A phase II study of amivantamab hyaluronidase in <i>MET</i> amplification–positive stage IV or recurrent non–small cell lung cancer (Lung-MAP Sub-Study).

Abstract

TPS8680 Background: MET amplification is a known oncogenic driver in non-small cell lung cancer (NSCLC), estimated to occur in approximately 3-4% of non-squamous (nsq) and squamous (sq) cases. While targeted therapies such as tyrosine kinase inhibitors (TKIs) have demonstrated activity in this population, with objective response rates (ORR) approximating 30%, there is a need for novel therapeutic approaches, particularly for patients who have progressed on standard systemic therapies. Amivantamab hyaluronidase is a fully human bispecific antibody targeting EGFR and MET co-formulated with recombinant human hyaluronidase (rHuPH20) for subcutaneous administration. The mechanism of action involves the inhibition of EGFR and MET signaling, receptor degradation, and the induction of antibody-dependent cellular cytotoxicity. S1900J is evaluating the efficacy of this subcutaneous formulation in specific histological cohorts. Methods: S1900J is a 2-stage, single arm phase II biomarker-driven Lung-MAP sub-study. The study includes 2 cohorts of Stage IV or recurrent NSCLC, based on histology (non-squamous and squamous NSCLC). Biomarker eligibility requires documentation of MET amplification as primary driver via tissue or ctDNA NGS. Participants must have received at least one prior line of systemic therapy; notably, patients who have received prior MET TKI therapy (e.g., crizotinib, capmatinib) or harboring other actionable alterations are excluded. Participants receive amivantamab hyaluronidase via subcutaneous injection weekly during Cycle 1 (Days 1, 8, 15, 22) and every 2 weeks thereafter (Days 1, 15). Dosing is weight-based: 1,600 mg amivantamab/20,000 units hyaluronidase for participants &lt; 80 kg, and 2,240 mg amivantamab/28,000 units hyaluronidase for patients ≥80 kg. The primary endpoint is response. with a goal of 40 evaluable participants per cohort. The study design has 90% power to rule out a 15% ORR at the 1-sided 5% level, if the true ORR is 35%. Secondary objectives include progression-free survival, duration of response, and response rates in the subset with MET amplification by FoundationOne CDx assays. Correlative studies of interest include the evaluation of concordance between tissue-based and liquid biopsy (ctDNA) next-generation sequencing for the detection of MET amplification. S1900J opened to accrual on 9/27/2024 and is actively enrolling patients. Clinical trial information: NCT06116682 .