Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC).

8604 Background: MCLA-129 is a common light chain, Biclonics, bispecific antibody targeting EGFR and c-MET with enhanced antibody-dependent cellular cytotoxicity. Here we describe the ongoing first-in-human phase 1/2 study of MCLA-129 in patients with NSCLC, including patients with MET exon 14 skipping (METex14) mutation (cohort A), EGFR exon 20 insertion (exon20ins)-mutated (cohort B) and sensitized EGFR-mutated disease (cohort C). Methods: Patients received MCLA-129 (100–2000 mg) IV biweekly or 1000-1500 mg IV weekly in a 28-day cycle in dose escalation. Doses at 1500 and 2000 mg IV biweekly are being explored in dose expansion. The primary endpoint was safety and tolerability. Objective response rate by investigator assessment per RECIST v1.1 of patients with NSCLC treated at 1500 and 2000 mg IV biweekly in three cohorts is reported. Results: As of 26 May 2023, 217 enrolled patients received MCLA-129 in China. The data cut-off was 24 Nov 2023. The most common treatment-emergent adverse events (TEAEs) were infusion related reaction (71.9%), hypoalbuminemia (54.8%), decreased neutrophil count (46.1%), and decreased white blood cell count (40.1%). TEAEs mostly were grade 1-2. Grade ≥3 TEAEs and drug-related TEAEs were reported in 51.6% and 39.2% of patients, respectively. 176 of the 215 NSCLC patients were evaluable. The confirmed objective response rates (ORR) in Cohort A, B and C were 43.5%, 28.6% and 21.8%, respectively. Especially, for patients in Cohort A receive prior MET TKI, the ORR was 37.5% and disease control rate (DCR) was 93.8%. Overall efficacy is shown (Table). Conclusions: MCLA-129 demonstrates robust and durable antitumor activity in patients with NSCLC harboring METex14, EGFR exon20ins and sensitized EGFR mutations, with a manageable safety profile; enrollment in dose expansion is ongoing. Clinical trial information: NCT04930432 . [Table: see text]