TR1801-ADC in Patients With Tumors That Express c-Met

A Phase 1, Open Label, First-in-human Study of TR1801-ADC, an Antibody Drug Conjugate (ADC), in Patients With Select Solid Tumors Expressing c-Met

First-in-human, Phase 1 study to assess safety, tolerability, and pharmacokinetics of TR1801-ADC in patients with select solid tumors that express c-Met.

Study Overview

• Status: Suspended
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Biological: TR1801-ADC

Detailed Description

First-in-human, Phase 1, multiple dose-dose escalation study designed to determine safety, tolerability, maximum tolerated dose, and recommended phase 2 dose of TR1801-ADC in patients with select solid tumors that express c-Met. This study will also assess pharmacokinetics (PK), anti-tumor activity, and correlation between clinical outcomes (safety, anti-tumor activity, and PK) and c-Met expression.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California Norris Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • John Hopkins - Sidney Kimmel Comprehensive Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington / Seattle Cancer Care

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Compliance with all study procedures and visits to the clinical research site
• Locally advanced or metastatic disease that is not amenable to definitive therapy
• Histologically confirmed diagnosis of a solid tumor which expresses c-Met
• Must have progressed or have been intolerant to all available therapies known to confer clinical benefit appropriate for the patient's tumor type
• Measurable baseline disease as defined by RECIST Version 1.1
• ECOG Performance Status 0-1
• Body weight within 40 and 150 kg
• Clinical laboratory values with the limits as defined by the protocol
• Not pregnant or breast feeding
• Males and women of child-bearing potential must agree to use an effective method of contraception

Exclusion Criteria:

• Any disease or condition that may be considered to pose an increased risk from study treatment or the ability of the patient to participate and comply with study procedures
• Treatment with anti-cancer therapy (including cytotoxic chemotherapy, major surgery, radiation, biologic and investigational agents) within 21 days before first dose of study treatment
• Brain metastases that has not stabilized for at least 28 days after therapy and who have discontinued steroids for <2 weeks
• Unresolved adverse events >= Grade 2 from prior anticancer therapies
• Acute myocardial infarction, cerebral ischemic infarct, or other arterial thrombosis within 6 months of screening for this study.
• Uncontrolled hypertension, unstable angina, or NYHA Class III/IV heart failure
• History of capillary leak syndrome
• Corticosteroid intolerance
• History of anasarca
• Untreated or uncontrolled bacterial, viral or fungal infection
• HIV infection or active infection with hepatitis B or C
• Significant liver disease
• History of alcoholism or current alcoholism
• Signs of significant portal hypertension
• Significant kidney disease within 2 years
• Active or unstable gallstone disease
• Prior treatment with a c-Met targeted agent
• Prior hypersensitivity reaction to treatment with another monoclonal antibody
• QTcF >=470 ms
• Patients may not start any new herbal or dietary supplement within 4 weeks before initiation of study treatment nor while receiving study treatment
• Administration of a live, attenuated vaccine within 28 days before the first dose of study treatment

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: TR1801-ADC; Humanized anti-c-Met monoclonal antibody conjugated to a cleavable pyrrolobenzodiazepine toxin	Biological: TR1801-ADC; Humanized anti-c-Met monoclonal antibody conjugated to a cleavable pyrrolobenzodiazepine toxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize safety of TR1801-ADC in patients with advanced solid tumor malignancies which express c-Met	Number of participants with treatment-related adverse events	4 years
Establish maximum tolerated dose	Number of participants with protocol-defined dose-limiting toxicity	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate pharmacokinetics of TR1801-ADC	Analyze blood plasma concentrations	4 years
Immunogenicity	Assess anti-drug antibodies of TR1801-ADC	4 years
Evaluate clinical activity of TR1801-ADC	Assess objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST V1.1)	5 years

Collaborators and Investigators

• Sponsor: Open Innovation Partners, Inc.
• Collaborators: Open Innovation Partners
• Investigators: Study Director: Gilad Gordon, MD, Open Innovation Partners

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2019
• Primary Completion (Actual): July 4, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 27, 2019
• First Posted (Actual): March 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 22, 2023
• Last Update Submitted That Met QC Criteria: September 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Phase 1; solid tumors; c-Met; antibody-drug conjugate
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: TR1801-CL-01

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