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 ; Yuan, Chunhui ; Jurcak, Noelle ; 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 ; Niu, Nan ; Henderson, MacKenzie ; Herbst, Brian ; Blair, Alex B ; 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

R&D Status

10 top R&D records.

to view more data

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

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

BMS-986301

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation