BeiGene Submits IND for First-in-Class Trispecific Antibody BG-T187 Targeting EGFR and c-MET in NSCLC

Sep 18, 2024 17:37 CST Updated 17:37

Johnson & Johnson

Medical Device R&D and Manufacturer

On September 18, the CDE website showed that BeiGene's Class 1 new drug, BG-T187 for injection, applied for clinical trials.BG-T187 is a trispecific antibody targeting EGFR and c-MET., and it is also the first trispecific antibody new drug developed by BeiGene to enter clinical trials.

Insight database shows that, for these two targets,Currently, there is only one bispecific antibody drug approved globally, and more than ten other drugs have entered the clinical application stage or above, from Johnson & Johnson,Hengrui,Jiahor,AstraZeneca and other companies。

Screenshot source: CDE official website

EGFR is a receptor tyrosine kinase that controls cell growth and division. EGFR mutations are one of the most common types of genetic mutations in non-small cell lung cancer (NSCLC). Globally, more than ten EGFR-targeted drugs have been approved for the treatment of NSCLC patients. In China alone, six third-generation EGFR-TKIs have been approved for marketing.

Currently,Drug resistance is a major challenge for EGFR-TKI in the clinical treatment of NSCLC.The study found that the drug resistance mechanisms in patients include secondary mutations in EGFR and c-MET, as well as amplifications of other downstream oncogenic pathways and alternative growth factor receptors. Among these,MET amplification or protein overexpression has been identified as one of the common mechanisms of clinical resistance to EGFR inhibitors such as osimertinib.。

Therefore, many companies are currently developing drugs that can simultaneously target EGFR and c-MET, hoping to provide better treatment options for NSCLC patients.

Insight database shows,Globally, more than ten drugs targeting both EGFR and c-MET have entered the clinical application and above stages., Drug types includeBispecific antibodies, trispecific antibodies, antibody-drug conjugates (ADC)。

GlobalOverview of EGFR × c-MET Targeted Drug Development Progress

Screenshot source: Insight database

In terms of EGFR × c-MET bispecific antibodies,Johnson & Johnson's Amivantamab has been approved in the United States and the European Union., for the treatment of EGFR ex20ins mutation NSCLC. In China, the drug was also submitted for marketing approval in October 2023. In addition,Four EGFR × c-MET bispecific antibodies have entered clinical trials in China., from Primus Bio/Hansoh Bio HS-20117 (Phase Ⅲ), Hengrui SHR-9839 (Phase Ⅰ/Ⅱ), Beida MCLA-129 (Phase Ⅰ/Ⅱ), EpimAb Biotherapeutics EMB-01 (Phase Ⅰ/Ⅱ）。

In terms of triple-target therapy, Genor Biopharma's GB263T is currently undergoing Phase I/II clinical trials in China and Australia.This drug is the world's first EGFR/cMET/cMET trispecific antibody.Targeting EGFR and two different cMET epitopes, this design can simultaneously inhibit primary and secondary EGFR mutations as well as the cMET signaling pathway.BG-T187, developed by BeiGene, is the second tri-specific antibody targeting EGFR and c-MET to enter clinical trials in China.

Triple Antibody TherapyNSCHow effective is LC?

At the recently concluded 2024 ESMO Annual Meeting, Genor Biopharma presented the latest clinical data for GB263T in the treatment of patients with advanced EGFR-mutated NSCLC. In this study, a total of 15 patients received at least one treatment with GB263T.All patients had previously received third-generation EGFR-TKI and platinum-based chemotherapy.，The median number of previous systemic treatments was 3 lines.。Data shows:

For patients with EGFR-sensitive mutations who have developed resistance to third-generation TKI treatment,The objective response rate (ORR) was 28.6%.
In 3 patients who previously failed third-generation EGFR-TKI treatment and had cMET alterations,A clear benefit can be observed.
In terms of safety, the incidence of infusion-related reactions is low and the severity is mild;Paronychia and rash were mild (Grade 1/2), and diarrhea was only Grade 1.No peripheral edema toxicity related to the MET target has occurred.

Moreover,Some companies are currently developing ADCs targeting EGFR and c-MET., including DM005 from Biocytogen/YuceBio (Phase Ⅰ Clinical), AstraZeneca's AZD9552 and AZD9592 (Phase Ⅰ Clinical), PRO1286 by Pufang (Clinical Trial Application Stage）。

Overall, except for bispecific antibodies, the trispecific antibodies and ADCs targeting EGFR and c-MET are still in the early stages of development. The specific therapeutic effects remain to be verified by more clinical trial data.

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