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

Exclusion Criteria

• •For colorectal cancer subjects, HER-2 positivity (IHC 2+/3+ or FISH/NGS+) confirmed by local or central laboratory genetic testing.
• •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). 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.
• •Have undergone a major surgery and radiotherapy (local palliative radiotherapy is allowed 2 weeks or more prior to the first dose) within 4 weeks prior to the first dose of MCLA-129.
• •For patients with colorectal cancerr, 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).
• •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).
• •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.
• •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.).
• •Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolve to Grade 1 or below (CTCAE 5.0 criteria), except for alopecia.
• •Have had other malignancies within the past 3 years, except for cancers that have been totally cured or locally cured, such as basal or squamous cell carcinoma of the skin, cervical cancer in situ, or breast cancer in situ.
• •Patients with primary malignant tumor of central nervous system, or metastases to meninges, spinal cord compression, or at risk of cerebral hemorrhage, or concomitantly with symptomatic brain metastases, or new therapy naive brain metastases. For cohorts E, F and G (excluding NSCLC patients): Patients with known brain metastases and/or meningeal metastases, or primary malignant tumor of central nervous system. Subjects with neurological symptoms shall have a brain CT/MRI scan to exclude brain metastases.
• •With clinically significant cardiovascular and cerebrovascular diseases.
• •Active hepatitis B (positive hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) and serum HBV DNA ≥ 2,000 IU/mL \[equivalent to 104 copies/mL\]), positive hepatitis C virus antibody, HIV antibody and treponema pallidum antibody.
• •Subjects with a history of interstitial lung disease or current clinical evidence of interstitial lung disease, including drug-induced Interstitial lung disease, radiation pneumonitis or pulmonary fibrosis. Subjects who could not be ruled out for suspected interstitial lung disease/pulmonary fibrosis through imaging examinations during screening, or those with uncontrolled/unstable non-infectious pneumonitis/pulmonary inflammation are excluded.
• •Presence of a serious disease or medical condition currently, including but not limited to uncontrolled active infection, uncontrolled pleural or peritoneal effusion, unstable/uncontrolled tuberculosis, active gastrointestinal diseases, gastrointestinal obstruction or perforation risks, and clinically significant pulmonary, metabolic or psychiatric diseases.
• •Females of childbearing potential, pregnant or breastfeeding women with a positive serum pregnancy test 7 days before the start of treatment, and male and female subjects who are unwilling to use effective contraceptive measures or plan to have a child throughout the treatment period and within 3 months after the end of treatment.
• •Patients with known allergic reactions and hypersensitivity reactions, or be allergic to MCLA-129 or any of its excipients.
• •Patients with poor compliance, inability or unwillingness to follow the study and/or follow-up procedure listed in the protocol, or patients who are not suitable to participate in this trial, as determined by the investigator.