Abstract 2780
Background
Advanced, 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 design
TOPAZ-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 identification
NCT03875235.
Editorial acknowledgement
Jubilee Stewart, PhD, of PAREXEL, was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
D. 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.
Resources from the same session
4413 - Infigratinib versus gemcitabine plus cisplatin multicenter, open-label, randomized, phase 3 study in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF trial
Presenter: Ghassan Abou-Alfa
Session: Poster Display session 2
Resources:
Abstract
4710 - Phase 3 (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Lorenza Rimassa
Session: Poster Display session 2
Resources:
Abstract
5509 - A Randomized Controlled, Open label, Adaptive Phase-3 Trial to Evaluate Safety and Efficacy of EndoTAG-1 Plus Gemcitabine versus Gemcitabine alone in Patients with Measurable Locally Advanced and/or Metastatic Adenocarcinoma of the Pancreas Failed on FOLFIRINOX Treatment (NCT03126435)
Presenter: Li-Tzong Chen
Session: Poster Display session 2
Resources:
Abstract
1463 - Modified FOLFOX versus modified FOLFOX plus nivolumab and ipilimumab in patients with previously untreated advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction – Moonlight, a randomized phase 2 trial of the German Gastric Group of the AIO.
Presenter: Sylvie Lorenzen
Session: Poster Display session 2
Resources:
Abstract
2392 - GLOW: Randomized Phase 3 Study of Zolbetuximab + CAPOX Compared With Placebo + CAPOX as First-line Treatment of Patients With CLD18.2⁺/HER2⁻ Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Manish Shah
Session: Poster Display session 2
Resources:
Abstract
5217 - PRODIGE67_UCGI33 ARION: Association of Radiochemotherapy and Immunotherapy for the treatment of unresectable Oesophageal caNcer: a comparative randomized phase II trial
Presenter: Rosine Guimbaud
Session: Poster Display session 2
Resources:
Abstract
1726 - Randomized phase II trial of weekly paclitaxel + ramucirumab versus weekly nab-paclitaxel + ramucirumab for unresectable advanced or recurrent gastric cancer with peritoneal dissemination refractory to first-line therapy: WJOG10617G/P-SELECT
Presenter: Kenro Hirata
Session: Poster Display session 2
Resources:
Abstract
2279 - FRONTiER: A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma
Presenter: Shun Yamamoto
Session: Poster Display session 2
Resources:
Abstract
4912 - A phase Ib/II study of AK104, a PD-1/CTLA-4 Bispecific Antibody, Combined With mXELOX as First-line Therapy for Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Presenter: Jiafu Ji
Session: Poster Display session 2
Resources:
Abstract
3780 - Perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: DANTE, a randomized, open-label phase II trial of the German Gastric Group of the AIO and the SAKK.
Presenter: Salah-Eddin Al-Batran
Session: Poster Display session 2
Resources:
Abstract