Phase 3 CheckMate-274 Meets Primary End Points in Urothelial Carcinoma

The pivotal, phase 3 CheckMate-274 trial, evaluating nivolumab (Opdivo) after surgery in patients with high-risk, muscle-invasive urothelial carcinoma, met its primary end points of improving disease-free survival (DFS) versus placebo in both all randomized patients and in patients whose tumor cells express PD-L1 ≥1%, according to Bristol Myers Squibb, the developer of the agent.

Additionally, the safety profile of nivolumab was consistent with previously reported studies in solid tumors.

“With currently available therapies, more than 50% of patients with bladder cancer will experience recurrence after surgery, and each year, the disease takes the lives of nearly 200,000 patients,” Matthew Galsky, MD, professor of medicine, director of Genitourinary Medical Oncology, director of the Novel Therapeutics Unit, and co-director of the Center of Excellence for Bladder Cancer at The Tisch Cancer Institute and the Icahn School of Medicine at Mount Sinai, said in a press release. “Advances like immunotherapy have helped bring hope to patients across a growing number of cancer types, including previously treated advanced urothelial carcinoma.”

“The positive results from CheckMate-274 point to the potential for nivolumab to become a new standard of care in the adjuvant setting, extending disease-free survival for post-surgery patients with muscle-invasive urothelial cancer without the use of chemotherapy,” Galsky added.

The randomized, double-blind, multi-center, phase 3 study is evaluating nivolumab compared to placebo in participants with muscle-invasive urothelial cancer at a high risk of recurrence after radical surgery. Patients enrolled in the study may or may not have received neoadjuvant chemotherapy prior to resection depending on their individual characteristics.

In total, 709 patients were randomized 1:1 to receive either nivolumab or placebo for up to 1 year. The dual primary end points of the trial are DFS in all randomized patients (ie the intention-to-treat population) and in the subset of patients whose tumors express PD-L1 ≥1%. Key secondary end points include overall survival (OS), non-urothelial tract recurrence free survival, and disease-specific survival.

Moving forward, the CheckMate-274 trial will continue as planned to allow for future analyses of secondary endpoints. Importantly, this study is the first and only phase 3 trial in which immunotherapy has reduced the risk of relapse in the adjuvant setting for these patients.

“As we advance the science of immunotherapy, we’re discovering that these treatments may play an important role in earlier stages of cancer, when the immune system is generally more intact and potentially more responsive,” Mark Rutstein, vice president of Opdivo Development at Bristol Myers Squibb, said in the release. “With the positive results from CheckMate-274, [nivolumab] has now demonstrated improved efficacy in the adjuvant treatment of 3 tumor types, including bladder cancer, melanoma, and esophageal/gastroesophageal junction cancer, as part of our broad development program across earlier stages of cancer. We would like to thank the patients and investigators who participated in the trial and contributed to our collective scientific understanding.”

Bristol Myers Squibb indicated it plans to complete a full evaluation of the CheckMate-274 data, work with investigators to present the results at an upcoming medical conference, and submit the data to health authorities.

Reference:

Opdivo (nivolumab) Significantly Improves Disease Free-Survival vs. Placebo as Adjuvant Therapy for Patients with High-Risk, Muscle-Invasive Urothelial Carcinoma in Phase 3 CheckMate -274 Trial [news release]. Princeton, New Jersey. Published September 24, 2020. Accessed September 24, 2020. https://news.bms.com/news/corporate-financial/2020/Opdivo-nivolumab-Significantly-Improves-Disease-Free-Survival-vs.-Placebo-as-Adjuvant-Therapy-for-Patients-with-High-Risk-Muscle-Invasive-Urothelial-Carcinoma-in-Phase-3-CheckMate--274-Trial/default.aspx