Nivolumab Granted FDA Priority Review for Hodgkin Lymphoma

The supplemental biologics license application (sBLA) was submitted by Bristol-Myers Squibb (BMS) under a 2014 breakthrough therapy designation nivolumab received for the treatment of patients with Hodgkin lymphoma following autologous stem cell transplant and brentuximab vedotin (Adcetris). Under the expedited priority review, the sBLA will be reviewed by the FDA within 6 months, compared with the standard 10-month review.

The sBLA was primarily based on data from the CheckMate-205 trial, which is evaluating nivolumab in both newly diagnosed and previously treated patients with cHL. Results from the study will be presented at a scientific meeting later this year, according to BMS.

“There is a significant burden on classical Hodgkin lymphoma patients who do not respond to initial treatment, and they need new treatment options that address the disease in a different way,” Jean Viallet, MD, oncology global clinical research lead at BMS, said in a statement.

“With the agency’s acceptance of our application, Opdivo has the potential to be the first PD-1 inhibitor in hematology, allowing us to expand immuno-oncology beyond solid tumors to patients with classical Hodgkin lymphoma and strengthen our hematology franchise.”

The multicohort, open-label phase II CheckMate-205 study has an estimated enrollment of nearly 300 patients with an ECOG performance status of 0 or 1. All previously treated patients must have received prior high-dose conditioning chemotherapy followed by autologous stem cell transplant as a part of salvage therapy for cHL. Prior brentuximab vedotin treatment is allowed, but not required.

Individuals enrolled in one of the study’s 3 pretreated patient cohorts will receive 3 mg/kg of nivolumab as an IV injection every 2 weeks. The treatment-naïve patient cohort will receive 240 mg of nivolumab as an IV injection every 2 weeks plus 25 mg/m²of doxorubicin, 6 mg/m2 of vinblastine, and 375 mg/m²of dacarbazine. The primary outcome measures are overall response rate (ORR) and safety.

Phase I data for single-agent nivolumab in cHL were previously reported at the 2015 ASH Annual Meeting. In 1 study (CA209-039), 23 patients with relapsed/refractory cHL received nivolumab at weeks 1 and 4, and then every 2 weeks for up to 2 years or until disease disease progression or unacceptable toxicity.¹

At a median follow-up of 86 weeks (range, 32-107 weeks) the ORR was 87% (n = 20), including 6 complete responses (CR) and 14 partial responses (PRs). Fifty percent of the responders had durable responses as defined by the study protocol.

The time to CR ranged from 3 to 88 weeks following initiation of nivolumab therapy, including 2 patients whose PRs converted to a CR. Of the 20 responses, 75% (n = 15) occurred within 16 weeks of starting treatment, including 5 patients who proceeded to stem cell transplant (1 CR, 4 PR). Three patients had a best overall response of stable disease.

Three patients discontinued nivolumab due to adverse events (AEs), including grade 2 peripheral neuropathy, grade 3 myelodysplastic syndrome, and grade 3 pancreatitis. Grade 1 or 2 immune-related AEs (IR-AEs) occurred in 4 of 10 evaluated patients, and resolved without treatment in 2 patients. The researchers noted that there was no correlation between time on treatment and an increased rate of IR-AEs.

A second study presented at the 2015 ASH Annual Meeting²retrospectively evaluated single-agent nivolumab in 12 patients with Hodgkin lymphoma who relapsed following allogeneic stem cell transplantation (allo-SCT). Patients had received a median of 9 (range, 7-11) prior systemic therapies, including allo-SCT. Nivolumab was dosed at 3 mg/kg every 2 weeks.

At a median follow-up of 60 days, 9 patients remained on treatment, 1 patient discontinued therapy due to progressive disease, and 2 patients stopped treatment due to GVHD. Among 8 evaluable patients, the ORR was 87.5% (n = 7), including 3 CRs and 5 PRs.

In March 2016, the European Medicines Agency validated an application for use of nivolumab for the same cHL indication the FDA is evaluating, also based on data from CheckMate-205. The centralized review process has now officially begun for final EU approval of the PD-1 inhibitor in this setting.

Nivolumab has regulatory approval in 48 countries, including the United States, EU, and Japan. In the United States, the drug has FDA-approved indications in renal cell carcinoma, melanoma, and non—small cell lung cancer.

References

1. Ansell S, Armand P, Timmerman JM , et al. Nivolumab in patients (Pts) with relapsed or refractory classical hodgkin lymphoma (R/R cHL): clinical outcomes from extended follow-up of a phase 1 study (CA209-039).Blood. 2015;126(23):583.
2. Herbaux C, Gauthier J, Brice P, et al. Nivolumab is effective and reasonably safe in relapsed or refractory hodgkin's lymphoma after allogeneic hematopoietic cell transplantation: a study from the Lysa and SFGM-TC.Blood. 2015;126(23):3979.