FDA grants BMS a premium Opdivo+Yervoy immunocombination therapy priority review

FDA grants BMS a premium Opdivo+Yervoy immunocombination therapy priority review

June 03, 2015 Source: Bio Valley

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In April of this year, Bristol-Myers Squibb (BMS) announced the top-line data for the first-line treatment of melanoma with the immunological combination therapy Opdivo+Yervoy. The data showed that combination therapy achieved a very high objective response rate (61% vs 11%) and complete response rate (22% vs 0%) compared with Yervoy monotherapy, and the risk of disease progression or death was reduced by 60%. The combination therapy is robust and has never been seen before in the clinical treatment of melanoma. The industry believes that this program will provide an important first-line treatment option for advanced melanoma, once again demonstrating the great potential of different immunotherapy combinations in the clinical treatment of tumors.

Recently, Opdivo+Yervoy's first-line supplemental new drug application (sBLA) for advanced melanoma has also received good news. The FDA has begun reviewing the combination therapy and has granted priority review. This marks the first regulatory milestone for the clinical treatment of tumors with the Optox+Yervoy combination therapy. Not surprisingly, the FDA will approve the Opdivo+Yervoy program on September 30 this year for first-line treatment of advanced melanoma.

Both Opdivo and Yervoy are tumor immunotherapies that use the body's own immune system to fight tumors by targeting specific regulatory elements in the immune system. Opdivo is able to bind to the immune checkpoint receptor PD-L1 expressed on activated T cells, blocking this pathway and allowing the immune system to attack tumors. Yervoy can effectively block the interaction between cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and its ligand CD80/CD86, and enhance the activation and proliferation of T cells.

About the CheckMate-069 study:

The first-line treatment of advanced melanoma sBLA with Opdivo+Yervoy combination therapy is based on data from a Phase II CheckMate-069 study. The study was conducted in patients with newly diagnosed advanced melanoma, including BRAF wild-type and BRAF mutant melanoma, and the combination therapy of PD-1 immunotherapy Opdivo (nivolumab) and Yervoy (ipilimumab) was evaluated relative to Yervoy monotherapy. Efficacy and safety of first-line treatment of unresectable (3-4 stage) melanoma in the late stage of initial treatment. The data showed that the Opdivo+Yervoy regimen achieved a higher objective response rate for BRAF wild-type melanoma (ORR=61%, n=44/72), compared with Yervoy monotherapy (ORR=11%, n=4/37 Compared with statistically significant differences (p < 0.001), the primary endpoint of the study was reached; at the same time, 22% (n = 16) of patients in the Opdivo + Yervoy treatment group achieved complete remission, and the Yervoy monotherapy group was 0%; Progression free survival (PFS) data has not been obtained.

For the BRAF mutant melanoma, the Opdivo+Yervoy protocol also achieved similar results with a median progression-free survival (PFS: 8.5 months vs 2.7 months) and a 60% reduction in the risk of disease progression or death. In addition, the objective response rate (ORR) was independent of the PD-L1 status: ORR was 58% in PD-L1 positive tumors and 55% in PD-L1 negative tumors. In this study, safety was consistent with previous studies evaluating the Opdivo+Yervoy protocol, including 3-4 grade colitis (17%), diarrhea (11%), and alanine aminotransferase elevation (11%).

About melanoma:

Melanoma is a highly malignant tumor with very high recurrence and mortality. Melanoma can be divided into 5 grades (0-4 stage) depending on its in situ characteristics (thickness, ulceration), whether it has spread to lymph nodes, and distant metastasis. Stage 3 melanoma has reached the regional lymph nodes, but has not spread to the distal lymph nodes or other parts of the body (metastasis), requiring surgical removal of the primary tumor and the lymph nodes involved. The risk of recurrence of stage 3 melanoma is high and overall survival has been low; many patients will relapse within 5 years of treatment, with nearly 90% of relapses occurring in people at high recurrence risk. Once the condition recurs, the survival rate will be very low, with historical data ranging from 11% to 20%.

Source: US Food and Drug Administration Accepts Supplemental Biologics License Application for Opdivo Yervoy Regimen in Patients with Previously Untreated Advanced Melanoma

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