Abstract 1190TiP
Background
Previously the standard of care for patients (pts) with locally advanced, unresectable, stage III NSCLC has been cCRT; however, 5-year overall survival (OS) rates are poor. Durvalumab (durva) is approved for pts without progressive disease (PD) after cCRT. However, long-term OS data are not yet available. Further evaluation of novel cancer immunotherapy combinations should be explored. Targeted inhibition of the PD-L1/PD-1 pathway may be further amplified by combining with novel anti-TIGIT agents such as tiragolumab (tira). In the phase II CITYSCAPE study (NCT03563716), atezo + tira was well tolerated and improved objective response rate (ORR) compared with atezo alone in 1L pts with metastatic PD-L1+ NSCLC; with greater benefit in the PD-L1-high (TPS ≥50%) subset.
Trial design
SKYSCRAPER-03 (NCT04513925) aims to evaluate the efficacy of atezo + tira vs single-agent anti-PD-L1 (durva) in pts with unresectable, stage III NSCLC who have not progressed after platinum-based cCRT. Data suggests that cCRT upregulates PD-L1 expression, potentially enabling PD-L1 low or negative tumours to derive benefit, so outcomes will be evaluated in all-comer (ITT) and PD-L1+ sub-populations. Approximately 800 pts with unresectable, stage III NSCLC without PD after ≥2 cycles of platinum-based cCRT per NCCN/ESMO guidelines, without EGFR/ALK mutations; known PD-L1 status; ECOG PS 0–1; will be randomised 1:1 to receive atezo 1680mg IV + tira 840mg IV Q4W or durva 10mg/kg IV Q2W/1500mg IV Q4W. Treatment will continue for up to 13 cycles of 28 days, or until unacceptable toxicity or symptomatic deterioration due to PD; in pts with radiographic PD (per RECIST v1.1) treatment may continue if evidence of ongoing clinical benefit. Stratification factors include PD-L1 status, histology, staging and ECOG PS. Primary endpoint: independent review facility-assessed progression-free survival (PFS) in the ITT and PD-L1+ (TC ≥1%) populations. Secondary endpoints: investigator-assessed PFS, OS, ORR and duration of response, safety and biomarker analyses. Recruitment is ongoing.
Clinical trial identification
NCT04513925.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Abigail Robertson, PhD, of Ashfield MedComms, an Ashfield Health company, and funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
R. Dziadziuszko: Financial Interests, Advisory Board: F. Hoffmann-La Roche Ltd., Pfizer, Boehringer Ingelheim, Bayer, Novartis, AstraZeneca, Merck Sharp & Dohme, Seattle Genetics, Foundation Medicine, Takeda; Financial Interests, Principal Investigator: F. Hoffmann-La Roche Ltd., Merck Sharp & Dohme, Amgen, Janssen, Bristol Myers Squibb, AstraZeneca; Non-Financial Interests, Product Samples: F. Hoffmann-La Roche Ltd., Novartis, Pfizer. M. Ahn: Financial Interests, Invited Speaker: AstraZeneca, Takeda, MSD, Ono, BMS, Lilly, Amgen, Merck, Roche; Financial Interests, Advisory Board: AstraZeneca, Takeda, MSD, Ono, BMS, Lilly, Amgen, Merck, Roche, Alpha Pharmaceuticals; Financial Interests, Funding: AstraZeneca, Roche. K.A. Kelly: Financial Interests, Full or part-time Employment: UC Davis Medical Center; Financial Interests, Advisory Board: Genentech, Inc., AstraZeneca; Financial Interests, Research Grant: Genentech, Inc., AstraZeneca. S. Popat: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, Beigene, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Guardant Health, Janssen, Lilly, Merck KGaA, Novartis, Roche, Takeda; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Other, Coordinating PI: Ariad, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Other, Local PI: AstraZeneca, GSK, Roche, Trizel; Financial Interests, Institutional, Other, Sub-Investigator: MSD; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor: ALK Positive UK; Non-Financial Interests, Leadership Role, Chair of Steering Committee: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Communications Committee Member: International Association for the Study of Lung Cancer; Non-Financial Interests, Advisory Role, Scientific Advisory Board Member: Lung Cancer Europe; Non-Financial Interests, Member of the Board of Directors: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Research Advisory Group Member: Ruth Strauss Foundation. H. Wakelee: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn; Financial Interests, Personal, Invited Speaker: Fishawack Facilitate LTD, Medscape, Research to Practice, MJH Holdings, Axis Medical Education, Nexus Oncology; Financial Interests, Personal, Other: Curio Science; Financial Interests, Personal, Writing Engagements: UpToDate; Financial Interests, Institutional, Other, Local PI: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/MedImmunne, BMS, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Other, Coordinating PI: Celgene; Financial Interests, Institutional, Member, Steering Committee Member: Genentech/Roche, Merck; Non-Financial Interests, Officer, President-Elect: International Association for the Study of Lung Cancer (IASLC); Non-Financial Interests, Leadership Role, Executive Committee: ECOG-ACRIN. A. Baird: Financial Interests, Invited Speaker, Honorarium: MSD Ireland, Roche Ireland; Financial Interests, Advisory Board, Honorarium: Roche Ireland; Non-Financial Interests, Leadership Role: Chair, IASLC Communications Committee; Non-Financial Interests, Other, I was a board member of LuCE (2018-2020) and have been president since May 2020. This is a non-remunerated position, however, LuCE has received support from the following organisations: Amgen, AstraZeneca, Bayer. Blueprint Medicines, BMS, Boehringer Ingelheim, Genzyme Corporation, Lilly, Merck, MSD, Novartis, Pfizer, Regeneron, Roche, Takeda; Janssen (honorarium). In this role, I also partake in patient Advisory Boards, Steering Committees and other patient related events: Lung Cancer Europe (LuCE). I.A. Rooney: Financial Interests, Full or part-time Employment: Roche-Genentech; Financial Interests, Stocks/Shares: Roche-Genentech. M. Afshari: Financial Interests, Full or part-time Employment: Genentech, Inc. E.S. Yao: Financial Interests, Full or part-time Employment: Roche/Genentech; Financial Interests, Stocks/Shares: Roche/Genentech. Z. Zhang: Financial Interests, Full or part-time Employment: Genentech, Inc. H. Kuriki: Financial Interests, Full or part-time Employment: Genentech, Inc., Chugai Pharmaceutical Co., Ltd.; Financial Interests, Stocks/Shares: Chugai Pharmaceutical Co., Ltd. N.S. Patil: Financial Interests, Full or part-time Employment: Genentech, Inc. X. Wen: Financial Interests, Full or part-time Employment: Genentech, Inc. J.D. Bradley: Financial Interests, Advisory Board, Honorarium: Mevion Medical Systems; AstraZeneca; Financial Interests, Research Grant, PI of research grant: Varian, Inc.; Financial Interests, Principal Investigator, Consultant: AstraZeneca; Financial Interests, Advisory Role, for Skyscraper 3: Genentech, Inc.