Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial PMID: 40450141

ADC Targets in Oncology

2026-04-10

Sasanlimab plus BCG in BCG-naive, high-risk non-muscle invasive bladder cancer: the randomized phase 3 CREST trial

Nat Med. 2025 Aug;31(8):2806-2814. doi: 10.1038/s41591-025-03738-z.

Neal D Shore ¹ , Thomas B Powles ² , Jens Bedke ³ , Matthew D Galsky ⁴ , Joan Palou Redorta ⁵ , Ja Hyeon Ku ⁶ , Michal Kretkowski ⁷ , Evanguelos Xylinas ⁸ , Boris Alekseev ⁹ , Dingwei Ye ¹⁰ , Félix Guerrero-Ramos ¹¹ , Alberto Briganti ¹² , Girish S Kulkarni ¹³ , Julia Brinkmann ¹⁴ , Anna-Maria Calella ¹⁵ , Rossano Cesari ¹⁶ , Anthony Eccleston ¹⁷ , Elisabete Michelon ¹⁸ , Jennifer Vermette ¹⁹ , Caimiao Wei ²⁰ , Gary D Steinberg ²¹

Affiliations

1. START Carolinas/Carolina Urologic Research Center, Myrtle Beach, SC, USA. [email protected].
2. Barts Health Biomedical NIHR Research Centre, Queen Mary University of London, London, UK.
3. Department of Urology & Transplantation Surgery, Eva Mayr-Stihl Cancer Center, Klinikum Stuttgart, Stuttgart, Germany.
4. The Tisch Cancer Institute, Mount Sinai, New York, NY, USA.
5. Department of Urology, Fundació Puigvert, Universitat Autònoma de Barcelona, Barcelona, Spain.
6. Department of Urology, Seoul National University Hospital, Seoul, Republic of Korea.
7. Clinical Research Center, Spolka z Ograniczona, Poznań, Poland.
8. Department of Urology, Bichat-Claude Bernard Hospital, AP-HP, Université de Paris Cité, Paris, France.
9. P. Hertsen Moscow Cancer Research Institute, Moscow, Russia.
10. Fudan University Shanghai Cancer Center, Shanghai, China.
11. Department of Urology, Hospital Universitario 12 de Octubre, Madrid, Spain.
12. Division of Experimental Oncology/Unit of Urology, Urological Research Institute (URI), IRCCS San Raffaele Scientific Institute, Milan, Italy.
13. Division of Urology, Department of Surgery, Princess Margaret Cancer, Center University of Toronto, Toronto, ON, Canada.
14. Pfizer Pharma GmbH, Berlin, Germany.
15. Pfizer SRL, Rome, Italy.
16. Pfizer SRL, Milan, Italy.
17. Pfizer Ltd., Tadworth, UK.
18. Pfizer Inc., New York, NY, USA.
19. Pfizer Inc., Cambridge, MA, USA.
20. Pfizer Inc., Groton, CT, USA.
21. Department of Urology, Rush University Medical Center, Chicago, IL, USA.

Abstract

Bacillus Calmette-Guérin (BCG) induction and maintenance (I+M) after transurethral resection of bladder tumor is standard of care (SOC) in high-risk non-muscle invasive bladder Cancer (NMIBC). However, disease recurrence/progression occurs in approximately 40% of patients at 2 years, with unfavorable prognosis. Limited bladder-sparing therapeutic options exist, and no improvements to response durability have been observed in decades. CREST is a global, phase 3, randomized trial evaluating subcutaneous sasanlimab in combination with BCG-I+M (Arm A), sasanlimab in combination with BCG-I (Arm B) or BCG-I+M (Arm C) in BCG-naive high-risk NMIBC. The primary endpoint was investigator-assessed event-free survival (EFS) for Arm A versus Arm C; key secondary endpoints were EFS (Arm B versus Arm C) and overall survival. Patients were randomized 1:1:1 to Arm A (N = 352), Arm B (N = 352) and Arm C (N = 351). The trial met its primary endpoint with a statistically significant and clinically meaningful prolongation of EFS (Arm A versus Arm C); hazard ratio, 0.68 (95% confidence interval: 0.49-0.94); one-sided P = 0.0095. The 36-month estimated EFS rates were 82.1% (Arm A) and 74.8% (Arm C). EFS benefit for Arm A versus Arm C was observed across prespecified subgroups, including carcinoma in situ (CIS) and T1. The safety profile of the combination was consistent with the known profiles. To our knowledge, sasanlimab is the first anti-PD-1 antibody to show a clinically meaningful prolongation of EFS when combined with BCG-I+M versus SOC in patients with BCG-naive high-risk NMIBC. Sasanlimab combined with BCG-I+M has the potential to redefine the treatment paradigm and clinical decision-making for patients with BCG-naive high-risk NMIBC. ClinicalTrials.gov identifier: NCT04165317 .