Study of MCLA-129 in the Treatment of Advanced Non-small Cell Lung Cancer with AGA and MET Amplification.

NCT ID: NCT06885840

Last Updated: 2025-03-20

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-03-31
• Study Completion Date: 2028-09-30

Brief Summary

This is a multi-center, open-label, phase II clinical study of MCLA-129 as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) with actionable gene alterations and MET amplification to evaluate the efficacy, safety, pharmacokinetic characteristics of MCLA-129.

Detailed Description

This is a multi-center, open-label, monotherapy, multi-cohort phase II study of MCLA-129 in patients with advanced non-small cell lung cancer (NSCLC) with actionable gene alterations and MET amplification, designed to evaluate the efficacy, safety, and PK profiles of MCLA-129 in the target population.

Subjects who must experience disease progression or intolerance after standard treatment eligible through screening will be divided into the following 4 cohorts:

Cohort 1 and Cohort 2: Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment which includes 1) first-generation or second-generation EGFR-TKIs, with T790M mutation requiring third-generation EGFR-TKIs and platinum-based chemotherapy; or 2) first-generation or second-generation EGFR-TKIs, with T790M mutation negative or unknown status.

Subjects in Cohort 1: Patients with MET amplification after failure of treatment with EGFR-TKIs.

Subjects in Cohort 2: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment.

Cohort 3 and Cohort 4: Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors and platinum-based chemotherapy.

Subjects in Cohort 3: Patients with MET amplification, after failure of treatment with the corresponding driver gene inhibitors.

Subjects in Cohort 4 should also meet: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment and with MET amplification after failure of treatment with EGFR-TKIs.

Group Type: EXPERIMENTAL

MCLA-129

Intervention Type: DRUG

MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

Cohort 2

Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment and with disease progression or intolerance after MET inhibitors and who have benefited from such treatment.

Group Type: EXPERIMENTAL

MCLA-129

Intervention Type: DRUG

MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

Cohort 3

Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors and platinum-based chemotherapy also with MET amplification after failure of treatment with the corresponding driver gene inhibitors.

Group Type: EXPERIMENTAL

MCLA-129

Intervention Type: DRUG

MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

Cohort 4

Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors, platinum-based chemotherapy and with disease progression or intolerance after MET inhibitors and who have benefited from such treatment.

Group Type: EXPERIMENTAL

MCLA-129

Intervention Type: DRUG

MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

Interventions

MCLA-129

MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects are ≥ 18 years of age, regardless of gender.
• Subjects must have histologically or cytologically confirmed locally advanced unresectable or metastatic NSCLC.
• Subjects who must experience disease progression or intolerance after standard treatment eligible through screening will be divided into the following 4 cohorts:

Cohort 1 and Cohort 2: Patients with advanced NSCLC with previously detected EGFR-sensitive mutations (exon 19 deletion or exon 21 L858R mutation) who have progressed after prior standard treatment which includes 1) first-generation or second-generation EGFR-TKIs, with T790M mutation requiring third-generation EGFR-TKIs and platinum-based chemotherapy; or 2) first-generation or second-generation EGFR-TKIs, with T790M mutation negative or unknown status.

Subjects in Cohort 1: Patients with MET amplification after failure of treatment with EGFR-TKIs.

Subjects in Cohort 2: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment.

Cohort 3 and Cohort 4: Patients with advanced NSCLC with previously detected actionable gene alterations who had progressed after treatment with corresponding inhibitors and platinum-based chemotherapy.

Subjects in Cohort 3: Patients with MET amplification after failure of treatment with the corresponding driver gene inhibitors.

Subjects in Cohort 4: Patients who experienced disease progression or intolerance after MET inhibitors and benefited from such treatment.

