Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors
A Phase I/II Study of MCLA-129, a Human Anti-EGFR and Anti-c-Met Bispecific Antibody, in Patients With Advanced NSCLC and Other Solid Tumors, Evaluating Safety, Pharmacokinetic Characteristics and Antitumor Activity
1 other identifier
interventional
400
1 country
87
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2021
Longer than P75 for phase_1
87 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 31, 2021
CompletedFirst Posted
Study publicly available on registry
June 18, 2021
CompletedStudy Start
First participant enrolled
September 24, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 30, 2028
February 10, 2026
February 1, 2026
6.6 years
May 31, 2021
February 5, 2026
Conditions
Outcome Measures
Primary Outcomes (4)
Dose-Limiting Toxicity (DLT) in Part 1
To determine the dose-limiting toxicity (DLT) of single agent MCLA-129 in patients with advanced solid tumors in Part 1.
First 28 days of treatment
Maximum Tolerated Dose (MTD) in Part 1
To determine the maximum tolerated dose (MTD) of single agent MCLA-129 in patients with advanced solid tumors in Part 1.
First 28 days of treatment
Overall Response Rate (ORR) in Part 2
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
Treatment-Emergent Adverse Event (TEAE) in Part 1 and 2
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
Secondary Outcomes (15)
Half-life [t1/2] in Part 1 and 2
Until 30 days after the last dosing
Apparent volume of distribution [VSS] in Part 1 and 2
Until 30 days after the last dosing
Maximum plasma concentration [Cmax] in Part 1 and 2
Until 30 days after the last dosing
Time to reach maximum concentration [Tmax] in Part 1 and 2
Until 30 days after the last dosing
Area under the concentration versus time curve from time zero to time t [AUC0-t] in Part 1 and 2
Until 30 days after the last dosing
- +10 more secondary outcomes
Study Arms (2)
Part 1: dose escalation and dose expansion
EXPERIMENTALParticipants will receive intravenous infusion of MCLA-129 every two weeks (Q2W) or every weeks (QW) at different dose in each dose level.
Part 2: cohort expansion
EXPERIMENTALParticipants will receive intravenous infusion of MCLA-129 every two weeks (Q2W) at the recommended Phase II dose (RP2D) in each cohort.
Interventions
MCLA-129 will be administered by intravenous infusion on the 28-day treatment cycle.
Eligibility Criteria
You may qualify if:
- 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 (Refusal of standard treatment does not apply to Part 2).
- 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.
- Cohort G: Patients with locally advanced or metastatic MET-amplified or MET-overexpressing other driver gene-negative non-small cell lung cancer, gastric/gastroesophageal junction adenocarcinoma \[including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma\], or recurrent/metastatic \[R/M\] head and neck squamous cell carcinoma \[primary sites: oral cavity, oropharynx, hypopharynx, or larynx\], who are not candidates for curative treatment.
- 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).
- +2 more criteria
You may not qualify if:
- For colorectal cancer subjects, HER-2 positivity (IHC 2+/3+ or FISH/NGS+) confirmed by local or central laboratory genetic testing.
- 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 cancerr, head and neck squamous cell carcinoma, or gastric/gastroesophageal junction adenocarcinoma: patients 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, EMB-01, GB263T, PM1080/HS-20117, TAVO412, YH013/ DM005, SHR-9839 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, spinal cord compression, or at risk of cerebral hemorrhage, or concomitantly with symptomatic brain metastases, or new therapy naive brain metastases. For cohorts E, F and G (excluding NSCLC patients): 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, radiation pneumonitis or pulmonary fibrosis. Subjects who could not be ruled out for suspected interstitial lung disease/pulmonary fibrosis through imaging examinations during screening, or those with uncontrolled/unstable non-infectious pneumonitis/pulmonary inflammation are excluded.
