Solid Advanced TumorPhase 1/2NCT07448116
Study of MCLA-129 in Combination With Ensartinib in Patients With Advanced Solid Tumors.
A Phase 1/2 study testing MCLA-129 and Ensartinib in people with Solid Advanced Tumor, run by Betta Pharmaceuticals Co., Ltd. at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Advanced Tumor
- What is being tested?
- MCLA-129 and Ensartinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 164 participants
- Where
- 1 siteChina
- Study dates
- 31 Jan 2026to 1 Aug 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 14Show fewer
- 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.
Who cannot join
- 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.
Show all 25Show fewer
- 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 clinically significant abnormal cardiovascular or cerebrovascular diseases, including but not limited to: Subjects with arterial thromboembolism, deep vein thrombosis, or pulmonary embolism within 3 months prior to the first dose of the study drug. Clinically insignificant non-obstructive catheter-related clots are not deemed as constituting an exclusion criterion. Subjects with a history of other venous thrombosis must be clinically stable for at least 4 weeks prior to the first dose of the study drug.
- 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.
- Subjects with other clinically significant cardiovascular or cerebrovascular diseases.
- Subjects with active hepatitis B (HBsAg positive and serum HBV DNA quantitative results ≥ the lower limit of detection (as per criteria of local laboratory)); positive for anti-hepatitis C virus antibody, anti-HIV antibody, or anti-treponema pallidum antibody (subjects with a history of HCV who have completed antiviral treatment and have laboratory test results showing HCV-RNA below the lower limit of quantification are eligible for enrollment; and subjects with negative syphilis titer tests are eligible for enrollment).
- Subjects with a history of interstitial lung disease or current clinical evidence of interstitial lung disease/pneumonia, including but not limited to drug-induced interstitial lung disease/pneumonia, radiation pneumonitis, or pulmonary fibrosis. Patients who cannot exclude suspected interstitial pneumonia/pulmonary fibrosis or uncontrolled stable non-infectious pneumonia/pulmonary inflammation by imaging examination during screening are not eligible for enrollment.
- Subjects with current severe illness or medical conditions, including but not limited to uncontrolled or poorly controlled active infections, uncontrolled pleural or peritoneal effusion, unstable tuberculosis, or other clinically significant pulmonary, metabolic, or psychiatric disorders.
- Subjects with gastric cancer/gastroesophageal junction adenocarcinoma with signs of active bleeding, active gastrointestinal (GI) diseases, or risk of gastrointestinal (GI) perforation, or other diseases that can significantly interfere with the absorption, distribution, metabolism, or excretion of the investigational drug.
- Subjects with hepatic encephalopathy, hepatorenal syndrome, or ≥ Child-Pugh class B cirrhosis.
- Women of childbearing potential with a positive serum pregnancy test within 7 days prior to the initiation of treatment, pregnant or breastfeeding women, and male or female subjects unwilling to use effective contraception or plan for pregnancy during the entire treatment period and for 3 months after treatment completion (see Appendix 3 for guidelines on contraception).
- Subjects with a history of allergy or suspected allergic symptoms to the study drug MCLA-129 or ensartinib or tartrazine (a dye used in ensartinib 100 mg capsules) or any other component or excipient
- Subjects judged by the investigator to have poor compliance, inability or unwillingness to adhere to the study and/or follow-up procedures listed in the protocol, or otherwise unsuitable for participation in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021
Jie Wang, M.D., +49 13910704669, zlhuxi@163.com
About this study
Official title: A Multi-cohort, Open-label Phase I/II Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of the Anti-EGFR/c-Met Bispecific Antibody MCLA-129 in Combination With Ensartinib Hydrochloride in Patients With Advanced Solid Tumors.
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.
Read the detailed description
This is a multi-center, open-label Phase I/II clinical study of MCLA-129 in combination with ensartinib in patients with advanced solid tumors to evaluate the efficacy, safety, and pharmacokinetics of MCLA-129 in combination with ensartinib. The study is divided into two parts: Phase I is a dose-exploration study to confirm the safe tolerability and recommended Phase II combination dose (RP2CD) of MCLA-129 in combination with ensartinib, and Phase II is a parallel cohort expansion study to further evaluate the efficacy, safety, and pharmacokinetics (PK) of MCLA-129 in combination with ensartinib in patients with advanced solid tumors in cohorts.
Primary Objectives of Phase I:
To evaluate the safety and tolerability of MCLA-129 in combination with ensartinib in patients with advanced solid tumors, and to determine potential dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) To determine the recommended Phase II combination dose (RP2CD) of MCLA-129 in combination with ensartinib.
Secondary Objectives of Phase I:
To evaluate the pharmacokinetic (PK) profile of MCLA-129 in combination with ensartinib in patients with advanced solid tumors To preliminarily evaluate the efficacy of MCLA-129 in combination with ensartinib in patients with advanced solid tumors To evaluate the immunogenicity of MCLA-129
Primary Objectives of Phase II:
To evaluate the efficacy of MCLA-129 in combination with ensartinib at the RP2CD in patients with advanced solid tumors across different cohorts.
Secondary Objectives of Phase II:
To evaluate the safety of MCLA-129 in combination with ensartinib at the RP2CD in patients with advanced solid tumors.
To evaluate the immunogenicity of MCLA-129.
- Conditions
- Solid Advanced Tumor
- Being tested
- MCLA-129, Ensartinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MCLA-129Drug
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.
