FDA Grants Breakthrough Therapy Designations to Nivolumab, Elotuzumab

Nivolumab and elotuzumab have each been granted breakthrough therapy designations by the FDA for the treatment of two types of blood cancers.

Nivolumab and elotuzumab, drugs that will be commercialized by Bristol-Myers Squibb (BMS), have each been granted breakthrough therapy designations by the FDA for the treatment of two types of blood cancers.

The new designation for nivolumab is focused on the treatment of patients with Hodgkin lymphoma following autologous stem cell transplant (ASCT) and brentuximab vedotin (Adcetris). For elotuzumab, the designation is in combination with lenalidomide and dexamethasone for patients with multiple myeloma following one or more prior therapies. Each designation was based on findings from early-phase clinical trials and is meant to fill an unmet need.

The Hodgkin lymphoma designation was based on a cohort of patients from a phase I dose escalation study that evaluated the PD-1 inhibitor nivolumab in patients with relapsed or refractory hematologic malignancies. The open-label, two-part study planned to enroll approximately 100 patients. Patients received intravenous nivolumab at 1 mg/kg or 3 mg/kg every 2 weeks. Results from this analysis have not yet been made available.

In a phase II analysis, labeled CheckMate 139, nivolumab is being explored as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma for patients who failed or were ineligible for ASCT. This study hopes to enroll 120 patients. Nivolumab will be administered at 3 mg/kg every 2 weeks. The primary outcome measure is objective response rate (ORR).

The PD-1 inhibitor nivolumab has been investigated heavily for its potential to elicit an antitumor immune response across a variety of tumors. In 2013 nivolumab received fast track designations from the FDA for non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma. In April 2014, BMS announced plans to initiate a rolling submission to the FDA for the potential approval of nivolumab as a third-line treatment for patients with squamous cell NSCLC.

“The breakthrough therapy designation granted by the FDA for nivolumab continues to support the development of innovative approaches designed to advance how cancer is treated,” Michael Giordano, senior vice president, head of development, Oncology & Immunosciences at BMS, said in a press release. “It is our goal to change the way patients live with cancer, especially in areas of high unmet medical need like Hodgkin lymphoma where patients may be underserved by currently available treatment options.”

The new designation for elotuzumab was supported by phase II results presented at the 18th Annual Congress of the European Hematology Association. In this analysis, the CS1 inhibitor elotuzumab was administered at 10 mg/kg (n = 36) and 20 mg/kg (n = 37) in combination with lenalidomide and low-dose dexamethasone. A phase III study is ongoing that utilizes the 10 mg/kg dose.

After a median 20.8-month follow-up, the median progression-free survival (PFS) was 33 months (95% CI, 14.9-NA) and the objective response rate (ORR) was 92% in the 10-mg/kg arm. After a shorter follow-up of 17.1 months, the median PFS was 18 months (95% CI, 12.91-32.36) and the ORR was 76% in the 20 mg/kg arm.

In patients receiving elotuzumab 10 mg/kg or 20 mg/kg, respectively, the most common grade 3/4 adverse events were lymphopenia (26% and 9%), neutropenia (21% and 22%), thrombocytopenia (21% and 17%), anemia (13% and 12%), leukopenia (8% and 7%), hyperglycemia (5% and 12%), pneumonia (8% and 5%), diarrhea (10% and 5 %), fatigue (8% and 9%), and hypokalemia (8% and 5%).

“Despite recent advances in the treatment of relapsed or refractory multiple myeloma, it remains an area of unmet need,” Giordano said. “This breakthrough therapy designation underscores the potential of elotuzumab in this setting and reinforces Bristol-Myers Squibb’s longstanding commitment to the research and development of novel medicines to treat hematologic malignancies.”

Elotuzumab is being co-developed in collaboration with AbbVie. In addition to the relapsed/refractory setting, a phase I/II trial is exploring elotuzumab with or without bortezomib, dexamethasone, and lenalidomide for newly diagnosed high-risk multiple myeloma.