Clinical Trial 18906

Cancer Type: Multiple
Interventions:BMS-936558 (Nivolumab); Nivolumab; TSR-022

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Zeynep Eroglu

Overview

Study Title

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an anti-TIM-3 Monoclonal Antibody, in Patients with Advanced Solid Tumors

Summary

This study is divided into 2 parts. The purpose of this research study is to: ¿ Part 1: Evaluate the safety and tolerability of TSR-022, the Study Drug. ¿ Part 2: Evaluate the ability of TSR-022 when taken alone or in combination with nivolumab (Opdivo®) to make the cancer smaller.

Objective

Primary Objectives: Part 1 - Dose Escalation Cohorts: - To evaluate the safety and tolerability of TSR-022 using Common Terminology Criteria for Adverse Events (CTCAE v.4.03) in patients with advanced solid tumors. - Part 1a: TSR-022 as monotherapy. - Part 1b: TSR-022 in combination with nivolumab. - To define the recommended Phase 2 dose (RP2D) and schedule of TSR-022 as monotherapy and in combination with nivolumab. Part 2 - Expansion Cohorts: - To evaluate the anti-tumor activity of TSR-022 in patients with solid tumors, in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as monotherapy and in combination therapy with nivolumab. - To confirm the RP2D and schedule of TSR-022 as monotherapy and in combination with nivolumab. Secondary Objectives: Part 2 - Expansion Cohorts: - To characterize the safety and tolerability of TSR-022 using CTCAE v.4.03. Part 1 and Part 2: - To characterize the pharmacokinetic (PK) profile of TSR-022. - To characterize the pharmacodynamic (PDy) profile of TSR-022. - To evaluate the immunogenicity of TSR-022. - To evaluate additional measures of clinical benefit, including: − ORR by RECIST v 1.1 for patients in Part 1; − ORR by immune-related RECIST (irRECIST); − Duration of response (DOR) by RECIST v 1.1; − Disease control rate (DCR) by RECIST v 1.1 and by irRECIST; − Progression-free survival (PFS) by RECIST v 1.1 and by irRECIST; − Overall survival (OS). Exploratory Objectives: - To identify a biomarker-based patient population that would derive clinical benefit from TSR-022 treatment based on the pre-treatment profile of tumor infiltrating lymphocytes (TILs), tumor characteristics, and/or circulating biomarkers. - To explore changes in biomarkers (eg, immune cells and immune proteins) in the tumor and circulating biomarkers in the blood following treatment with TSR-022 and correlate with clinical benefit.

Inclusion Criteria

  • At least 18 years of age
  • Patient with advanced or metastatic solid tumor and has disease progression or treatment intolerance after treatment with available therapies
  • Agreement to biopsies before and during treatment, depending on study part
  • Female participants must have a negative serum pregnancy test or be of non-childbearing potential.
  • Two methods of contraception required for males and females of childbearing potential
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 and adequate organ function
  • Additional criteria may apply

  • Exclusion Criteria

  • Received prior therapy with an anti-CTLA-4, anti-PD-1, anti-PD1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) agent within 8 weeks prior to initiation of study treatment depending on study part
  • Known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis or known malignancy that progressed or required active treatment within the last 2 years
  • Pregnant, breastfeeding, or expecting to conceive children within projected duration of study
  • History of human immunodeficiency virus (HIV), interstitial lung disease, active Hepatitis B or Hepatitis C
  • Autoimmune disease that required systemic treatment in past 2 years
  • Not recovered from radiation and chemotherapy-induced AEs or received blood transfusion
  • Participated in another investigational study (drug or device) within 4 weeks of first dose
  • Received prior anticancer therapy within 21 days of first dose
  • Not recovered from AEs and/or complications from major surgery prior to first dose
  • Received a vaccine within 7 days of first dose
  • Additional criteria may apply