Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors

Required: EGFR mutation

EGFR positive is defined as: EGFR mutation or EGFR amplification

Required: EGFR amplification

EGFR positive is defined as: EGFR mutation or EGFR amplification

Required: EGFR exon 20 insertion

Cohort B: Advanced NSCLC patients diagnosed with EGFR exon 20 insertion mutation (Exon20ins)

Required: EGFR high expression (high)

EGFR positive is defined as: High EGFR expression

Required: MET amplification

MET positive is defined as: MET amplification

Required: MET exon 14 skipping

MET positive is defined as: MET exon 14 skipping mutation

Required: MET high expression (high)

MET positive is defined as: c-Met high expression

Excluded: HER2 (ERBB2) positive

For colorectal cancer subjects, HER-2 positivity (IHC 2+/3+ or FISH/NGS+) confirmed by local or central laboratory genetic testing

Must have received: standard treatment

disease progression after standard treatment, or are intolerant to standard treatment, or refuse standard treatment

Cannot have received: EGFR/c-Met bispecific antibody or ADC drugs (Amivantamab, EMB-01, GB263T, PM1080/HS-20117, TAVO412, YH013/DM005, SHR-9839, AZD9592)

Prior use of EGFR/c-Met bispecific antibody or ADC drugs (such as Amivantamab, EMB-01, GB263T, PM1080/HS-20117, TAVO412, YH013/ DM005, SHR-9839 or AZD9592 etc.)

Cannot have received: EGFR monoclonal antibody

Exception: Cohort E1: interval between last dose and first dose of MCLA-129 < 6 months

For cohort E1, the interval between the last dose of EGFR monoclonal antibody and the first dose of MCLA-129 was less than 6 months

Cannot have received: EGFR tyrosine kinase inhibitor (poziotinib, TAK-788, DZD9008, CLN-081, furmonertinib)

Exception: For advanced NSCLC patients with EGFR Exon20ins mutation: have received prior EGFR-TKI therapy known to be effective against Exon20ins

For advanced NSCLC patients with EGFR Exon20ins mutation: have received prior EGFR-TKI therapy (e.g., poziotinib, TAK-788, DZD9008, CLN-081, or furmonertinib, etc.) that is known to be effective against Exon20ins

Cannot have received: systemic anti-tumor therapy

Exception: For colorectal cancer, head and neck squamous cell carcinoma, or gastric/gastroesophageal junction adenocarcinoma: more than 3 prior lines (excluding maintenance therapy)

For patients with colorectal cancer, head and neck squamous cell carcinoma, or gastric/gastroesophageal junction adenocarcinoma: patients who have previously received systemic anti-tumor therapy beyond the third line (excluding maintenance therapy)

Cannot have received: cytotoxic chemotherapy

Exception: For NSCLC only: more than 2 prior lines for locally advanced or metastatic disease (excluding maintenance therapy)

For subjects with non-small cell lung cancer only: have received more than 2 prior lines of cytotoxic chemotherapy for locally advanced or metastatic diseases (excluding maintenance therapy)

Cannot have received: investigational product or anti-tumor drug

Exception: within 14 days before first dose of MCLA-129 or within 5 half-lives of the drug (whichever is longer)

Have received an investigational product or anti-tumor drug treatment within 14 days before the first dose of MCLA-129 or within 5 half-lives of the drug (whichever is longer)