Peter F. Lebowitz, MD, PhD
The combination of the investigational PD-1 immune checkpoint inhibitor nivolumab (Opdivo) and the oral BTK inhibitor ibrutinib (Imbruvica) will be evaluated in a phase I/II trial as a treatment for patients with non-Hodgkin lymphoma (NHL), the companies developing the agents announced.
The study will look at the combination in patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL).
The trial will be conducted by Janssen, the company that co-developed ibrutinib along with Pharmacyclics. Bristol-Myers Squibb (BMS) will provide nivolumab for the study. The exact details of the study were not released.
“We are excited about the opportunity to understand and evaluate the potential activity of Imbruvica and Opdivo together, and the benefits this combination may offer patients,” Peter F. Lebowitz, MD, PhD, Global Oncology Head, Janssen said in a statement. “We look forward to working with Bristol-Myers Squibb and Pharmacyclics on this study as we continue to grow the body of knowledge about Imbruvica in different settings and patient populations.”
Nivolumab and ibrutinib demonstrated promising efficacy as single agents for patients with hematologic malignancies in early phase clinical trials. Additionally, preclinical evidence suggests that ibrutinib and nivolumab could have synergistic effects for patients with hematologic malignancies.
In May 2014, the FDA granted a breakthrough therapy designation to nivolumab as a treatment for patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) and brentuximab vedotin. This designation was based on a cohort of patients from a phase I dose escalation study that evaluated nivolumab in patients with relapsed or refractory hematologic malignancies. Additionally, a phase II study is exploring nivolumab as a treatment for patients with relapsed or refractory DLBCL who failed or were ineligible for ASCT.
Ibrutinib is approved for the treatment of patients with CLL who have received at least one prior therapy, and for the treatment of CLL patients with del 17p, a genetic mutation that occurs when part of chromosome 17 has been lost. Ibrutinib also received approval for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on overall response rate (ORR).
In addition to these approved indications, Ibrutinib continues to be studied alone and in combination with other treatments in several blood cancers, including CLL, MCL, Waldenström's macroglobulinemia, DLBCL, FL, and multiple myeloma.
“Our collaboration to study Opdivo in combination with Imbruvica is an innovative approach to accelerating Bristol-Myers Squibb’s progress in the study of immuno-oncology and hematologic malignancies, gaining further insight into promising areas of drug development and research,” Michael Giordano, senior vice president, Head of Development, Oncology, BMS, said in a statement. “We look forward to working with Pharmacyclics and Janssen to evaluate the potential of these two therapies as options for patients with lymphomas.”
Nivolumab was granted Fast Track Designation by the FDA in 2013 for the treatment of non-small cell lung cancer (NSCLC), melanoma and renal cell carcinoma. This April, BMS initiated a rolling submission with the FDA for nivolumab in third-line pre-treated squamous cell NSCLC and expects to complete the submission by year-end.
In September, the FDA assigned a priority review designation to nivolumab as a treatment for pretreated patients with advanced melanoma, based on phase III data comparing the drug with dacarbazine. Based on this review timeline, the agency plans to take action on the drug's application within 6 months, placing a decision date on March 30, 2015.