On March 20, the U.S. Food and Drug Administration (FDA) approved nivolumab (Opdivo) with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients aged 12 years and older with previously untreated stage III or IV classical Hodgkin lymphoma. The FDA also granted traditional approval to nivolumab for the following indications in adults with relapsed or refractory classical Hodgkin lymphoma:
- After autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin
- After three or more lines of systemic therapy that includes autologous HSCT.
Nivolumab received accelerated approval for these indications in 2016 and 2017, respectively.
CA209-8UT/SWOG 1826
Efficacy of nivolumab in combination with AVD was evaluated in Study CA209-8UT (SWOG 1826; ClinicalTrials.gov identifier NCT03907488), a randomized, open-label, multicenter trial in patients 12 years and older with previously untreated, stage III and IV classical Hodgkin lymphoma. A total of 994 patients were randomly assigned 1:1 to receive either nivolumab plus AVD or brentuximab vedotin plus AVD for six cycles.
The primary efficacy outcome measure was progression-free survival per investigator. The study demonstrated superiority of progression-free survival in the nivolumab plus AVD arm, with a hazard ratio of 0.42 (95% confidence interval = 0.27–0.67, P < .0001). The median progression-free survival was not reached in either arm after a median follow-up of 13.7 months. After a median follow-up of 36.7 months, 1.8% of patients in the nivolumab plus AVD arm had died vs 3.4% in the brentuximab vedotin plus AVD arm.
In the nivolumab plus AVD arm, serious adverse reactions occurred in 39% and immune-mediated adverse reactions occurred in 9% of patients (Grade 3 or 4 in 2.7%).
The recommended dosing of nivolumab is 240 mg (for adults and pediatric patients weighing ≥ 40 kg) or 3 mg/kg (for pediatric patients weighing < 40 kg), administered intravenously in combination with AVD on days 1 and 15 of each 28-day cycle for up to 6 cycles. Primary granulocyte colony–stimulating factor prophylaxis is recommended starting in cycle 1.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence which provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Israeli Ministry of Health, Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The applications may still be under review at the other regulatory agencies.
This review was conducted as a Summary Review and used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted Priority Review and Orphan Drug designation.
