BMS's Opdivo-Yervoy Combo Fails to Outperform Opdivo Monotherapy in Adjuvant Melanoma Setting

Compiled by Keke

Although Bristol-Myers Squibb’s (BMS) anticancer combination of Opdivo and Yervoy (referred to as the OY combination) has achieved success in lung cancer and other indications, it is not effective for every type of cancer.

On November 20, Bristol-Myers Squibb (BMS) announced partial primary endpoint data from the Phase III CheckMate-915 clinical trial. The study compared the OY combination versus Opdivo monotherapy as adjuvant therapy in patients with completely resected Stage IIIb/c/d or IV melanoma. The results showed that,In patients with tumor PD-L1 expression <1%, the OY combination did not meet the primary endpoint of recurrence-free survival. Following the release of the results, BMS shares fell 1.03% in pre-market trading.

This was a randomized, placebo-controlled, double-blind study that enrolled 1,943 patients with melanoma. Except for those who underwent neurosurgical resection of central nervous system lesions followed by surgery for melanoma lesions and/or adjuvant radiotherapy, patients had not previously received anticancer therapy for melanoma. Patients were randomized to receive either Opdivo 240 mg intravenously every two weeks in combination with Yervoy 1 mg/kg every six weeks, or Opdivo 480 mg intravenously every four weeks for one year.

Melanoma is a type of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) in the skin. Metastatic melanoma is the most lethal form of the disease, occurring when the cancer spreads to organs beyond the skin surface. Over the past 30 years, the incidence of melanoma has been steadily increasing. According to data from the World Health Organization, there will be 424,100 melanoma cases worldwide by 2035, with 94,300 associated deaths. Melanoma is curable at an early stage; however, if local lymph nodes are involved, the survival rate is approximately halved. Patients diagnosed with advanced melanoma are classified as Stage IV, with a five-year survival rate typically ranging from only 15% to 20%, and a ten-year survival rate of 10% to 15%.

However, the Data Monitoring Committee recommended that Bristol-Myers Squibb (BMS) continue the study without making any changes. The study will remain double-blind and will proceed to investigate whether the OY combination is superior to Opdivo in preventing patient recurrence within the full intent-to-treat population (i.e., patients with any level of PD-L1 expression).

Analysts suggest that Bristol-Myers Squibb (BMS) has reason to believe that subsequent trials may succeed, as previous studies of Opdivo and other PD-1/L1 inhibitors have demonstrated superior efficacy in patients with higher levels of these proteins. Currently, however, the results are unfavorable to BMS’s potential plans to expand the therapeutic scope of combination therapy for melanoma and to increase revenue in the adjuvant setting.

In the immuno-oncology market, melanoma has long been the cornerstone of Opdivo’s sales. The drug was first approved by the U.S. FDA in 2014 for the adjuvant treatment of unresectable or metastatic melanoma that no longer responds to other therapies, and its indications have since expanded to include lung cancer and renal cell carcinoma. The product, both as monotherapy and in combination regimens, continues to pursue additional new indications.

Previously, the OY combination had already been approved for the treatment of patients with unresectable or metastatic melanoma. In September this year, Bristol-Myers Squibb (BMS) added further evidence to support the use of this combination in advanced melanoma. Data from the CheckMate-067 study, presented at the European Society for Medical Oncology (ESMO) Annual Meeting, showed that the OY combination enabled more than half of previously untreated patients with unresectable Stage III or Stage IV melanoma to survive for five years. Therefore, the final results of the CheckMate-915 study are also highly anticipated.

Despite the temporary setback in its immunotherapy combination regimen, Bristol-Myers Squibb (BMS) has recently received positive news. The U.S. Federal Trade Commission (FTC) finally approved its massive acquisition of Celgene last Friday. Announced on January 3, 2019, the deal had been pending due to divergent shareholder opinions and overlaps in the two companies’ product portfolios and distribution channels. Earlier this year, BMS divested Celgene’s blockbuster psoriasis and psoriatic arthritis drug, Otezla (which generated $1.6 billion in sales in 2018), because BMS had a competing candidate, BMS-986165, in Phase III clinical trials. Although BMS’s product was still in the clinical stage, the FTC insisted on the divestiture. Now that BMS has met all regulatory requirements set by the FTC, it expects to close the transaction immediately.

References:

[1] Bristol's Opdivo-Yervoy combo fails to top Opdivo in adjuvant melanoma

[2] Bristol-Myers Squibb’s Opdivo-Yervoy Combo Misses the Mark in Melanoma Study