Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors

NCT ID: NCT04930432

Last Updated: 2024-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-24

Study Completion Date

2028-12-30

Brief Summary

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This is a multi-center, open-label, Phase I/II clinical study of MCLA-129 as monotherapy in patients with advanced solid tumors to evaluate the safety, pharmacokinetic characteristics and antitumor activity of MCLA-129.

Detailed Description

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This is a multicenter, open-label, single-agent phase I/II clinical study of MCLA-129 in patients with advanced solid tumors to evaluate the safety, pharmacokinetic profile, and antitumor activity of MCLA-129. The study consists of two parts: Part I is a phase I dose- finding study in patients with advanced solid tumors, including a dose escalation phase and a dose expansion phase; Part II is a phase II parallel cohort expansion study to further evaluate the efficacy, safety and PK profile of MCLA-129 in sub-cohorts of patients with advanced non-small cell lung cancer and other solid tumors.

Conditions

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Solid Tumor Non-Small Cell Lung Cancer Head and Neck Cancer Colorectal Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: dose escalation and dose expansion

Participants will receive intravenous infusion of MCLA-129 every two weeks (Q2W) or every weeks (QW) at different dose in each dose level.

Group Type EXPERIMENTAL

MCLA-129

Intervention Type DRUG

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

Part 2: cohort expansion

Participants will receive intravenous infusion of MCLA-129 every two weeks (Q2W) at the recommended Phase II dose (RP2D) in each cohort.

Group Type EXPERIMENTAL

MCLA-129

Intervention Type DRUG

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

Interventions

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MCLA-129

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Subjects are ≥ 18 years of age, regardless of gender.
* Subjects must have histologically or cytologically confirmed metastatic or unresectable advanced NSCLC or other solid tumors (including but not limited to head and neck cancer, colorectal cancer, etc.), have disease progression after standard treatment, or are intolerant to standard treatment, or refuse standard treatment.
* For Part 1, subjects must be diagnosed with EGFR positive and/or MET positive by testing.

For patients with advanced NSCLC, EGFR positive is defined as: EGFR mutation or EGFR amplification. MET positive is defined as: MET amplification or MET exon 14 skipping mutation.

For patients with other advanced solid tumors other than NSCLC, EGFR positive is defined as: High EGFR expression or EGFR amplification. MET positive is defined as: c-Met high expression or MET amplification.


Cohort A: Patients with advanced NSCLC who are previously diagnosed with EGFR mutations and treated with third-generation EGFR-TKIs for drug resistance.

Cohort B: Advanced NSCLC patients diagnosed with EGFR exon 20 insertion mutation (Exon20ins).

Cohort C: Advanced NSCLC patients with MET amplification.

Cohort D: Advanced NSCLC patients with MET exon 14 skipping mutation (Exon14 skipping).

Cohort E: Patients with locally advanced or recurrent metastatic colorectal cancer (CRC) could not undergo curative treatment.

Cohort F: Other advanced solid tumors that have failed or are intolerant to standard therapy.

* For subjects in the dose escalation phase of Part 1, evaluable lesions must be present; other subjects must have measurable lesions that meet the definition of 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.

Exclusion Criteria

* Have received an investigational product or anti-tumor drug treatment within 14 days before the first dose of MCLA-129 or within 5 half-lives of the drug (whichever is longer). For cohort E1, the interval between the last dose of EGFR monoclonal antibody and the first dose of MCLA-129 was less than 6 months.
* 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.
* For patients with colorectal cancer: patients with colorectal cancer who have previously received systemic anti-tumor therapy beyond the third line (excluding maintenance therapy).
* For subjects with non-small cell lung cancer only: have received more than 2 prior lines of cytotoxic chemotherapy for locally advanced or metastatic diseases (excluding maintenance therapy).
* For advanced NSCLC patients with EGFR Exon20ins mutation: have received prior EGFR-TKI therapy (e.g., poziotinib, TAK-788, DZD9008, CLN-081, or furmonertinib, etc.) that is known to be effective against Exon20ins.
* Prior use of EGFR/c-Met bispecific antibody or ADC drugs (such as Amivantamab \[JNJ-61186372\], EMB-01 or GB263T or AZD9592 etc.).
* Prior to the first dose of MCLA-129, previous treatment-related toxicities have not resolve 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. For cohorts E and F: Patients with known brain metastases and/or meningeal metastases, or primary malignant tumor of central nervous system. Subjects with neurological symptoms shall have a brain CT/MRI scan to exclude brain metastases.
* With clinically significant cardiovascular and cerebrovascular diseases.
* Active hepatitis B (positive hepatitis B surface antigen (HBsAg) or core antibody (HBcAb) 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

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Betta Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jie Wang, PhD

Role: STUDY_CHAIR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

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Affiliated Hospital of Hebei University

