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LBA2 Updated analysis and patient-reported outcomes (PROs) from CITYSCAPE: A randomised, double-blind, phase II study of the anti-TIGIT antibody tiragolumab + atezolizumab (TA) versus placebo + atezolizumab (PA) as first-line treatment for PD-L1+ NSCLC

2021; Elsevier BV; Volume: 32; Linguagem: Inglês

10.1016/j.annonc.2021.10.217

1569-8041

B.C. Cho, Delvys Rodríguez‐Abreu, Maen Hussein, Manuel Cobo, A. Patel, Nevena Sečen, Gregory J. Gerstner, Dong‐Wook Kim, Y-G. Lee, Wu‐Chou Su, E.P. Huang, Namrata S. Patil, Mo Huang, Z. Zhang, X. Wen, Diana Mendus, Tien Hoang, Robin Meng, Melissa L. Johnson,

Immune Cell Function and Interaction

BackgroundTIGIT is a novel immune checkpoint present on activated T cells and NK cells; inhibition of TIGIT may further amplify the inhibition of the PD-L1/PD-1 pathway. CITYSCAPE (NCT03563716) is the first randomised Phase II study of an anti-TIGIT antibody; the combination of TA showed clinically meaningful improvement in ORR and PFS compared with PA in patients (pts) with metastatic PD-L1+ NSCLC. Here we present updated PFS, OS, and PROs.MethodsEligible pts with chemotherapy-naïve PD-L1+ (TPS ≥1% by local or central 22C3 IHC pharmDX assay) locally advanced, unresectable or metastatic NSCLC were randomised 1:1 to receive TA (T 600 mg IV + A 1200 mg IV) or PA (A 1200 mg IV) every 3 weeks until disease progression or loss of clinical benefit. The EORTC QLQ-C30 was administered at baseline and throughout study treatment. Co-primary endpoints: investigator-assessed ORR and PFS. Additional endpoints: DOR, OS, safety, association of tumour PD-L1 expression levels with clinical outcomes and PROs from the ITT population.ResultsTable: LBA2ITTPD-L1 TPS >=50%PATAPATAn68672929ORR, % (95% CI)20.6 (10.2, 30.9)38.8 (26.4, 51.2)24.1 (6.8, 41.4)69.0 (50.4, 87.5)mDOR, mo (95% CI)10.7 (6.0, 18.8)17.6 (9.1, 26.1)8.2 (5.6, 10.4)15.7 (9.1, NE)mPFS, mo (95% CI)3.9 (2.7, 4.5)5.6 (4.2, 10.4)4.1 (2.1, 6.8)16.6 (5.5, 22.3)HR (95% CI)0.62* (0.42, 0.91)0.29† (0.15, 0.53)mOS, mo (95% CI)14.5 (9.6, 20.4)23.2 (14.1, 31.5)12.8 (4.7, 24.2)NE (30.3, NE)HR (95% CI)0.69* (0.44, 1.07)0.23† (0.10, 0.53)*Stratified; †Unstratified. NE, non-evaluable. Open table in a new tab ConclusionTA continues to provide a clinically meaningful benefit in pts with metastatic NSCLC, driven by the PD-L1+ TPS ≥50% subgroup. TA has a manageable safety profile consistent with PD-L1/PD-1 inhibitors. Patients on TA maintained global health status and functioning and showed improvements in dyspnea and pain. Durable response and encouraging OS continue to support evaluating TA in metastatic PD-L1-high NSCLC.Clinical trial identificationNCT03563716.Editorial acknowledgementMedical 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.DisclosureB.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc., Brigebio therapeutics, Cyrus therapeutics, Guardant Health, Joseah BIO; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc., Interpark Bio Convergence Corp.; Financial Interests, Personal, Full or part-time Employment: Yonsei University College of Medicine; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GIInnovation, Eli Lilly, Blueprint medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines; Other, Personal, Other, Founder: DAAN Biotherapeutics. D. Rodriguez-Abreu: Financial Interests, Personal, Other, honoraria: Roche, AstraZeneca, Bristol-Myers Squibb, MSD, Eli Lilly, Pfizer, and Novartis; Financial Interests, Institutional, Invited Speaker, travel support: Roche, Bristol-Myers Squibb, MSD and Novartis. M. Hussein: Financial Interests, Personal, Advisory Role: IntegraConnect, Coherus Biosciences, Athenex, Karyopharm Therapeutics, BMS, AstraZeneca, Mirati Therapeutics, Exelixis. N. Secen: Non-Financial Interests, Personal and Institutional, Principal Investigator: Institute for Pulmonary Diseases of Vojvodina, Serbia. D. Kim: Financial Interests, Institutional, Research Grant: Alpha Biopharma, Amgen, Astrazeneca/Medimmune, Boehringer-Ingelheim, Daiichi-Sankyo, Hanmi, Janssen, Merus, Mirati Therapeutics, MSD, Novartis, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Chong Keun Dang,Bridge Bi; Financial Interests, Personal, Other, Travel support for advisory board meeting attendance: Amgen, Daiichi-Sankyo. E. Huang: Financial Interests, Personal, Full or part-time