Study of MCLA-129 in Combination With Ensartinib in Patients With Advanced Solid Tumors.

NCT07448116 | Recruiting Phase 1 DMC

• 1 other identifier: BTP-21714
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, open-label Phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of the anti-EGFR/c-Met bispecific antibody MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors.

Conditions

Solid Advanced Tumor

Outcome Measures

Primary Outcomes (4)

• Dose-Limiting Toxicity (DLT) in Phase I

  To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of dose-limiting toxicity (DLT)

  Until 28 days after the first dosing in MCLA-129 1500mg Q2W group or 21 days after the first dosing in MCLA-129 2000mg Q3W group

• Maximum Tolerated Dose (MTD) in Phase I

  To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of maximum tolerated dose (MTD)

  From date of first treatment until the end of Phase I, approximately 6 months

• Treatment-Emergent Adverse Events (TEAE) in Phase I

  To evaluate the safety of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of treatment-emergent adverse event (TEAE)

  From date of first treatment until 30 days after the last dose or the start of other anti-tumor treatment (whichever occurs first)

• Overall Response Rate (ORR) in Phase II

  To evaluate the efficacy of MCLA-129 in combination with Ensartinib hydrochloride at RP2D in patients with advanced solid tumors in each cohort in Phase II in terms of overall response rate (ORR)

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

Secondary Outcomes (9)

• Clinical benefit rate (CBR) in Phase I and II

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

• Disease Control Rate (DCR) in Phase I and II

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

• Progression-Free Survival (PFS) in Phase I and II

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

• Duration of Response (DOR) in Phase I and II

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

• Time to response (TTR) in Phase I and II

  From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years

Study Arms (3)

Patients with locally advanced NSCLC.

EXPERIMENTAL

Patients with locally advanced NSCLC with previously detected EGFR-sensitizing mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment and with MET amplification or overexpression. Drug: MCLA-129 and Ensartinib MCLA-129 will be administered intravenously at two different frequencies: 1500 mg every two weeks and 2000 mg every three weeks, in combination with Ensartinib. Ensartinib will be administered orally at 200 mg every day; if dose-limiting toxicity (DLT) is observed and deemed intolerable, a lower dose of 150 mg will be explored in combination with MCLA-129. Other Names: * MCLA-129 and Ensartinib Hydrochloride * MCLA-129 and Ensacove

Drug: MCLA-129; Drug: Ensartinib

Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck.

EXPERIMENTAL

Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (primary site in the oral cavity, oropharynx, hypopharynx, or larynx) who have progressed after prior standard treatment and with MET amplification or overexpression. Drug: MCLA-129 and Ensartinib MCLA-129 will be administered intravenously at two different frequencies: 1500 mg every two weeks and 2000 mg every three weeks, in combination with Ensartinib. Ensartinib will be administered orally at 200 mg every day; if dose-limiting toxicity (DLT) is observed and deemed intolerable, a lower dose of 150 mg will be explored in combination with MCLA-129. Other Names: * MCLA-129 and Ensartinib Hydrochloride * MCLA-129 and Ensacove

Drug: MCLA-129; Drug: Ensartinib

Patients with locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma

EXPERIMENTAL

Patients with locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma (including signet ring cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma) who have progressed after prior standard treatment and with MET amplification or overexpression. Drug: MCLA-129 and Ensartinib MCLA-129 will be administered intravenously at two different frequencies: 1500 mg every two weeks and 2000 mg every three weeks, in combination with Ensartinib. Ensartinib will be administered orally at 200 mg every day; if dose-limiting toxicity (DLT) is observed and deemed intolerable, a lower dose of 150 mg will be explored in combination with MCLA-129. Other Names: * MCLA-129 and Ensartinib Hydrochloride * MCLA-129 and Ensacove

Drug: MCLA-129; Drug: Ensartinib

Interventions

MCLA-129 DRUG

MCLA-129 is a bispecific antibody that targets both EGFR and c-Met, simultaneously blocking the signaling pathways of both EGFR and c-Met, thereby inhibiting tumor growth and survival.

Patients with locally advanced NSCLC.; Patients with locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma; Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck.

Ensartinib DRUG

Ensartinib acted as a c-MET inhibitor in this study.

