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

Inclusion Criteria:

• Subjects are ≥ 18 years of age, regardless of gender.

• Subjects must have histologically or cytologically confirmed metastatic orunresectable advanced NSCLC or other solid tumors (including but not limited to headand neck cancer, colorectal cancer, etc.), have disease progression after standardtreatment, or are intolerant to standard treatment, or refuse standard treatment.

• For Part 1, subjects must be diagnosed with EGFR positive and/or MET positive bytesting.

For patients with advanced NSCLC, EGFR positive is defined as: EGFR mutation or EGFR amplification. MET positive is defined as: MET amplification or MET exon 14 skipping mutation.

For patients with other advanced solid tumors other than NSCLC, EGFR positive is defined as: High EGFR expression or EGFR amplification. MET positive is defined as: c-Met high expression or MET amplification.

• For Part 2, patients shall meet the inclusion criteria for each cohort by biomarker testing.

Cohort A: Patients with advanced NSCLC who are previously diagnosed with EGFR mutations and treated with third-generation EGFR-TKIs for drug resistance.

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

Cohort C: Advanced NSCLC patients with MET amplification.

Cohort D: Advanced NSCLC patients with MET exon 14 skipping mutation (Exon14 skipping).

Cohort E: Patients with locally advanced or recurrent metastatic colorectal cancer (CRC) could not undergo curative treatment.

Cohort F: Other advanced solid tumors that have failed or are intolerant to standard therapy.

• For subjects in the dose escalation phase of Part 1, evaluable lesions must bepresent; other subjects must have measurable lesions that meet the definition ofRECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

• Expected survival ≥3 months.

• Have adequate organ function (no blood transfusion or use of blood component orG-CSF support within 14 days before testing).

• Willing and able to follow the trial and follow-up procedures.

• Able to understand the nature of the trial and voluntarily sign the written informedconsent form.

Exclusion Criteria:

• Have received an investigational product or anti-tumor drug treatment within 14 daysbefore the first dose of MCLA-129 or within 5 half-lives of the drug (whichever islonger). For cohort E1, the interval between the last dose of EGFR monoclonalantibody and the first dose of MCLA-129 was less than 6 months.

• Have undergone a major surgery and radiotherapy (local palliative radiotherapy isallowed 2 weeks or more prior to the first dose) within 4 weeks prior to the firstdose of MCLA-129.

• For patients with colorectal cancer: patients with colorectal cancer who havepreviously received systemic anti-tumor therapy beyond the third line (excludingmaintenance therapy).

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

• For advanced NSCLC patients with EGFR Exon20ins mutation: have received priorEGFR-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 [JNJ-61186372], EMB-01 or GB263T or AZD9592 etc.).

• Prior to the first dose of MCLA-129, previous treatment-related toxicities have notresolve 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 havebeen totally cured or locally cured, such as basal or squamous cell carcinoma of theskin, cervical cancer in situ, or breast cancer in situ.

• Patients with primary malignant tumor of central nervous system, or metastases tomeninges, or concomitantly with symptomatic brain metastases, or new therapy naivebrain metastases. For cohorts E and F: Patients with known brain metastases and/ormeningeal metastases, or primary malignant tumor of central nervous system. Subjectswith neurological symptoms shall have a brain CT/MRI scan to exclude brainmetastases.

• 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]), positivehepatitis C virus antibody, HIV antibody and treponema pallidum antibody.

• Subjects with a history of interstitial lung disease or current clinical evidence ofinterstitial lung disease, including drug-induced Interstitial lung disease orradiation pneumonitis.

• Presence of a serious disease or medical condition currently, including but notlimited to uncontrolled active infection, uncontrolled pleural or peritonealeffusion, and clinically significant pulmonary, metabolic or psychiatric diseases.

• Females of childbearing potential, pregnant or breastfeeding women with a positiveserum pregnancy test 7 days before the start of treatment, and male and femalesubjects who are unwilling to use effective contraceptive measures or plan to have achild throughout the treatment period and within 3 months after the end oftreatment.

• Patients with known allergic reactions and hypersensitivity reactions, or beallergic to MCLA-129 or any of its excipients.

• Patients with poor compliance, inability or unwillingness to follow the study and/orfollow-up procedure listed in the protocol, or patients who are not suitable toparticipate in this trial, as determined by the investigator.