Employment: Roche Products Ltd. N. Patil: Financial Interests, Personal, Full or part-time Employment: Genentech. M. Huang: Financial Interests, Personal, Full or part-time Employment: Roche. X. Wen: Financial Interests, Personal, Full or part-time Employment: Roche Genentech. D. Mendus: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. T. Hoang: Financial Interests, Personal, Full or part-time Employment: Roche Genentech; Financial Interests, Personal, Stocks/Shares: Roche Genentech. R.D. Meng: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, Boehringer Ingelheim, Calithera Biosciences, Checkpoint Therapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi; Financial Interests, Personal, Advisory Role: Achilles Therapeutics, Bristol-Myers Squibb, Editas Medicine, Eisai, G1 Therapeutics, Ideaya Biosciences, Lilly Association of Community Cancer Centers. All other authors have declared no conflicts of interest. BackgroundTIGIT is a novel immune checkpoint present on activated T cells and NK cells; inhibition of TIGIT may further amplify the inhibition of the PD-L1/PD-1 pathway. CITYSCAPE (NCT03563716) is the first randomised Phase II study of an anti-TIGIT antibody; the combination of TA showed clinically meaningful improvement in ORR and PFS compared with PA in patients (pts) with metastatic PD-L1+ NSCLC. Here we present updated PFS, OS, and PROs. TIGIT is a novel immune checkpoint present on activated T cells and NK cells; inhibition of TIGIT may further amplify the inhibition of the PD-L1/PD-1 pathway. CITYSCAPE (NCT03563716) is the first randomised Phase II study of an anti-TIGIT antibody; the combination of TA showed clinically meaningful improvement in ORR and PFS compared with PA in patients (pts) with metastatic PD-L1+ NSCLC. Here we present updated PFS, OS, and PROs. MethodsEligible pts with chemotherapy-naïve PD-L1+ (TPS ≥1% by local or central 22C3 IHC pharmDX assay) locally advanced, unresectable or metastatic NSCLC were randomised 1:1 to receive TA (T 600 mg IV + A 1200 mg IV) or PA (A 1200 mg IV) every 3 weeks until disease progression or loss of clinical benefit. The EORTC QLQ-C30 was administered at baseline and throughout study treatment. Co-primary endpoints: investigator-assessed ORR and PFS. Additional endpoints: DOR, OS, safety, association of tumour PD-L1 expression levels with clinical outcomes and PROs from the ITT population. Eligible pts with chemotherapy-naïve PD-L1+ (TPS ≥1% by local or central 22C3 IHC pharmDX assay) locally advanced, unresectable or metastatic NSCLC were randomised 1:1 to receive TA (T 600 mg IV + A 1200 mg IV) or PA (A 1200 mg IV) every 3 weeks until disease progression or loss of clinical benefit. The EORTC QLQ-C30 was administered at baseline and throughout study treatment. Co-primary endpoints: investigator-assessed ORR and PFS. Additional endpoints: DOR, OS, safety, association of tumour PD-L1 expression levels with clinical outcomes and PROs from the ITT population. ResultsTable: LBA2ITTPD-L1 TPS >=50%PATAPATAn68672929ORR, % (95% CI)20.6 (10.2, 30.9)38.8 (26.4, 51.2)24.1 (6.8, 41.4)69.0 (50.4, 87.5)mDOR, mo (95% CI)10.7 (6.0, 18.8)17.6 (9.1, 26.1)8.2 (5.6, 10.4)15.7 (9.1, NE)mPFS, mo (95% CI)3.9 (2.7, 4.5)5.6 (4.2, 10.4)4.1 (2.1, 6.8)16.6 (5.5, 22.3)HR (95% CI)0.62* (0.42, 0.91)0.29† (0.15, 0.53)mOS, mo (95% CI)14.5 (9.6, 20.4)23.2 (14.1, 31.5)12.8 (4.7, 24.2)NE (30.3, NE)HR (95% CI)0.69* (0.44, 1.07)0.23† (0.10, 0.53)*Stratified; †Unstratified. NE, non-evaluable. Open table in a new tab *Stratified; †Unstratified. NE, non-evaluable. ConclusionTA continues to provide a clinically meaningful benefit in pts with metastatic NSCLC, driven by the PD-L1+ TPS ≥50% subgroup. TA has a manageable safety profile consistent with PD-L1/PD-1 inhibitors. Patients on TA maintained global health status and functioning and showed improvements in dyspnea and pain. Durable response and encouraging OS continue to support evaluating TA in metastatic PD-L1-high NSCLC. TA continues to provide a clinically meaningful benefit in pts with metastatic NSCLC, driven by the PD-L1+ TPS ≥50% subgroup. TA has a manageable safety profile consistent with PD-L1/PD-1 inhibitors. Patients on TA maintained global health status and functioning and showed improvements in dyspnea and pain. Durable response and encouraging OS continue to support evaluating TA in metastatic PD-L1-high NSCLC.