Bristol-Myers Squibb Company (BMS), a global biopharmaceutical company, and Eli Lilly and Company announced a clinical trial collaboration to evaluate the safety, tolerability and preliminary efficacy of Bristol-Myers Squibb's immunotherapy Opdivo (nivolumab) in combination with Lilly's galunisertib (LY2157299).
The phase 1/2 trial will evaluate the investigational combination of Opdivo and galunisertib as a potential treatment option for patients with advanced (metastatic and/or unresectable) glioblastoma, hepatocellular carcinoma and non-small cell lung cancer.
Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells. Galunisertib (pronounced gal ue" ni ser'tib) is a TGF beta R1 kinase inhibitor that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumour growth, suppresses the immune system and increases the ability of tumours to spread in the body. This collaboration will address the hypothesis that co-inhibition of PD-1 and TGF beta negative signals may lead to enhanced anti-tumour immune responses than inhibition of either pathway alone.
"Advanced solid tumours represent a serious unmet medical need among patients with cancer," said 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 tumour 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.
The US Food and Drug Administration (FDA) approved Opdivo (nivolumab) injection, for intravenous use. Opdivo is a PD-1 blocking antibody indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following Yervoy (ipilimumab) and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumour 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. Bristol-Myers Squibb has a broad, global development program to study Opdivo in multiple tumour types consisting of more than 50 trials - as monotherapy or in combination with other therapies - in which more than 7,000 patients have been enrolled worldwide.
Galunisertib (pronounced gal ue" ni ser'tib) is Lilly's TGF beta R1 kinase inhibitor that in vitro selectively blocks TGF beta signaling. TGF beta promotes tumours growth, suppresses the immune system, and increases the ability of tumours to spread in the body.
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
Galunisertib is currently under investigation as an oral treatment for advanced/metastatic malignancies, including Phase 2 evaluation in hepatocellular carcinoma, myelodysplastic syndromes (MDS), glioblastoma, and pancreatic cancer.