Efficacy and Safety of an EGFR/c-MET Bispecific Antibody, MCLA-129, in Advanced NSCLC

MCLA-129 is a Biclonics-based product that can be categorized as a common light chain/bispecific antibody used to target EGFR and c-MET while enhancing antibody-dependent cellular cytotoxicity. This analysis outlines the current phase 1/2 clinical trial of MCLA-129 in individuals diagnosed with non–small cell lung cancer (NSCLC). This includes 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).

Patients were administered MCLA-129 intravenously (IV) biweekly, with doses ranging from 100 mg to 2000 mg, or weekly with doses of 1000 mg to 1500 mg, following a 28-day cycle in a dose-escalation study. This investigation also includes exploring the effects of doses at 1500 mg and 2000 mg IV biweekly in a dose-expansion phase.

The primary end point was to assess the treatment’s safety and tolerability. The objective response rate, as assessed by the investigator using RECIST (version 1.1) criteria, is reported for patients with NSCLC who were treated with doses of 1500 mg and 2000 mg IV biweekly in 3 separate cohorts.

As of January 29, 2024, 260 patients with NSCLC, 2 with gastric cancer, and 1 with cholangiocarcinoma received MCLA-129 in China. The most common treatment-emergent adverse events (TEAEs) included infusion-related reactions (71%), hypoalbuminemia (54%), decreased neutrophil count (46%), and a decreased white blood cell count (40%). The majority of TEAEs observed were grades 1-2. Grade ≥3 TEAEs and drug-related TEAEs were reported in 53% and 41% of patients, respectively.

In cohorts A, B, and C, the confirmed objective response rates (ORRs) were 43.4%, 28.6%, and 23.2%, respectively. Notably, patients in cohort A who received a prior MET tyrosine kinase inhibitor had an ORR of 38.2% with a disease control rate of 82.4%.

MCLA-129 demonstrated robust and durable antitumor activity in patients with NSCLC harboring METex14, EGFR exon20ins, and sensitized EGFR mutations, with a manageable safety profile. Enrollment in the dose-expansion study is currently ongoing.

Source:

Wang J, Zhong J, Wu L, et al. Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC). Chicago, IL, & online: presented at 2024 ASCO Annual Meeting; June 3, 2024: abstract 8604.