Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas

Part of paid clinical trials in Aurora, Colorado.

Sponsor
University of Colorado, Denver
Study ID
NCT04028063
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • Advanced Soft Tissue Sarcoma
  • Metastatic Soft Tissue Sarcoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 100 Years
Healthy Volunteers
Not accepted

Interventions

  • Balstilimab — DRUG
    Balstilimab (AGEN2034) is a human monoclonal antibody that targets programmed cell death 1 (PD-1). Engagement of PD-1 by its ligands, programmed death ligand (PD-L1) and PD-L2, leads to signal transduction that inhibits important aspects of T cell function including proliferation, cytokine production and cytolytic activity. Balstilimab (AGEN2034) potently inhibits PD-1 binding to PD- L1 and PD- L2 and is intended to reverse the immunosuppressive effects of this signaling pathway in the context of tumor immuno-surveillance by T cells. Balstilimab (AGEN2034) is intended for development as a treatment for advanced malignancies as a single agent or in combinations.
  • Zalifrelimab — DRUG
    Zalifrelimab (AGEN1884) is a fully human monoclonal immunoglobulin G1 κ subclass (IgG1κ) antibody that specifically recognizes cytotoxic T lymphocyte-associated protein 4 (CTLA-4, also known as CD152). Zalifrelimab (AGEN1884) is being developed as a monotherapy for cancer indications with potential for future development in combination with other immunotherapies.
  • Doxorubicin — DRUG
    Doxorubicin is the standard of care first-line therapy for most subtypes of metastatic soft tissue sarcomas. Doxorubicin monotherapy administered at 75 mg/m2 has resulted in objective response rate of 14%, and median progression-free survival of 4.6 months, and another study reported progression-free survival at 6 months of 46.3%, with a median PFS of 5.8 months, and best objective response rate of 19%.
  • Botensilimab — DRUG
    Botensilimab (AGEN1181) is a novel, human, fragment-crystallizable (Fc)-engineered immunoglobulin G1 (IgG1) anti-CTLA-4 antibody designed to exploit a novel mechanism by which increased Fc engagement enhances antigen-specific effector T cell responses.

Study Details

This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. The overall objective is to determine the efficacy of combination doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1 antibody AGEN2034. The investigators will estimate the progression-free survival rate at 6 months (PFS6mo) of doxorubicin plus AGEN1884/AGEN2034 in comparison to historical PFS6mo with doxorubicin monotherapy, calculated as the mean from two large randomized Phase 3 clinical trials.

Key Dates

Start date
Jan 28, 2020
Status verified
Jan 2026
Primary completion
Apr 7, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
65 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Part 1: Stage 1, Safety Lead-In
    The safety lead-in will enroll 6 participants. Balstilimab 300mg flat q3 weeks up to 2 years; Zalifrelimab 1mg/kg q6 weeks x 4; Doxorubicin 75mg/m2 q3 weeks x 2, starts at C2 The participants will complete a dose-limiting toxiciy (DLT) observation period of 9 weeks.
  • Experimental: Part 1: Stage 2, Expansion
    Balstilimab 300mg flat q3 weeks up to 2 years; Zalifrelimab 1mg/kg q6 weeks up to 2 years; Doxorubicin 75mg/m2 q3 weeks x 6
  • Experimental: Part 2: Stage 2, Dose 1
    Doxorubicin 60mg/m2 q3 weeks x 6 doses Botensilimab 75mg q6 weeks up to two years
  • Experimental: Stage 2, Dose 2
    Doxorubicin 75mg/m2 q3 weeks x 6 doses Botensilimab 75mg q6 weeks up to two years
  • Experimental: Stage 2, Dose 3 Combination of Doxorubicin with Botensilimab and Balstilimab
    Doxorubicin 75mg/m2 q3 weeks x 6 doses Botensilimab 75mg flat q6 weeks up to 2 years Balstilimab 450mg q3 weeks up to 2 years

Primary Outcome Measure

Determine the progression-free survival rate [ Time Frame: 6 months ]

Locations (1)

FacilityCityStateZIPSite coordinators
University of Colorado HospitalAuroraColorado80045-

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By research site
University of Colorado Hospital· Aurora, CO

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