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Protocol # 17-392

Status

Recruiting

Description

This is a multicenter, open-label, first-in-human Phase 1 study evaluating the anti-lymphocyte activation gene-3 (LAG-3) antibody TSR-033 alone, in combination with the anti-PD-1 antibody dostarlimab, and in combination with dostarlimab, modified folinic acid (FOL)/leucovorin, 5-fluorouracil and oxaliplatin (OX) (mFOLFOX6) or FOL/leucovorin, 5-fluorouracil and irinotecan (IRI) (FOLFIRI), and bevacizumab in participants with advanced solid tumors in a broad range of solid tumors. Participants with disease types selected for evaluation in this study are expected to derive clinical benefit with addition of an anti-PD-1. The study will be conducted in two parts with Part 1 consisting of dose escalation to determine the recommended phase 2 dose (RP2D) of TSR-033 as a single agent (Part 1a) and in combination with dostarlimab (Part 1c). RP2D decisions will be based on the occurrence of dose-limiting toxicities (DLTs), pharmacokinetics (PK), as well as pharmacodynamics (PDy) data. Part 2A of the study will investigate the anti-tumor activity of TSR-033 and dostarlimab in combination in participants with advanced or metastatic microsatellite stable colorectal cancer (MSS-CRC). Part 2B of the study will investigate the safety and anti-tumor activity of TSR-033 and dostarlimab in combination with chemotherapy (Cohort B1: mFOLFOX6 and Cohort B2: FOLFIRI) and bevacizumab in participants with advanced or metastatic MSS-CRC.

Condition

  • Neoplasms

Interventions

  • TSR-033
  • Dostarlimab
  • mFOLFOX6
  • FOLFIRI
  • Bevacizumab

Phase

Phase 1

Study Type

Interventional

Further Study Details

Primary Outcome:

  • Part 1a, Part 1c and 2B: Number of participants experiencing DLT
  • Part 1: Number of participants with serious adverse events (SAEs), treatment-emergent AEs (TEAEs) and immune-related AEs (irAEs)
  • Part 2: Number of participants with SAEs, TEAEs and irAEs
  • Part 1: Number of participants with abnormality in hematology parameters
  • Part 2: Number of participants with abnormality in hematology parameters
  • Part 1: Number of participants with abnormality in clinical chemistry parameters
  • Part 2: Number of participants with abnormality in clinical chemistry parameters
  • Part 1: Number of participants with abnormality in thyroid function
  • Part 2: Number of participants with abnormality in thyroid function
  • Part 1: Number of participants with abnormality in routine urinalysis parameters
  • Part 2: Number of participants with abnormality in routine urinalysis parameters
  • Part 1: Number of participants with abnormality in vital signs
  • Part 2: Number of participants with abnormality in vital signs
  • Part 1: Number of participants with abnormality in electrocardiogram (ECG) parameters
  • Part 2: Number of participants with abnormality in ECG parameters
  • Part 1: Number of participants with abnormality in physical examination
  • Part 2: Number of participants with abnormality in physical examination
  • Part 1: Number of participants with abnormality in Eastern cooperative Oncology Group performance status (ECOG PS)
  • Part 2: Number of participants with abnormality in ECOG PS
  • Part 1: Number of participants using concomitant medications
  • Part 2: Number of participants using concomitant medications
  • Part 2: Objective response rate (ORR)

Secondary Outcome:

  • Part 1a: Area under the concentration-time curve from time zero to last measurable concentration (AUC [0-last]) of TSR-033
  • Part 1b: AUC (0-last) of TSR-033
  • Part 1c: AUC (0-last) of TSR-033 and dostarlimab
  • Part 2: AUC (0-last) of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: AUC extrapolated from time zero to infinity (AUC[0-inf]) of TSR-033
  • Part 1b: AUC (0-inf) of TSR-033
  • Part 1c: AUC (0-inf) of TSR-033 and dostarlimab
  • Part 2: AUC (0-inf) of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: AUC at steady state (AUCss) of TSR-033
  • Part 1b: AUCss of TSR-033
  • Part 1c: AUCss of TSR-033 and dostarlimab
  • Part 2: AUCss of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Minimum concentration (Cmin) of TSR-033
  • Part 1b: Cmin of TSR-033
  • Part 1c: Cmin of TSR-033 and dostarlimab
  • Part 2: Cmin of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Minimum concentration at steady state (C[min,ss]) of TSR-033
  • Part 1b: C(min,ss) of TSR-033
  • Part 1c: C(min,ss) of TSR-033 and dostarlimab
  • Part 2: C(min,ss) of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Maximum concentration (Cmax) of TSR-033
  • Part 1b: Cmax of TSR-033
  • Part 1c: Cmax of TSR-033 and dostarlimab
  • Part 2: Cmax TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Maximum concentration at steady state (C[max,ss]) of TSR-033
  • Part 1b: (C[max,ss]) of TSR-033
  • Part 1c:(C[max,ss]) of TSR-033 and dostarlimab
  • Part 2: (C[max,ss]) of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Clearance (CL) of TSR-033
  • Part 1b: CL of TSR-033
  • Part 1c: CL of TSR-033 and dostarlimab
  • Part 2: CL of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Volume of distribution (Vz) of TSR-033
  • Part 1b: Vz of TSR-033
  • Part 1c: Vz of TSR-033 and dostarlimab
  • Part 2: Vz of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1a: Terminal half-life (t1/2) of TSR-033
  • Part 1b: t1/2 of TSR-033
  • Part 1c: t1/2 of TSR-033 and dostarlimab
  • Part 2: t1/2 of TSR-033 and dostarlimab with chemotherapy and bevacizumab
  • Part 1: Number of participants with anti-TSR-033 antibodies
  • Part 2: Number of participants with anti-TSR-033 antibodies
  • Part 1: Number of participants with anti-dostarlimab antibodies
  • Part 2: Number of participants with anti-dostarlimab antibodies
  • Part 1: ORR
  • Part 1: Duration of response (DOR)
  • Part 2: DOR
  • Part 1: Disease control rate (DCR)
  • Part 2: DCR
  • Part 1: Progression-free survival (PFS)
  • Part 2: PFS
  • Part 1: Overall survival (OS)
  • Part 2: OS

Enrollment

55

Study Start Date

August 8, 2017

Eligibility

  • Gender:     All
  • Minimum age:     18 Years
  • Maximum age:     N/A
  • Healthy volunteers:     No

Sponsors

Tesaro, Inc.

Source

Tesaro, Inc.

Official title

A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-033, an Anti-LAG-3 Monoclonal Antibody, Alone and in Combination With an Anti-PD-1 in Patients With Advanced Solid Tumors

Clinicaltrials.gov Identifier

NCT03250832

     

Source: Clinicaltrials.gov. Through our founding membership in the Dana-Farber/Harvard Cancer Center, an NCI-designated Comprehensive Cancer Center, these clinical trials are conducted at the Massachusetts General Hospital Cancer Center and may be available at other partner institutions.