PMID- 37768658
OWN - NLM
STAT- MEDLINE
DCOM- 20231117
LR  - 20240312
IS  - 2374-2445 (Electronic)
IS  - 2374-2437 (Print)
IS  - 2374-2437 (Linking)
VI  - 9
IP  - 11
DP  - 2023 Nov 1
TI  - Anti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With 
      Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial.
PG  - 1574-1582
LID - 10.1001/jamaoncol.2023.3867 [doi]
AB  - IMPORTANCE: Inhibition of the T-cell immunoreceptor with Ig and ITIM domains 
      (TIGIT)/poliovirus receptor pathway may amplify the antitumor immune response of 
      atezolizumab in programmed death ligand 1-selected tumors. OBJECTIVE: To evaluate 
      the safety and antitumor activity of the anti-TIGIT antibody tiragolumab and its 
      combination with atezolizumab in patients with advanced solid tumors. DESIGN, 
      SETTING, AND PARTICIPANTS: The GO30103 open-label, first-in-human phase 1a/1b 
      dose-escalation and dose-expansion nonrandomized controlled trial was conducted 
      at 13 sites in 6 countries (Australia, Canada, France, Korea, Spain, and the US). 
      The start dates were May 23, 2016, for phase 1a and October 11, 2016, for phase 
      1b. Patients were aged 18 years or older with measurable disease at baseline. The 
      clinical cutoff date was October 1, 2021. Data analysis was performed on January 
      24, 2022. INTERVENTIONS: Patients received fixed-dose intravenous tiragolumab on 
      day 1 of each 21-day cycle (2 mg escalating to 1200 mg) in phase 1a, plus 
      fixed-dose intravenous atezolizumab (1200 mg every 3 weeks) in phase 1b. Patients 
      were treated until disease progression, loss of clinical benefit, or development 
      of unacceptable toxicity. MAIN OUTCOMES AND MEASURES: The primary end points 
      included the safety, tolerability, and recommended phase 2 dose (RP2D) of 
      tiragolumab or combination tiragolumab plus atezolizumab. The secondary end point 
      included the investigator-assessed objective response rate (ORR). Counts and 
      percentages are used for categorical variables, and medians and ranges are used 
      for continuous variables. RESULTS: Among the phase 1a (n = 24) and 1b (n = 49) 
      dose-escalation cohorts, the median age was 60 (range, 40-77) and 54 (range, 
      25-81) years, respectively. More than half of patients were women (14 of 24 [58%] 
      and 25 of 49 [51%]), and more than a third (10 [42%] and 18 [37%]) had received 4 
      or more prior cancer therapies. No dose-limiting toxicities occurred, and the 
      maximum tolerated dose of tiragolumab was not reached (NR). The most frequent 
      treatment-related adverse events (AEs) were fatigue (5 of 24 [21%]) in phase 1a 
      and pruritus (5 of 49 [10%]) in phase 1b; the majority of AEs were grade 1 or 2. 
      Immune-mediated AEs occurred in 4 of 24 (17%) and 29 of 49 (59%) patients during 
      phases 1a and 1b, respectively (primarily grade 1 or 2). The RP2D of tiragolumab 
      was 600 mg intravenously every 3 weeks, which was tested in phase 1b dose 
      expansion. The confirmed ORR was 0% during phase 1a, with evidence of antitumor 
      activity in 6% of patients (n = 3) during phase 1b. The safety profile of 
      combination tiragolumab plus atezolizumab in phase 1b was similar in the 
      dose-escalation and dose-expansion cohorts. The confirmed ORR was 46% (6 of 13) 
      in the non-small cell lung cancer (NSCLC) cohort (median duration of response 
      [DOR], NR) and 28% (5 of 18) in the esophageal cancer (EC) cohort (median DOR, 
      15.2 [95% CI, 7.0 to NR] months). CONCLUSIONS AND RELEVANCE: In this 
      nonrandomized controlled trial, tiragolumab was well tolerated with or 
      without atezolizumab; no new safety signals were observed. Preliminary antitumor 
      activity was demonstrated for the combination regimen in patients with cancer 
      immunotherapy-naive metastatic NSCLC or EC. TRIAL REGISTRATION: 
      ClinicalTrials.gov Identifier: NCT02794571.
FAU - Kim, Tae Won
AU  - Kim TW
AD  - Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Korea.
FAU - Bedard, Philippe L
AU  - Bedard PL
AD  - Princess Margaret Cancer Center, Toronto, Ontario, Canada.
FAU - LoRusso, Patricia
AU  - LoRusso P
AD  - Yale Cancer Center, New Haven, Connecticut.
FAU - Gordon, Michael S
AU  - Gordon MS
AD  - HonorHealth Research and Innovation Institute, Scottsdale, Arizona.
FAU - Bendell, Johanna
AU  - Bendell J
AD  - Sarah Cannon Research Institute, Tennessee Oncology, Nashville, Tennessee.
AD  - now with F. Hoffmann-La Roche Ltd, Basel, Switzerland.
FAU - Oh, Do-Youn
AU  - Oh DY
AD  - Seoul National University Hospital, Cancer Research Institute, Seoul National 
      University College of Medicine, Integrated Major in Innovative Medical Science, 
      Seoul National University Graduate School, Seoul, South Korea.
FAU - Ahn, Myung-Ju
AU  - Ahn MJ
AD  - Samsung Medical Center, Seoul, Korea.
FAU - Garralda, Elena
AU  - Garralda E
AD  - Vall d'Hebron University Hospital, Barcelona, Spain.
FAU - D'Angelo, Sandra P
AU  - D'Angelo SP
AD  - Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New 
      York, New York.
FAU - Desai, Jayesh
AU  - Desai J
AD  - Department of Cancer Medicine, Peter MacCallum Cancer Center, Melbourne, 
      Victoria, Australia.
FAU - Hodi, F Stephen
AU  - Hodi FS
AD  - Dana-Farber Cancer Institute, Boston, Massachusetts.
FAU - Wainberg, Zev
AU  - Wainberg Z
AD  - Jonsson Comprehensive Cancer Center, University of California, Los Angeles.
FAU - Delord, Jean-Pierre
AU  - Delord JP
AD  - Institut Universitaire du Cancer de Toulouse, Toulouse, France.
FAU - Cassier, Phillippe A
AU  - Cassier PA
AD  - Department of Medical Oncology, Centre Leon Berard, Lyon, France.
FAU - Cervantes, Andres
AU  - Cervantes A
AD  - Department of Medical Oncology, Hospital Clinico Universitario de Valencia, 
      Valencia, Spain.
FAU - Gil-Martin, Marta
AU  - Gil-Martin M
AD  - Department of Medical Oncology, Catalan Institute of Oncology, Bellvitge 
      Biomedical Research Institute, Barcelona, Spain.
FAU - Wu, Benjamin
AU  - Wu B
AD  - Clinical Pharmacology, Genentech Inc, South San Francisco, California.
FAU - Patil, Namrata S
AU  - Patil NS
AD  - Biomarkers, Genentech Inc, South San Francisco, California.
FAU - Jin, Yanling
AU  - Jin Y
AD  - Biostatistics, F. Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada.
FAU - Hoang, Tien
AU  - Hoang T
AD  - Clinical Science, Genentech Inc, South San Francisco, California.
FAU - Mendus, Diana
AU  - Mendus D
AD  - Clinical Science, Genentech Inc, South San Francisco, California.
FAU - Wen, Xiaohui
AU  - Wen X
AD  - Safety Science, Genentech Inc, South San Francisco, California.
FAU - Meng, Raymond
AU  - Meng R
AD  - Clinical Science, Genentech Inc, South San Francisco, California.
FAU - Cho, Byoung Chul
AU  - Cho BC
AD  - Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of 
      Medicine, Seoul, South Korea.
LA  - eng
SI  - ClinicalTrials.gov/NCT02794571
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - UL1 TR001863/TR/NCATS NIH HHS/United States
PT  - Comment
PT  - Journal Article
PL  - United States
TA  - JAMA Oncol
JT  - JAMA oncology
JID - 101652861
RN  - 52CMI0WC3Y (atezolizumab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (TIGIT protein, human)
RN  - 0 (Receptors, Immunologic)
SB  - IM
CON - JAMA Oncol. 2023 Nov 1;9(11):1503-1504. PMID: 37768657
MH  - Humans
MH  - Female
MH  - Middle Aged
MH  - Male
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy
MH  - *Lung Neoplasms/drug therapy
MH  - Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antibodies, Monoclonal/therapeutic use
MH  - *Antineoplastic Agents/adverse effects/administration & dosage
MH  - *Esophageal Neoplasms/drug therapy
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/administration & 
      dosage
MH  - Receptors, Immunologic/therapeutic use
PMC - PMC10540058
COIS- Conflict of Interest Disclosures: Dr Kim reported receiving grants (to University 
      of Ulsan) from Genentech outside the submitted work. Dr Bedard reported receiving 
      grants from Genentech/Roche during the conduct of the study and from AstraZeneca, 
      Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), Lilly, Merck, Amgen, Novartis, 
      SeaGen, Sanofi, Bicara, Zymeworks, Medicenna, Bayer, Pfizer, and Takeda outside 
      the submitted work. Dr Bedard also reported participating on advisory boards 
      (uncompensated) for BMS, SeaGen, Merck, Lilly, Amgen, and Zymeworks outside the 
      submitted work. Dr LoRusso reported receiving grants from Genentech/Roche during 
      the conduct of the study and advisory board fees from Genentech/Roche outside the 
      submitted work. Dr Gordon reported receiving clinical trial support (to Pinnacle 
      Oncology Hematology and HonorHealth Research Institute) from Roche and Astellas 
      during the conduct of the study and from Serono, Amgen, Gilead, BMS, Five Prime, 
      Lilly, Merck, MedImmune, GSK, Novartis, Macrogenics, OncoMed, Daiichi-Sankyo, 
      Incyte, SynDevRx, AbbVie, Array Biopharma, Celldex, Tracon, Synthorx, Revolution 
      Medicine, Tizona, Tolero, Aadi, Agenus, Alpine Immune Sciences, Arcus, Corcept, 
      Deciphera, Dracen, Endocyte, Forma Therapeutics, FujiFilm, Tesaro, Toray, and 
      Syndax outside the submitted work. Dr Bendell reported receiving grants (to Sarah 
      Cannon Research Institute) from Genentech/Roche during the conduct of the study 
      and from Genentech/Roche, Gilead, BMS, Five Prime, Lilly, Merck, Medimmune, EMD 
      Serono, Taiho, AstraZeneca, Celgene, GSK, Novartis, Macrogenics, Oncomed, LEAP 
      Therapeutics, TG Therapeutics, Boehringer Ingelheim, Daiichi Sankyo, Bayer, 
      Incyte, Apexigen, Koltan, SynDevRx, Forty Seven, AbbVie, Array, Onyx, Sanofi, 
      Takeda, Eisai, Celldex, Agios, Cytomx, Nektar, ARMO, Boston Biomedical, Ipsen, 
      Merrimack, Tarveda, Tyrogenex, Oncogenex, Merrimack, Ipsen, Marshall Edwards, 
      Pieris, Mersana, Calithera, Blueprint Medicines, Evelo, FORMA, Merus, Jacobio, 
      Effector, Novocare, Arrys, Tracon, Sierra, Innate, Arch Oncology, Prelude, UNUM, 
      Vyriad, Harpoon, Amgen, ADC Therapeutics, Pfizer, Millenium, Imclone, Acerta, 
      Rgenix, Bellicum, Gossamer, Arcus, Seattle Genetics, Tempestx, Shattuck Labs, 
      Synthorx, Revolution Medicines, Bicycle, Zymeworks, Relay, Scholar Rock, NGM 
      Biopharma, Stemcentrix, BeiGene, Cyteir, Foundation Bio, Morphotex, OncXerna, 
      NuMAb, Atlas MedX, Treadwell Therapeutics, IGM, Mabspace, Hutchinson Medipharma, 
      REPARE, NeoImmune Tech, Regeneron, and PureTech Health outside the submitted 
      work. Dr Bendell also reported receiving other support (to Sarah Cannon Research 
      Institute) from Molecular Partners, Tizona, Janssen, Tolero, Seattle Genetics, 
      Moderna, Agios, and Samsung Bioepios outside the submitted work. Dr Oh reported 
      receiving grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, 
      MSD, and Handok and participating on advisories for AstraZeneca, Novartis, 
      Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, 
      BMS/Celgene, BeiGene, Basilea, Turning Point, and Yuhan outside the submitted 
      work. Dr Ahn reported receiving personal fees from AstraZeneca, Merck, Yuhan, 
      MSD, Takeda, Roche, Alpha Pharmaceuticals, Amgen, Ono, BMS, Daiichi Sankyo, and 
      Arcus outside the submitted work. Dr Garralda reported receiving grants from 
      Novartis, Roche, Thermo Fisher Scientific, AstraZeneca, Taiho, BeiGene, and 
      Janssen; consulting/advisory fees from F. Hoffmann-La Roche, Ellipses Pharma, 
      Neomed Therapeutics Inc, Boehringer Ingelheim, Janssen Global Services, Seattle 
      Genetics, Thermo Fisher Scientific, MabDiscovery, Anaveon, F-Star Therapeutics, 
      Hengrui, Sanofi, and Incyte; and speaking fees from Merck Sharp & Dohme, Roche, 
      Thermo Fisher Scientific, Lilly, Novartis, and Seattle Genetics during the 
      conduct of the study. Dr D'Angelo reported receiving personal fees from Aadi 
      Bioscience, Adaptimmune, GI Innovation, GSK, Incyte, Pfizer, Rain Therapeutics, 
      and Servier outside the submitted work. Dr Desai reported receiving grants from 
      Genentech/Roche during the conduct of the study. Dr Desai also reported receiving 
      grants from BMS, GSK, AstraZeneca, Genentech/Roche, and BeiGene; and personal 
      fees from Genentech/Roche, Amgen, Bayer, Pierre-Fabre, Merck KGaA, Boehringer 
      Ingelheim, Daiichi Sankyo Europe GmbH, Novartis, and BeiGene outside the 
      submitted work. Dr Hodi reported receiving clinical trial support (to Dana-Farber 
      Cancer Institute) from Genentech/Roche during the conduct of the study. Dr Hodi 
      also reported receiving personal fees from BMS, Merck, Novartis, Surface, 
      Compass, Apricity, Bicara, Checkpoint, Bioentre, Gossamer, Iovance, Catalym, 
      Immunocore, Zumutor, Corner, Curis, and AstraZeneca; and being an inventor on 
      pending patents (20170248603, 20160340407, 20160046716, 10279021, 10106611, and 
      20170343552) for Dana-Farber Cancer Institute outside the submitted work. Dr 
      Wainberg reported receiving grants from AbbVie and Arcus and consulting fees from 
      Amgen, Astellas, AstraZeneca, Daiichi Sankyo, Roche, Merck, Novartis, SeaGen, 
      BMS, Ipsen, Incyte, Pfizer, and Lilly outside the submitted work. Dr Delord 
      reported receiving grants (to Institut Universitaire du Cancer de Toulouse) from 
      BMS, Merck Serono, MSD, Roche, Amgen, AstraZeneca, Genentech, and Transgene 
      outside the submitted work. Dr Cassier reported receiving personal fees from 
      Genentech/Roche during the conduct of the study and from Boehringer Ingelheim, 
      Ose Immunotherapeutics, and BMS outside the submitted work. Dr Cassier also 
      reported receiving nonfinancial support from Novartis outside the submitted work. 
