BMS and Clovis Oncology announce a broad clinical collaboration to evaluate combination of Opdivo an

Pivotal Phase III trials planned for 2017 will evaluate Rubraca + Opdivo, Rubraca as monotherapy, and Opdivo as monotherapy in first line maintenance treatment for advanced ovarian and advanced triple-negative breast cancers.

Bristol-Myers Squibb (BMS) and Clovis Oncology have entered into a clinical collaboration agreement to evaluate the combination of BMS’s immunotherapy Opdivo and Clovis Oncology’s poly (ADP-ribose) polymerase (PARP) inhibitor Rubraca in pivotal Phase III clinical trials in:

Advanced ovarian cancer: First-line maintenance treatment study to evaluate Rubraca + Opdivo, Rubraca, Opdivo and placebo in newly diagnosed patients with stage III/IV high-grade ovarian, fallopian tube, or primary peritoneal cancer who have completed platinum-based chemotherapy.

Advanced triple-negative breast cancers (TNBC): First-line maintenance treatment study to evaluate Rubraca + Opdivo, Rubraca, Opdivo and chemotherapy in patients with stage IV or recurrent locally advanced inoperable TNBC associated with a homologous recombination deficiency (HRD).

The collaboration will also include a Phase II study to evaluate the safety and efficacy of Opdivo in combination with Rubraca in patients with metastatic castration-resistant prostate cancer (mCRPC). The Opdivo + Rubraca combination in mCRPC will be conducted as an arm of a larger BMS-sponsored study.

Rubraca is an oral, small molecule inhibitor of PARP enzymes, including PARP-1, PARP-2, and PARP-3, being developed for the treatment of solid tumours associated with homologous recombination deficiency (HRD), defined as the presence of a deleterious BRCA1 or BRCA2 mutation, a deleterious mutation in another gene involved in DNA damage repair, and/or a high percentage of tumour genome with LOH, a phenotypic consequence of HRD. Opdivo is a human programmed death receptor-1 (PD-1) blocking antibody that binds to the PD-1 receptor expressed on activated T-cells and other immune cells. The overlap in immuno-biology linked to these agents supports the potential for synergy of PARP inhibition and PD-1 blockade. Preclinical evidence has demonstrated that PARP inhibition can trigger inflammation, cell death and increase T-cell infiltration within tumors.

"We are very enthusiastic about studying Rubraca and Opdivo in combination, and the potential to create new treatment options for patients with multiple tumour types, as well as for patients beyond those with BRCA mutations," said Patrick J. Mahaffy, President, and CEO of Clovis Oncology. "This substantial clinical collaboration in ovarian, triple-negative breast and prostate cancers represents a significant effort by Clovis and Bristol-Myers Squibb to realize that potential."

"This clinical collaboration addresses areas of unmet medical need where the combination of Opdivo and Rubraca may lead to an additional treatment option for patients with difficult to treat cancers," said Fouad Namouni, head of Oncology Development, BMS. "We are committed to investigating a wide range of oncology therapies and look forward to studying the combination of Clovis’ PARP inhibitor and our immunotherapy."

The planned multi-arm clinical trials will be conducted in the US, Europe, and possibly additional countries. Clovis will be the study sponsor and conducting party for the ovarian cancer study and BMS will be the study sponsor and conducting party for the breast and prostate cancer studies. Specific terms of the agreement were not disclosed. All three studies are expected to begin before the end of 2017.