The main purpose of this study is to characterize the safety, tolerability, dose limiting toxicities, best route of administration, maximum tolerated dose, maximum administered dose, or alternative dose of BMS-986301 alone or in combination with nivolumab and ipilimumab in participants with cancers that have failed to respond to T cell checkpoint inhibiting antibodies.

Start Date26 Mar 2019

Sponsor / Collaborator

Bristol Myers Squibb Co.

100 Clinical Results associated with BMS-986301

100 Translational Medicine associated with BMS-986301

100 Patents (Medical) associated with BMS-986301

Literatures (Medical) associated with BMS-986301

Journal of Hematology & Oncology

Overcome the challenge for intratumoral injection of STING agonist for pancreatic cancer by systemic administration

Letter

Author: Funes, Vanessa ; Jurcak, Noelle ; Yuan, Chunhui ; Osipov, Arsen ; Espinoza, Birginia ; Liu, Xubao ; Li, Keyu ; Lyman, Melissa ; Zhang, Rui ; Rozich, Noah ; Yuan, Jialong ; Wang, Jianxin ; Zhou, Jiawei ; He, Mengni ; Zheng, Lei ; Wichroski, Michael ; Fu, Juan ; Trafton, Diego ; Herbst, Brian ; Henderson, MacKenzie ; Blair, Alex B ; Niu, Nan ; Wang, Junke

AbstractDue to the challenge for intratumoral administration, innate agonists have not made it beyond preclinical studies for efficacy testing in most tumor types. Pancreatic ductal adenocarcinoma (PDAC) has a hostile tumor microenvironment that renders T cells dysfunctional. Innate agonist treatments may serve as a T cell priming mechanism to sensitize PDACs to anti-PD-1 antibody (a-PD-1) treatment. Using a transplant mouse model with spontaneously formed liver metastasis, a genetically engineered KPC mouse model that spontaneously develops PDAC, and a human patient-derived xenograft model, we compared the antitumor efficacy between intrahepatic/intratumoral and intramuscular systemic administration of BMS-986301, a next-generation STING agonist. Flow cytometry, Nanostring, and cytokine assays were used to evaluate local and systemic immune responses. This study demonstrated that administration of STING agonist systemically via intramuscular injection is equivalent to its intratumoral injection in inducing both effector T cell response and antitumor efficacy. Compared to intratumoral administration, T cell exhaustion and immunosuppressive signals induced by systemic administration were attenuated. Nonetheless, either intratumoral or systemic treatment of STING agonist was associated with increased expression of CTLA-4 on tumor-infiltrating T cells. However, the combination of a-PD-1 and anti-CTLA-4 antibody with systemic STING agonist demonstrated the antitumor efficacy in the KPC mouse spontaneous PDAC model. The mouse pancreatic and liver orthotopic model of human patient-derived xenograft reconstituted with PBMC also showed that antitumor and abscopal effects of both intratumoral and intramuscular STING agonist are equivalent. Taken together, this study supports the clinical development of innate agonists via systemic administration for treating PDAC.

100 Deals associated with BMS-986301

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Indication	Highest Phase	Country/Location	Organization	Date
Solid tumor	Phase 1	CA	Bristol Myers Squibb Co.	26 Mar 2019
Solid tumor	Phase 1	US	Bristol Myers Squibb Co.	26 Mar 2019

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