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

NCT06885840 | Not Yet Recruiting Phase 2

• 1 other identifier: BTP-21723
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 20

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.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

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

• 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)

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

• Time to response (TTR)

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

Study Arms (4)

Cohort 1

EXPERIMENTAL

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

Cohort 2

EXPERIMENTAL

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

Cohort 3

EXPERIMENTAL

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

Cohort 4

EXPERIMENTAL

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

Interventions

MCLA-129 DRUG

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Betta Pharmaceuticals Co., Ltd.: lead

Study Sites (20)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, China

Location

The First Hospital of Lanzhou University

Lanzhou, Gansu, China

Location

Dongguan People's Hospital

Dongguan, Guangdong, China

Location

Foshan First People's Hospital

Foshan, Guangdong, China

Location

Guangdong General Hospital

Guangzhou, Guangdong, China

Location

Hebei University Affiliated Hospital

Baoding, Hebei, China

Location

Harbin Medical University Affiliated Cancer Hospital

Harbin, Heilongjiang, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, China

Location

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

Wuhan, Hubei, China

Location

Hunan Cancer Hospital

Changsha, Hunan, China

Location

Nantong Cancer Hospital

Nantong, Jiangsu, China

Location

Jilin Cancer Hospital

Changchun, Jilin, China

Location

The First Hospital of Jilin University

Changchun, Jilin, China

Location

The First Affiliated Hospital of China Medical University

Shenyang, Liaoning, China

Location

Shandong Cancer Hospital

Jinan, Shandong, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, China

Location

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, China

Location

The First Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Location

Beijing Chest Hospital

Beijing, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Wanlin Chen, Master

CONTACT

18258270120; wanlin.chen@bettapharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2025
• First Posted: March 20, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (20)