Abstract 970TiP
Background
For resectable NSCLC, surgery (often with neoadjuvant or adjuvant CT), is the standard of care. However, benefit is modest and there is need to improve outcomes. Atezo (anti-PD-L1) has shown promising efficacy as monotherapy and in combination with CT in NSCLC. Inhibition of the PD-L1 pathway may be amplified by inhibition of TIGIT signaling. In CITYSCAPE (phase II; NCT03563716), tira (anti-TIGIT) + atezo was well tolerated and improved objective response rate vs atezo alone in 1L metastatic PD-L1+ NSCLC. Hypothesis: tira + atezo may provide clinical benefit in the neoadjuvant setting by enhancing anti-tumour immune response and eradicating micrometastases, reducing risk of disease recurrence. SKYSCRAPER-05 (NCT04832854) will evaluate safety, tolerability and preliminary efficacy of neoadjuvant tira + atezo ± CT in pts with resectable NSCLC.
Trial design
In this global, open-label study, ∼82 pts with histologically/cytologically confirmed, resectable Stage II, IIIA, or select IIIB (T3N2 only) NSCLC who are eligible for R0 resection with curative intent; without EGFR/ALK mutations; ECOG PS 0–1; with no prior cancer immunotherapy, CT or radiotherapy for NSCLC will be enrolled into two cohorts. Cohort A: pts with PD-L1 TC ≥50% tumours or Cohort B: pts independent of PD-L1 status. Pts will receive 4 cycles of neoadjuvant tira 600 mg IV + atezo 1200 mg IV Q3W (Cohort A) (CT-free option) or in combination with platinum-doublet CT Q3W (Cohort B). Following resection, pts will receive adjuvant tira + atezo or platinum-based CT Q3W (Cohort A) or adjuvant tira + atezo for 16 cycles (Cohort B) until disease recurrence or unacceptable toxicity. Investigator-selected CT options are cisplatin or carboplatin + pemetrexed, carboplatin + paclitaxel, and cisplatin or carboplatin + gemcitabine. Primary endpoints: central pathology laboratory-assessed major pathological response, treatment-related surgical delays, cancellations/complications and safety. Secondary endpoints: pathological complete response and event-free survival. Exploratory biomarkers will be evaluated. Recruitment is ongoing.
Clinical trial identification
NCT04832854.
Editorial acknowledgement
Medical writing assistance, under the direction of the authors, was provided by Ashfield MedComms, an Ashfield Health company.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
H. Pass: Financial Interests, Speaker’s Bureau: BeiGene, Genentech Inc; Financial Interests, Royalties: NIH cell lines, Mesothelioma Book; Financial Interests, Advisory Board: genentech/Roche; Financial Interests, Research Grant: NCI/NIH, AACR; Financial Interests, Funding: NCI/NIH, AACR; Financial Interests, Advisory Role: Genentech/Roche. A.W. Kim: Non-Financial Interests, Advisory Board: Roche/Genentech Inc. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristrol Meyers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristrol Meyers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono; Financial Interests, Personal, Invited Speaker, Independent member: Grifols; Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc; Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO; Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer). C.A. Shu: Financial Interests, Advisory Board: Genentech Inc, Mirati, AstraZeneca, Janssen. M. Frueh: Financial Interests, Advisory Board: Roche. B.J. Gitlitz: Financial Interests, Full or part-time Employment: Roche/Genentech; Financial Interests, Stocks/Shares: Roche/Genentech. S. Troutman: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Stocks/Shares: Roche. X. Liu: Financial Interests, Full or part-time Employment: Genentech Inc. J. Hsu: Financial Interests, Full or part-time Employment: Roche/Genentech Inc; Financial Interests, Stocks/Shares: Roche/Genentech. N. Patil: Financial Interests, Full or part-time Employment: Roche/Genentech Inc. R.D. Meng: Financial Interests, Full or part-time Employment: Genentech Inc; Financial Interests, Stocks/Shares: Genentech Inc. All other authors have declared no conflicts of interest.