CREST: Sasanlimab hits primary end point of EFS for NMIBC

The phase 3 CREST trial (NCT04165317) evaluating sasanlimab, an investigational anti-PD-1 monoclonal antibody, in combination with BCG as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC), has met its primary end point of event-free survival (EFS) by investigator assessment, Pfizer announced in a news release.¹

Treatment with sasanlimab/BCG was associated with clinically meaningful and statistically significant improvement in EFS vs BCG alone.

Neal D. Shore, MD

CREST lead investigator Neal D. Shore, MD, commented on the trial in the news release, saying, “Patients with BCG-naïve high-risk non-muscle invasive bladder cancer have high rates of recurrence and progression. These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naïve, high-risk non-muscle invasive bladder cancer, including patients with carcinoma in-situ (CIS), providing prolonged event-free survival 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.”

Shore is medical director of Carolina Urologic Research Center in Myrtle Beach, South Carolina.

Pfizer reported that the overall safety profile of sasanlimab/BCG “was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab.”

According to the company, sasanlimab is “a humanized immunoglobulin G4 mAb that binds to human programmed death-1 (PD-1) to block its interaction with PD-1 and PD-L1/PD-L2.” Pfizer added that the investigational treatment has demonstrated clinical efficacy in advanced solid tumors and advanced urothelial cancer in early-stage clinical studies.

The CREST trial is a multinational, randomized, open-label, 3 parallel-arm study comparing treatment with sasanlimab in combination with BCG (BCG induction with or without BCG maintenance) vs BCG (induction and maintenance) in patients with BCG-naïve, high-risk NMIBC.

Study participants were randomly assigned to receive sasanlimab 300 mg by subcutaneous injection every 4-week cycle up to cycle 25 in combination with BCG once weekly for 6 consecutive weeks (induction period) followed (arm A) or not followed (arm B) by maintenance with BCG, or BCG induction and maintenance up to cycle 25 (arm C). The primary end point was investigator-assessed EFS between arms A and C. EFS was defined as “the time from randomization to the earliest of recurrence of high-grade disease, progression of disease, persistence of CIS, or death.” Secondary end points included but were not limited to investigator-assessed EFS between arms B and C, overall survival (arm A vs arm C and arm B vs arm C), complete response rate in participants with CIS at randomization, disease-specific survival, and health-related quality of life as measured by European Organization for Treatment of Cancer Quality of Life Questionnaire for cancer patients.²

“The initial therapy of high-risk, non-muscle invasive bladder cancer 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-naïve, high-risk, non-muscle invasive cancer in over 30 years,” said Roger Dansey, MD, chief oncology officer for Pfizer, in the news release. “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.”¹

Results from CREST will be presented at an upcoming medical conference.

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