A Clinical Study of MIL93 in Solid Tumors.

A Phase I Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of MIL93 in Advanced or Metastatic Solid Tumors.

MIL93 is a recombinant humanized anti-Claudin 18.2 (CLDN18.2) IgG1 monoclonal antibody. This is an open label Phase I study to evaluate safety, tolerability, pharmacokinetics and efficacy of MIL93 in Advanced or Metastatic solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Malignancies
• Intervention / Treatment: Drug: Recombinant Humanized Monoclonal Antibody MIL93

Detailed Description

This study is composed of two stages:Part I is mono-therapy dose escalation and dose expansion study, and Part II is the study of combination therapy.

The dose escalation study will be conducted using Part I for testing optimal doses at 0.3,1, 3, 10, 20, 30 mg/kg every 3 weeks (Q3W). An accelerated titration followed by traditional 3+3 design will be used in this study with a 21-day dose-limiting toxicity (DLT) observation period. Based on the data of dose escalation study, determine whether to carry out dose escalation at frequency of every 2 weeks(Q2W) and how many cohorts will be added in dose expansion study.

Based on the data of Part I, one or two doses will be conducted in the study of combination therapy. The study of PART II is composed of two cohorts. Cohort 1:Subjects with untreated CLDN18.2 positive gastric/gastroesophageal junction adenocarcinoma(G/GEJAC) will be treated with MIL93 and standard first-line chemotherapy.Cohort 2:Subjects with untreated CLDN18.2 positive pancreatic cancer will be treated with MIL93 and standard first-line chemotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 228
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jing Huang, doctor; Phone Number: (+86)010-87788293; Email: huangjingwg@163.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Jing Huang, doctor; Phone Number: (+86)010-87788293; Email: huangjingwg@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients, >=18 years of age;

2. Suffer from advanced unresectable or metastatic malignant solid tumors confirmed by histological diagnosis and meet the criteria of the enrolled group as follows:

   Mono-therapy dose escalation study: The subjects for whom no standard treatment regimens are available or who is intolerable to standard treatments.

   Mono-therapy dose expansion study: The subjects with positive CDLN18.2 expression in tumor tissue (through immunohistochemistry (IHC) test) confirmed by the central laboratory at enrollment.

   Combination study is composed of 2 cohorts.Cohort 1:Subjects with untreated CLDN18.2 positive G/GEJAC; Cohort 2:Subjects with untreated CLDN18.2 positive pancreatic cancer.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
4. Life expectancy >=3 months;
5. Sufficient organ and bone marrow function;
6. At least one measurable lesion or evaluable lesion (recist v1.1);
7. Able and willing to provide written informed consent and to comply with the study protocol.

Exclusion Criteria:

1. Prior use of any anti-cancer therapy(including chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc) within 4 weeks of study start;
2. Previous exposure to any drug targeting CLDN 18.2;
3. Major surgery within 8 weeks prior to the first administration or expected to undergo major surgery during the study treatment;
4. Systemic immunosuppressive therapy was required within 14 days prior to the first administration;
5. Central nervous system metastasis;
6. History of other primary malignant tumors in 5 years;
7. Evidence of significant, uncontrolled concomitant disease;
8. Infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C(including HBsAg,HBcAb positive with abnormal HBV DNA or HCV RNA );
9. Suffering from serious or uncontrollable gastro-intestinal tract bleed;
10. Known severe allergic reaction or/and infusion reaction to monoclonal antibody;
11. Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual contact during the following time periods related to this study: 1) while participating in the study; 2) for at least 6 months after discontinuation of all study treatments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MIL93

Drug: Recombinant Humanized Monoclonal Antibody MIL93; PART I :The patients confirming to the eligibility criteria will be assigned to the 6 dose groups (0.3mg/kg, 1mg/kg, 3mg/kg, 10mg/kg, 20mg/kg, 30mg/kg,respectively) based on the sequence of inclusion. Each patient will receive an intravenous infusion of MIL93 every 3 or 2 week on Day 1. PART II:One recommended dose will be conducted from 6 dose groups based on results of PART I.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Adverse Events	Percentage of Participants with AEs and SAEs assessed by NCI CTCAE v5.0.	up to 1year after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics:AUC	The area under the curve (AUC) of serum concentration of the drug after the administration	up to 1year after enrollment
Pharmacokinetics: Cmax	Maximum concentration(Cmax) of the drug after administration	up to 1year after enrollment
Objective response rate (ORR)	To evaluate preliminary anti-tumor activity of MIL93 in subjects with advanced malignancies.ORR includes complete remission(CR) and partial remission(PR) assessed by RECIST v1.1 criteria.	up to 1year after enrollment
Duration of response (DoR)	DOR is defined as the time from the initial response (CR or PR) to the time of disease progression or death, whichever occurs first.	up to 1year after enrollment
Progression free survival (PFS)	Defined as the time from the first day of study treatment to disease progression or death, whichever occurs first.	up to 1year after enrollment
Immunogenicity	Anti-Drug Antibodies (ADA) will be tested and percentage of ADA positive patients will be calculated to evaluate immunogenicity of MIL93.	up to 1year after enrollment

Collaborators and Investigators

• Sponsor: Beijing Mabworks Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: MIL93-CT101

Drug and device information, study documents

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