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to findings from an analysis of cohort 5 of the PALOMA-2 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract MA08.05).
“Subcutaneous amivantamab dosed once a month offers a less burdensome treatment option without compromising efficacy,” said Susan C. Scott, MD, Thoracic Medical Oncologist with the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center at Sibley Memorial Hospital and Assistant Professor of Oncology at the Johns Hopkins University School of Medicine. “These data support the potential for [every-4-week] administration to enhance quality of life for patients with EGFR-mutant NSCLC.”
Background and Study Methods
The combination of intravenous amivantamab given every 2 weeks and lazertinib are already approved for use in patients with EGFR-mutated advanced NSCLC in the first-line setting based on findings from the MARIPOSA trial. In the study, the combination extended overall survival but was associated with more grade 3 or higher adverse events.
PALOMA-2 was considered a bridging study. Cohorts 1 and 6 of the study confirmed that first-line subcutaneous amivantamab every 2 weeks plus lazertinib had a similar response rate to that of the intravenous approach from the FDA-approved regimen, but the safety profile was improved. Cohort 5 evaluated the efficacy, safety, and pharmacokinetics of subcutaneous amivantamab administered every 4 weeks plus lazertinib in the first-line setting for patients with EGFR-mutated NSCLC.
Patients in the cohort (n = 77) had exon 19 deletion or L858R EGFR mutations and advanced NSCLC. Subcutaneous amivantamab, co-formulated with hyaluronidase, was administered via abdominal injection every 4 weeks at a dose of 1,600 mg (or 2,240 mg if ≥ 80 kg), weekly for the first 4 weeks, and 3,520 mg (or 4,640 mg if ≥ 80 kg) every 4 weeks after that plus daily oral lazertinib at 240 mg. For the first 4 months of treatment prophylactic anticoagulation was recommended.
Key Study Findings
Patients in the cohort were followed for a median of 6.5 months, and 87% of patients were continuing on study treatment at the time of data cutoff. The objective response rate was 82% (95% confidence interval [CI] = 71%–90%) by investigator review and 87% (95% CI = 77%–94%) by independent central review. The confirmed objective response rates were 79% (95% CI = 69%–88%) and 83% (95% CI = 73%–91%) by investigator and independent review, respectively.
The median time to response was 8.1 weeks. The median duration of response, progression-free survival, and overall survival were all not yet reached.
Most treatment-related adverse events were related to EGFR/MET, including paronychia, hypoalbuminemia, and rash most commonly. Administration-related reactions were reported in 12% of patients and were grade 3 or higher in only one patient. No new safety signals were identified in the cohort.
Eighty-seven percent of patients received any prophylactic anticoagulation. Events of venous thromboembolism were observed in 13% of patients, but none were grade 3 or higher. Bleeding events of grade 3 or higher were only seen in 1%. Eight percent of patients discontinued amivantamab due to treatment-related adverse events.
The mean amivantamab concentration level on cycle 2 day 1 was 366 μg/mL, which was consistent with levels seen in the intravenous and subcutaneous every 2 weeks administration datasets.
“These findings support the continued development of subcutaneous [every-4-week] amivantamab as a convenient, effective front-line therapy for EGFR-mutated NSCLC,” Dr. Scott reported.
Disclosure: For full disclosures of the study authors, visit abstractsonline.com.
