BMS Announces Phase 3 CheckMate-498 Trial Failure of Opdivo in First-Line Glioblastoma, Casting Doubt on Sales Outlook Against Keytruda
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
Giant in Tumor ImmunotherapyBristol-Myers Squibb (BMS)Recently announced the evaluation of its PD-1 tumor immunotherapyOpdivo(Opdivo, generic name: nivolumab) treatmentGlioblastoma Multiforme (GBM)Phase III Clinical StudyCheckMate-498（NCT02617589）Failed to meet the primary endpoint of prolonging overall survival (OS)。
This study is a randomized, multicenter trial conducted in adult patients with newly diagnosed glioblastoma (GBM) featuring an unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter, evaluatingOpdivo Combined with RadiotherapyRelative toChemotherapy (temozolomide, Temozolomide)Combined Radiotherapyefficacy and safety. In the study, patients were randomly assigned to either the experimental group or the active control group after surgery: patients in the experimental group received intravenous infusions of Opdivo every 2 weeks concurrently with radiotherapy, followed by Opdivo maintenance therapy every 4 weeks until disease progression or unacceptable toxicity; patients in the active control group received temozolomide chemotherapy and radiotherapy. The primary endpoint of the study was overall survival (OS), and secondary endpoints included progression-free survival (PFS) and the two-year overall survival rate.
The results showed that, at the final analysis, the experimental group did not demonstrate a significant improvement in OS compared to the positive control group. The safety profile of Opdivo in this study was consistent with that observed in previous clinical studies in solid tumors. Bristol-Myers Squibb will conduct a comprehensive evaluation of the data from this study, and relevant data will be presented at future medical conferences.
Dr. Fouad Namouni, Head of BMS Development, stated, “Although we are disappointed that the CheckMate-498 study did not meet its primary endpoint, GBM is a well-known aggressive cancer. We thank all individuals who participated in this study and remain committed to exploring the potential of immunotherapy to address the significant unmet medical needs in the patient population suffering from this devastating disease.”
Currently, BMS is conducting another Phase III clinical study.CheckMate-548(NCT02667587), evaluationOpdivo in Combination with Current Standard of Care(Radiotherapy + Temozolomide)TreatmentNewly Diagnosed MGMT-Methylated GBM in AdultsEfficacy and Safety in Patients.MGMT Methylation StatusIt is the most commonly used biomarker in GBM. Studies have shown that this biomarker can predict the likelihood of response to alkylating chemotherapy (such as temozolomide) in GBM patients. Compared with GBM patients with MGMT methylation, those with non-methylated MGMT have a poorer prognosis.
OpdivoIt is a PD-1 immune checkpoint inhibitor designed to help restore anti-tumor immune responses by blocking the interaction between PD-1 and its ligands, leveraging the body’s own immune system, and has become an important treatment option for various types of cancer. Currently, BMS is conducting extensive clinical trials to evaluate the potential of Opdivo in treating different types of tumors. To date, the Opdivo clinical development program has enrolled more than 25,000 patients.
GBMIt is the most common and aggressive primary malignant tumor of the central nervous system, with a 5-year survival rate of less than 5%.Globally, approximately 300,000 people are diagnosed with brain cancer or central nervous system (CNS) cancer each year, and 241,000 die from these diseases. The standard of care for newly diagnosed glioblastoma multiforme (GBM) patients includes surgery, radiation therapy, and chemotherapy, but treatment options remain limited. In 2005, the U.S. FDA approvedThe last oneTemodar (Temozolomide), a drug that improves survival in patients with newly diagnosed GBM.
Current Status of Cancer Immunotherapy: 9 Drugs Approved GloballyPD-(L)1 monoclonal antibodyApproved
Sales Forecast for Overseas Marketed PD-(L)1 Inhibitors (Image Source: EvaluatePharma)
To date, eight PD-1/PD-L1 cancer immunotherapies have been approved for marketing worldwide: Bristol-Myers Squibb’s Opdivo (targeting PD-1), Merck & Co.’s Keytruda (pembrolizumab, targeting PD-1), Roche’s Tecentriq (atezolizumab, targeting PD-L1), AstraZeneca’s Imfinzi (durvalumab, targeting PD-L1), Pfizer/Merck KGaA’s Bavencio (avelumab, targeting PD-L1), Sanofi/Regeneron’s Libtayo (cemiplimab), Junshi Biosciences’ Tuoyi (JS001, toripalimab, targeting PD-1), and Innovent Biologics’ sintilimab (targeting PD-1). Additionally, there is one new entrant.Hengrui MedicineCamrelizumab (a PD-1 inhibitor) has recently had its approval status updated by the Center for Drug Evaluation in China to “approved for marketing,” for third-line treatment of relapsed/refractory Hodgkin lymphoma, although no official announcement has yet been released.. (See details:Breaking: Hengrui’s PD-1 Monoclonal Antibody Approved for Market Launch）
Last month, the international biotechnology website GEN published"Top 10 Best-Selling Anti-Cancer Drugs in 2018" List, Opdivo is the second best-selling anticancer drug globally, with sales reaching $7.57 billion in 2018; Keytruda ranked third on the list, with sales of $7.171 billion.
However, thanks to its unprecedented success in the field of lung cancer, Keytruda’s sales have surpassed those of Opdivo since 2019, making it the best-selling PD-1 cancer immunotherapy. According to the Q1 2019 performance reports released by Bristol-Myers Squibb and Merck & Co., Opdivo’s sales in the first quarter of this year amounted to$1.8 billion, a 19% increase from the same period last year, while Keytruda’s first-quarter sales reached$2.3 billion, representing a year-on-year increase of as much as 55%. The temporary setback in GBM treatment has further clouded its performance outlook.(Compiled by Sina Medicine/newborn, Edited by Kerr)
Article Reference Sources:
*Disclaimer: This article was written by an author contributing to Sina Medical News. The views expressed are solely those of the author and do not represent the position of Sina Medical News.