On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported the first presentation of results from the Phase 3 CheckMate -901 trial, in which Opdivo (nivolumab) in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy demonstrated statistically significant and clinically meaningful improvements in the primary efficacy endpoints of overall survival (OS) and progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) compared to standard-of-care cisplatin-based chemotherapy as a first-line treatment for patients with unresectable or metastatic urothelial carcinoma who are cisplatin-eligible (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;901-Trial/default.aspx [SID1234636058]).
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With a median follow-up of approximately 33 months, treatment with Opdivo in combination with cisplatin-based chemotherapy reduced the risk of death by 22%, demonstrating a median OS of 21.7 months vs. 18.9 months with chemotherapy alone (Hazard Ratio [HR] 0.78; 95% Confidence Interval [CI]: 0.63 to 0.96; p=0.0171). At the 12- and 24-month landmark analyses, patients treated with upfront Opdivo plus chemotherapy experienced OS rates of 70.2% and 46.9%, respectively, compared to 62.7% and 40.7% with chemotherapy. In patients receiving the Opdivo-based combination, the risk of death or disease progression was reduced by 28%, with median PFS at 7.9 months compared to 7.6 months with chemotherapy (HR 0.72; 95% CI: 0.59 to 0.88; p=0.0012). The landmark 12- and 24-month PFS rates were 34.2% and 23.5%, compared to 21.8% and 9.6% with chemotherapy. The combination of Opdivo with cisplatin-based chemotherapy had a tolerable safety profile consistent with the known safety profiles of the individual components of the regimen. No new safety concerns have been identified.
Additionally, in exploratory analyses, Opdivo with cisplatin-based chemotherapy resulted in an approximately 15% higher objective response rate (ORR) compared to chemotherapy alone (57.6% vs. 43.1%), and nearly doubled the number of patients who achieved a complete response (CR; 21.7% vs. 11.8%). Opdivo in combination with cisplatin-based chemotherapy was associated with longer duration of response than chemotherapy, and median duration of complete response was nearly tripled (37.1 months vs. 13.2 months).
The first disclosure of these data will be featured in a Presidential Symposium during the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 22, 2023, from 10:30 a.m. to 12:15 p.m. EDT / 16:30 to 18:15 CEST (Abstract #LBA7).
"In patients with metastatic urothelial carcinoma, we often see poor durability of responses with chemotherapy alone in the first-line treatment setting. This has long been a major challenge in the treatment of patients with this hard-to-treat disease," said Michiel S. van der Hejiden, M.D., Ph.D., Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands. "This survival benefit seen with nivolumab in combination with cisplatin-based chemotherapy represents a momentous accomplishment that may provide hope for urothelial cancer patients as the first concurrent chemo-immunotherapy combination to demonstrate such an improvement compared to standard-of-care cisplatin-based combinations. The implications of these data have the potential to be practice-changing and transform the way cisplatin-eligible patients are treated."
"Historically, there have been no effective immunotherapy-based options available in the front-line setting for patients with unresectable or metastatic urothelial carcinoma who are cisplatin-eligible. We are proud to see these results demonstrating that Opdivo with cisplatin-based chemotherapy may provide patients hope and offer survival benefits with this immunotherapy approach," said Dana Walker, M.D., M.S.C.E., vice president, global program lead, genitourinary cancers, Bristol Myers Squibb. "The CheckMate -901 results bolster our existing body of research, which has shown overall survival improvements with Opdivo-based treatments across multiple tumor types, including in genitourinary cancers. We look forward to discussing these data with global health authorities in the coming months and have great hope that we may potentially provide these patients with a new and much needed treatment regimen."
Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -901 clinical trial.
Opdivo and Opdivo-based combinations have shown significant improvements in OS in Phase 3 clinical trials across several tumors, including metastatic urothelial carcinoma, advanced renal cell carcinoma, non-small cell lung cancer, malignant pleural mesothelioma, metastatic melanoma and esophageal squamous cell carcinoma.
About CheckMate -901
CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy or Opdivo in combination with cisplatin-based chemotherapy followed by Opdivo monotherapy compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.
In the CheckMate -901 study, evaluating Opdivo with cisplatin-based chemotherapy vs. standard-of-care chemotherapy, a total of 608 patients eligible for cisplatin-based chemotherapy were randomized to receive either Opdivo 360 mg in combination with cisplatin-based chemotherapy every 3 weeks or chemotherapy alone followed by 480mg/Q4 Opdivo monotherapy until disease progression or death up to a maximum of two years. The primary endpoints of this study are overall survival (OS) and progression-free survival (PFS). The study is ongoing to assess Opdivo plus Yervoy vs. standard-of-care chemotherapy.
The OS and PFS outcomes for patients who are eligible for cisplatin-based chemotherapy are based on the final efficacy analyses of these endpoints.
About Urothelial Carcinoma
Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases. In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis. The majority of urothelial carcinomas are diagnosed at an early stage, but approximately 50% of patients who undergo surgery will experience disease progression and recurrence within two-to-three years post-surgery. Approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease. The poor durability of responses seen with chemotherapy alone in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.