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

December 19, 2021 updated by: Betta Pharmaceuticals Co., Ltd.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Baoding, China
        • Not yet recruiting
        • Affiliated Hospital of Hebei University
      • Beijing, China
        • Recruiting
        • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Beijing, China
        • Not yet recruiting
        • Beijing Cancer Hospital
      • Beijing, China
        • Not yet recruiting
        • Peking University International Hospital
      • Beijing, China
        • Not yet recruiting
        • The Fifth Medical Center of PLA Ceneral Hospital
      • Bengbu, China
        • Recruiting
        • The First Affiliated Hospital of Bengbu Medical college
      • Cangzhou, China
        • Not yet recruiting
        • Cangzhou Hospital of Integrated TCM-WM·Hebei
      • Ch'ang-ch'un, China
        • Not yet recruiting
        • China-Japan Union Hospitai Of Jilin University
      • Changchun, China
        • Not yet recruiting
        • Ji Lin Cancer Hospital
      • Changsha, China
        • Not yet recruiting
        • Hunan Cancer Hospital
      • Changsha, China
        • Not yet recruiting
        • The Second Xiangya Hospital of Central South University
      • Chengdu, China
        • Not yet recruiting
        • Sichuan Cancer Hospital
      • Chengdu, China
        • Not yet recruiting
        • West China Hospital, Sichuan University
      • Chifeng, China
        • Not yet recruiting
        • Chifeng Municipal Hospital
      • Chongqing, China
        • Not yet recruiting
        • Chongqing University Cancer Hospital
      • Chongqing, China
        • Not yet recruiting
        • Army Medical Center of PLA
      • Fuzhou, China
        • Not yet recruiting
        • Fujian cancer hospital
      • Fuzhou, China
        • Not yet recruiting
        • Fuzhou Pulmonary Hospital of Fujian
      • Ganzhou, China
        • Not yet recruiting
        • First Affiliated hospital of GANNAN Medical University
      • Guangzhou, China
        • Not yet recruiting
        • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
      • Guangzhou, China
        • Not yet recruiting
        • Guangdong Province Traditional Chinese Medical Hospital
      • Guangzhou, China
        • Not yet recruiting
        • The Frist Affiliated Hospital of GUANGZHOU Medical College
      • Ha'erbin, China
        • Not yet recruiting
        • Cancer Hospital Affiliated to Harbin Medical University
      • Hangzhou, China
        • Recruiting
        • Cancer Hospital of The University of Chinese Academy of Sciences
      • Hangzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital, Zhejiang University
      • Hanzhong, China
        • Not yet recruiting
        • Hanzhong Central Hospital
      • Hefei, China
        • Not yet recruiting
        • The Second Hospital of Anhui Medical University
      • Hohhot, China
        • Not yet recruiting
        • Inner Mongolia People's Hospital
      • Jinan, China
        • Not yet recruiting
        • Shandong Cancer hospital & Institute
      • Kunming, China
        • Not yet recruiting
        • Yunnan Cancer Hospital
      • Lanzhou, China
        • Not yet recruiting
        • The First Hospital of Lanzhou University
      • Nanjing, China
        • Not yet recruiting
        • Nanjing Drum Tower Hospital
      • Nanjing, China
        • Not yet recruiting
        • General Hospital of Eastern Theater Command
      • Nanjing, China
        • Not yet recruiting
        • Jiangsu Cancer Hospital
      • Nantong, China
        • Not yet recruiting
        • Nantong Tumor Hospital
      • Qingdao, China
        • Recruiting
        • The Affiliated Hospital of Qingdao University
      • Qingdao, China
        • Not yet recruiting
        • Qingdao Central Hospital
      • Qinhuangdao, China
        • Not yet recruiting
        • First Hospital of Qinhuangdao
      • Shanghai, China
        • Not yet recruiting
        • Shanghai Chest Hospital
      • Shenyang, China
        • Not yet recruiting
        • The First Hospital of China Medical University
      • Shenyang, China
        • Not yet recruiting
        • Liaoning Cancer Hospital&Institute
      • Shenzhen, China
        • Not yet recruiting
        • ShenZhen People's Hospital
      • Shenzhen, China
        • Not yet recruiting
        • Cancer Hospital of Chinese Academy of Medical Sciences Shenzhen Hospital
      • Suzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital of Soochow University
      • Taiyuan, China
        • Not yet recruiting
        • Shanxi Provincial Cancer Hospital
      • Taizhou, China
        • Not yet recruiting
        • Taizhou Hospital of Zhejiang Province
      • Tianjin, China
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute & Hospital
      • Tianjin, China
        • Not yet recruiting
        • General Hospital of Tianjin Medical University
      • Tonghua, China
        • Not yet recruiting
        • Tonghua Central Hospital
      • Weifang, China
        • Not yet recruiting
        • WeiFang People's Hospital
      • Wenzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
      • Wuhan, China
        • Not yet recruiting
        • Renmin Hospital of Wuhan University/Hubei General Hospital
      • Wuhan, China
        • Recruiting
        • Union Hospital, Tongji Medical College Huazhong University of Science and Technolog
      • Wuhan, China
        • Not yet recruiting
        • Zhongnan Hospital affiliated to Wuhan University
      • Wuhu, China
        • Not yet recruiting
        • The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital)
      • Xi'an, China
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
      • Xiamen, China
        • Not yet recruiting
        • The First Affiliated Hospital Of Ximen University
      • Xuzhou, China
        • Not yet recruiting
        • Xuzhou Central Hospital
      • Yantai, China
        • Not yet recruiting
        • Yantai Yuhuangding Hospital
      • Yibin, China
        • Not yet recruiting
        • The No. 2 People's Hospital of Yibin Sichuan
      • Yinchuan, China
        • Not yet recruiting
        • Hospital of Ningxia Medical University
      • Zhengzhou, China
        • Not yet recruiting
        • Henan Provincial People's Hospital
      • Zhengzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
      • Zhengzhou, China
        • Not yet recruiting
        • He Nan Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: MCLA-129
In the dose escalation phase 1 part, MCLA-129 will be administered every two weeks with increasing doses to patients with advanced solid tumors. In Part 2, patients with NSCLC and other advanced solid tumors in each corhort will be dosed with MCLA-129 every two weeks at the RP2D.
Drug: MCLA-129
MCLA-129 will be administered by intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose-Limiting Toxicity (DLT) in Part 1
Time Frame: 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.
First 28 days of treatment
Maximum Tolerated Dose (MTD) in Part 1
Time Frame: 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.
First 28 days of treatment
Overall Response Rate (ORR) in Part 2
Time Frame: 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 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
Treatment-Emergent Adverse Event (TEAE) in Part 1 and 2
Time Frame: 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)
Until 30 days after the last dosing

