Clinical trial NCT04930432: Study of MCLA-129, a Human Bispecific EGFR and cMet Antibody, in Patients With Advanced NSCLC and Other Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Non-Small Cell Lung Cancer
Head and Neck Cancer
Colorectal Cancer
Lead sponsor: Betta Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-06-18
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

• 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.

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.

Primary outcomes:
measure: Dose-Limiting Toxicity (DLT) in Part 1
timeFrame: First 28 days of treatment
measure: Maximum Tolerated Dose (MTD) in Part 1
timeFrame: First 28 days of treatment
measure: Overall Response Rate (ORR) in Part 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Treatment-Emergent Adverse Event (TEAE) in Part 1 and 2
timeFrame: Until 30 days after the last dosing
Secondary outcomes:
measure: Half-life [t1/2] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Apparent volume of distribution [VSS] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Maximum plasma concentration [Cmax] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Time to reach maximum concentration [Tmax] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Area under the concentration versus time curve from time zero to time t [AUC0-t] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Area under the concentration versus time curve [AUC0-∞] in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Overall Response Rate (ORR) in Part 1
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Disease Control Rate (DCR) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Progression-Free Survival (PFS) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Clinical benefit rate (CBR) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Duration of Response (DOR) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Time to response (TTR) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
measure: Overall Survival (OS) in Part 1 and 2
timeFrame: From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years
measure: Anti-Drug Antibody (ADA) in Part 1 and 2
timeFrame: Until 30 days after the last dosing
measure: Cytokines in Part 1
timeFrame: Before and after each administration on day 1 and day 15
Other outcomes:
Locations:
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Beijing
country: China
facility: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking University International Hospital
city: Beijing
country: China
facility: The Fifth Medical Center of PLA Ceneral Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Cangzhou
country: China
facility: Cangzhou Hospital of Integrated TCM-WM·Hebei
city: Ch'ang-ch'un
country: China
facility: China-Japan Union Hospitai Of Jilin University
city: Changchun
country: China
facility: Ji Lin Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: Hunan Cancer Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Chengdu
country: China
facility: Sichuan Cancer Hospital
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
city: Chongqing
country: China
facility: Army Medical Center of PLA
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
city: Fuzhou
country: China
facility: Fuzhou Pulmonary Hospital of Fujian
city: Fuzhou
country: China
facility: The 900 Hospital of the Joint Service Support Force of the People's Liberation Army of China
city: Ganzhou
country: China
facility: First Affiliated Hospital Of Gannan Medical University
city: Guangzhou
country: China
facility: Guangdong Province Traditional Chinese Medical Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangzhou
country: China
facility: The Frist Affiliated Hospital of Guangzhou Medical College
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital, Sun Yat-sen University
city: Ha'erbin
country: China
facility: Cancer Hospital affiliated to Harbin Medical University
city: Ha'erbin
country: China
facility: Harbin Medical University cancer hospital
city: Hangzhou
country: China
facility: Cancer Hospital of The University of Chinese Academy of Sciences
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
city: Hanzhong
country: China
facility: Hanzhong Central Hospital
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
city: Hohhot
country: China
facility: Inner Mongolia People's Hospital
city: Jiangxi
country: China
facility: Jiangxi cancer hospital
city: Jilin
country: China
facility: The First Hospital of Jilin University
city: Jinan
country: China
facility: Shandong Cancer Hospital & institute
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
city: Nanjing
country: China
facility: General Hospital of Eastern Theater Command
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
city: Nantong
country: China
facility: Nantong Tumor Hospital
city: Qingdao
country: China
facility: Qingdao Central Hospital
city: Qingdao
country: China
facility: The Affiliated Hospital of Qingdao University
city: Qinhuangdao
country: China
facility: First Hospital of Qinhuangdao
city: Shanghai
country: China
facility: ShangHai Chest Hospital
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Shenyang
country: China
facility: Liaoning Cancer Hospital & Institute
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Shenzhen
country: China
facility: Cancer Hospital of Chinese Academy of Medical Sciences Shenzhen Hospital
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: Shanxi Provincial Cancer Hospital
city: Taizhou
country: China
facility: Taizhou Hospital of Zhejiang Province
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Tonghua
country: China
facility: Tonghua Central Hospital
city: Weifang
country: China
facility: Weifang People's Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University/Hubei General Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College Huazhong University of Science and Technolog
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Zhongnan Hospital Affiliated to Wuhan University
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital)
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital Of Xiamen University
city: Xuzhou
country: China
facility: Xuzhou Central Hospital
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
city: Yibin
country: China
facility: The No. 2 People's Hospital of Yibin Sichuan
city: Yinchuan
country: China
facility: Hospital of Ningxia Medical University
city: Zhengzhou
country: China
facility: He Nan Cancer Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
city: Zhenzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Jie Wang, PhD
role: STUDY_CHAIR
References: