Abstract 798TiP
Background
Platinum-containing chemotherapy is the standard of care for patients (pts) with metastatic urothelial carcinoma (mUC) in the first line (1L) setting. PD-1/PD-L1 inhibitors pembrolizumab (P) and atezolizumab are approved for 1L cisplatin (cis) ineligible pts (US and EU) and for those who are platinum-ineligible (P, US only) with high tumor PD-L1 expression. Enfortumab vedotin (EV) is an antibody drug conjugate (ADC) directed to Nectin-4, which is highly expressed in UC. Recently, EV received accelerated approval in the US for locally advanced (la)/mUC following treatment with PD 1/PD-L1 inhibitors and platinum-containing therapies in the neoadjuvant/adjuvant or la/mUC setting. In the EV-103 study (NCT03288545), EV + P showed a promising ORR of 73% in the cis-ineligible 1L setting with a manageable safety profile (Rosenberg ASCO-GU 2020). With only modest advances to date, the need for novel drug combinations to improve outcomes in the 1L setting for la/mUC remains.
Trial design
EV-302 (NCT04223856) began as a global 3-arm, open-label, randomized phase 3 study evaluating the efficacy and safety of EV + P (Arm A) and EV + P + cis/carboplatin (carbo) (Arm C) against standard gemcitabine (gem) + cis/carbo (Arm B) in pts with unresectable, previously untreated la/mUC. Recently, based on data from chemotherapy + PD-1/PD-L1 combinations, the study was modified to remove Arm C. The updated 2-arm design randomizes pts to EV + P or gem + cis/carbo. Randomization is 1:1 with the following stratification factors: cis eligibility, PD-L1 expression, and liver metastases. Pts must have measurable disease, an ECOG status of ≤2, and be able to receive EV, P and cis or carbo. EV (1.25 mg/kg) will be given on Days 1 and 8 of every 3-wk cycle. P (200 mg) will be given on Day 1. Gem (1000 mg/m2) will be given on Days 1 and 8 and cis (70 mg/m2) or carbo (AUC 4.5 or 5) on Day 1. The primary endpoints are PFS, assessed by blinded independent central review, and OS. Other endpoints include ORR, duration of response, disease control rate, AEs, and patient reported outcomes, as well as PK and biomarkers. The study opened in March 2020.
Clinical trial identification
NCT04223856.
Editorial acknowledgement
Medical writing assistance was funded by Seattle Genetics, Inc., and provided by Sarah Dreumont of Seattle Genetics, Inc.
Legal entity responsible for the study
Seattle Genetics, Astellas, Merck.
Funding
Seattle Genetics, Astellas, Merck.
Disclosure
M.S. van der Heijden: Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Roche; Advisory/Consultancy: Merck; Advisory/Consultancy: MSD; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Janssen. S. Gupta: Honoraria (self), Speaker Bureau/Expert testimony: Exelixis; Honoraria (self), Speaker Bureau/Expert testimony: Janssen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Astellas. M.D. Galsky: Advisory/Consultancy: Aileron Therapeutics; Advisory/Consultancy: Astellas; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): BioMotiv; Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Dendreon; Advisory/Consultancy: Dracen; Advisory/Consultancy: EMD Serono; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Advisory/Consultancy: GlaxoSmithKline; Advisory/Consultancy: Incyte; Advisory/Consultancy: Inovio Pharma; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: NuMab; Advisory/Consultancy: Pfizer; Advisory/Consultancy: SeaGen; Shareholder/Stockholder/Stock options: Rappta Therapeutics; Licensing/Royalties, Application Number 20120322792 : Mount Sinai School of Medicine. C. Derleth: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Seattle Genetics. J. Steinberg: Travel/Accommodation/Expenses, Full/Part-time employment: Astellas Pharma. R. Kataria: Full/Part-time employment: Merck. T.B. Powles: Honoraria (self): BMS; Honoraria (self), Research grant/Funding (self): AstraZeneca; Honoraria (self), Research grant/Funding (self): Merck-KGA; Honoraria (self): MSD; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Research grant/Funding (self): Roche; Honoraria (self): Astellas; Honoraria (self): Ipsen; Honoraria (self), Research grant/Funding (self): Seattle Genetics; Honoraria (self), Research grant/Funding (self): Exelixis; Honoraria (self): Johnson and Johnson; Honoraria (self): Novartis; Honoraria (self): Ferring Asia.