Among patients with Bacillus Calmette-Guérin (BCG)-naïve, high-risk non-muscle invasive bladder cancer (NMIBC), treatment with the investigational anti-PD-1 monoclonal antibody sasanlimab, in combination with BCG, was reportedly found to result in positive outcomes.
The phase 3 CREST trial has shown a clinically meaningful and statistically significant improvement in event-free survival associated with induction and maintenance treatment with the combination versus induction and maintenance treatment with BCG alone, according to a news release from sasanlimab manufacturer Pfizer, Inc. announcing topline results from the trial.
“Patients with BCG-naïve high-risk non-muscle invasive bladder cancer have high rates of recurrence and progression,” said Dr. Neal Shore, Medical Director for the Carolina Urologic Research Center, and lead investigator for the CREST trial, in the news release. “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 four weeks, sasanlimab, if approved, could also help lower the treatment burden on both patients and healthcare systems.”
Sasanlimab, according to the National Cancer Institute, binds to the PD-1 protein and blocks its interaction with PD-L1 and PD-L2, which may restore immune function by activating natural killer cells and cytotoxic T lymphocytes against tumor cells.
Glossary:
Bacillus Calmette-Guérin (BCG): a weakened bacteria that, according to the National Cancer Institute, is used in a solution to stimulate the immune system in the treatment of bladder cancer.
Carcinoma in-situ: when, according to the National Cancer Institute, abnormal cells that look like cancer cells under a microscope are found only in the place where they first formed and haven’t spread to nearby tissue.
Subcutaneous: under the skin.
Primary endpoint: the main information researchers are trying to learn in a clinical trial.
Pfizer stated that in early-stage clinical studies 300 milligrams of subcutaneous sasanlimab administered every four weeks was shown to have clinical efficacy in advanced solid tumors and advanced urothelial cancer.
The CREST trial, with an enrollment of 1,070 patients, is estimated to be completed in December 2026, according to its listing on clinicaltrials.gov. In the trial, participants with BCG-naïve, high-risk NMIBC received 300 milligrams of subcutaneous sasanlimab every four weeks up to cycle 25 in combination with weekly BCG for six consecutive weeks, followed in Arm A or not in Arm B by maintenance with BCG, or BCG induction and maintenance up to cycle 25 in Arm C, according to the news release.
The study’s primary endpoint is event-free survival assessed between Arms A and C, or the time from randomization to the earliest incidence of recurrence of high-grade disease, progression of disease, persistence of carcinoma in-situ or death, with key secondary endpoints including EFS assessed between Arms B and C.
“The combination of PD-(L)1 inhibitors and BCG may increase anti-tumor effects compared with either agent alone for patients with high-risk NMIBC,” researchers concluded in information on the trial published in Future Oncology. “CREST aims to evaluate the efficacy and safety of the SC PD-1 inhibitor sasanlimab in combination with BCG (induction with or without maintenance period) for participants with BCG-naive high-risk NMIBC. SC sasanlimab in combination with BCG in this population of patients may provide a greater benefit with longer EFS versus BCG monotherapy.”
According to the news release, induction therapy with BCG followed by maintenance therapy has been the standard of care for patients with high-risk NMIBC for decades, with 40% to 50% of patients experiencing recurrent disease.
“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 Dr. Roger Dansey, Chief Oncology Officer, 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.”
Pfizer, which reported that the overall safety profile of the combination was generally consistent with the known profile of BCG and data reported from clinical trials involving sasanlimab and that sasanlimab’s profile was also generally consistent with the reported safety profile of PD-1 inhibitors, stated that results from the trial will be submitted for presentation at an upcoming medical congress,
The overall safety profile of sasanlimab in combination with BCG was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab. The profile of sasanlimab was also generally consistent with the reported safety profile of PD-1 inhibitors.
Reference:
“CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer” by Dr. Gary D. Steinberg et al., Future Oncology.
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
