FDA Grants Accelerated Approval to Nivolumab and Ipilimumab Combination For Hepatocellular Carcinoma (HCC)

March 11, 2020

From the American Society of Clinical Oncology in cooperation with the Food and Drug Administration (FDA) and as a service to our members, ASCO will periodically distribute information about newly approved therapies for cancer patients. This helps FDA inform oncologists and professionals in oncology-related fields about recent approvals in a timely manner. Included in the email from the FDA will be a link to the product label, which will provide the relevant clinical information on the indication, contraindications, dosing, and safety. In sending this information, ASCO does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described. The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On March 10, 2020, the Food and Drug Administration granted accelerated approval to the combination of nivolumab and ipilimumab (OPDIVO® and YERVOY®, Bristol-Myers Squibb Co.) for patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

Efficacy of the combination was investigated in Cohort 4 of CHECKMATE-040,  (NCT01658878) a multicenter, multiple cohort, open-label trial conducted in patients with HCC who progressed on or were intolerant to sorafenib. A total of 49 patients  received nivolumab 1 mg/kg in combination with ipilimumab 3 mg/kg every 3 weeks for four doses, followed by single-agent nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate  and duration of response as determined by blinded independent central review (BICR) using RECIST v1.1. ORR was 33% (n=16; 95% CI: 20, 48), with 4 complete responses and 12 partial responses. Response duration ranged from 4.6 to 30.5+ months, with 31% of responses lasting at least 24 months.

The most common adverse reactions (³20%) with nivolumab in combination with ipilimumab are: fatigue, diarrhea, rash, pruritus, nausea, musculoskeletal pain, pyrexia, cough, decreased appetite, vomiting, abdominal pain, dyspnea, upper respiratory tract infection, arthralgia, headache, hypothyroidism, decreased weight, and dizziness.

For HCC, the recommended doses are nivolumab 1 mg/kg followed by ipilimumab 3 mg/kg on the same day every 3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks or 480 mg every 4 weeks.

View full prescribing information:

OPDIVO

YERVOY

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

FDA had previously granted Breakthrough Therapy Designation for this indication and the application received priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Follow the Oncology Center of Excellence on Twitter @FDAOncology.