- Presence of a serious disease or medical condition currently, including but not limited to uncontrolled active infection, uncontrolled pleural or peritoneal effusion, unstable/uncontrolled tuberculosis, active gastrointestinal diseases, gastrointestinal obstruction or perforation risks, 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (87)
Affiliated Hospital of Hebei University
Baoding, China
Beijing Cancer Hospital
Beijing, China
Beijing Friendship Hospital, Capital Medical University
Beijing, China
Beijing Tongren Hospital
Beijing, China
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, China
Peking University International Hospital
Beijing, China
The Fifth Medical Center of PLA Ceneral Hospital
Beijing, China
The First Affiliated Hospital of Bengbu Medical College
Bengbu, China
The First Affiliated Hospital of Bengbu Medical University
Bengbu, China
Cangzhou Hospital of Integrated TCM-WM·Hebei
Cangzhou, China
Ji Lin Cancer Hospital
Changchun, China
Hunan Cancer Hospital
Changsha, China
The Second Xiangya Hospital of Central South University
Changsha, China
Xiangya Hospital of Central South University
Changsha, China
Sichuan Cancer Hospital
Chengdu, China
West China Hospital, Sichuan University
Chengdu, China
Chifeng Municipal Hospital
Chifeng, China
Army Medical Center of PLA
Chongqing, China
Chongqing University Cancer Hospital
Chongqing, China
China-Japan Union Hospitai Of Jilin University
Ch’ang-ch’un, China
The First Affiliated Hospital of Dalian Medical University
Dalian, China
Fujian Cancer Hospital
Fuzhou, China
Fuzhou Pulmonary Hospital of Fujian
Fuzhou, China
The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China
Fuzhou, China
First Affiliated Hospital Of Gannan Medical University
Ganzhou, China
Guangdong Province Traditional Chinese Medical Hospital
Guangzhou, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, China
The Frist Affiliated Hospital of Guangzhou Medical College
Guangzhou, China
The Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, China
Cancer Hospital of The University of Chinese Academy of Sciences
Hangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, China
Zhejiang Cancer Hospital
Hangzhou, China
Hanzhong Central Hospital
Hanzhong, China
Harbin Medical University Cancer Hospital
Harbin, China
Cancer Hospital affiliated to Harbin Medical University
Ha’erbin, China
Harbin Medical University cancer hospital
Ha’erbin, China
The Second Hospital of Anhui Medical University
Hefei, China
Henan Cancer Hospital (Affiliated Cancer Hospital of Zhengzhou University)
Henan, China
Inner Mongolia People's Hospital
Hohhot, China
Jiangxi cancer hospital
Jiangxi, China
The First Hospital of Jilin University
Jilin, China
Shandong Cancer Hospital & institute
Jinan, China
Yunnan Cancer Hospital
Kunming, China
The First Hospital of Lanzhou University
Lanzhou, China
Jiangxi Cancer Hospital
Nanchang, China
General Hospital of Eastern Theater Command
Nanjing, China
Jiangsu Cancer Hospital
Nanjing, China
Jiangsu Province Hospital
Nanjing, China
Nanjing Drum Tower Hospital
Nanjing, China
Guangxi Medical University Cancer Center
Nanning, China
Nantong Tumor Hospital
Nantong, China
Qingdao Central Hospital
Qingdao, China
The Affiliated Hospital of Qingdao University
Qingdao, China
First Hospital of Qinhuangdao
Qinhuangdao, China
ShangHai Chest Hospital
Shanghai, China
Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine
Shanghai, China
Cancer Hospital of Shantou University Medical College
Shantou, China
Liaoning Cancer Hospital & Institute
Shenyang, China
Liaoning Cancer Hospital
Shenyang, China
The First Hospital of China Medical University
Shenyang, China
Cancer Hospital of Chinese Academy of Medical Sciences Shenzhen Hospital
Shenzhen, China
Shenzhen People's Hospital
Shenzhen, China
The First Affiliated Hospital of Soochow University
Suzhou, China
Shanxi Provincial Cancer Hospital
Taiyuan, China
Taizhou Hospital of Zhejiang Province
Taizhou, China
General Hospital of Tianjin Medical University
Tianjin, China
Tianjin Medical University Cancer Institute & Hospital
Tianjin, China
Tonghua Central Hospital
Tonghua, China
Weifang People's Hospital
Weifang, China
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, China
Hubei Cancer Hospital
Wuhan, China
Renmin Hospital of Wuhan University/Hubei General Hospital
Wuhan, China
Union Hospital, Tongji Medical College Huazhong University of Science and Technolog
Wuhan, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
Zhongnan Hospital Affiliated to Wuhan University
Wuhan, China
The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital)
Wuhu, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
The First Affiliated Hospital Of Xiamen University
Xiamen, China
Xuzhou Central Hospital
Xuzhou, China
Yantai Yuhuangding Hospital
Yantai, China
The No. 2 People's Hospital of Yibin Sichuan
Yibin, China
Hospital of Ningxia Medical University
Yinchuan, China
He Nan Cancer Hospital
Zhengzhou, China
Henan Provincial People's Hospital
Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, China
Henan Provincial People's Hospital
Zhenzhou, China
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Jie Wang, PhD
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 31, 2021
First Posted
June 18, 2021
Study Start
September 24, 2021
Primary Completion (Estimated)
April 30, 2028
Study Completion (Estimated)
December 30, 2028
Last Updated
February 10, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will not share