Bristol-Myers Squibb (BMS) and Celldex Therapeutics said today they will collaborate on a Phase I/II clinical trial intended to assess a combination treatment that joins cancer immunotherapies under development by each company.
The companies said BMS will make a one-time $5 million payment to Celldex, with both companies agreeing to share development costs.
Celldex will have responsibility for conducting the Phase I/II trial, set to begin in the fourth quarter. The study will evaluate the safety, tolerability and preliminary efficacy of nivolumab, BMS’ investigational PD-1 immune checkpoint inhibitor, and varlilumab, Celldex’ CD27-targeting investigational antibody.
The combination therapy will be examined for its effects on multiple tumor types—which the companies said could include non-small cell lung cancer (NSCLC), metastatic melanoma, ovarian, colorectal (CRC) and squamous cell head and neck cancers.
Nivolumab binds to the checkpoint receptor PD-1 (programmed death-1) expressed on activated T-cells. By blocking this pathway, nivolumab can enable the immune system to resume its ability to recognize, attack and destroy cancer cells, the companies reason.
Varlilumab induces activation and proliferation of human T cells when combined with T-cell receptor stimulation. In lymphoid malignancies that express CD27 at high levels, CDX-1127 has an additional mechanism through a direct antitumor effect.
Preclinical data suggest the combination of the cancer immunotherapeutic candidates may enhance anti-tumor immune response over each drug individually, according to BMS and Celldex.
“Based on our clinical data and preclinical models for both programs, we think the combination of varlilumab and nivolumab could play an important role in maximizing the body’s immune response to cancer,” Anthony Marucci, Celldex’ president and CEO said in a statement. “We are excited to begin this study and look forward to initiating additional combination studies of varlilumab that explore other important mechanisms outside of this collaboration in the near future.”
Under their collaboration, BMS and Celldex also agreed to work exclusively with each other to explore combination regimens of anti-PD-1 antagonist antibodies and anti-CD27 agonist antibodies. BMS will have a time-limited right of first negotiation if Celldex wishes to out-license varlilumab.
An existing agreement related to its CD27 program between Celldex and Medarex was restructured, with Medarex—acquired by BMS in 2009—agreeing to waive some undisclosed future milestone payments and reduce future royalty rates that would have been due from Celldex.
Oncology is one of BMS’ six therapeutic focus areas. The other five are cardiovascular, immunoscience, metabolics, neuroscience, and virology.