BMS a Pioneer in Muscle-Invasive Bladder Cancer with Interim Phase III Opdivo Results

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Bristol Myers Squibb’s adjuvant immunotherapy Opdivo (nivolumab) is taking a chink from the armor of muscle-invasive urothelial carcinoma (MIUC), a particularly impervious bladder cancer, with Phase III results showing significant improvement in disease-free survival rates.

Urothelial carcinoma is the tenth most common cancer worldwide and steals the lives of close to 200,000 patients each year. While relatively treatable in the early stages, it is persistent, with a more than 50% relapse rate.

Immune checkpoint inhibitors like Opdivo block “checkpoint” proteins from binding with their partner proteins. This prevents communication of the “off” signal, thereby allowing the T cells to kill cancer cells.

BMS’s ongoing Phase III randomized, double-blind, multi-center study – named CheckMate-274 – compares Opdivo against a placebo in 709 participants deemed to be at a high risk of recurrence after radical surgery.  At a 1:1 ratio, the patients were given either Opdivo or the placebo for up to a year.

The primary endpoints BMS was looking to attain were disease-free-survival (DFS) in all randomized patients, as well as in a specific subset whose tumors express PD-L1 ≥1%. On Thursday, the company announced in an interim analysis that these endpoints had been met. 

With the results, BMS becomes a pioneer in the adjuvant treatment of bladder cancer. 

“No immunotherapies have been approved in this setting. CheckMate -274 is the first and only Phase III trial in which an immunotherapy has reduced the risk of relapse in the adjuvant setting for patients with high-risk MIUC,” said Mark Rutstein, Vice President of Opdivo Development at BMS.  “Currently, there is a lack of effective treatment options to address the high risk of recurrence after surgery. We believe that, if approved, Opdivo has the potential to become a new standard of care in this setting.”

 Importantly, Opdivo’s safety profile was on par with previously reported studies in solid tumors.

The standard front-line treatment for muscle-invasive urothelial carcinoma is a radical cystectomy, where the entire bladder is removed, often along with nearby lymph nodes. In some cases, the more aggressive decision is made to begin systemic chemotherapy before surgery. 

The Opdivo PD-1 checkpoint inhibitor is a top-seller for BMS, which became an even more dominant player in the oncology market after its 2019 acquisition of Celgene. Opdivo itself has been a BMS staple since 2014 for multiple indications, including advanced non-small cell lung cancer, and advanced melanoma.

Rutstein told BioSpace that in addition to CheckMate-274, BMS has several ongoing trials in urothelial cancer exploring the use of Opdivo and Opdivo-based combinations in cancers such as advanced or metastatic urothelial carcinoma.

So, what’s next for the Opdivo Development team?  Rutstein stated, “Looking ahead, we’re anticipating results from ongoing trials in the adjuvant, neo-adjuvant and peri-adjuvant settings of lung cancer, as well as in adjuvant melanoma and renal cell carcinoma.”   

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