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

A Multi-cohort, Open-label Phase II Study to Evaluate the Efficacy and Safety of the Anti-EGFR/c-Met Bispecific Antibody MCLA-129 in Patients with Advanced Non-Small Cell Lung Cancer with Actionable Gene Alterations and MET Amplification.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Wanlin Chen, Master; Phone Number: 18258270120; Email: wanlin.chen@bettapharma.com

Study Locations

• China
  • Beijing, China
    • Beijing Chest Hospital
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated Hospital of Anhui Medical University
  • Gansu
    • Lanzhou, Gansu, China
      • The First Hospital of Lanzhou University
  • Guangdong
    • Dongguan, Guangdong, China
      • Dongguan People's Hospital
    • Foshan, Guangdong, China
      • Foshan First People's Hospital
    • Guangzhou, Guangdong, China
      • Guangdong General Hospital
  • Hebei
    • Baoding, Hebei, China
      • Hebei University Affiliated Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Affiliated Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Nantong, Jiangsu, China
      • Nantong Cancer Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • The First Affiliated Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital
  • Shanxi
    • Xi'an, Shanxi, China
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

  • Arterial thromboembolism, deep vein thrombosis or lung embolism diagnosed within 3 month before first administration of the investigational drug. Non-obstructive catheter related clot and other clinically irrelevant thrombosis are not included in the exclusion criteria. Patients with a history of related thrombosis diagnosed 3 months ago must be clinically stable for at least 4 weeks before initial administration.
  • 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: MCLA-129; MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.
Experimental: 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.	Drug: MCLA-129; MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.
Experimental: 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.	Drug: MCLA-129; MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.
Experimental: 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.	Drug: MCLA-129; MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	To evaluate the efficacy of MCLA-129 at RP2D in patients with advanced NSCLC and other solid tumors in each cohort in Part 2 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of clinical benefit rate (CBR).	From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years.
Disease Control Rate (DCR)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of disease control rate (DCR)	From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years.
Progression-Free Survival (PFS)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of progression-free survival (PFS).	From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years.
Duration of Response (DOR)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of duration of response (DOR).	From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years.
Time to response (TTR)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of time to response (TTR).	From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years.
Overall Survival (OS)	To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of overall survival (OS).	From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years.
Treatment-Emergent Adverse Event (TEAE)	To evaluate the safety of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of treatment-emergent adverse event (TEAE).	Until 30 days after the last dosing
Area under the concentration versus time curve [AUC0-∞]	To evaluate the population PK profile of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 and 2 in terms of area under the concentration versus time curve [AUC0-∞].	: Until 30 days after the last dosing.
Anti-Drug Antibody (ADA)	To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129.	Until 30 days after the last dosing.

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: March 14, 2025
• First Submitted That Met QC Criteria: March 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BTP-21723

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No