Opdivo Approved for Advanced Melanoma

The PD-1 inhibitor Opdivo (nivolumab) was granted accelerated approval for patients with unresectable or metastatic melanoma following treatment with Yervoy (ipilimumab) or a BRAF inhibitor, such as Zelboraf (vemurafenib).

The approval by the Food and Drug Administration (FDA) was based on data from the phase 3 CheckMate-037 trial. In the study, Opdivo demonstrated an overall response rate (ORR) of 32 percent compared with 11 percent in patients treated with chemotherapy. At the six-month analysis, 95 percent of responses were ongoing. Fewer serious adverse events were reported with Opdivo compared with chemotherapy.

The FDA's decision on Opdivo was expected before April 1, 2015. The accelerated approval was given under the FDA's breakthrough therapy and priority review designations. Opdivo is the second PD-1 inhibitor to gain approval in 2014; the first was Keytruda (pembrolizumab), which was approved in September for melanoma.

Debra Black, co-founder of the Melanoma Research Alliance, applauded this latest approval for advanced melanoma. “When we started MRA seven years ago, there was little hope for patients with advanced melanoma,” Black said in a statement. “Now we are in an amazing time of discovery and progress with new treatments that can save lives, not only for people with melanoma but also those with other diseases. Melanoma is really leading the way.”

The open-label CheckMate-037 trial randomized 405 patients with advanced melanoma to Opdivo or chemotherapy, including dacarbazine or intravenous carboplatin plus paclitaxel.

Patients in the trial were pretreated with Yervoy or a BRAF inhibitor, if the patient had a BRAF-mutation positive cancer. The primary endpoints were ORR and overall survival. Results were stratified by PD-L1 expression, BRAF status and best overall response to anti-CTLA-4 therapy.

Early findings for ORR were presented at a European oncology meeting earlier this year, which analyzed 120 patients treated with Opdivo and 47 treated with chemotherapy. The complete response rate with Opdivo was 3 percent, partial response rate was 28 percent and 23 percent of patients had stable disease. Of the 38 patients who responded to Opdivo, 82 percent experienced a greater than 50 percent reduction in target lesion burden compared with 60 percent in the five patients who responded to chemotherapy.

The median time to response in Opdivo treated patients was 2.1 versus 3.5 months with chemotherapy. The median duration of response has not yet been reached with Opdivo versus 3.6 months with chemotherapy.

In patients with BRAF-mutated melanoma, the ORR was 23 percent with Opdivo compared with 9 percent for chemotherapy. In BRAF wild-type patients, the ORR was 34 percet with Opdivo versus 11 percent with chemotherapy. Patients with PD-L1 positive tumors experienced an ORR of 44 percent versus 20 percent for PD-L1-negative.

Serious adverse events occurred in 9 percent of patients treated with Opdivo compared with 31 percent in the chemotherapy arm. Fewer patients discontinued treatment with Opdivo as a result of adverse events compared with chemotherapy. There were also fewer serious drug-related adverse events of any grade in Opdivo-treated patients compared with 10 percent with chemotherapy.

The average wholesale price of the drug will be approximately $12,500 a month, but the drug is expected to be covered by insurance and Medicare. The company developing the drug, Bristol-Myers Squibb, also has announced that several patient assistance programs are in place to help patients pay for the treatment, including BMS Access Support. Information on the programs can be found by calling 800-861-0048 or visiting BMSAccessSupport.com.

Opdivo continues to be explored across a variety of cancers, including non-small cell lung cancer (NSCLC) and renal cell carcinoma. Earlier this year, Bristol-Myers Squibb announced it planned to initiate a rolling submission for Opdivo as a third-line treatment for patients with squamous cell NSCLC.

Opdivo has been explored across a variety of settings for patients with advanced melanoma. In the phase 3 CheckMate-066 trial, treatment with Opdivo improved OS and progression-free survival compared with dacarbazine. Following the demonstration of an improvement in survival at the interim analysis, the study was unblinded and patients being treated with chemotherapy were allowed to receive Opdivo. In PD-L1-positive patients, OS was improved by 70 percent and ORR was 52.7 percent versus 10.8 percent, for Opdivo and dacarbazine, respectively. Moreover, serious side effects were less common in the Opdivo arm.

Additional reporting by Elizabeth Whittington.