LBA2 - SKYSCRAPER-06: Efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy (tira + atezo + chemo) vs pembrolizumab plus chemotherapy (pembro + chemo) in patients (pts) with advanced non-squamous non-small cell lung cancer (NSq NSCLC)

Background

Pembro + chemo is a standard of care 1L treatment in pts with advanced NSCLC, regardless of PD-L1 expression. SKYSCRAPER-06 (NCT04619797) is a global, phase II/III, randomised, double-blind, placebo-controlled trial assessing the efficacy and safety of tira + atezo + chemo vs pembro + chemo in pts with advanced NSq NSCLC.

Methods

Eligible pts were ≥18 years old with previously untreated locally advanced unresectable/metastatic NSq NSCLC, known PD-L1 status, an ECOG PS of 0/1, and no EGFR or ALK alterations. Pts were randomised 1:1 to receive tira 600 mg IV + atezo 1200 mg IV + carboplatin/cisplatin + pemetrexed IV or placebo + pembro 200 mg IV + carboplatin/cisplatin + pemetrexed IV, every 3 weeks for 4 cycles, followed by maintenance therapy with tira + atezo + pemetrexed or placebo + pembro + pemetrexed until disease progression, loss of clinical benefit, unacceptable toxicity or consent withdrawal. Stratification factors included PD-L1 expression (tumour proportion score [TPS] or tumour cells [TC] <1% vs 1–49% vs ≥50%). Primary endpoints: investigator-assessed PFS; OS. Secondary endpoints: other efficacy and safety endpoints.

Results

At data cut-off (19 Apr 24; median follow-up: 11.8 months), 542 pts were accrued to the study. Baseline characteristics were similar across arms; there were more men (68% vs 62%), fewer pts with PD-L1 TPS <1% (34% vs 42%) and more pts with liver metastases (14% vs 9%) in the tira + atezo + chemo vs the pembro + chemo arm. Median PFS was 8.3 vs 9.9 months and median OS was 18.9 vs 23.1 months in the tira + atezo + chemo and the pembro + chemo arms, respectively (Table). Tira + atezo + chemo demonstrated an acceptable safety profile with no new safety signals; safety was generally similar between arms. Table: LBA2

Conclusions

In the SKYSCRAPER-06 study, tira + atezo + chemo failed to improve PFS and OS vs pembro + chemo in pts with advanced NSq NSCLC.

Clinical trial identification

NCT04619797, Release date: 6 Nov 2020

Editorial acknowledgement

Third-party medical writing assistance, under the direction of authors, was provided by Rebecca Benatan, BSc, of Ashfield MedComms, an Inizio company, and was 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