      Dr Cervantes reported receiving grants (to Hospital Clinico Universitario de 
      Valencia) from Genentech during the conduct of the study and from Merck Serono, 
      MSD, BMS, Roche, BeiGene, Bayer, Servier, Lilly, Novartis, Takeda, Astellas, 
      Natera, Amgen, AbbVie, and GSK outside the submitted work. Dr Gil-Martin reported 
      receiving honoraria from AstraZeneca, MSD, and Clovis and meeting support from 
      PharmaMar, MSD, Clovis, and GSK. Dr Wu reported being employed by Genentech 
      during the conduct of the study and holding stock in Genentech/Roche outside the 
      submitted work. Dr Patil reported being employed by Genentech during the conduct 
      of the study and holding stock in Genentech/Roche outside the submitted work. Dr 
      Jin reported being employed by Roche during the conduct of the study and holding 
      stock in Roche outside the submitted work. Dr Hoang reported being employed by 
      Genentech during the conduct of the study and receiving other Genentech employee 
      compensation (salary, stocks, bonus, etc) outside the submitted work. In 
      addition, Dr Hoang reported being employed by Genentech during the conduct of the 
      study and receiving other Genentech employee compensation (salary, stocks, bonus, 
      etc) outside the submitted work. Dr Mendus reported being employed by Genentech 
      during the conduct of the study and receiving other Genentech employee 
      compensation (salary, stocks, bonus, etc) outside the submitted work. In 
      addition, Dr Mendus reported having a patent pending for tiragolumab licensed to 
      Genentech. Dr Wen reported being employed by Genentech during the conduct of the 
      study and holding stock in Genentech/Roche outside the submitted work. Dr Meng 
      reported being employed by Genentech during the conduct of the study and 
      receiving other Genentech employee compensation (salary, stocks, bonus, etc) 
      outside the submitted work. Dr Cho reported receiving royalties from Champions 
      Oncology, Crown Bioscience, and Imagen; grants from MOGAM Institute, LG Chem, 
      Oscotec, Interpark Bio Convergence Corp, GI Innovation, GI Cell, Abion, AbbVie, 
      AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions 
      Oncology, CJ Bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, 
      Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio 
      Therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph Therapeutics, Therapex, J INTS 
      Bio, Hanmi, and CHA Bundang Medical Center; and consulting fees from Abion, 
      BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, 
      Cyrus Therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI 
      Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc, Janssen, Takeda, MSD, 
      Janssen, Medpacto, Blueprint Medicines, Rand Bio, and Hanmi outside the submitted 
      work. Dr Cho also reported receiving personal fees for advisory board service 
      from Yonsei University Health System, Kanaph Therapeutics, Bridgebio 
      Therapeutics, Cyrus Therapeutics, Guardant Health, and Oscotec Inc; and speaking 
      fees from the American Society of Clinical Oncology, AstraZeneca, Guardant, 
      Roche, the European Society for Medical Oncology, the International Association 
      for the Study of Lung Cancer, the Korean Cancer Association, the Korean Society 
      of Medical Oncology, the Korean Society of Thyroid-Head and Neck Surgery, the 
      Korean Cancer Study Group, Novartis, MSD, the Chinese Thoracic Oncology Society, 
      and Pfizer outside the submitted work. Dr Cho also reported holding stock or 
      shares in TheraCanVac Inc, Gencurix Inc, Bridgebio Therapeutics, Kanaph 
      Therapeutics, Cyrus Therapeutics, Interpark Bio Convergence Corp, and J INTS BIO; 
      founding DAAN Biotherapeutics; and serving on the board of directors of Interpark 
      Bio Convergence Corp and J INTS BIO outside the submitted work. No other 
      disclosures were reported.
EDAT- 2023/09/28 12:41
MHDA- 2023/11/17 15:31
PMCR- 2023/09/28
CRDT- 2023/09/28 11:33
PHST- 2023/11/17 15:31 [medline]
PHST- 2023/09/28 12:41 [pubmed]
PHST- 2023/09/28 11:33 [entrez]
PHST- 2023/09/28 00:00 [pmc-release]
AID - 2810007 [pii]
AID - coi230050 [pii]
AID - 10.1001/jamaoncol.2023.3867 [doi]
PST - ppublish
SO  - JAMA Oncol. 2023 Nov 1;9(11):1574-1582. doi: 10.1001/jamaoncol.2023.3867.