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MCLA-129 treatment for advanced solid tumors

A Phase I/II Study of MCLA-129, a Human Anti-EGFR and Anti-c-Met Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors, Evaluating Safety, Pharmacokinetic Characteristics and Antitumor Activity

Phase1; Phase2 Interventional Betta Pharmaceuticals Co., Ltd. · NCT04930432

This study is testing a new treatment called MCLA-129 for people with advanced solid tumors, like lung or colorectal cancer, to see if it can help them after other treatments haven’t worked.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment400 (estimated)
Ages18 Years and up
SexAll
SponsorBetta Pharmaceuticals Co., Ltd. Industry-sponsored
Drugs / interventionsAmivantamab, poziotinib, furmonertinib, chemotherapy, radiation
Locations87 sites (Baoding and 86 other locations)
Trial IDNCT04930432 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates MCLA-129, a bispecific antibody targeting EGFR and cMet, in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), head and neck cancer, and colorectal cancer. The study is divided into two parts: a Phase I dose-finding segment to assess safety and pharmacokinetics, followed by a Phase II expansion to further evaluate efficacy in specific patient cohorts. Participants must have confirmed advanced tumors that have progressed after standard treatments or are intolerant to them.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced NSCLC or other solid tumors that are EGFR and/or MET positive and have experienced disease progression after standard treatments.

Not a fit: Patients with early-stage tumors or those who have not progressed after standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors who have limited treatment alternatives.

How similar studies have performed: Other studies targeting EGFR and cMet have shown promise, suggesting potential for success with this novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Subjects are ≥ 18 years of age, regardless of gender.
* Subjects must have histologically or cytologically confirmed metastatic or unresectable advanced NSCLC or other solid tumors (including but not limited to head and neck cancer, colorectal cancer, etc.), have disease progression after standard treatment, or are intolerant to standard treatment, or refuse standard treatment (Refusal of standard treatment does not apply to Part 2).
* For Part 1, subjects must be diagnosed with EGFR positive and/or MET positive by testing.

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.

Cohort G: Patients with locally advanced or metastatic MET-amplified or MET-overexpressing other driver gene-negative non-small cell lung cancer, gastric/gastroesophageal junction adenocarcinoma \[including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma\], or recurrent/metastatic \[R/M\] head and neck squamous cell carcinoma \[primary sites: oral cavity, oropharynx, hypopharynx, or larynx\], who are not candidates for curative treatment.

* For subjects in the dose escalation phase of Part 1, evaluable lesions must be present; other subjects must have measurable lesions that meet the definition of RECIST 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 or G-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 informed consent form.

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.

Where this trial is running

Baoding and 86 other locations

+37 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Solid TumorNon-Small Cell Lung CancerHead and Neck CancerColorectal Cancer
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.