• Subjects must have measurable lesions that meet the definition of RECIST v1.1. Selected target lesions must meet one of the following two criteria: 1) no prior local therapy or radiation or 2) subsequent progression occurs within the prior local therapy area as determined by RECIST v1.1..
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Expected survival ≥3 months.
• Have certain functions of organ systems (no blood transfusion or use of blood component or G-CSF support within 14 days before testing), defined as follows:

• Absolute neutrophil count (ANC) ≥1.5×10^9 /L.
• Platelet count (PLT）≥75×10^9 /L.
• Hemoglobin (HGB) ≥100 g/L.
• Serum albumin ≥ 30 g/L.
• Total bilirubin ≤1.5 times the upper limit of normal (ULN).
• Alanine amino transferase (ALT) and aspartate amino transferase (AST) ≤3×ULN.
• Creatinine ≤1.5×ULN. If creatinine is >1.5×ULN, creatinine clearance ≥50 mL/min as calculated by Cockcroft-Gault formula, or 24-hour urine creatinine clearance ≥50 mL/min is measured, the patients can still be enrolled.
• 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

• Have received an investigational product or antitumor drug treatment (including known anti-tumor traditional Chinese medicine treatment) within 14 days before the first dose of MCLA-129 or within 5 half-lives of the drug (whichever is longer) (for a drug with a long half-life, it is required that the interval from the last dose to be at most 4 weeks; for chemotherapy with delayed toxicity, such as nitrosourea or mitomycin C, it shall be 6 weeks before [the treatment]).
• 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.
• Have previously received systemic anti-tumor therapy beyond the fourth line (excluding maintenance therapy).
• Prior use of EGFR/c-Met bispecific antibody or ADC drugs (Amivantamab [JNJ-61186372], EMB-01, GB263T, PM1080/HS-20117, TAVO412, YH013/DM005, AZD9592, or SHR-9839).
• Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolved to Grade 1 or below (CTCAE 5.0 criteria), except for alopecia.
• Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolved 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, or concomitantly with symptomatic brain metastases, or new therapy naive brain metastases.

Note: Patients with brain metastases who have received treatment for brain metastases (including systemic and local therapies against brain metastases) with no obvious symptoms and stable condition, and do not require drug therapy such as steroids and/or dehydration to reduce intracranial pressure within 2 weeks before enrollment and have no risk of brain bleeding can be enrolled.

• With clinically significant cardiovascular and cerebrovascular diseases.

• With any of the following medical history within 6 months before first administration of the investigational drug: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary or peripheral artery bypass, or any acute coronary syndrome.
• With abnormal ECG corrected QT interval (QTcF) at rest in the screening period. Remeasurement is made twice at intervals of more than 5 minutes. For average QTcF of 3 ECG inspections: male: ≥ 450 msec, and female: ≥ 470 msec. With clinically significant abnormal heart rate, conduction, and ECG form at rest, e.g. complete left bundle branch block, third-degree conduction block, second-degree conduction block, and PR interval > 250 msec, double law, triple law, preexcitation syndrome, etc.
• Poorly controlled hypertension in the investigator's opinion (systolic blood pressure > 180 mmHg, or diastolic blood pressure > 100 mmHg).
• New York Heart Association Grade III-IV congestive heart failure, or hospitalization due to congestive heart failure within 6 months before first administration of the investigational drug.
• Pericarditis/clinically significant pericardial effusion.
• Cardiomyopathy.
• Other clinically significant cardiovascular disorders as believed by investigators.
• Active hepatitis B (positive hepatitis B surface antigen (HBsAg) 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 or radiation pneumonitis.
• Presence of a serious disease or medical condition currently, including but not limited to uncontrolled active infection, uncontrolled pleural or peritoneal effusion, 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Betta Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

Dongguan People's Hospital

Dongguan, Guangdong, China

Foshan First People's Hospital

Foshan, Guangdong, China

Guangdong General Hospital

Guangzhou, Guangdong, China

Hebei University Affiliated Hospital

Baoding, Hebei, China

Harbin Medical University Affiliated Cancer Hospital

Harbin, Heilongjiang, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Hunan Cancer Hospital

Changsha, Hunan, China

Nantong Cancer Hospital

Nantong, Jiangsu, China

Jilin Cancer Hospital

Changchun, Jilin, China

The First Hospital of Jilin University

Changchun, Jilin, China

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, China

Shandong Cancer Hospital

Jinan, Shandong, China

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Beijing Chest Hospital

Beijing, , China

Countries

China

Central Contacts

Wanlin Chen, Master

Role: CONTACT

wanlin.chen@bettapharma.com

18258270120

Other Identifiers

BTP-21723

Identifier Type: -

Identifier Source: org_study_id