Colorectal Cancer Clinical Trial
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
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.
Status | Recruiting |
Enrollment | 400 |
Est. completion date | June 30, 2025 |
Est. primary completion date | June 30, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Aged = 18, regardless of gender. - Subjects with histologically or cytologically confirmed diagnosis of metastatic or unresectable advanced NSCLC or other solid tumors (including but not limited to head and neck cancer, colorectal, etc.) who have disease progression on, or were not resistant to, or reject the standard treatment. - For Part 1, subjects must be diagnosed with EGFR positive and/or MET positive after testing. - For Part 2, patients need to undergo the centralized biomarker testing. - Subjects of the dose escalation phase in Part 1 must have evaluable diseases, and others must have measurable diseases as defined in RECIST v1.1. - Eastern Cooperative Oncology Group (ECOG) performance status scores are 0-1. - Expected survival is =3 months. - With certain organ system functions (without transfusion, use of blood components, or G-CSF support within 14 days before testing), as defined below: - Absolute Neutrophil Count (ANC) =1.5×10^9 /L - Platelet count (PLT)=75×10^9 /L - Hemoglobin (HB) =10 g/dL - Total bilirubin =1.5 times the upper limit of normal (ULN) - Alanine amino transferase (ALT) and aspartate amino transferase (AST) =3×ULN - Creatinine =1.5×ULN. If creatinine is >1.5×ULN, creatinine clearance is =50 mL/min as calculated by Cockcroft-Gault formula, or =50 mL/min within 24 h as measured, the patients can still be included. - Willing to and capable of following the trial and follow-up schedule. - Capable of understanding the trial nature and voluntarily signing the written informed consent form. - The subjects of Part 2 must agree that the tumor tissue samples before treatment of the investigational drug can be collected or provided. Exclusion Criteria: - Use of certain investigational drug or antineoplastic agent within 14 days before first administration of MCLA-129 or within 5 half lives (whichever is longer). - Execution of large surgery and radiotherapy (except focal palliative radiotherapy at least 2 weeks before first administration), immunotherapy, chemotherapy (for Nitrosoureas or Mitomycin C and other chemotherapeutics with delayed toxicity, it shall be 6 weeks before first administration) within 4 weeks before first administration of MCLA-129. - Patients with colorectal who are diagnosed with AS or BRAF gene mutation through testing. - Subjects with NSCLC who previously received more than 2 lines of cytotoxicity chemotherapy for treatment of focal advanced or metastatic disease (excluding maintenance therapy). - Subjects who previously received EGFR-TKI (e.g. Poziotinib or TAK-788) that is known to be effective to exon 20 insertion mutation - Prior use of EGFR/c-Met bispecific antibody drugs. - Response of toxic reactions related to prior therapy (except alopecia) not up to Grade 1 or below (CTCAE 5.0 criteria) before first administration of MCLA-129. - With other malignant tumors in the past 3 years, except cancers that have been cured significantly or can be focally cured, e.g. basosquamous carcinoma of skin, carcinoma cervix in situ, or in situ breast carcinoma. - 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. - With clinically significant cardiovascular disorder, including but not limited to: - Deep vein thrombosis or lung embolism diagnosed within 1 month before first administration of the investigational drug. Non-obstructive catheter related clot and other clinically irrelevant thrombosis are not included in the exclusion criteria. - 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. Re-measurement is made twice at an interval of 4 h above. 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. - 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. - Cardiomyopathy. - With clinically significant cardiovascular disorder as believed by other investigators. - Active hepatitis B (hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive, and serum HBV DNA = 2000 IU/mL (equal to 104 copies/mL)), hepatitis C virus antibody, HIV antibody and treponema pallidum antibody positive. - Patients with Interstitial lung disease, including drug-induced Interstitial lung disease or radiation pneumonitis. - Current severe disease or medical condition, including but not limited to uncontrolled active infection, and clinically significant lung, metabolic or psychiatric disorders. - Women with child bearing potential, pregnant women or lactating women with pregnancy test positive 7 days before treatment, and male and female unwilling to take effective contraception measures or having a birth plan during the treatment and within 3 months after end of treatment. - Patients who are known to have allergic reactions and hypersensitivity reactions, or be allergic to MCLA-129 or any other excipients. - Patients poorly compliant, unable or unwilling to follow the study and/or follow-up procedure listed in the protocol, or patients unsuitable to participate in this trial in the investigator's opinion. |
