Efficacy of talazoparib and avelumab as a maintenance treatment in patients with advanced/metastatic urothelial carcinoma (mUC) whose disease did not progress after a first-line platinum-based chemotherapy (PBCT): The GETUG-TALASUR trial

BackgroundAvelumab (Ave), an anti-PDL1 antibody, is the standard maintenance treatment after a 1st line PBCT in mUC. Talazoparib (Tal) is an oral PARP inhibitor. Based on preclinical and clinical data of the synergy between PARP and immune checkpoint inhibitors, this phase II trial aimed to assess the efficacy of Tal plus Ave combination as a maintenance treatment in patients (pts) with mUC who obtained objective response (OR) or stable disease (SD) after a 1st -line PBCT.MethodsTALASUR was a single arm phase II trial in pts with advanced transitional cell UC, without progression after 4-6 cycles of 1st line PBCT. Patients (pts) received Tal 1 mg per os daily and Ave 800 mg IV every 2 weeks, in a 28-day cycle. Primary endpoint was progression-free survival (PFS).ResultsBetween June 2021 and July 2023, 47 assessable pts were included in 12 French centers. Median age was 69 yrs [min 40-max 82]; ECOG, PS 0 30% / PS 1 70%; 48% cisplatin / 52% carboplatin 1st-line treatment. On April 2024, after a median follow-up of 16.8 months (mo) [min 2-max 33], median PFS was 5.5 mo [95%CI: 3.7-9.1]. Median overall survival time was 23.9 mo, with 23 (48.9%) deaths (no toxic death). ORR was 12.8%. Tal dose reduction was needed for 25 pts (53%). Definitive treatment interruption for Tal or Ave related-toxicity occurred in 3 (G4 thrombocypenia, G3 asthenia, G3 renal failure) and 2 (G3 interstitial lung disease, G2 nausea) pts, respectively. Most common Tal and/or Ave-related AEs were anemia (44.7%, G3-4 19.1%), thrombocytopenia (55.3%, G3-4 19.1%), neutropenia (12.8%, G3-4 6.4%), fatigue (36.2%, G3 2.1%) and nausea (14.9% all G<3). Immune-related AEs G2-3 were reported in 6 pts (G3 interstitial lung disease, G2 nausea, G2 infusion related reaction, G2 hyperglycemia, G2/G3 hyperlipasemia).ConclusionsTal plus Ave in maintenance treatment of mUC did not reach the 5.9 months expected PFS threshold. Results are consistent with the clinical outcomes of Ave monotherapy reported in the JAVELIN bladder100 trial. Efficacy according to DNA damage repair genes will be presented (work in progress).Clinical trial identificationEudraCT 2020-001105-24.Legal entity responsible for the studyCentre François Baclesse.FundingIpsen.DisclosureE. Coquan: Financial Interests, Institutional, Funding: Pfizer, Ipsen; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, AAA; Financial Interests, Personal, Invited Speaker: MSD, Janssen. D. Pouessel: Financial Interests, Personal, Advisory Board, + support for travel: Pfizer; Financial Interests, Personal, Invited Speaker: Astellas, BMS, MSD, AstraZeneca, Eisai, Ipsen, Janssen. F. Calcagno: Financial Interests, Personal, Advisory Board: Merck, Pfizer. S. Ladoire: Financial Interests, Personal, Advisory Board, advisory board: Pfizer, Novartis, AstraZeneca, Sanofi, Daiichi, Gilead, Menarini-Stemline; Financial Interests, Personal, Advisory Board, advisory board, expert testimony: Astellas; Financial Interests, Personal, Advisory Board, expert testimony, invited speaker: Janssen, Ipsen; Financial Interests, Personal, Invited Speaker, invited speaker: BMS, Seagen, Exact Science; Financial Interests, Personal, Invited Speaker, invited speaker, expert testimony: Lilly; Financial Interests, Institutional, Research Grant, research grant: Novartis, Eisai, BMS. D. Borchiellini: Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Bristol Myer Squibb, Ipsen, Janssen, Merck, Pfizer; Financial Interests, Institutional, Advisory Board: Bayer, MSD; Financial Interests, Personal, Invited Speaker: Accord HealthCare; Financial Interests, Institutional, Local PI, Clinical Research: Astellas, AstraZeneca, Bayer, Bristol Myer Squibb, Exelixis, Infinity, Janssen, MSD, Roche, Taiho Oncology; Financial Interests, Institutional, Local PI: Aveo, Gilead, Seagen. A. Flechon: Financial Interests, Personal, Advisory Board: AstraZeneca, Astellas, Janssen, AAA, Bayer, MSD, Pfizer, Merck, BMS; Financial Interests, Personal, Invited Speaker: Novartis. G. Gravis: Financial Interests, Institutional, Invited Speaker: AAA, Amgen, Astellas, BMS, Janssen, MSD, Pfizer, Ipsen, AstraZeneca, alliance Merck Pfizer, Bayer, Eisai; Financial Interests, Institutional, Advisory Board: Alliance Merck-Pfizer, BMS, Janssen, Pfizer, ipsen, Bayer, Eisai; Financial Interests, Institutional, Funding: Janssen; Financial Interests, Institutional, Coordinating PI: BMS; Non-Financial Interests, Principal Investigator: Ipsen, BMS, Merck. B. Clarisse: Financial Interests, Institutional, Other, Institutional financial support and drug supply for TALASUR trial conduction: Pfizer; Financial Interests, Institutional, Other, Institutional financial support for the CogPRO trial: Astellas; Non-Financial Interests, Institutional, Product Samples, drug supply for patients enrolled in the TALASUR trial: Pfizer. A. Thiery Vuillemin: Financial Interests, Institutional, Funding: Pfizer; Financial Interests, Institutional, Local PI: Pfizer; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Ipsen, Janssen, MSD, Novartis, Pfizer, Roche Genentech, Sanofi; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Full or part-time Employment, Since 2023: BMS. F. Joly Lobbedez: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca, MSD, Janssen, Ipsen, Bayer, Astellas, Eisai, Seagen, Novocure, Pfizer; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, MSD, Janssen, Ipsen, Amgen, Novartis/3A, Eisai, Amgen, Eisai; Financial Interests, Institutional, Invited Speaker: Viatris; Financial Interests, Institutional, Coordinating PI: GSK, AstraZeneca; Financial Interests, Institutional, Research Grant: BMS, Astellas; Financial Interests, Institutional, Funding: Janssen; Non-Financial Interests, Member: GCIG; Other, travel and congress: MSD, Ipsen, Chugai; Other, travel: GSK, Eisai. All other authors have declared no conflicts of interest.