Dr Necchi on the Efficacy and Safety of TAR-200 Plus Cetrelimab in MIBC

Andrea Necchi, MD, associate professor, oncology, Vita-Salute San Raffaele University, director, Genitourinary Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, discusses findings from the interim analysis of the phase 2 SunRise-4 trial (NCT04919512) evaluating TAR-200 plus cetrelimab in patients with muscle-invasive bladder cancer (MIBC).

SunRise-4 enrolled patients with MIBC who were ineligible for or refused treatment with neoadjuvant cisplatin-based chemotherapy. Patients were randomly assigned to receive cetrelimab alone (n = 41) or in combination with TAR-200 (n = 79).

Among efficacy-evaluable patients in the TAR-200 arm (n = 53), the pathologic complete response (pCR) rate was 42% (95% CI, 28%-56%), and the pathologic overall response (pOR) rate was 60% (95% CI, 46%-74%). In the cetrelimab arm (n = 31), these respective rates were lower, at 23% (95% CI, 10%-41%) and 36% (95% CI, 19%-55%). In the subgroup of patients with clinical T2 disease who received TAR-200 plus cetrelimab (n = 40), the pCR rate was 48% (95% CI, 32%-64%), and the pOR rate was 68% (95% CI, 51%-81%).

Based on these findings, the addition of TAR-200 to cetrelimab appears to generate pCR and downstaging benefits regardless of prior trans-urethral resection of bladder tumor (TURBT) status, Necchi says. Patients with residual disease after TURBT appeared to derive the same amount of benefit from the combination as those with completely resected disease following TURBT, he notes.

Furthermore, investigators noted a positive correlation between prolonged TAR-200 exposure and improved pCR, Necchi explains. Most patients who completed 4 courses of treatment with TAR-200 benefitted from the therapy, with a pCR rate of 50% (95% CI, 32%-68%); the rate of pOR was also high in this population, he emphasizes. These findings indicate that urologic oncologists should become comfortable with administering TAR-200 to patients, he adds.

TAR-200 plus cetrelimab was also safe and associated with manageable treatment-related adverse effects (AEs), according to Necchi. In the TAR-200 arm, the rate of immune-related AEs was 6.3%, and few patients interrupted therapy because of AEs. Furthermore, no patients in the combination arm experienced a delay in time to radical cystectomy, he says. Overall, the efficacy and safety profiles of the combination support the use of this regimen in patients with bladder cancer, Necchi concludes.

Disclosures: Dr Necchi reports receiving institutional grants/research funding from AstraZeneca, Bristol Myers Squibb, Gilead, Ipsen, and Merck; reciving consulting/advisory fees from Astellas, AstraZeneca, Bristol Myers Squibb, Catalym, Gilead, Johnson & Johnson, Samsung Bioepis, Bicycle Therapeutics, and Merck; serving in a leadership role for the Global Society of Rare Genitourinary Tumors; and serving as an Associate Editor for the Journal of Clinical Oncology.