Pfizer’s Sasanlimab Combination Significantly Extends Event-Free Survival in BCG-Naïve, High-Risk Non-Muscle Invasive Bladder Cancer Patients
Pfizer Inc. (NYSE: PFE) today announced encouraging results from the pivotal Phase 3 CREST trial, evaluating the efficacy and safety of sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with standard-of-care Bacillus Calmette-Guérin (BCG) therapy. The combination was tested as induction therapy, with or without maintenance, in patients diagnosed with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC).
The CREST trial successfully met its primary endpoint, with investigator-assessed event-free survival (EFS) showing a clinically meaningful and statistically significant improvement for patients receiving the combination therapy compared to those treated with BCG alone. Specifically, the combination regimen achieved a hazard ratio (HR) of 0.68 (95% Confidence Interval [CI]: 0.49-0.94; two-sided p=0.019), corresponding to a 32% reduction in the risk of disease-related events such as high-grade recurrence or disease progression. Notably, the median EFS was not yet reached at the time of analysis, highlighting the potential durability of the combination’s benefit.
Subgroup analyses further reinforced the strength of these findings. Among patients presenting with T1 disease, the EFS hazard ratio was 0.63 (95% CI: 0.41-0.96), and for those diagnosed with carcinoma in situ (CIS), the hazard ratio was even more favorable at 0.53 (95% CI: 0.29-0.98). These results consistently favor the sasanlimab-BCG combination across key high-risk patient populations.
The trial’s definition of EFS encompassed the time from randomization to the earliest occurrence of high-grade disease recurrence, disease progression, persistence of CIS, or death from any cause. At 36 months, the probability of being event-free was 82.1% (95% CI: 77.4-85.9) for the sasanlimab plus BCG group, compared to 74.8% (95% CI: 69.7-79.2) for patients receiving BCG alone. These results were presented in a plenary oral session at the 2025 American Urological Association (AUA) Annual Meeting, highlighting the significance of the findings within the medical community.
“New bladder cancer treatment options that help reduce rates of disease recurrence or progression are long overdue,” stated Dr. Neal Shore, Medical Director for START Carolina Research Center and lead investigator for the CREST trial. “Historically, up to 50% of patients with high-risk NMIBC have experienced failure of BCG therapy, which, despite being the gold standard after tumor resection, has remained largely unchanged for decades. These Phase 3 results demonstrate that early combination of sasanlimab with BCG induction and maintenance therapy significantly prolongs event-free survival. This highlights the potential of sasanlimab to redefine treatment approaches and meaningfully reduce the disease burden on patients.”
Bladder cancer remains a major global health challenge, ranking as the ninth most common cancer worldwide and accounting for approximately 220,000 deaths annually. Non-muscle invasive bladder cancer constitutes roughly 75% of all newly diagnosed bladder cancer cases. In the United States alone, about 38,000 individuals are estimated to live with high-risk NMIBC. Despite the established role of BCG therapy in reducing recurrence risk, around 40–50% of patients eventually experience disease recurrence or progression despite optimal BCG treatment.
In this context, the CREST trial’s findings represent a significant milestone. Megan O’Meara, M.D., Interim Chief Development Officer for Pfizer Oncology, emphasized, “Today’s pivotal Phase 3 CREST results represent a much-needed therapeutic breakthrough. Sasanlimab is now positioned as the first immunotherapy combination with BCG to demonstrate significant outcome improvements in BCG-naïve, high-risk NMIBC in over three decades. This progress is particularly meaningful for patients in early stages of bladder cancer who stand to benefit most from innovative therapeutic approaches aimed at delaying disease progression.”
O’Meara continued, “The subcutaneous administration route of sasanlimab, combined with its mechanism as a PD-1 checkpoint inhibitor, offers the potential for a patient-friendly and highly effective regimen. These results affirm our commitment to transforming treatment options across all stages of bladder cancer, and we look forward to working closely with global regulatory agencies to make sasanlimab available as a new treatment option for high-risk NMIBC patients.”
Despite the encouraging primary endpoint results, one key secondary endpoint of the CREST study did not meet expectations. Specifically, sasanlimab combined with BCG induction alone, without maintenance therapy, failed to prolong EFS when compared to standard BCG treatment with induction and maintenance. The hazard ratio in this group was 1.16 (95% CI: 0.87-1.55; p=0.312). This outcome highlights the critical role of ongoing BCG maintenance not only as part of current standard-of-care but also in combination regimens incorporating novel agents like sasanlimab.
An early interim analysis for overall survival (OS), another key secondary endpoint, showed no significant differences between the treatment arms, with a median follow-up of 40.9 months. Survival follow-up will continue until the final OS analysis is conducted.
Additional secondary endpoints focused on complete response (CR) and the durability of CR among patients presenting with CIS at baseline. Impressively, the CR rate at any time during treatment was 89.8% for patients receiving the sasanlimab and BCG combination, compared to 85.2% for those treated with BCG alone. Among those who achieved a CR, the probability of remaining in complete response at 36 months was substantially higher in the sasanlimab plus BCG group (91.7%) compared to BCG alone (67.7%). This suggests that the combination not only induces deeper remissions but also maintains disease control more effectively over time.
In terms of safety, the overall profile of sasanlimab combined with BCG was consistent with previously known safety data for both BCG and PD-1 inhibitors. No unexpected adverse events were observed. Pfizer has already shared the CREST data with global health authorities to support potential regulatory submissions and anticipates initiating discussions regarding approval pathways.
The CREST trial results are poised to reshape expectations for early bladder cancer treatment, offering a new hope to thousands of patients who currently face high rates of disease recurrence or progression even with best-available therapies.
As the oncology community gathers momentum toward making immunotherapy a mainstay of treatment across various cancer types, Pfizer’s announcement underscores the potential for sasanlimab to usher in a new era of innovation in high-risk NMIBC treatment — one where patients have more effective, durable, and manageable options earlier in their disease course.
About Pfizer Oncology
At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.
