Opdivo might be the first PD-1 inhibitor approved for a hematologic malignancy after FDA review and approval.
Opdivo (nivolumab) can potentially become the first PD-1 inhibitor approved for a hematologic malignancy, as the FDA granted it a priority review for use of previously-treated patients with classical Hodgkin lymphoma (cHL).
The supplemental biologics license application (sBLA) was submitted by Bristol-Myers Squibb (BMS) under a 2014 breakthrough therapy designation that Opdivo received for the treatment of patients with Hodgkin lymphoma following autologous stem cell transplant and Adcetris (brentuximab vedotin). Under the expedited priority review, the sBLA will be reviewed by the FDA within six months, compared with the standard 10-month review.
The sBLA was primarily based on data from the CheckMate-205 trial, which is evaluating Opdivo 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, 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 multi-cohort, open-label phase 2 CheckMate-205 study has an estimated enrollment of nearly 300 patients with an ECOG performance status of zero or one. 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 Adcetris treatment is allowed, but not required.
Individuals enrolled in one of the study’s three pretreated patient cohorts will receive three mg/kg of Opdivo as an IV injection every two weeks. The treatment-naïve patient cohort will receive 240 mg of Opdivo as an IV injection every two weeks plus 25 mg/m2 of Doxil (doxorubicin), six mg/m2 of vinblastine, and 375 mg/m2 of dacarbazine. The primary outcome measures are overall response rate (ORR) and safety.
Phase 1 data for single-agent Opdivo in cHL were previously reported at the 2015 ASH Annual Meeting. In one study (CA209-039), 23 patients with relapsed/refractory cHL received Opdivo at weeks one and four, and then every two weeks for up to two years or until disease disease progression or unacceptable toxicity.1
At a median follow-up of 86 weeks the ORR was 87 percent for 20 patients, including six 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 three to 88 weeks following initiation of Opdivo therapy, including two patients whose PRs converted to a CR. Of the 20 responses, 15, 75 percent occurred within 16 weeks of starting treatment, including five patients who proceeded to stem cell transplant (one CR, four PR). Three patients had a best overall response of stable disease.
Three patients discontinued Opdivo 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 two 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 Meeting2 retrospectively evaluated single-agent Opdivo in 12 patients with Hodgkin lymphoma who relapsed following allogeneic stem cell transplantation (allo-SCT). Patients had received a median of nine prior systemic therapies, including allo-SCT. Opdivo was dosed at three mg/kg every two weeks.
At a median follow-up of 60 days, nine patients remained on treatment, one patient discontinued therapy due to progressive disease, and two patients stopped treatment due to GVHD. Among eight evaluable patients, the ORR was 87.5 percent, including three CRs and five PRs.
In March 2016, the European Medicines Agency validated an application for use of Opdivo 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.
Opdivo 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.
References1. 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):397