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Half-life [t1/2] in Part 1 and 2
Time Frame: 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)
Until 30 days after the last dosing
Apparent volume of distribution [VSS] in Part 1 and 2
Time Frame: 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]
Until 30 days after the last dosing
Maximum plasma concentration [Cmax] in Part 1 and 2
Time Frame: 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]
Until 30 days after the last dosing
Time to reach maximum concentration [Tmax] in Part 1 and 2
Time Frame: 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]
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
Time Frame: 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]
Until 30 days after the last dosing
Area under the concentration versus time curve [AUC0-∞] in Part 1 and 2
Time Frame: 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-∞]
Until 30 days after the last dosing
Overall Response Rate (ORR) in Part 1
Time Frame: 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)
From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Disease Control Rate (DCR) in Part 1 and 2
Time Frame: 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)
From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Progression-Free Survival (PFS) in Part 1 and 2
Time Frame: 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)
From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Duration of Response (DOR) in Part 1 and 2
Time Frame: 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)
From date of first treatment every 6 weeks until disease progression, death or withdrawal, whichever came first, approximately 2 years
Overall Survival (OS) in Part 1 and 2
Time Frame: 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)
From date of first treatment every 6 weeks until death or withdrawal, whichever came first, approximately 2 years
Anti-Drug Antibody (ADA) in Part 1 and 2
Time Frame: 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
Until 30 days after the last dosing
Cytokine TNF-α in Part 1
Time Frame: Before and after each administration on day 1 and day 15
To assess the changes in TNF-α in serum blood following administration of MCLA-129
Before and after each administration on day 1 and day 15
Cytokine IFN-γ in Part 1
Time Frame: Before and after each administration on day 1 and day 15
To assess the changes in IFN-γ in serum blood following administration of MCLA-129
Before and after each administration on day 1 and day 15
Cytokine IL-1β in Part 1
Time Frame: Before and after each administration on day 1 and day 15
To assess the changes in IL-1β in serum blood following administration of MCLA-129
Before and after each administration on day 1 and day 15
Cytokine IL-2 in Part 1
Time Frame: Before and after each administration on day 1 and day 15
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
Cytokine IL-6 in Part 1
Time Frame: Before and after each administration on day 1 and day 15
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
Cytokine IL-8 in Part 1
Time Frame: Before and after each administration on day 1 and day 15
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
Cytokine IL-10 in Part 1
Time Frame: Before and after each administration on day 1 and day 15
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Betta Pharmaceuticals Co., Ltd.

Investigators

  • Study Chair: Jie Wang, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 24, 2021

Primary Completion (ANTICIPATED)

June 30, 2024

Study Completion (ANTICIPATED)

June 30, 2025

Study Registration Dates

First Submitted

May 31, 2021

First Submitted That Met QC Criteria

June 15, 2021

First Posted (ACTUAL)

June 18, 2021

Study Record Updates

Last Update Posted (ACTUAL)

December 21, 2021

Last Update Submitted That Met QC Criteria

December 19, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BTP-21711

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Head and Neck Cancer

Clinical Trials on MCLA-129

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malaysia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe