Sasanlimab Plus BCG Meets EFS End Point in BCG-Naive, High-Risk NMIBC

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The addition of the anti–PD-1 monoclonal antibody sasanlimab (PF-06801591) to Bacillus Calmette-Guérin (BCG) as induction therapy with or without maintenance led to a clinically meaningful and statistically significant improvement in event-free survival (EFS) compared with BCG induction and maintenance alone in patients with BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC), meeting the primary end point of the phase 3 CREST trial (NCT04165317).¹

Regarding safety, the toxicity profile of sasanlimab plus BCG was consistent with the known safety data for BCG and previously reported clinical trial findings for sasanlimab.

Full results from CREST will be submitted for presentation at an upcoming medical conference. Pfizer, the developer of sasanlimab, intends to share the data with global health authorities.

“Patients with BCG-naive, high-risk NMIBC have high rates of recurrence and progression,” Neal Shore, MD, FACS, medical director for the Carolina Urologic Research Center in Myrtle Beach and lead investigator for the CREST trial, stated in a news release. “These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naive, high-risk NMIBC, including patients with carcinoma in situ [CIS], providing prolonged EFS, which may delay or reduce the need for more aggressive treatment options. Administered subcutaneously every 4 weeks, sasanlimab, if approved, could also help lower the treatment burden on both patients and health care systems.”

The multinational, randomized, open-label, 3 parallel-arm CREST trial enrolled patients at least 18 years of age with histologically confirmed high-risk non–muscle-invasive transitional cell carcinoma (TCC) of the urothelium of the urinary bladder.² Patients with tumors of mixed transitional or nontransitional cell histology were permitted to enroll; however, TCC needed to be the predominant histology.

Patients needed to be ineligible for or refuse radical cystectomy. They also were required to undergo complete resection of all Ta/T1 papillary disease, including patients with concurrent CIS. The most recent positive transurethral resection of bladder tumor (TURBT) needed to occur within 12 weeks before randomization or study intervention, and a second TURBT must have been performed if indicated.

Investigators excluded patients with evidence of muscle-invasive, locally advanced or metastatic urothelial cancer or concurrent extravesical, non–muscle-invasive TCC of the urothelium.

Patients were randomly assigned to 1 of 3 treatment arms to receive subcutaneous sasanlimab at 300 mg once every 4 weeks for up to 25 cycles in combination with BCG once per week for 6 consecutive weeks, followed by maintenance with BCG (arm A); the same regimen of sasanlimab plus BCG as induction only (arm B); or BCG induction and maintenance alone up to cycle 25 (arm C).¹

Investigator-assessed EFS between arms A and C served as the trial’s primary end point. EFS between arms B and C was a key secondary end point. Other secondary end points included overall survival, complete response rate in patients with CIS at randomization, disease-specific survival, time to recurrence of low-grade disease, and quality of life.²

“The initial therapy [for] high-risk NMIBC with BCG has not advanced in decades. Today’s pivotal phase 3 CREST results are potentially practice changing, representing the first advance in therapy for BCG-naive, high-risk NMIBC in over 30 years,” Roger Dansey, MD, chief oncology officer at Pfizer, added in the news release.¹ “These results reinforce Pfizer’s leadership in genitourinary cancer research and development, demonstrating our ongoing commitment to deliver new treatment options for patients with bladder cancer.”

CREST previously included another part where sasanlimab was being evaluated in patients with NMIBC who had previously received BCG; however, enrollment in this portion of the trial was discontinued in August 2022.² Safety was not a reason for the discontinuation of this portion of the trial.

References

1. Pfizer’s sasanlimab in combination with BCG improves event-free survival in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer. News release. Pfizer. January 10, 2025. Accessed January 10, 2025. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-sasanlimab-combination-bcg-improves-event-free
2. A study of sasanlimab in people with non-muscle invasive bladder cancer (CREST). ClinicalTrials.gov. Updated November 25, 2024. Accessed January 10, 2025. https://clinicaltrials.gov/study/NCT04165317