FDA Approves BMS’ Opdivo (Nivolumab) for Adjuvant Treatment of Eligible Patients with Completely Resected Stage IIB or IIC Melanoma

Opdivo is the only PD-1 inhibitor that is indicated as an adjuvant treatment for eligible patients with stages IIB, IIC, III, as well as stage IV completely resected melanoma.

The U.S. Food and Drug Administration (FDA) has given its nod to Opdivo (nivolumab) for the adjuvant treatment of eligible adult and pediatric patients 12 years and older with completely resected stage IIB or IIC melanoma. 

This approval was based on the Phase 3 CheckMate -76K trial, which compared Opdivo to placebo and follows the recent European Commission approval of Opdivo in the same setting.  

This marks the fifth Opdivo-based indication in earlier stages of cancer and expands upon the existing indication of this treatment option in the adjuvant melanoma setting, speaking to the value of Opdivo.   

In the trial, Opdivo reduced the risk of recurrence, new primary melanoma, or death in patients with completely resected stage IIB or IIC melanoma by 58% compared to placebo. At one year, the recurrence-free survival (RFS) rate was 89% for Opdivo versus 79% for placebo. Additionally, in a pre-specified, exploratory subgroup analysis, the RFS unstratified HR was 0.34 in patients with stage IIB melanoma, and 0.51 in stage IIC melanoma patients. One-year RFS rates by stage for patients who received Opdivo were 93% in stage IIB versus 84% with placebo, and 84% in stage IIC versus 72% with placebo. 

“Following surgical removal of melanoma, patients may believe they are free of disease,” says John M. Kirkwood, M.D., Distinguished Professor of Medicine at the University of Pittsburgh School of Medicine and Co-Director of the Melanoma Center at UPMC Hillman Cancer Center. “However, within five years of diagnosis, one-third of patients with surgically resected stage IIB and nearly one-half of patients with surgically resected IIC melanoma see their cancer return, underscoring the need for additional treatment options that may help reduce the risk of cancer coming back. The significant recurrence-free survival improvement observed with nivolumab in CheckMate -76K is an important step forward for these patients.”

“Stage IIB and IIC melanoma patients may still face the threat of disease recurrence, despite the benefit of surgery, which can impact outcomes,” adds Catherine Owen, senior vice president and general manager, U.S. Cardiovascular, Immunology and Oncology at Bristol Myers Squibb. “This approval builds on our existing adjuvant indication in completely resected stage III or IV disease and now provides eligible patients with completely resected stage IIB or IIC melanoma an additional treatment option which may help prevent recurrence. BMS remains committed to its goal of helping improve patient outcomes in melanoma and bringing immunotherapy to more patients, including in the earlier stages of disease.”

The FDA previously approved Opdivo for the adjuvant treatment of adult and pediatric patients 12 years and older with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection, based upon data from the CheckMate -238 trial.

Additional CheckMate -76K follow-up data will be presented at the Society for Melanoma Research Annual Meeting in November.  

"Checkpoint inhibitor immunotherapies have transformed what it means to be diagnosed with and treated for advanced melanoma," says Melanoma Research Alliance (MRA) Chief Science Officer Joan Levy, PhD. "We are pleased to see these same transformational medicines are now becoming available to patients with Stage II melanoma who are at risk for recurrence."

"The expanded approval of nivolumab gives patients with high risk melanoma a new option to prevent recurrence following surgery," says MRA Chief Executive Officer Marc Hurlbert, PhD. "This is an important milestone in MRA's mission of ending suffering and death due to melanoma."

 About CheckMate -76K 

CheckMate -76K is a Phase 3, randomized, double-blind study evaluating adjuvant Opdivo (nivolumab) 480 mg IV Q4W (n=526) versus placebo IV Q4W (n=264) in patients with completely resected stage IIB or IIC melanoma.

The primary endpoint of the trial is recurrence-free survival (RFS) as assessed by the investigator. Secondary endpoints of the trial include overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival through next-line therapy (PFS2), and safety.  Patients were treated for up to 1 year, or until disease recurrence or unacceptable toxicity. The trial excluded patients with ocular/uveal or mucosal melanoma, autoimmune disease, any condition requiring systemic treatment with either corticosteroids (≥10 mg daily prednisone or equivalent) or other immunosuppressive medications, as well as patients with prior therapy for melanoma except surgery.

The FDA-approved dosing for Opdivo for adjuvant treatment of adult and pediatric patients 12 years and older with completely resected stage IIB/C melanoma and weighing ≥40kg is Opdivo 240 mg every 2 weeks or 480 mg every 4 weeks administered as an IV infusion over 30 minutes until disease recurrence or unacceptable toxicity for up to 1 year. The FDA-approved dosing for Opdivo in pediatric patients age 12 years and older and weighing <40kg is Opdivo 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks administered as an IV infusion over 30 minutes until disease recurrence or unacceptable toxicity for up to 1 year.