If approved, Pfizer’s sasanlimab will distinguish itself from Merck’s blockbuster Keytruda as the first PD-1 inhibitor indicated in combination with BCG for high-risk non-muscle invasive bladder cancer patients who had not previously undergone BCG treatment.
Pfizer’s investigational PD-1 inhibitor sasanlimab achieves significant efficacy in patients with high-risk non-muscle invasive bladder cancer, according to a topline readout from the Phase III CREST trial revealed on Friday.
CREST is a pivotal randomized and open-label study that enrolled 1,070 non-muscle invasive bladder cancer (NMIBC) patients who had not yet been treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Participants were assigned to one of three parallel arms: Two underwent an induction regimen of BCG plus 300-mg subcutaneous sasanlimab followed (arm A) or not (arm B) by maintenance BCG. Patients in the third groupreceived the control treatment of a BCG induction and maintenance regimen.
The study’s primary outcome is event-free survival (EFS) between arm A and controls, defined as the time from group assignment to disease progression, persistence of carcinoma, the first high-grade disease recurrence or death. EFS measured between arm B and the control group was set as a key secondary endpoint.
Pfizer did not provide specific data in its news release on Friday, revealing only that sasanlimab plus BCG—given as induction and maintenance—leads to “clinically meaningful and statistically significant” improvements in EFS versus BCG alone. As for safety, CREST found sasanlimab to be well-tolerated overall, with adverse events that were consistent with what had been reported in previous trials and with the PD-1 class more broadly.
Pfizer COO Roger Dansey in a statement called these results “potentially practice-changing” for BCG-naïve, high-risk NMIBC patients, for which the initial therapy “has not advanced in decades.” In this indication, induction and maintenance treatment with BCG has been the standard regimen for years—even though up to half of patients suffer from recurrence and require surgery, according to Pfizer.
CREST’s findings represent “the first advance in therapy for BCG-naïve, high-risk, non-muscle invasive cancer in over 30 years,” Dansey added.
While Pfizer will continue to test potential combination regimens of the PD-1 blocker with its other antibody-drug conjugates, the company plans on using CREST’s data to support a regulatory filing for sasanlimab in this indication, according to the announcement.
If approved, Pfizer claims that sasanlimab would become the first PD-1 inhibitor indicated as a combination therapy with BCG that can prolong EFS specifically in high-risk patients who had never been treated with BCG.
This dosing profile will help set sasanlimab apart in a space dominated by Merck’s blockbuster PD-1 inhibitor Keytruda, which is widely considered to be a cornerstone oncology asset. In NMIBC, Keytruda can only be used on patients who have already undergone BCG treatment but were found to be unresponsive, as per its label. Sasanlimab is also designed to be administered subcutaneously, as opposed to Keytruda’s intravenous route.
