AbbVie and Bristol-Myers Squibb Company announced a clinical trial collaboration to evaluate the safety, tolerability and efficacy of AbbVie's investigational biomarker-specific antibody drug conjugate Rova-T (rovalpituzumab tesirine) in combination with Bristol-Myers Squibb's Opdivo (nivolumab) and Opdivo + Yervoy (ipilimumab) regimen as a treatment for relapsed extensive-stage small cell lung cancer (SCLC).

The phase 1/2 clinical programme will explore the potential of combining Bristol-Myers Squibb's immuno-oncology agents, which are designed to alleviate immune suppression, in conjunction with AbbVie's investigational antibody drug conjugate, Rova-T, to drive improved and sustained efficacy and tolerability above the current standard of care. Rova-T is a novel antibody drug conjugate that targets and eliminates tumor initiating cells and other bulk tumor cells. This collaboration will determine if the targeted cell killing and antigen release caused by Rova-T may further enhance the effect of immunotherapy.

"We are excited to explore the potential benefits of combining Bristol-Myers Squibb's immunotherapies with a targeted approach like Rova-T in small cell lung cancer where the need for new therapies is particularly acute for this aggressive form of lung cancer," said Jean Viallet, M.D., global clinical research lead, oncology, Bristol-Myers Squibb. "As the science around cancer research continues to rapidly evolve, we are building on our leadership in Immuno-Oncology with numerous collaborations that may help advance new therapies for cancers in need of better options."

"We believe the combination of these cancer-fighting agents may offer patients a new treatment option in a disease with limited therapies," said Scott J. Dylla, Ph.D., vice president, research and development, AbbVie. "By combining immune-checkpoint inhibitors that prime the body's immune system to fight cancer cells with Rova-T's approach to target cancer stem cells, we hope to build on our goal to develop differentiated treatments with therapeutic benefit that elevate the standard of care for small cell lung cancer patients."

Small cell lung cancer is a difficult-to-treat form of cancer that accounts for approximately 15 percent of all lung cancers. The five-year survival rate for extensive-stage SCLC is less than 5 percent and treatment options are limited for the more than 234,000 people diagnosed annually.

Rova-T is a novel biomarker-specific therapy that targets cancer stem cells and combines a targeted antibody that delivers a cytotoxic agent directly to cancer cells expressing a delta-like protein 3 (DLL3). DLL3 is expressed in more than 80 percent of SCLC patient tumors and is not present in healthy tissue. Rova-T is currently in investigational studies as a third-line treatment for SCLC. AbbVie will initiate a first-line clinical study for Rova-T in SCLC and several other types of tumors in the near term.

Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014, and currently has regulatory approval in 54 countries including the United States, Japan, and in the European Union. Yervoy is a CTLA-4 immune checkpoint inhibitor approved in 50 countries globally for patients with unresectable or metastatic melanoma.

Rova-T is an investigational antibody drug conjugate targeting the cancer-stem cell-associated target delta-like protein 3 (DLL3), which is expressed in more than 80 percent of small cell lung cancer (SCLC) patient tumors, where it is prevalent on tumor cells, including cancer stem cells, but not present in healthy tissue. Rova-T combines a targeted antibody that delivers a cytotoxic agent directly to the DLL3-expressing cancer cells while minimizing toxicity to healthy cells. Rova-T is under investigation as a third-line treatment in SCLC. Studies evaluating Rova-T as a first-line SCLC regimen will be starting in the near term. The expression of DLL3 suggests Rova-T may be useful across multiple tumor types, including metastatic melanoma, glioblastoma multiforme and some prostate, pancreatic and colorectal cancers.

Rova-T is an investigational compound and its efficacy and safety have not been established by the FDA or any other health authority.

Cancer cells may exploit "regulatory" pathways, such as checkpoint pathways, to hide from the immune system and shield the tumor from immune attack. Opdivo is a PD-1 immune checkpoint inhibitor that binds to the checkpoint receptor PD-1 expressed on activated T-cells, and blocks the binding of PD-L1 and PD-L2, preventing the PD-1 pathway's suppressive signaling on the immune system, including the interference with an anti-tumor immune response.

Opdivo's broad global development program is based on Bristol-Myers Squibb's understanding of the biology behind Immuno-Oncology. Our company is at the forefront of researching the potential of Immuno-Oncology to extend survival in hard-to-treat cancers. This scientific expertise serves as the basis for the Opdivo development program, which includes a broad range of phase 3 clinical trials evaluating overall survival as the primary endpoint across a variety of tumor types. The Opdivo trials have also contributed toward the clinical and scientific understanding of the role of biomarkers and how patients may benefit from Opdivo across the continuum of PD-L1 expression. To date, the Opdivo clinical development program has enrolled more than 18,000 patients.