The U.S. Food and Drug Administration (FDA) has approved Opdivo (nivolumab), a PD-1 inhibitor, for the treatment of classical Hodgkin lymphoma (cHL) in patients who relapsed or progressed after autologous hematopoietic stem cell transplant (HSCT) and post-transplantation brentuximab vedotin (Adcetris).
“Today’s approval of Opdivo delivers a transformational and exciting new option for these patients and the hematologists who treat them. By expanding this Immuno-Oncology therapy into a hematologic malignancy, we continue to deliver upon our unwavering commitment to provide treatments that work directly with the body’s immune system for patients who are in need of new options,” Chris Boerner, Head of U.S. Commercial for Bristol-Myers Squibb, the drug’s manufacturer, said in a press release. “This is our second Immuno-Oncology agent in blood cancer in less than a year for patients impacted by diseases with a deep unmet need.”
Opdivo’s accelerated approval by the FDA was based on its efficacy, as shown in a combined analysis data from two single-arm, multicenter trials that evaluated the drug for this particular patient population, regardless of PD-L1 expression: the ongoing Phase 2 CheckMate-205 and the Phase 1 CheckMate-039.
Based on that analysis, in 95 patients, Opdivo was seen to have an objective response rate (ORR) of 65 percent, a primary study endpoint. A total 7 percent of the patients had a complete response, and 58 percent were seen to have a partial response. Median time to response was 2.1 months, and response was maintained for a median of 8.7 months.
Patients in both studies had undergone a median of five prior systemic regimens, and received a median of 17 doses of Opdivo over 8.3 months of therapy.
Bristol-Myers plans to present results from CheckMate-205, a single-arm, open-label, multicohort study, at the American Society of Clinical Oncology (ASCO) 2016 Annual Meeting, taking place in Chicago, Illinois, in June.
The drug’s safety was evaluated in 263 adult cHL patients in the two trials — CheckMate-205 (240 patients) and CheckMate-039 (23 patients). Serious adverse reactions were reported in 21% of these people, with the most frequent events (less than or equal to 1%) being infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.
Ten patients died from causes other than disease progression, including six from complications of allogeneic HSCT — which led to a new “warning and precautions” label being issued for complications of allogeneic HSCT after nivolumab treatment, and a requirement of further study of such reactions by the company.
Opdivo’s continued approval as a cHL treatment may be contingent upon verification of clinical benefit through a randomized Phase 3 trial.The FDA-recommended a dose schedule is 3 mg/kg of nivolumab via intravenous (IV) administration every two weeks, until disease progression or unacceptable toxicity.
The drug, a programmed death receptor-1 (PD-1) blocking antibody, is also FDA-approved for the treatment of advanced melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma.
“It is important to have new treatment options for patients with difficult-to-treat diseases who have exhausted the current available options. Because of the unique pathology and biology of classical Hodgkin lymphoma, it makes sense from a scientific standpoint to investigate a PD-1 inhibitor,” said Anas Younes, MD, an oncologist and chief of Lymphoma Service at Memorial Sloan Kettering Cancer Center. “The recent clinical data with Opdivo in patients with classical Hodgkin lymphoma who have relapsed or progressed after auto-HSCT and post-transplantation brentuximab vedotin is encouraging and has the potential to impact our approach to treating these individuals in the future.”