Regulatory Decision Summary for OPDIVO

The results from a Phase II trial (CA209205) and a Phase Ib trial (CA209039) were provided to support efficacy and safety of Opdivo in treatment of the patients with relapsed, refractory classical Hodgkin Lymphoma (cHL).

Efficacy results of Opdivo in the treatment of cHL patients who received prior brentuximab vedotin (BV) therapy after failure of ASCT were reported from 15 patients in CA209039 and 80 patients from CA209205. In CA209039, objective response rate (ORR) was 60.0% (9/15 patients) and all responders achieved a partial remission (PR). The median duration of response (DOR) was 12.0 months with a median study follow-up of 22 months. In CA209205, an ORR of 67.5% (60/80 patients) was reported. Complete remission (CR) and PR rates were 7.5% and 60.0 %, respectively. Median DOR was 13.1 months. Median progression-free survival (PFS) was 14.8 months while median over-all survival (OS) has not been reached after a minimum study follow-up of 12 months.

Efficacy of Opdivo in the treatment of cHL patients who were BV-naïve and received 3 or more lines of systemic therapy including ASCT was reported from Cohort A (n = 63) of CA209205. An ORR of 68.3% (43/63 patients) was reported. CR and PR rates were 22.2% and 46.0 %, respectively. Median and 95% CI for DOR, PFS and OS have not been reached after a minimum study follow-up of 9 months.

No new safety concerns with Opdivo monotherapy were identified compared with those reported in studies of patients with solid tumors. There were no treatment-related deaths. Most drug-related select adverse events (AEs) and immune-mediated AEs were low grade and were manageable. Complications of allogeneic SCT post-Opdivo therapy were reported. Among 35 patients who received the procedure, 14 had acute graft-versus-host disease (GVHD) of Grade 1, 2 or 4, and 2 of those patients experienced hyperacute GVHD. Chronic GVHD was reported in 2 patients and one patient had hepatic veno-occlusive disease (VOD). Two fatal cases were attributed to the complications of allogeneic SCT with involvement of multiple organs. The causality to Opdivo treatment cannot be either positively established or completely ruled out.

Promising efficacy of Opdivo in treatment of refractory, relapsed cHL patients, who have unmet medical needs, has been demonstrated and the safety profile of Opdivo in the treatment of the cHL patients is similar to that established from the treatment of other solid tumour patients. The results of a proposed Phase III confirmatory trial in cHL patients may further confirm the favourable benefit/risk profile of Opdivo. A Notice of Compliance with Conditions (NOC/c) has been issued.