Abstract 720TiP
Background
Treatment options are suboptimal and limited for cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. Sacituzumab govitecan (SG) is a Trop-2 directed antibody-drug conjugate (ADC) coupled with SN-38 through a hydrolysable linker. In the phase II TROPHY-U-01 study, SG demonstrated an objective response rate (ORR) of 27% and median overall survival (OS) of 10.5 months in mUC patients who progressed after platinum-based chemotherapy and immune checkpoint inhibitors (ICI), receiving accelerated approval by the US FDA. In CheckMate 032 study, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1+I3) every 3 weeks (Q3W) x 4 cycles followed by nivolumab monotherapy 3mg/kg Q2W showed promising activity post-platinum that led to the ongoing phase III trial in the first-line setting (NCT03036098). Given potential synergism between immunogenic cell death induced by ADC and ICI, we hypothesized that the combination of SG and IPI-NIVO would benefit patients with manageable toxicities. We designed this study to assess the safety and clinical activity of IPI-NIVO with SG as first-line therapy for cisplatin-ineligible mUC patients.
Trial design
This is a phase I/II, single arm, multicenter study for cisplatin-ineligible mUC, enrolling up to 46 patients. The Phase I component will enroll up to 12 patients with 3+3 design with feasibility and RP2D as the primary endpoint, followed by a phase II component with ORR as the primary endpoint. Phase I will evaluate fixed doses of IPI-NIVO (N1+I3) IV Q3Wx 4 cycles combined with a starting dose of SG at 8 mg/kg IV on days 1, 8 Q3W x 4 cycles. This is followed by maintenance nivolumab 360 mg IV Q3W with SG on days 1, 8 Q3W. One dose escalation to 10 mg/kg and one dose reduction to 6 mg/kg of SG is allowed. Phase II will be conducted using Simon 2 stage design (n=34) with a futility interim analysis after 13 patients. The null hypothesis of ORR ≤ 38% will be tested with a desirable ORR of >60% under a statistical power of 80% and a one-sided type I error rate of 5%. Exploratory biomarker analyses will be conducted using tumor and blood samples collected during screening and at progression.
Clinical trial identification
NCT04863885.
Editorial acknowledgement
Legal entity responsible for the study
R.K. Jain.
Funding
BMS.
Disclosure
R.K. Jain: Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Speaker’s Bureau: Gilead; Financial Interests, Personal, Speaker’s Bureau: Seattle Genetics; Financial Interests, Personal, Advisory Board: EMD Soreno; Financial Interests, Personal, Advisory Board: Seattle Genetics. J. Chahoud: Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Pfizer. R. Li: Financial Interests, Personal, Advisory Board: CG Oncology. J. Zhang: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Astellas. G.P. Sonpavde: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Genetech; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Exelixis; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Pfizer. All other authors have declared no conflicts of interest.