Patients with locally advanced NSCLC.; Patients with locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma; Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects should be aged 18-75 years (both inclusive), regardless of gender.
• Subjects must have histologically or cytologically confirmed, locally advanced or metastatic solid tumors (including but not limited to non-small cell lung cancer, squamous cell carcinoma of the head and neck (primary site of oral cavity, oropharynx, hypopharynx, or larynx), gastric/gastroesophageal junction adenocarcinoma, etc.) that are not amenable to curative therapy.
• Subjects must have MET amplification or MET overexpression as confirmed by the tests conducted by local or central laboratory.\[MET amplification for Cohort 1 and Cohort 3 is defined as: MET copy number (CN) ≥ 5 by next-generation sequencing (NGS); or MET gene copy number (GCN) ≥ 5 or MET/CEP7 ≥ 2 by fluorescence in situ hybridization (FISH). MET amplification for Cohort 2 is defined as: MET copy number (CN) ≥ 3 by next-generation sequencing (NGS); or MET gene copy number (GCN) ≥ 3 or MET/CEP7 ≥ 2 by fluorescence in situ hybridization (FISH). MET overexpression is defined as 2+ or 3+ staining of ≥50% of tumor cells in tumor tissue samples by immunohistochemistry (IHC).\]
• For phase I study: subjects must meet the following conditions: with disease progression or intolerance to standard treatment after standard treatment, or evaluated by the investigator as ineligible for platinum-based chemotherapy (the standard treatment for the patient population enrolled in each cohort can refer to that for the phase II cohort study).
• For phase II study, each cohort is defined as follows:
• Cohort 1: Patients with locally advanced or metastatic non-small cell lung cancer with confirmed MET amplification or MET overexpression. Prior treatment should meet the following criteria: 1) If a previous test had identified an EGFR-sensitizing mutation (exon 19 deletion or exon 21 L858R mutation), the following requirements must be met: a) Disease progression after treatment with a third-generation EGFR-TKI and platinum-based chemotherapy ± PD-1/PD-L1 inhibitor, or intolerance to such treatment, or deemed unsuitable for platinum-based chemotherapy by the investigator; or b) Disease progression after first-or second-generation EGFR-TKI treatment with T790M mutation-negative or unknown gene mutation status, followed by disease progression after treatment with platinum-based chemotherapy ± PD-1/PD-L1 inhibitor, or intolerance to such treatment, or deemed unsuitable for platinum-based chemotherapy by the investigator. 2)If a previous test had identified an EGFR non-sensitizing mutation or MET exon 14 skipping mutation, disease progression after treatment with the corresponding inhibitors and platinum-based chemotherapy ± PD-1/PD-L1 inhibitor is required, or intolerance to such treatment, or deemed unsuitable for platinum-based chemotherapy by the investigator. 3)If no other driver gene alterations were identified in previous tests, disease progression after treatment with platinum-based chemotherapy ± PD-1/PD-L1 inhibitor is required, or intolerance to such treatment, or deemed unsuitable for platinum-based chemotherapy by the investigator.
• Cohort 2: Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (primary site in the oral cavity, oropharynx, hypopharynx, or larynx) with confirmed MET amplification or MET overexpression. Patients must have experienced disease progression or intolerance after previous treatment of platinum-based chemotherapy ± PD-1/PD-L1 inhibitor/EGFR monoclonal antibody therapy.
• Cohort 3: Locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma (including signet ring cell carcinoma, mucinous adenocarcinoma, hepatoid adenocarcinoma) with detected MET amplification or MET overexpression. Prior treatment should meet the following criteria:1)Disease progression or intolerance after treatment with a chemotherapy regimen consisting of platinum agents (cisplatin or oxaliplatin),paclitaxel/docetaxel, and fluoropyrimidines (5-FU,capecitabine or S-1),with or without PD-1/PD-L1 inhibitor;2)For patients with HER-2 positivity, disease progression after treatment with anti-HER-2 agents is required, or intolerance to such treatment, or deemed unsuitable for anti-HER-2 treatment by the investigator;3)For patients with Claudin 18.2 expression, disease progression after treatment with anti-Claudin 18.2 agents is required, or intolerance to such treatment.
• Subjects in the phase I dose-exploration study must have evaluable lesions; other subjects (including dose-backfill stage in phase I and phase II) must have measurable lesions as per 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.

