Pfizer Inc. announced promising results from its pivotal phase III CREST trial evaluating sasanlimab, an investigational anti-PD-1 monoclonal antibody, in combination with standard-of-care Bacillus Calmette-Guérin (BCG) therapy for patients with high-risk non-muscle invasive bladder cancer (NMIBC) who had not previously received BCG treatment.
The trial results, released on April 26, showed that the combination of sasanlimab with BCG as induction therapy, with or without maintenance therapy, demonstrated significant clinical benefit compared to BCG alone in this patient population.
Trial Design and Patient Population
The CREST trial focused specifically on BCG-naïve patients with high-risk NMIBC. This patient population represents a significant unmet need in bladder cancer treatment, as approximately 75% of newly diagnosed bladder cancers are non-muscle invasive, with high-risk patients facing substantial rates of recurrence and progression despite current standard treatments.
The study evaluated sasanlimab in combination with BCG as induction therapy, and also assessed the potential benefits of adding maintenance therapy to the treatment regimen. The trial design reflects the current treatment paradigm for high-risk NMIBC, where BCG induction followed by maintenance therapy has been the standard approach.
Clinical Significance
High-risk NMIBC presents a challenging clinical scenario, with patients facing recurrence rates as high as 70% and progression to muscle-invasive disease in up to 30% of cases. The addition of immunotherapy to BCG represents a potentially important advancement in treatment options.
The positive results from the CREST trial align with a growing trend of combining immunotherapies with established treatments to improve outcomes in difficult-to-treat cancers. By targeting the PD-1 pathway, sasanlimab may enhance the immune response against cancer cells when used alongside BCG's immune-stimulating effects.
Broader Context in Bladder Cancer Treatment
The CREST trial results come amid similar developments in the field. AstraZeneca recently reported positive high-level results from their POTOMAC phase III trial, which showed that one year of treatment with Imfinzi (durvalumab) plus standard-of-care BCG induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with high-risk NMIBC compared to BCG therapy alone.
Additionally, Johnson & Johnson recently announced new data from cohort 2 of their pivotal phase IIB SunRISe-1 study evaluating TAR-200, an intravesical gemcitabine releasing system, for certain types of bladder cancer, further highlighting the active research landscape in this disease area.
Implications for Treatment Paradigms
If approved, the sasanlimab-BCG combination could offer a new option for patients with high-risk NMIBC who have not previously received BCG therapy. This is particularly important given the limited treatment options available for patients who fail or are intolerant to BCG therapy.
The development of effective combination therapies is crucial in bladder cancer management, where preserving the bladder and avoiding radical cystectomy (surgical removal of the bladder) remains a primary goal for patients with NMIBC.
Future Directions
While the high-level results are promising, detailed efficacy and safety data from the CREST trial will be important to fully understand the potential role of sasanlimab in the treatment landscape. Pfizer has indicated that complete results will be presented at an upcoming medical meeting and submitted to regulatory authorities.
The company will likely pursue regulatory approval for this combination therapy based on the positive phase III results, potentially adding another immunotherapy option to the armamentarium against high-risk NMIBC.
As research continues in this field, the focus remains on improving long-term outcomes while maintaining quality of life for patients with this challenging form of bladder cancer.
