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

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04930432
• Other study ID #: BTP-21711
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 24, 2021
• Est. completion date: June 30, 2025

Study information

• Verified date: December 2021
• Source: Betta Pharmaceuticals Co., Ltd.
• Contact: Wanlin Chen, Master
• Phone: 18258270120
• Email: wanlin.chen[@]bettapharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• MCLA-129
MCLA-129 will be administered by intravenous infusion.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Betta Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

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