831TiP - A phase III, randomized, double-blind, placebo-controlled, international study of durvalumab in combination with gemcitabine plus cisplatin for patients with advanced biliary tract cancers: TOPAZ-1

Abstract

BackgroundAdvanced, unresectable biliary tract cancer (BTC) represents an area of unmet medical need due to its aggressive nature, limited treatment options, and poor prognosis. BTCs express PD-L1 and high levels of soluble PD-L1 correlate with poor prognosis in BTC patients (pts) treated with chemotherapy. PD-1/PD-L1 antagonists such as durvalumab (D; an anti–PD-L1 mAb) in combination with cytotoxic chemotherapy may contribute to a more effective antitumor immune response. Early clinical data demonstrate safety and efficacy for D as a single agent, but also in combination with chemotherapy in pts with BTC. Together, these data support the evaluation of D combined with the established chemotherapy regimen of gemcitabine (G) and cisplatin (C) for treatment of pts with previously untreated, unresectable locally advanced or metastatic BTC. Trial designTOPAZ-1 (NCT03875235) is the first large, phase III, randomized, double-blind, placebo-controlled, international study to evaluate immunotherapy + chemotherapy in pts with BTC in the first-line setting. Approximately 474 pts with previously untreated, unresectable locally advanced, recurrent or metastatic BTC will be randomized 1:1 to Arm A (D + G/C for up to 8 cycles, followed by D until progressive disease [PD]) or Arm B (placebo + G/C for up to 8 cycles, followed by placebo until PD). Pts will be stratified by disease status (initially unresectable vs recurrent) and primary tumor location. Eligibility criteria include previously untreated disease if unresectable or metastatic at initial diagnosis (and pts with recurrent disease >6 months after curative surgery or completion of adjuvant therapy), WHO/ECOG PS of 0 or 1, and no history of another primary malignancy, brain metastases or spinal cord compression. Pts with ampullary cancer or prior locoregional therapy will be excluded and major surgery must have been completed >28 days prior to the study. The primary endpoint is overall survival for Arm A vs Arm B. Secondary endpoints include progression-free survival, objective response rate, and duration of response by investigator assessment using RECSIST v1.1. Clinical trial identificationNCT03875235. Editorial acknowledgementJubilee Stewart, PhD, of PAREXEL, was funded by AstraZeneca. Legal entity responsible for the studyAstraZeneca. FundingAstraZeneca. DisclosureD. Oh: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca. L. Chen: Honoraria (self), Advisory / Consultancy: AstraZeneca; Bristol-Myers Squibb; Lilly; MSD; Ono Pharmaceutical; PharmaEngine; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; TTY; Biopharm; Advisory / Consultancy: Five Prime Therapeutics; Syncore; Research grant / Funding (institution): Celgene; GlaxoSmithKline; Merck Serono; Novartis; Pfizer; Polaris; Syncore; Licensing / Royalties: anti-alpha-enolase (ENO-1) monoclonal antibody to HuniLife Technology, Taiwan. T. Okusaka: Honoraria (self), Research grant / Funding (institution): Eisai; Lilly; Novartis; Yakult Honsha; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Dainippon Sumitomo Pharma; Advisory / Consultancy: Zeria Pharmaceutical; Honoraria (self): AbbVie; AstraZeneca Japan; Bayer Yakuhin; Celgene; Chugai Pharma; EA Pharma; Fujifilm; Nobelpharma; Ono Pharmaceutical; Pfizer; Shire; Takara Bio; Teijin Pharma; Zeria Pharmaceutical. S. Chin: Full / Part-time employment: AstraZeneca. N. Rokutanda: Full / Part-time employment: AstraZeneca. H. Uchinda: Full / Part-time employment: AstraZeneca. A. Vogel: Honoraria (self): Amgen; Bayer; Bristol-Myers Squibb; Delcath Systems; Lilly; MSD; Novartis; Roche; Sanofi, Incyte, AstraZeneca; Advisory / Consultancy: Amgen; Bayer; Bristol-Myers Squibb; Delcath Systems; Lilly; MSD; Novartis; Roche; Sanofi, Incyte, AstraZeneca; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Bayer; Ipsen; Roche. J.W. Valle: Honoraria (self): Ipsen; Advisory / Consultancy: Agios; AstraZeneca; Delcath Systems; Genoscience Pharma; Incyte; Ipsen; Keocyt; Merck; Novartis; PCI Biotech; Pfizer; Pieris Pharmaceuticals; QED; Speaker Bureau / Expert testimony: Ipsen; Novartis; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Celgene; Nucana. H. Kim: Full / Part-time employment: AstraZeneca. All other authors have declared no conflicts of interest.