Two is better than one

NEW YORK—Bristol-Myers Squibb Co. (BMS) and Summit, N.J.-based Celgene Corp. have launched a Phase 1 clinical trial collaboration to evaluate whether a combination regimen of the BMS investigational PD-1 immune checkpoint inhibitor Opdivo and Celgene’s chemotherapy drug Abraxane can effectively treat HER2-negative metastatic breast cancer, pancreatic cancer, non-small cell lung cancer (NSCLC) and other multiple tumor types.

The Opdivo/Abraxene one-two punch in the cancer arena could be a game-changer for cancer patients.

“Bristol-Myers Squibb continues to forge partnerships focused on exploring the effects of combination regimens that utilize promising therapies from our immuno-oncology portfolio,” stated Michael Giordano, senior vice president of oncology development for BMS. “Through this collaboration, Bristol-Myers Squibb and Celgene will work together to advance the science and understanding of how to fight cancer.”

Ken Dominski of BMS public affairs tells DDNews, “BMS believes that combination therapies have the potential to provide long-term survival benefits to a broader patient population, and that includes research into combining immunotherapies with a diverse number of approaches to treating cancer, including standard-of-care chemotherapy.”

BMS has a “robust clinical trial program investigating these multiple immune pathways, both as monotherapy and as combination regimens,” Dominski said. “We continue to explore external opportunities to combine our innovative portfolio with other assets where we feel there is a scientific rationale that the combination could provide a better treatment alternative to patients.”

Opdivo is part of a new class of cancer treatments known as immunotherapies, designed to harness the body’s own immune system in fighting cancer, BMS has stated. Optivo targets distinct regulatory components of the immune system, while Abraxene works by interfering with the ability of cancer cells to divide. By combining an immunotherapy with a standard chemotherapy, the companies will explore whether these two agents may lead to an enhanced antitumor response compared to either agent acting alone.

As a monotherapy, Opdivo “was approved in Japan on July 4, 2014 for the treatment of patients with unresectable melanoma and is studied in multiple tumor types consisting of more than 35 trials—as monotherapy or in combination with other therapies—in which more than 7,000 patients have been enrolled worldwide,” Dominski says.

On July 4, Ono Pharmaceutical Co. announced that Opdivo’s manufacturing and marketing approval in Japan for unresectable melanoma made Opdivo the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world, adds Dominksi.

“Among these [trials of Opdivo] are several potentially registrational trials in NSCLC, melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma and non-Hodgkin lymphoma,” he points out.

In 2013, the U.S. Food and Drug Administration (FDA) granted Fast Track designation for Opdivo in NSCLC, melanoma and RCC, Dominski notes. In May 2014, the FDA granted Opdivo Breakthrough Therapy designation for the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant and brentuximab.

Dr. Markus Renschler, senior vice president and global head of hematology and oncology medical affairs at Celgene, stated, “Our collaboration with Bristol-Myers Squibb further underscores our commitment to understanding and modulating the immune system to advance the treatment paradigm in cancer. We believe that Abraxane is appropriate as a combination partner for novel immuno-oncology therapies due to its proven antitumor activity and that it can be administered without steroid premedication.”

“Both Celgene and BMS believe that combination therapies have the potential to provide long-term survival benefits to a broader patient population, and that includes research into combining immunotherapies with a diverse number of approaches to treating cancer, including standard-of-care chemotherapy,” Renschler tells DDNews.

Celgene has collaborated with BMS before on combination studies of revlimid and elotuzumab, to support their Eloquent 1 and Eloquent 2 studies.

Celgene will conduct the Phase 1 study and lead the operational aspects of the study, while a joint development committee will oversee collaboration activities, Renschler explains.

The study, which is expected to begin in the fourth quarter of 2014, will be conducted by Celgene. Patients with HER2-negative breast cancer will be treated with Abraxane and Opdivo; patients with NSCLC will be treated with the combination of Abraxane, carboplatin and Opdivo; and patients with pancreatic adenocarcinoma will be treated with Abraxane, gemcitabine and Opdivo. Additional details of the collaboration were not disclosed.

“It is premature to speculate on the approved use of Opdivo and Abraxane, as we are only now conducting a Phase 1 study,” Renschler asserts.

“It is important to note that for the pancreatic cancer approval, the Abraxane plus gemcitabine Phase 3 study showed the greatest improvement in survival of any approved treatment for pancreatic cancer—median overall survival of 8.7 months, with 35 percent one-year, 10 percent two-year and 4 percent three-year survival,” he says.

“Since 1997, only three of 30-plus Phase 3 trials involving 16,000-plus patients have improved survival versus gemcitabine (Abraxane being one of them),” Renschler says. “This cumulative approach to medical innovation has helped double the number of cancer survivors in the United States to 14 million since 1990, and is expected to add another 8 million by 2025.”

“The rapid advance of innovative cancer therapies has reduced mortality rate by more than 20 percent, and has significantly reduced hospitalizations, thus reducing the burden on our healthcare system,” he adds.

In the U.S., Abraxane was first approved in January 2005 by the FDA for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy.

In October 2012, Abraxane was approved by the FDA for the first-line treatment of locally advanced or metastatic NSCLC, in combination with carboplatin, in patients who are not candidates for curative surgery or radiation therapy. Abraxane is also approved for the treatment of NSCLC in Argentina, Australia, Chile, Ecuador, Japan and New Zealand.

In September 2013, the FDA approved Abraxane as first-line treatment of patients with metastatic adenocarcinoma of the pancreas, in combination with gemcitabine. Abraxane is also approved for the treatment of metastatic pancreatic cancer in Europe, Argentina, Australia, Canada, Ecuador, Lebanon and New Zealand.

“It is premature to speculate how this drug combination would be considered as we are evaluating safety, tolerability and preliminary efficacy of the combination in a Phase 1 study,” Renschler said. “Both Celgene and BMS believe that combination therapies have the potential to provide long-term survival benefits to a broader patient population, and that includes research into combining immunotherapies with a diverse number of approaches to treating cancer, including standard of care chemotherapy.”