BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors.

Autor: Kesari S; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA., Bessudo A; California Cancer Associates for Research & Excellence, San Diego, CA 92127, USA., Gastman BR; Department of Dermatology & Plastic Surgery, Cleveland Clinic, Cleveland, OH 44195, USA., Conley AP; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Villaflor VM; Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA 91010, USA., Nabell LM; Comprehensive Cancer Center, University of Alabama, Birmingham, AL 35205, USA., Madere D; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA., Chacon E; Saint John's Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA., Spencer C; California Cancer Associates for Research & Excellence, San Diego, CA 92127, USA., Li L; Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Larson C; EpicentRx, Inc., La Jolla, CA 92037, USA., Reid T; EpicentRx, Inc., La Jolla, CA 92037, USA., Caroen S; EpicentRx, Inc., La Jolla, CA 92037, USA., Oronsky B; EpicentRx, Inc., La Jolla, CA 92037, USA., Stirn M; EpicentRx, Inc., La Jolla, CA 92037, USA., Williams J; EpicentRx, Inc., La Jolla, CA 92037, USA., Barve MA; Mary Crowley Cancer Research, Dallas, TX 75230, USA.
Jazyk: angličtina
Zdroj: Future oncology (London, England) [Future Oncol] 2022 Sep; Vol. 18 (29), pp. 3245-3254. Date of Electronic Publication: 2022 Aug 11.
DOI: 10.2217/fon-2022-0481
Abstrakt: AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-β receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-β. In preclinical studies with an immunocompetent mouse model, AdAPT-001 eradicated directly treated 'cold' tumors as well as distant untreated tumors, and, from its induction of systemic CD8 + T cell-mediated antitumor immunity, protected the mice from rechallenge with tumor cells. AdAPT-001 also sensitized resistant tumors to checkpoint blockade. This manuscript describes the rationale and design of the first-in-human phase I, dose-escalation and dose-expansion study of AdAPT-001 alone and in combination with a checkpoint inhibitor in adults with treatment-refractory superficially accessible solid tumors.
Databáze: MEDLINE