Baoding, , China

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, , China

Site Status RECRUITING

Beijing Friendship Hospital, Capital Medical University

Beijing, , China

Site Status NOT_YET_RECRUITING

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Site Status RECRUITING

Peking University International Hospital

Beijing, , China

Site Status RECRUITING

The Fifth Medical Center of PLA Ceneral Hospital

Beijing, , China

Site Status RECRUITING

The First Affiliated Hospital of Bengbu Medical College

Bengbu, , China

Site Status RECRUITING

Cangzhou Hospital of Integrated TCM-WM·Hebei

Cangzhou, , China

Site Status RECRUITING

Ji Lin Cancer Hospital

Changchun, , China

Site Status RECRUITING

Hunan Cancer Hospital

Changsha, , China

Site Status RECRUITING

Hunan Cancer Hospital

Changsha, , China

Site Status NOT_YET_RECRUITING

The Second Xiangya Hospital of Central South University

Changsha, , China

Site Status RECRUITING

Sichuan Cancer Hospital

Chengdu, , China

Site Status RECRUITING

West China Hospital, Sichuan University

Chengdu, , China

Site Status RECRUITING

Chifeng Municipal Hospital

Chifeng, , China

Site Status RECRUITING

Army Medical Center of PLA

Chongqing, , China

Site Status RECRUITING

Chongqing University Cancer Hospital

Chongqing, , China

Site Status RECRUITING

China-Japan Union Hospitai Of Jilin University

Ch’ang-ch’un, , China

Site Status RECRUITING

The First Affiliated Hospital of Dalian Medical University

Dalian, , China

Site Status NOT_YET_RECRUITING

Fujian Cancer Hospital

Fuzhou, , China

Site Status RECRUITING

Fuzhou Pulmonary Hospital of Fujian

Fuzhou, , China

Site Status RECRUITING

The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China

Fuzhou, , China

Site Status RECRUITING

First Affiliated Hospital Of Gannan Medical University

Ganzhou, , China

Site Status RECRUITING

Guangdong Province Traditional Chinese Medical Hospital

Guangzhou, , China

Site Status RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, , China

Site Status RECRUITING

The Frist Affiliated Hospital of Guangzhou Medical College

Guangzhou, , China

Site Status RECRUITING

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, , China

Site Status NOT_YET_RECRUITING

Cancer Hospital of The University of Chinese Academy of Sciences

Hangzhou, , China

Site Status RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, , China

Site Status RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, , China

Site Status NOT_YET_RECRUITING

Hanzhong Central Hospital

Hanzhong, , China

Site Status RECRUITING

Cancer Hospital affiliated to Harbin Medical University

Ha’erbin, , China

Site Status RECRUITING

Harbin Medical University cancer hospital

Ha’erbin, , China

Site Status NOT_YET_RECRUITING

The Second Hospital of Anhui Medical University

Hefei, , China

Site Status RECRUITING

Inner Mongolia People's Hospital

Hohhot, , China

Site Status RECRUITING

Jiangxi cancer hospital

Jiangxi, , China

Site Status RECRUITING

The First Hospital of Jilin University

Jilin, , China

Site Status RECRUITING

Shandong Cancer Hospital & institute

Jinan, , China

Site Status RECRUITING

Yunnan Cancer Hospital

Kunming, , China

Site Status RECRUITING

The First Hospital of Lanzhou University

Lanzhou, , China

Site Status RECRUITING

General Hospital of Eastern Theater Command

Nanjing, , China

Site Status RECRUITING

Jiangsu Cancer Hospital

Nanjing, , China

Site Status RECRUITING

Nanjing Drum Tower Hospital

Nanjing, , China

Site Status RECRUITING

Nantong Tumor Hospital

Nantong, , China

Site Status RECRUITING

Qingdao Central Hospital

Qingdao, , China

Site Status RECRUITING

The Affiliated Hospital of Qingdao University

Qingdao, , China

Site Status RECRUITING

First Hospital of Qinhuangdao

Qinhuangdao, , China

Site Status RECRUITING

ShangHai Chest Hospital

Shanghai, , China

Site Status RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, , China

Site Status RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, , China

Site Status NOT_YET_RECRUITING

The First Hospital of China Medical University

Shenyang, , China

Site Status RECRUITING

Cancer Hospital of Chinese Academy of Medical Sciences Shenzhen Hospital

Shenzhen, , China

Site Status RECRUITING

Shenzhen People's Hospital

Shenzhen, , China

Site Status RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, , China

Site Status RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, , China

Site Status RECRUITING

Taizhou Hospital of Zhejiang Province

Taizhou, , China

Site Status RECRUITING

General Hospital of Tianjin Medical University

Tianjin, , China

Site Status RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status NOT_YET_RECRUITING

Tonghua Central Hospital

Tonghua, , China

Site Status RECRUITING

Weifang People's Hospital

Weifang, , China

Site Status RECRUITING

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, , China

Site Status RECRUITING

Hubei Cancer Hospital

Wuhan, , China

Site Status NOT_YET_RECRUITING

Renmin Hospital of Wuhan University/Hubei General Hospital

Wuhan, , China

Site Status RECRUITING

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

Wuhan, , China

Site Status RECRUITING

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

Wuhan, , China

Site Status NOT_YET_RECRUITING

Zhongnan Hospital Affiliated to Wuhan University

Wuhan, , China

Site Status RECRUITING

The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital)

Wuhu, , China

Site Status RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

Site Status RECRUITING

The First Affiliated Hospital Of Xiamen University

Xiamen, , China

Site Status RECRUITING

Xuzhou Central Hospital

Xuzhou, , China

Site Status RECRUITING

Yantai Yuhuangding Hospital

Yantai, , China

Site Status RECRUITING

The No. 2 People's Hospital of Yibin Sichuan

Yibin, , China

Site Status RECRUITING

Hospital of Ningxia Medical University

Yinchuan, , China

Site Status RECRUITING

He Nan Cancer Hospital

Zhengzhou, , China

Site Status RECRUITING

Henan Provincial People's Hospital

Zhengzhou, , China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, , China

Site Status RECRUITING

Henan Provincial People's Hospital

Zhenzhou, , China

Site Status NOT_YET_RECRUITING

Countries

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China

Central Contacts

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Wanlin Chen, Master

Role: CONTACT

Phone: 18258270120

Email: [email protected]

Other Identifiers

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BTP-21711

Identifier Type: -

Identifier Source: org_study_id