Country | Name | City | State |
---|---|---|---|
China | Affiliated Hospital of Hebei University | Baoding | |
China | Beijing Cancer 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 | Cangzhou Hospital of Integrated TCM-WM·Hebei | Cangzhou | |
China | China-Japan Union Hospitai Of Jilin University | Ch'ang-ch'un | |
China | Ji Lin Cancer Hospital | Changchun | |
China | Hunan Cancer Hospital | Changsha | |
China | The Second 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 | Fujian Cancer Hospital | Fuzhou | |
China | Fuzhou Pulmonary Hospital of Fujian | 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 | Cancer Hospital affiliated to Harbin Medical University | Ha'erbin | |
China | Cancer Hospital of The University of Chinese Academy of Sciences | Hangzhou | |
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 | General Hospital of Eastern Theater Command | Nanjing | |
China | Jiangsu Cancer Hospital | Nanjing | |
China | Nanjing Drum Tower Hospital | Nanjing | |
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 | Liaoning Cancer Hospital&Institute | 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 | Renmin Hospital of Wuhan University/Hubei General Hospital | Wuhan | |
China | Union Hospital, Tongji Medical College Huazhong University of Science and Technolog | 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 Ximen 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 |
Lead Sponsor | Collaborator |
---|---|
Betta Pharmaceuticals Co., Ltd. |
China,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | 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 corhort 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 | |
Primary | 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 | Half-life [t1/2] in Part 1 and 2 | 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) | Until 30 days after the last dosing | |
Secondary | Apparent volume of distribution [VSS] in Part 1 and 2 | 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] | Until 30 days after the last dosing | |
Secondary | Maximum plasma concentration [Cmax] in Part 1 and 2 | 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] | Until 30 days after the last dosing | |
Secondary | Time to reach maximum concentration [Tmax] in Part 1 and 2 | 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] | Until 30 days after the last dosing | |
Secondary | Area under the concentration versus time curve from time zero to time t [AUC0-t] in Part 1 and 2 | 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] | Until 30 days after the last dosing | |
Secondary | Area under the concentration versus time curve [AUC0-8] in Part 1 and 2 | 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 [AUC0-8] | Until 30 days after the last dosing | |
Secondary | Overall Response Rate (ORR) in Part 1 | 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) | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | |
Secondary | Disease Control Rate (DCR) in Part 1 and 2 | 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) | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | |
Secondary | Progression-Free Survival (PFS) in Part 1 and 2 | 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) | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | |
Secondary | Duration of Response (DOR) in Part 1 and 2 | 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) | From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years | |
Secondary | Overall Survival (OS) in Part 1 and 2 | 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) | From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years | |
Secondary | Anti-Drug Antibody (ADA) in Part 1 and 2 | To assess the Incidence of anti-drug antibodies in serum blood against MCLA-129 following administration of MCLA-129 | Until 30 days after the last dosing | |
Secondary | Cytokine TNF-a in Part 1 | To assess the changes in TNF-a in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IFN-? in Part 1 | To assess the changes in IFN-? in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IL-1ß in Part 1 | To assess the changes in IL-1ß in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IL-2 in Part 1 | To assess the changes in IL-2 in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IL-6 in Part 1 | To assess the changes in IL-6 in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IL-8 in Part 1 | To assess the changes in IL-8?IL-10 in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 | |
Secondary | Cytokine IL-10 in Part 1 | To assess the changes in IL-10 in serum blood following administration of MCLA-129 | Before and after each administration on day 1 and day 15 |
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