M.A. Socinski: Non-Financial Interests, Personal, Advisory Board: Summit, BMS, Beigene, Genentech; Non-Financial Interests, Personal, Leadership Role: Elsevier Clinical Pathways; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Regeneron, Lilly, Guardant, Janssen, Jazz, Foundation, Gilead, Mirati, Abbvie, Merck, G1Therapeutics, Novartis; Financial Interests, Institutional, Research Funding: Roche/Genentech, Beigene, Lilly, Spectrum, Enliven, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, Spectrum, Summit, BMS, Beigene. D. Rodriguez Abreu: Financial Interests, Personal, Advisory Board: MSD, Regeneron, BMS, GSK, Lilly; Financial Interests, Personal, Invited Speaker, Honoraria for lectures: MSD, Roche, BMS, Lilly, AstraZeneca, Johnson ; Financial Interests, Personal, Local PI: Roche; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Steering Committee Member: Roche. D.H. Lee: Financial Interests, Personal, Advisory Board: ST Cube; Financial Interests, Personal, Coordinating PI: Abion; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, ChongKeunDang, Janssen, Merck, MSD, Novartis, Ono, Roche, Pfizer, Abbvie, Takeda; Non-Financial Interests, Personal, Steering Committee Member: Roche; Non-Financial Interests, Personal, Trial Chair: Abion. F. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, ILLUMINA, Thermofisher, Beigene, MSD; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, Beigene, MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, Beigene, MSD; Financial Interests, Institutional, Principal Investigator: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, Beigene, MSD; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Novocure, Mirati, Galecto, OSE, Illumina, Thermofisher, Beigene, MSD. 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Ozyilkan: Financial Interests, Personal, Advisory Role, Advisory/Consultancy: AstraZeneca; Financial Interests, Personal, Expert Testimony, Speaker Bureau/Expert Testimony: AstraZeneca, MSD; Financial Interests, Personal, Leadership Role: ESMO Palliative Working Group; Financial Interests, Personal, Other, Travel expenses, including accommodations: Pfizer, Roche, AstraZeneca, BMS; Financial Interests, Institutional, Research Funding: Pfizer, Novartis, Roche, Servier, AstraZeneca, Takeda, Gilead, Lilly, Janssen, Nobel, Paraxel, AbbVie, MSD, BMS, Astellas, ICON Iqvia. M.L. Johnson: Financial Interests, Institutional, Advisory Role: AbbVie, Alentis Therapeutics, Amgen, Arcus Biosciences, Arrivent, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Gilead Sciences, GSK; Financial Interests, Institutional, Principal Investigator: AbbVie, Adaptimmune, Amgen, Arcus Biosciences, Array Biopharma, Arrivent BioPharma, Artios Pharma, AstraZeneca, Bayer, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol-Myers Squibb, Calithera Biosciences, Carisma Therapeutics; Financial Interests, Institutional, Advisory Role: Gritstone Oncology, Hookipa Biotech, Immunocore, Janssen, Jazz Pharmaceuticals, Lilly, Merck, Mirati Therapuetics, ModeX Therapeutics, Normunity, Novartis, Novocure, Pfizer, Pyramid Biosciences, Regeneron Pharmaceuticals, Revolution Medicines; Financial Interests, Institutional, Principal Investigator: City of Hope National Medical Center, Conjupro Biotherapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab; Financial Interests, Institutional, Advisory Role: Sanofi-Aventis, Seagen, Synthekine, Takeda Pharmaceuticals, Zai Laboratory ; Financial Interests, Institutional, Principal Investigator: Genocea Biosciences, GSK, Gritstone Oncology, Harpoon, Helsinn Healthcare, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immuneering Corporation, Immunitas Therapeutics, Immunocore, Impact Therapeutics; Financial Interests, Institutional, Principal Investigator: Incyte, Janssen, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, NextPoint Therapeutics, Novartis, Numab Therapeutics, Nuvalent; Financial Interests, Institutional, Principal Investigator: OncoC4, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals,; Financial Interests, Institutional, Principal Investigator: Shattuck Labs, Silicon Therapeutics, Summit Therapeutics, Syndax Pharmaceuticals, Systimmune, Taiho Oncology, Takeda Pharmaceuticals, TCR2 Therapeutics, Tempest Therapeutics, TheRas, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Vividion, Vyriad, Y-mAbs Therapeutics. E.B. Garon: Financial Interests, Personal, Advisory Board: Abbvie; Arcus; AstraZeneca; Arrivent; Atreca; Black Diamond Therapeutics; BridgeBio; Bristol Myers Squibb; Daiichi-Sankyo; EMD Serono; Eli Lilly; Gilead; Hookipa; I-Mab; iTeos; LianBio; Merck; Merus; Novartis; Nuvalent; Pfizer; Regeneron; Sanofi; Seagen; Financial Interests, Institutional, Local PI: ABL-Bio; Arrivent; AstraZeneca; BridgeBio; Bristol Myers Squibb; Daiichi Sanyko; Eli Lilly; EMD Serono; Genentech; Gilead; Iovance Biotherapeutics; Merck; Mirati Novartis; Prelude; Regeneron; Synthekine; TILT Biotherapeutics; Financial Interests, Personal, Steering Committee Member: Arrivent; AstraZeneca; Bayer; Bristol Myers Squibb; Merck; Regeneron; Financial Interests, Personal, Advisory Board: Sensei; Sumitomo; Strata; Summit; Synthekine. J. 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Rooney: Financial Interests, Personal, Full or part-time Employment: Roche - Genentech. S. Troutman: Financial Interests, Personal, Full or part-time Employment: Genentech. P. Wen: Financial Interests, Personal, Full or part-time Employment: Genentech. N.S. Patil: Financial Interests, Personal, Stocks or ownership: Genentech Roche; Financial Interests, Personal, Full or part-time Employment: Genentech Roche. W. Zou: Financial Interests, Personal, Full or part-time Employment: Roche. R.A. Stahel: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, Gilead, Guardant, iTeos, Janssen, Merck, MSD, Novocure, Pfizer, PharmaMar, Roche; Financial Interests, Personal, Invited Speaker: Amgen, AstraZeneca, Boehringer Ingelheim, MSD, Roche; Financial Interests, Institutional, Other, President, ETOP IBCSG Partners Foundation: Amgen, AstraZeneca, BMS, Celgene, Daiichi Sankyo, GSK, Ipsen, Janssen, Mirati, MSD, Novartis, Pfizer, Pierre Fabre, Roche; Financial Interests, Personal, Steering Committee Member: Roche. All other authors have declared no conflicts of interest.