Bristol-Myers Squibb Company and Eli Lilly and Company have agreed to collaborate on the evaluation of the safety, tolerability and preliminary efficacy of the immunotherapy nivolumab (Opdivo?; Bristol-Myers Squibb) in combination with galunisertib (LY2157299; Lilly and Company).

The Phase I/II trial will evaluate the investigational combination of nivolumab and galunisertib as a potential treatment option for patients with advanced (metastatic and/or unresectable) glioblastoma, hepatocellular carcinoma and non-small cell lung cancer.

…This approach helps us to explore combination regimens in immuno-oncology drugs with other mechanisms of action that may accelerate the development of new treatment options for patients…

Nivolumab is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. The U.S. Food and Drug Administration (FDA) approved nivolumab injection, for intravenous use for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab (Yervoy?; Bristol-Meyers Squibb) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Galunisertib in clinical trials
Galunisertib is Lilly?s TGF beta R1 kinase inhibitor that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumors growth, suppresses the immune system, and increases the ability of tumors to spread in the body.

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Immune function is suppressed in cancer patients, and TGF beta worsens immunosuppression by enhancing the activity of immune cells called T regulatory cells. TGF beta also reduces immune proteins, further decreasing immune activity in patients.

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Galunisertib is currently under investigation as an oral treatment for advanced/metastatic malignancies, including Phase II evaluation in hepatocellular carcinoma, myelodysplastic syndromes (MDS), glioblastoma, and pancreatic cancer.

The collaboration is expected to address the hypothesis that co-inhibition of PD-1 and TGF beta negative signals may lead to enhanced anti-tumor immune responses than inhibition of either pathway alone.

?Advanced solid tumors represent a serious unmet medical need among patients with cancer,? noted Michael Giordano, senior vice president, Head of Development, Oncology, Bristol-Myers Squibb. ?Our clinical collaboration with Lilly underscores Bristol-Myers Squibb?s continued commitment to explore combination regimens from our immuno-oncology portfolio with other mechanisms of action that may accelerate the development of new treatment options for patients.?

?Combination therapies will be key to addressing tumor heterogeneity and the inevitable resistance that is likely to develop to even the most promising new tailored therapies,? said Richard Gaynor, M.D., senior vice president, Product Development and Medical Affairs, Lilly Oncology. ?To that end, having multiple cancer pathways and technology platforms will be critical in an era of combinations to ensure sustainability beyond any single asset.?

The study will be conducted by Lilly. Additional details of the collaboration were not disclosed. Earlier this year Bristol-Meyers Squibb and Seattle Genetics agreed to evaluate the investigational combination of the antibody-drug conjugate or ADC brentuximab vedotin (Adcetris?; Seattle Genetics) and the immunotherapy nivolumab (Opdivo?; Bristol-Myers Squibb) in two planned Phase I/II clinical trials.[1]

Last Editorial Review: January 13, 2015

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