Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors
- Conditions
- Non-Small Cell Lung CancerHead and Neck CancerColorectal CancerSolid Tumor
- Interventions
- Drug: MCLA-129
- Registration Number
- NCT04930432
- Lead Sponsor
- Betta Pharmaceuticals Co., Ltd.
- 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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- 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.
• For Part 2, patients shall meet the inclusion criteria for each cohort by biomarker testing.
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: dose escalation and dose expansion MCLA-129 Participants 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 MCLA-129 Participants will receive intravenous infusion of MCLA-129 every two weeks (Q2W) at the recommended Phase II dose (RP2D) in each cohort.
- Primary Outcome Measures
Name Time Method Dose-Limiting Toxicity (DLT) in Part 1 First 28 days of treatment To determine the dose-limiting toxicity (DLT) of single agent MCLA-129 in patients with advanced solid tumors in Part 1.
Maximum Tolerated Dose (MTD) in Part 1 First 28 days of treatment To determine the maximum tolerated dose (MTD) of single agent MCLA-129 in patients with advanced solid tumors in Part 1.
Overall Response Rate (ORR) in Part 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Treatment-Emergent Adverse Event (TEAE) in Part 1 and 2 Until 30 days after the last dosing 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)
- Secondary Outcome Measures
Name Time Method Half-life [t1/2] in Part 1 and 2 Until 30 days after the last dosing 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 half-life (t1/2)
Apparent volume of distribution [VSS] in Part 1 and 2 Until 30 days after the last dosing 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 apparent volume of distribution \[VSS\]
Maximum plasma concentration [Cmax] in Part 1 and 2 Until 30 days after the last dosing 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 maximum plasma concentration \[Cmax\]
Time to reach maximum concentration [Tmax] in Part 1 and 2 Until 30 days after the last dosing 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 time to reach maximum concentration \[Tmax\]
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 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 from time zero to time t \[AUC0-t\]
Area under the concentration versus time curve [AUC0-∞] in Part 1 and 2 Until 30 days after the last dosing 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 \[AUC0-∞\]
Overall Response Rate (ORR) in Part 1 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years To evaluate the efficacy of MCLA-129 in patients with advanced NSCLC and other solid tumors in Part 1 in terms of overall response rate (ORR)
Disease Control Rate (DCR) in Part 1 and 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Progression-Free Survival (PFS) in Part 1 and 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Clinical benefit rate (CBR) in Part 1 and 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Duration of Response (DOR) in Part 1 and 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Time to response (TTR) in Part 1 and 2 From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years 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)
Overall Survival (OS) in Part 1 and 2 From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years 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)
Anti-Drug Antibody (ADA) in Part 1 and 2 Until 30 days after the last dosing To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129
Cytokines in Part 1 Before and after each administration on day 1 and day 15 To assess the changes in cytokine levels in serum blood following administration of MCLA-129
Trial Locations
- Locations (66)
Guangdong Province Traditional Chinese Medical Hospital
🇨🇳Guangzhou, China
Cancer Hospital affiliated to Harbin Medical University
🇨🇳Ha'erbin, China
Qingdao Central Hospital
🇨🇳Qingdao, China
ShangHai Chest Hospital
🇨🇳Shanghai, China
The First Affiliated Hospital Of Ximen University
🇨🇳Xiamen, China
General Hospital of Eastern Theater Command
🇨🇳Nanjing, China
Xuzhou Central Hospital
🇨🇳Xuzhou, China
Hospital of Ningxia Medical University
🇨🇳Yinchuan, China
He Nan Cancer Hospital
🇨🇳Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Union Hospital, Tongji Medical College Huazhong University of Science and Technolog
🇨🇳Wuhan, China
The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital)
🇨🇳Wuhu, China
Zhongnan Hospital Affiliated to Wuhan University
🇨🇳Wuhan, China
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, China
The No. 2 People's Hospital of Yibin Sichuan
🇨🇳Yibin, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, China
Affiliated Hospital of Hebei University
🇨🇳Baoding, China
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, China
The Fifth Medical Center of PLA Ceneral Hospital
🇨🇳Beijing, China
The First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu, China
Hunan Cancer Hospital
🇨🇳Changsha, China
Army Medical Center of PLA
🇨🇳Chongqing, China
Chifeng Municipal Hospital
🇨🇳Chifeng, China
Chongqing University Cancer Hospital
🇨🇳Chongqing, China
Fuzhou Pulmonary Hospital of Fujian
🇨🇳Fuzhou, China
First Affiliated Hospital Of Gannan Medical University
🇨🇳Ganzhou, China
The Frist Affiliated Hospital of GUANGZHOU Medical College
🇨🇳Guangzhou, China
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
🇨🇳Guangzhou, China
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, China
Hanzhong Central Hospital
🇨🇳Hanzhong, China
The Second Hospital of Anhui Medical University
🇨🇳Hefei, China
Inner Mongolia People's Hospital
🇨🇳Hohhot, China
Shandong Cancer Hospital & institute
🇨🇳Jinan, China
Yunnan Cancer Hospital
🇨🇳Kunming, China
The First Hospital of Lanzhou University
🇨🇳Lanzhou, China
Nantong Tumor Hospital
🇨🇳Nantong, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, China
First Hospital of Qinhuangdao
🇨🇳Qinhuangdao, China
Liaoning Cancer Hospital&Institute
🇨🇳Shenyang, China
The First Hospital of China Medical University
🇨🇳Shenyang, China
Cancer Hospital of The University of Chinese Academy of Sciences
🇨🇳Hangzhou, 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
Tonghua Central Hospital
🇨🇳Tonghua, China
General Hospital of Tianjin Medical University
🇨🇳Tianjin, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, China
Weifang People's Hospital
🇨🇳Weifang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, China
Renmin Hospital of Wuhan University/Hubei General Hospital
🇨🇳Wuhan, China
Jiangsu Cancer Hospital
🇨🇳Nanjing, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Peking University International Hospital
🇨🇳Beijing, China
Cangzhou Hospital of Integrated TCM-WM·Hebei
🇨🇳Cangzhou, China
China-Japan Union Hospitai Of Jilin University
🇨🇳Ch'ang-ch'un, China
Sichuan Cancer Hospital
🇨🇳Chengdu, China
Ji Lin Cancer Hospital
🇨🇳Changchun, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, China
The First Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, China