EnsartinibDrug
Ensartinib acted as a c-MET inhibitor in this study.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Drug: MCLA-129; Drug: Ensartinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
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 I and II in terms of clinical benefit rate (CBR)
Measured: 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
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 I and II in terms of disease control rate (DCR)
Measured: 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
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 I and II in terms of progression-free survival (PFS)
Measured: 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
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 I and II in terms of duration of response (DOR)
Measured: 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
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 I and II in terms of time to response (TTR)
Measured: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Overall Survival (OS) 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 survival (OS)
Measured: From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years
Treatment-Emergent Adverse Event (TEAE) in Phase II
To evaluate the safety 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 treatment-emergent adverse event (TEAE)
Measured: Until 30 days after the last dosing
Area under the concentration versus time curve [AUC0-∞] in Phase I
To evaluate the population PK profile of of MCLA-129 in combination with Ensartinib hydrochloride in patients with advanced solid tumors in terms of area under the concentration versus time curve [AUC0-∞]
Measured: Until 30 days after the last dosing
Anti-Drug Antibody (ADA) in Phase I and II
To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129
Measured: Until 30 days after the last dosing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2026
- Study start31 Jan 2026
- Primary completion1 Feb 2029 (estimated)
- Study completion1 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Advanced TumorStudies of the same condition, open and under way.
- More trials run by Betta Pharmaceuticals Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Betta Pharmaceuticals Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07448116
- Sponsor's protocol ID
- BTP-21714
- Status last verified
- Mar 2026
- First submitted
- 31 Jan 2026
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-cohort, Open-label Phase I/II Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of the Anti-EGFR/c-Met Bispecific Antibody MCLA-129 in Combination With Ensartinib Hydrochloride in Patients With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT07448116
- Acronym / sponsor ID
- BTP-21714
- Conditions
- Solid Advanced Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 164 participants (estimated)
- Lead sponsor
- Betta Pharmaceuticals Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 31 Jan 2026 (actual)
- Primary completion
- 1 Feb 2029 (estimated)
- Study completion
- 1 Aug 2029 (estimated)
- First posted
- 4 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a multi-center, open-label Phase I/II clinical study of MCLA-129 in combination with ensartinib in patients with advanced solid tumors to evaluate the efficacy, safety, and pharmacokinetics of MCLA-129 in combination with ensartinib. The study is divided into two parts: Phase I is a dose-exploration study to confirm the safe tolerability and recommended Phase II combination dose (RP2CD) of MCLA-129 in combination with ensartinib, and Phase II is a parallel cohort expansion study to further evaluate the efficacy, safety, and pharmacokinetics (PK) of MCLA-129 in combination with ensartinib in patients with advanced solid tumors in cohorts.
Primary Objectives of Phase I:
To evaluate the safety and tolerability of MCLA-129 in combination with ensartinib in patients with advanced solid tumors, and to determine potential dose-limiting toxicities (DLT) and the maximum tolerated dose (MTD) To determine the recommended Phase II combination dose (RP2CD) of MCLA-129 in combination with ensartinib.
Secondary Objectives of Phase I:
To evaluate the pharmacokinetic (PK) profile of MCLA-129 in combination with ensartinib in patients with advanced solid tumors To preliminarily evaluate the efficacy of MCLA-129 in combination with ensartinib in patients with advanced solid tumors To evaluate the immunogenicity of MCLA-129
Primary Objectives of Phase II:
To evaluate the efficacy of MCLA-129 in combination with ensartinib at the RP2CD in patients with advanced solid tumors across different cohorts.
Secondary Objectives of Phase II:
To evaluate the safety of MCLA-129 in combination with ensartinib at the RP2CD in patients with advanced solid tumors.
To evaluate the immunogenicity of MCLA-129.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Patients with locally advanced NSCLC. | Experimental | Drug: MCLA-129, Drug: EnsartinibPatients 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 |
| Patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck. | Experimental | Drug: MCLA-129, Drug: EnsartinibPatients 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 |
| Patients with locally advanced or metastatic gastric cancer/gastroesophageal junction adenocarcinoma | Experimental | Drug: MCLA-129, Drug: EnsartinibPatients 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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:
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MCLA-129MCLA-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. | Drug | 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. |
| EnsartinibEnsartinib acted as a c-MET inhibitor in this study. | Drug | 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. |
Primary outcome
Dose-Limiting Toxicity (DLT) in Phase I
Time frame: 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
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)
Maximum Tolerated Dose (MTD) in Phase I
Time frame: From date of first treatment until the end of Phase I, approximately 6 months
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)
Treatment-Emergent Adverse Events (TEAE) in Phase I
Time frame: From date of first treatment until 30 days after the last dose or the start of other anti-tumor treatment (whichever occurs first)
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)
Overall Response Rate (ORR) in Phase II
Time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
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)
9 secondary outcomes
Clinical benefit rate (CBR) in Phase I and II
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Overall Survival (OS) in Phase II
Time frame: From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years
Treatment-Emergent Adverse Event (TEAE) in Phase II
Time frame: Until 30 days after the last dosing
Area under the concentration versus time curve [AUC0-∞] in Phase I
Time frame: Until 30 days after the last dosing
Anti-Drug Antibody (ADA) in Phase I and II
Time frame: Until 30 days after the last dosing
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Individual participant dataSharing planned: No
Related trials for Solid Advanced Tumor
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 1
A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
Neoplasms
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MCLA-129 and Ensartinib in people with Solid Advanced Tumor, run by Betta Pharmaceuticals Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ming Ma, M.D. (+49 13927255392, ming.ma@bettapharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) in Phase I (time frame: 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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.