2020TiP - SOGUG-NEOWIN: A phase II, open-label, multi-centre trial evaluating the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab (CET) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) and FGFR gene alterations

Background

Neoadjuvant cisplatin-based therapy followed by radical cystectomy (RC) is the standard treatment for non-metastatic MIBC. Many patients (pts) are not eligible for cisplatin. Immune checkpoint inhibitors (ICIs) are being tested for resectable urothelial cancer (UC). ERDA, a fibroblast Growth Factor Receptor (FGFR) inhibitor, has shown efficacy in metastatic (m)UC with certain FGFR2/3 alterations. ERDA + CET showed clinically meaningful outcomes in pts with FGFR-altered mUC (NORSE trial). This study evaluates whether ERDA + CET can improve the pathological complete response (pCR) rate in pts with FGFR+ MIBC who are eligible for RC but ineligible/refuse cisplatin-based therapy.

Trial design

SOGUG-NEOWIN is a prospective, non-comparative, open-label, multicentre trial to assess the efficacy of 9 or 12 weeks of neoadjuvant ERDA (cohort 1) or CET + ERDA (cohort 2) in MIBC pts (cT2-Ta N0/1 M0) and FGFR+. Key eligibility criteria: ECOG PS 0-1; pure or predominant UC histology; decline or ineligible for cisplatin-based therapy (impaired renal function (GFR < 60 mL/min), ≥ grade 2 hearing loss, or ≥ grade 2 peripheral neuropathy); pts are considered fit for RC; no prior FGFR-targeted or anti-PD-(L)1 therapy; no prior systemic therapy, for bladder cancer; prior BCG was allowed if completed ≥ 6 weeks before initiation of study treatment; no current retinopathy. 45 pts will be allocated to each cohort by a centralized system. Co-primary endpoints are pCR rate and percentage of pathological downstaging response (

Clinical trial identification

EudraCT 2022-002586-15.

Editorial acknowledgement

Pivotal S.L.U provided medical writing support.

Legal entity responsible for the study

SOGUG (Spanish Oncology Genitourinary Group).

Funding

Janssen Pharmaceutica NV.

Disclosure

Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, Seattle Genetics, Tahio; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisory boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, Celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Tahio; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelixis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). G.A. De Velasco Oria: Financial Interests, Personal, Advisory Board: Pfizer, Astellas, BMS, MSD, Ipsen, Bayer, AstraZeneca, EISAI; Financial Interests, Personal, Invited Speaker: Pfizer, Astellas, BMS, MSD, Roche, Ipsen, Merck, Novartis, Janssen, Bayer; Financial Interests, Institutional, Research Grant: Roche. All other authors have declared no conflicts of interest.