Pfizer’s Sasanlimab + BCG Boosts Event-Free Survival in High-Risk Bladder Cancer
Pfizer Inc. (NYSE: PFE) has announced promising topline results from its pivotal Phase 3 CREST trial, which evaluated sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with Bacillus Calmette-Guérin (BCG) as induction therapy, with or without maintenance, for patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). The study successfully met its primary endpoint of event-free survival (EFS), demonstrating a statistically significant and clinically meaningful improvement with sasanlimab and BCG combination therapy (both induction and maintenance) compared to BCG alone.
Non-muscle invasive bladder cancer is a significant health issue, with about 100,000 new cases of high-risk NMIBC diagnosed globally each year. The standard treatment has long been induction therapy with BCG, followed by maintenance therapy. However, despite this treatment, up to 50% of patients experience disease recurrence, often requiring radical cystectomy, a procedure associated with significant risks. Patients who experience recurrence have few bladder-sparing treatment options.
Dr. Neal Shore, the lead investigator for the CREST trial and Medical Director for the Carolina Urologic Research Center, noted that the results of this study are encouraging for the BCG-naïve high-risk NMIBC population, which has high rates of recurrence and progression. He explained, “These study results demonstrate the potential of 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). This combination therapy could help provide prolonged event-free survival, potentially delaying or reducing the need for more aggressive treatment options.” He added that if approved, sasanlimab administered subcutaneously every four weeks could reduce the treatment burden on both patients and healthcare systems.
Pfizer’s Chief Oncology Officer, Dr. Roger Dansey, expressed optimism about the trial results, highlighting that this marks the first significant advancement in the treatment of high-risk, non-muscle invasive bladder cancer in over 30 years. “The initial therapy for high-risk, non-muscle invasive bladder cancer with BCG has not advanced in decades. The CREST trial results represent a potentially practice-changing breakthrough,” he stated. “These results reinforce Pfizer’s leadership in genitourinary cancer research and development and demonstrate our ongoing commitment to delivering new treatment options for patients with bladder cancer.”
The study assessed the safety profile of sasanlimab in combination with BCG, which was found to be generally consistent with the known safety profile of BCG and similar to data from other clinical trials with sasanlimab. Additionally, sasanlimab’s safety profile was comparable to other PD-1 inhibitors.
Sasanlimab, the investigational drug, is a humanized immunoglobulin G4 monoclonal antibody that targets programmed death-1 (PD-1), a protein expressed on T-cells and other immune cells. PD-1 plays a significant role in suppressing immune responses, which can allow tumors to evade detection by the immune system. By blocking the PD-1/PD-L1 pathway, sasanlimab enhances the immune system’s ability to target and destroy cancer cells. The drug is administered as a subcutaneous injection every four weeks.
The CREST trial was a Phase 3, randomized, open-label study involving three arms. Patients were randomized to receive sasanlimab (300 mg) every four weeks, in combination with BCG induction therapy (once weekly for six consecutive weeks), followed by either BCG maintenance or no maintenance therapy. The primary endpoint was EFS, defined as the time from randomization to recurrence of high-grade disease, disease progression, persistence of CIS, or death.
Key secondary endpoints focused on EFS between maintenance and no-maintenance groups, and additional exploratory outcomes included overall survival and safety profiles. The study’s results are expected to be submitted for presentation at an upcoming medical congress. Pfizer also plans to discuss the data with global health authorities to support potential regulatory filings for sasanlimab.
Sasanlimab is currently being investigated in several other clinical trials in combination with Pfizer’s antibody-drug conjugate (ADC) portfolio in advanced solid tumors.
As part of its commitment to oncology research, Pfizer continues to advance its portfolio, which includes therapies targeting a range of cancers. Through its dedication to science and innovation, the company aims to offer new solutions for cancers with high unmet needs. Pfizer’s oncology pipeline also includes treatments for breast cancer, genitourinary cancer, hematology, and thoracic cancers such as lung cancer.
In conclusion, the positive results from the Phase 3 CREST trial represent a significant step forward in the treatment of high-risk, non-muscle invasive bladder cancer. If approved, sasanlimab, in combination with BCG, could provide a transformative treatment option for patients with BCG-naïve high-risk NMIBC. This therapy not only has the potential to improve patient outcomes but may also reduce the need for more invasive procedures, offering hope to those with limited treatment options.
