RecruitingPhase 2NCT04028063

Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas

An Open-Label, Phase II Efficacy Trial of Doxorubicin in Combination With Dual Checkpoint Blockade Using Zalifrelimab (AGEN1884) or Botensilimab (AGEN1181) With Balstilimab (AGEN2034) for Advanced or Metastatic Soft Tissue Sarcomas

Sponsor

University of Colorado, Denver

Enrollment

65 participants

Start Date

Jan 28, 2020

Study Type

INTERVENTIONAL

Conditions

Metastatic Soft Tissue Sarcoma Advanced Soft Tissue Sarcoma

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 100 Years

Plain Language Summary

Simplified for easier understanding

This trial tests whether combining a chemotherapy drug called doxorubicin with two immune-boosting drugs (called checkpoint inhibitors) works better than chemotherapy alone for advanced soft tissue sarcomas — cancers that grow in muscles, fat, and connective tissue. **You may be eligible if...** - You are 18 or older with an advanced or metastatic soft tissue sarcoma that cannot be cured by surgery - Your specific sarcoma type is on the study list (e.g., synovial sarcoma, liposarcoma, leiomyosarcoma, angiosarcoma, and others) - You have had 0 or 1 prior treatments for metastatic disease (Part One) or any number of prior treatments (Part Two) - You have never received anthracycline chemotherapy or immune checkpoint drugs before - You are in good general health (ECOG performance status 0 or 1) - Your heart, kidneys, and liver are functioning adequately - You can agree to tumor biopsies at two time points during the study **You may NOT be eligible if...** - You have previously received anthracycline or immune checkpoint therapy - You have an active autoimmune disease requiring systemic treatment - You have HIV, hepatitis, or tuberculosis - You are pregnant or breastfeeding - Your heart ejection fraction is below 50% - You have active, untreated brain metastases - You have another active cancer (some skin cancers excepted) Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGBalstilimab

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.

DRUGZalifrelimab

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.

DRUGDoxorubicin

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%.

DRUGBotensilimab

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.