Bladder Preservation With Sacituzumab Govitecan + Zimberelimab for Muscle-Invasive Bladder Cancer

Summary

Patients with MIBC N0/N1 unwilling or unfit for cystectomy will receive SG + Zimberelimab for 3 cycles of treatment prior of first radiological and TURB re-evaluation. Patients with stable disease or downstaging will continue Zimberelimab up to 1 year. The goal of this trial is to demonstate that Sacituzumab Govitecan + Zimberelimab can avoid cistectomy and can prolong or avoid recurrence to metastatic disease in selected patients with muscle-invasive bladder cancer. The primary endpoint of this trial is Event Free Survival that is defined as clinical evidence of new or progressing nodal or any distant metastatic disease, radical cystectomy, or death due to any cause from date of inclusion to the first documentation of a EFS event.

Timeline

Start

2024-12-02

Primary completion

2026-12-31

Completion

2029-12-31

Publications

• Background Bokarica P, Hrkac A, Gilja I. Re: J. Alfred Witjes, Thierry Lebret, Eva M. Comperat, et al. Updated 2016 EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. Eur Urol 2017;71:462-75. Eur Urol. 2017 Aug;72(2):e45. doi: 10.1016/j.eururo.2017.02.031. Epub 2017 Mar 6. No abstract available.
• Background Softness K, Kaul S, Fleishman A, Efstathiou J, Bellmunt J, Kim SP, Korets R, Chang P, Wagner A, Olumi AF, Gershman B. Radical cystectomy versus trimodality therapy for muscle-invasive urothelial carcinoma of the bladder. Urol Oncol. 2022 Jun;40(6):272.e1-272.e9. doi: 10.1016/j.urolonc.2021.12.015. Epub 2022 Jan 17.
• Background Royce TJ, Feldman AS, Mossanen M, Yang JC, Shipley WU, Pandharipande PV, Efstathiou JA. Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer. Clin Genitourin Cancer. 2019 Feb;17(1):23-31.e3. doi: 10.1016/j.clgc.2018.09.023. Epub 2018 Oct 4.
• Background Mitin T, Hunt D, Shipley WU, Kaufman DS, Uzzo R, Wu CL, Buyyounouski MK, Sandler H, Zietman AL. Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial. Lancet Oncol. 2013 Aug;14(9):863-72. doi: 10.1016/S1470-2045(13)70255-9. Epub 2013 Jul 1.
• Background James ND, Hussain SA, Hall E, Jenkins P, Tremlett J, Rawlings C, Crundwell M, Sizer B, Sreenivasan T, Hendron C, Lewis R, Waters R, Huddart RA; BC2001 Investigators. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med. 2012 Apr 19;366(16):1477-88. doi: 10.1056/NEJMoa1106106.
• Background Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.
• Background Powles T, Bellmunt J, Comperat E, De Santis M, Huddart R, Loriot Y, Necchi A, Valderrama BP, Ravaud A, Shariat SF, Szabados B, van der Heijden MS, Gillessen S; ESMO Guidelines Committee. Electronic address: [email protected]. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022 Mar;33(3):244-258. doi: 10.1016/j.annonc.2021.11.012. Epub 2021 Nov 30. No abstract available.
• Background Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017 Jan;67(1):7-30. doi: 10.3322/caac.21387. Epub 2017 Jan 5.
• Background Lin N, Zhang M, Bai H, Liu H, Cui J, Ke X, Zhang H, Liu L, Yan D, Jiang Y, Zang A, Qi J, Wang L, Liu Z, Xu B, Zhang Y, Zhang Z, Zhao X, Hu C, Yang S, Zhou H, Shi J, Shao Z, Xiang Y, Zhu J, Song Y, Zhu J. Efficacy and safety of GLS-010 (zimberelimab) in patients with relapsed or refractory classical Hodgkin lymphoma: A multicenter, single-arm, phase II study. Eur J Cancer. 2022 Mar;164:117-126. doi: 10.1016/j.ejca.2021.07.021. Epub 2021 Aug 27.
• Background Loriot Y, Petrylak DP, Rezazadeh Kalebasty A, Flechon A, Jain RK, Gupta S, Bupathi M, Beuzeboc P, Palmbos P, Balar AV, Kyriakopoulos CE, Pouessel D, Sternberg CN, Tonelli J, Sierecki M, Zhou H, Grivas P, Barthelemy P, Tagawa ST. TROPHY-U-01, a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors: updated safety and efficacy outcomes. Ann Oncol. 2024 Apr;35(4):392-401. doi: 10.1016/j.annonc.2024.01.002. Epub 2024 Jan 18.
• Background Grivas P, Pouessel D, Park CH, Barthelemy P, Bupathi M, Petrylak DP, Agarwal N, Gupta S, Flechon A, Ramamurthy C, Davis NB, Recio-Boiles A, Sternberg CN, Bhatia A, Pichardo C, Sierecki M, Tonelli J, Zhou H, Tagawa ST, Loriot Y. Sacituzumab Govitecan in Combination With Pembrolizumab for Patients With Metastatic Urothelial Cancer That Progressed After Platinum-Based Chemotherapy: TROPHY-U-01 Cohort 3. J Clin Oncol. 2024 Apr 20;42(12):1415-1425. doi: 10.1200/JCO.22.02835. Epub 2024 Jan 23.

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