Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China

A Phase I, Multi-center, Open-label, Single-dose Escalation and Expansion, Dose Escalation and Expansion Combination With Chemotherapy Study Evaluating the Safety, Tolerability and Pharmacokinetic Profile of M108 Monoclonal Antibody in Patients With Advanced Unresectable Solid Tumors in China

M108 is a monoclonal antibody specific for gastric and gastroesophageal adenocarcinomas. The aim of this phase I study is to establish safety and Tolerability of different Dosage regimen in patients With Advanced Unresectable Solid Tumors in China.

Study Overview

• Status: Recruiting
• Conditions: Advanced Unresectable Solid Tumors
• Intervention / Treatment: Drug: M108; Drug: M108

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhaoyu Jin, Ph.D; Phone Number: 010-60709130; Email: pr@futuregenbiopharm.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Principal Investigator: Lin Shen, PHD
      • Contact: Lin Shen, PhD; Phone Number: 010-88196358; Email: doctorshenlin@sina.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent.
2. Advanced Unresectable solid tumors proven by histology
3. At least 1 measurable site of the disease according RECIST 1.1 criteria
4. ECOG performance status (PS) 0-1
5. Life expectancy > 3 months
6. Age ≥ 18 years and ≤75 years
7. Adequate haematological function; absolute neutrophil count ≥1.5 x 109/L; white blood cell count ≥3.0 x 109/L; platelets ≥100 x 109/L; haemoglobin ≥9 g/dL.
8. Adequate coagulation function; international normalized ratio ( INR) ≤ 1.5 x upper limit of normal (ULN), or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
9. Adequate hepatic function; bilirubin ≤1.5 x ULN, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤2.5 x ULN.
10. Adequate renal function; creatinine ≤1.5 x ULN, or reatinine clearance rate ≥60 mL/minute calculated.

Exclusion Criteria:

1. Previous received or planned to be vaccinated with 2019-nCoV vaccine or other vaccines within 3 months prior to the start of study treatment or during the study or within 3 months after the end of the study;
2. Previous radiotherapy within 4 weeks prior to the start of study treatment. (if palliative radiotherapy was given to bone metastatic side peripherally and the patient recovered from acute toxicity was allowed).
3. Previous anti-tumor therapy within 4 weeks prior to the start of study treatment.
4. Previous major operation within 8 weeks prior to the start of study treatment.
5. Prior severe allergic reaction or intolerance to a monoclonal antibody, including humanised or chimeric antibodies.
6. Symptomatic cerebral metastases.
7. Uncontrolled or severe illness.
8. Known human immunodeficiency virus infection or known symptomatic hepatitis
9. Other clinically significant disease which may have adversely affected the safe delivery of treatment within this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort; Monotherapy: Five dose levels of M108 will be tested according to an accelerated titration method followed by a conventional 3 + 3 study design. Combined with chemotherapy: Three dose levels of M108 will be tested by a conventional 3 + 3 study design. The dose-limiting toxicity (DLT) will be assessed from the first administration to the end of the first cycle (21 days).	Drug: M108; Monotherapy: Accelerated titration method, IV infusion Q3W; Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles) Combined with chemotherapy: Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles); Other Names: Chemotherapy; Drug: M108; IV infusion Q3W. (21-day cycles); Other Names: Chemotherapy.
Experimental: Dose Expansion Cohort; Once the effective dose has been determined, 1~2 expansion cohorts will be opened to evaluate the efficacy and safety of the selected dose.	Drug: M108; Monotherapy: Accelerated titration method, IV infusion Q3W; Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles) Combined with chemotherapy: Conventional 3 + 3 study design, IV infusion Q3W. (21-day cycles); Other Names: Chemotherapy; Drug: M108; IV infusion Q3W. (21-day cycles); Other Names: Chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	defined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE V5.0)	From enrollment until 28+7 days after the last dose
Maximum Tolerated Dose	MTD	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum measured plasma concentration of M108	Cmax	From enrollment until 28 days after the last dose
Time to maximum plasma concentration of M108	Tmax	From enrollment until 28 days after the last dose
Half-life of M108	T1/2	From enrollment until 28 days after the last dose
Immunogenicity profile of M108	Blood samples will be collected from subjects post treatment for assessment to detect the presence of anti-drug antibodies(ADA).	From enrollment until 28 days after the last dose
Objective Response Rate	ORR	From first dose to disease progression , death or end of study，an average of 1 year
Progression free survival	PFS	From first dose to disease progression , death or end of study，an average of 1 year

Collaborators and Investigators

• Sponsor: FutureGen Biopharmaceutical (Beijing) Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2021
• Primary Completion (Estimated): July 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: May 12, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 23, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: M108-Ⅰ

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No