Sasanlimab Plus BCG Demonstrates EFS Benefit in NMIBC

Bladder cancer: © vitanovski - stock.adobe.com

Sasanlimab (PF-06801591) in combination with Bacillus Calmette-Guérin (BCG) led to an improved event-free survival (EFS) compared with BCG alone in patients with non-muscle invasive bladder cancer (NMIBC), according to a press release from Pfizer.¹

The addition of sasanlimab to BCG met the primary end point of the phase 3 CREST trial (NCT04165317), showing clinically meaningful and statistically significant improvement for induction and maintenance with the combination over BCG alone by investigator assessment.

“Patients with BCG-naive high-risk NMIBC have high rates of recurrence and progression,” Neal Shore, MD, FACS, Medical Director for the Carolina Urologic Research Center, and lead investigator for the CREST trial, stated in the press release. “These study results demonstrate the potential for sasanlimab in combination with BCG to redefine the treatment paradigm for patients living with BCG-naive, high-risk NMIBC, including patients with carcinoma in-situ, providing prolonged EFS which may delay or reduce the need for more aggressive treatment options.”

Induction therapy with BCG followed by maintenance is the standard of care for patients with high-risk NMIBC but carries a significant risk of recurrence leading to radical cystectomy and additional risks. Sasanlimab is an investigational humanized immunoglobulin G4 anti–PD-1 monoclonal antibody that can be administered subcutaneously.

In the phase 3, multinational, randomized, open-label CREST trial, patients were assigned to 3 parallel arms. In arm A and B, patients received sasanlimab 300 mg every 4 weeks for 25 cycles plus BCG once weekly for 6 weeks. In arm A, patients continued with maintenance BCG whereas in arm B they did not. In arm C, they received BCG induction and maintenance up to cycle 25.

Patients enrolled in the trial were randomly assigned to treatment within 12 weeks of transurethral resection of bladder tumor. They must have NMIBC, have refused or be ineligible for radical cystectomy, and have received no prior immunotherapy.

The primary end point was EFS comparing arm A with arm C at 55 months after the randomization of the first participant. Secondary end points included EFS comparing arm B and arm C, as well as safety.

Investigators reported that the overall safety profile of the combination was consistent with the known safety profile of BCG and the data reported in clinical trials of sasanlimab.

“Administered subcutaneously every 4 weeks, sasanlimab, if approved, could also help lower the treatment burden on both patients and healthcare systems,” Shore added.

In a phase 1 dose-escalation trial (NCT02573259), 40 patients with advanced solid tumors including melanoma, non–small cell lung cancer, ovarian cancer, sarcoma, and urothelial carcinoma received sasanlimab intravenously or subcutaneous with an overall response rate of 18.4%. Grade 3 or higher toxicities were reported in 4 (16%) patients treated intravenously and 1 (6.7%) treated subcutaneously in this trial. These included fatigue, dermatitis bullous, pancreatic failure, peripheral sensory neuropathy, and hyperglycemia.²

More detailed results from CREST will be presented at an upcoming medical congress.

“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-naive, high-risk, non-muscle invasive cancer in over 30 years,” said Roger Dansey, MD, chief oncology officer, Pfizer, in the press release.¹

References

1. Pfizer’s sasanlimab in combination with bcg improves event-free survival in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer. News release. Pfizer. January 10, 2025. Accessed January 10, 2025. https://tinyurl.com/5t5a3x2h

2. Johnson ML, Braiteh F, Grilley-Olson JE, et al. Assessment of subcutaneous vs intravenous administration of anti-PD-1 antibody PF-06801591 in patients with advanced solid tumors: a phase 1 dose-escalation trial. JAMA Oncol. 2019;5(7):999-1007. doi:10.1001/jamaoncol.2019.0836