Abstract 799TiP
Background
Radical surgery is the mainstay of treatment for urothelial bladder cancer (UBC) and invasive upper tract urothelial cancer (UTUC), but even when combined with cisplatin-based (neo)adjuvant chemotherapy (NAC) recurrence rates are high. Furthermore, many patients are ineligible for or do not respond to NAC. Fibroblast growth factor receptor 3 (FGFR3) genetic alterations occur in up to 70% of UTUC and up to 20% of UBC and are candidates for targeted therapy. Infigratinib (BGJ398), an FGFR1–3 selective oral tyrosine kinase inhibitor, has shown clinical activity and tolerability in patients with advanced urothelial carcinoma with FGFR3 alterations. PROOF 302 was designed to investigate the efficacy and safety of infigratinib as adjuvant therapy in patients with high-risk invasive urothelial carcinoma with FGFR3 alterations.
Trial design
PROOF 302 is a randomized, double-blind, placebo-controlled, phase 3 trial (NCT04197986). Eligibility criteria: high-risk muscle invasive UTUC or UBC with susceptible FGFR3 alterations (i.e. activating mutations, gene fusions or rearrangements); ≤120 days following radical surgery; ineligible for cisplatin-based adjuvant chemotherapy; residual disease after cisplatin-based NAC. Patients who received non-cisplatin-based NAC are eligible if they have residual disease and are ineligible for adjuvant cisplatin. Patients receive oral infigratinib 125 mg or placebo (1:1 ratio) QD on days 1–21 every 28 days for up to 52 weeks or until recurrence, unacceptable toxicity, or death. Primary endpoint: disease-free survival (DFS), which is centrally reviewed, analyzed via stratified log-rank test, Kaplan-Meier method (Brookmeyer-Crowley CI) and Cox model (hazard ratio). Secondary endpoints: DFS (investigator reviewed); metastasis-free survival; overall survival; safety/tolerability. Exploratory endpoints: quality of life; pharmacokinetics; cell-free DNA and/or RNA for resistance mechanisms. PROOF 302 will include >200 patients from approx. 120 centers worldwide. The study was initiated in late 2019, is enrolling patients and is expected to end in 2024.
Clinical trial identification
NCT04197986.
Editorial acknowledgement
Medical editing/writing assistance was provided by Lee Miller (Miller Medical Communications).
Legal entity responsible for the study
QED Therapeutics Inc.
Funding
QED Therapeutics Inc.
Disclosure
D.M. Somford: Advisory/Consultancy, Research grant/Funding (institution): Astellas; Advisory/Consultancy: Janssen. S. Daneshmand: Honoraria (self), Advisory/Consultancy: Ferring; Honoraria (self): MDxHealth; Honoraria (self): Olympus; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Photocure; Honoraria (self), Advisory/Consultancy: QED Therapeutics; Honoraria (self): Spectrum Pharmaceuticals; Honoraria (self): pacific edge; Advisory/Consultancy: Taris. P. Grivas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Biocept; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational unbranded activity (2017): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Driver; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: EMD Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Exelixis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Genzyme; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron Therapeutics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Mirati Therapeutics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: QED Therapeutics; Honoraria (institution): KureIT; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Oncogenex; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): Debiopharm. S. Sridhar: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Sanofi. S. Gupta: Honoraria (self): AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen Oncology; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Exelixis; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Astellas Medivation; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Moderna Therapeutics; Research grant/Funding (institution): Pfizer; Shareholder/Stockholder/Stock options: Nektar. J. Bellmunt: Honoraria (self): UpToDate; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: AstraZeneca/MedImmune; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Genentech; Advisory/Consultancy: Merck; Advisory/Consultancy: Novartis; Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Pierre Fabre; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Pfizer/EMD Serono; Research grant/Funding (institution): Sanofi; Travel/Accommodation/Expenses: Ipsen; Travel/Accommodation/Expenses: MSD Oncology; Shareholder/Stockholder/Stock options: Rainier Therapeutics. G. Sonpavde: Honoraria (self): UpToDate; Advisory/Consultancy: Agensys; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Eisai; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Genentech; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy, Research grant/Funding (institution): Merck; Advisory/Consultancy: Novartis; Speaker Bureau/Expert testimony: OncLive; Speaker Bureau/Expert testimony: Physician Education Resource; Speaker Bureau/Expert testimony: Research to Practice; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Celgene; Research grant/Funding (institution): Onyx; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Sanofi. M.T. Fleming: Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen Oncology; Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Genentech; Travel/Accommodation/Expenses: Medivation/Astellas; Full/Part-time employment: Virginia Oncology Associates. S.P. Lerner: Honoraria (self), Travel/Accommodation/Expenses: DAVA Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Merck Sharp & Dohme; Honoraria (self), Travel/Accommodation/Expenses: Nucleix; Advisory/Consultancy: Anchiano; Advisory/Consultancy, Travel/Accommodation/Expenses: Ferring; Advisory/Consultancy: miR Scientific; Advisory/Consultancy: QED Therapeutics; Advisory/Consultancy, Research grant/Funding (self): Roche/Genentech; Advisory/Consultancy, Research grant/Funding (self): Urogen pharma; Advisory/Consultancy, Research grant/Funding (self): Vaxiion; Advisory/Consultancy: Verity Pharmaceuticals; Research grant/Funding (self): Endo Pharmaceuticals; Research grant/Funding (self): FKD Therapies; Research grant/Funding (self): Japan BCG Laboratory; Research grant/Funding (self): Viventia Biotech; Licensing/Royalties: TCGA expression subtype single patient classifier. Y. Loriot: Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (institution): Clovis Oncology; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD Oncology; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): CureVac; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Medivation; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Oncogenex. A. Li: Full/Part-time employment: QED Therapeutics Inc.. H. Takkele: Full/Part-time employment: QED Therapeutics Inc.. C. Andresen: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: QED Therapeutics Inc.. J. Rearden: Full/Part-time employment: QED Therapeutics Inc.; Spouse/Financial dependant: Merck. S. Peacock Shepherd: Full/Part-time employment: QED Therapeutics Inc.. S.K. Pal: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Aveo; Advisory/Consultancy: Myriad Pharmaceuticals; Advisory/Consultancy: Genentech; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Eisai; Research grant/Funding (self): Medivation. All other authors have declared no conflicts of interest.