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
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract