As we all know, the third-generation EGFR TKIs are already the preferred choice for patients with EGFR-mutant NSCLC. However, acquired resistance is inevitable and c-MET amplification is one of the most common resistant mechanisms. So, what we developed is a EGFR c-MET bispecific antibody, TQB2922, to provide a new option for them.

What was the study design?

This is a phase I study of two parts. The first part is dose escalation and dose expansion across multiple doses with a primary endpoint of MTD and safety. The second part is TQB2922 combined with chemotherapy and bevacizumab in patients resistant to third-generation TKIs and without chemotherapy before. The primary endpoints were ORR and PFS.

What were the key findings?

So in total we enrolled 62 patients in the monotherapy and 38 patients in the combination therapy. In the monotherapy group over 30 patients had three or more prior lines of therapy, representing heavily pretreated but we also observed a confirmed ORR of 23% with a median DOR of 5.6 months, which suggests a durable response.

Besides, for the combination therapy we found that TQB2922 combined with bevacizumab and chemotherapy showed better efficacy with an ORR of 64% and a DCR of 97%. This is encouraging and our median PFS was not reached yet and we are looking forward to the final results.

What could be the clinical significance of these results?

c-MET amplification is one of the most common resistances for TKI treatment. So an EGFR/c-MET bispecific antibody proves a novel treatment option for these patients. Besides, we are also exploring TQB2922 combined with other third-generation EGFR TKIs or other drugs like KRAS inhibition. This combination might be more effective and provide more promising efficacy.