You may not qualify if:

• Subjects with non-small cell lung cancer who have been tested positive for ALK in the genetic tests conducted by the local or central laboratory.
• Subjects have received any investigational drug or antitumor agent (for drugs with a long half-life, the time interval since the last dose should be no more than 4 weeks; for chemotherapy with delayed toxicity, such as nitrosoureas or mitomycin C, within the previous 6 weeks) within 14 days prior to the first dose of the study drug or within 5 half-lives of the drug (whichever is longer). Subjects have used any traditional Chinese medicine or Chinese herbal preparations with antitumor indications or definitive antitumor effects within 14 days prior to the first dose of the study drug.
• Subjects who have undergone any major surgery or radiotherapy within 4 weeks prior to the first dose of the study drug (palliative local radiotherapy is allowed if it was administered at least 2 weeks prior to the first dose of the study drug).
• For subjects with non-small cell lung cancer, prior receipt of more than two lines of systemic chemotherapy is required; for subjects with squamous cell carcinoma of the head and neck and gastric cancer/gastroesophageal junction adenocarcinoma, prior receipt of more than three lines of systemic anti-tumor treatment (excluding maintenance therapy) is required. For subjects who have received neoadjuvant/adjuvant therapy (chemotherapy or radio chemotherapy), if recurrence or metastasis occurs during treatment or within 6 months after discontinuation of treatment, it should be considered as first-line treatment.
• Prior use of EGFR/c-Met bispecific antibody or ADC drugs.
• Subjects who require concomitant use of strong CYP3A inhibitors or inducers within 14 days before the first administration of the investigational drug or during the study period.
• Toxicities related to prior treatment have not resolved to Grade 1 or below (CTCAE 5.0 criteria) prior to the first dose of the study drug, except for alopecia.
• Subjects who have had other malignancies within the past 3 years, except for malignancies that have been clearly cured or are locally curable, such as basal or squamous cell skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast.
• Cohort 1: Patients with primary central nervous system malignancy, or presence of meningeal metastases, or presence of spinal cord compression, or risk of cerebral hemorrhage, or symptomatic brain metastases, or unstable brain metastases requiring treatment with steroids and/or dehydration to reduce cranial pressure 2 weeks prior to enrollment.
• Cohorts 2 and 3: Patients with known brain and/or meningeal metastases, or primary central nervous system malignancies are excluded. Subjects with neurological symptoms shall have a brain CT/MRI scan to exclude brain metastases.
• Subjects with any of the following medical history within 6 months prior to the first dose of the study drug: myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, transient myocardial ischemia, coronary or peripheral artery bypass grafting (including coronary intervention), or any acute coronary syndrome.
• With abnormal ECG corrected QT interval (QTcF) of ECG at rest in the screening period, with the test been repeated twice at an interval 5 minutes above, and with the average QTcF of three ECG examinations: ≥ 450 msec for male, and ≥ 470 msec for female. Various clinically significant abnormalities in rhythm, conduction, resting ECG morphology within 3 months prior to the first dose of investigational drug, such as complete left bundle branch block, third degree block, second degree block, PR interval \>250 msec, bigeminy, trigeminy, pre-excitation syndrome, ST-segment elevation, atrial fibrillation, ventricular fibrillation, etc.
• Poorly controlled hypertension judged by investigators (systolic blood pressure \> 180 mmHg, or diastolic blood pressure \> 100 mmHg).
• New York Heart Association (NYHA) Class III-IV congestive heart failure (see Appendix 2) or hospitalization for congestive heart failure within 6 months prior to the first dose of investigational drug; left ventricular ejection fraction (LVEF) \<50%.
• Pericarditis/clinically significant pericardial effusion. Subjects with cardiomyopathy, including dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and myocarditis.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (1)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

MeSH Terms

Interventions

ensartinib

Central Study Contacts

Ming Ma, M.D.

CONTACT

+49 13927255392; ming.ma@bettapharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2026
• First Posted: March 4, 2026
• Study Start: January 31, 2026
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)