Article Text

Download PDFPDF
A non-comparative, randomized, phase II trial of atezolizumab or atezolizumab plus tiragolumab for programmed death-ligand 1-positive recurrent cervical cancer (SKYSCRAPER-04)
  1. Ritu Salani1,
  2. Mary McCormack2,
  3. Yong-Man Kim3,
  4. Sharad Ghamande4,
  5. Shaundra L Hall5,
  6. Domenica Lorusso6,
  7. Lisa Barraclough7,
  8. Lucy Gilbert8,
  9. Adrian Guzman Ramirez9,
  10. Chien-Hsing Lu10,
  11. Renaud Sabatier11,
  12. Nicoletta Colombo12,13,
  13. Youyou Hu14,
  14. Venkatesh Krishnan15,
  15. Luciana Molinero15,
  16. Yuning Feng15,
  17. Nicole Kim15,
  18. Marcela Castro15,
  19. Yvonne G Lin15 and
  20. Bradley J Monk16
    1. 1Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, California, USA
    2. 2Department of Oncology, University College London Hospitals, London, UK
    3. 3Gynecologic Cancer Center, Asan Cancer Institute, Asan Medical Center, University of Ulsan, Seoul, Korea (the Republic of)
    4. 4Georgia Cancer Center, Augusta University, Augusta, Georgia, USA
    5. 5National Cervical Cancer Coalition, Research Triangle Park, North Carolina, USA
    6. 6Gynecologic Oncology Unit, Fondazione Policlinico Gemelli IRCCS and Catholic University of the Sacred Heart, Rome, Italy
    7. 7Clinical Oncology, The Christie NHS Foundation Trust, Manchester, UK
    8. 8The Gerald Bronfman Department of Oncology, McGill University Health Centre, McGill University, Montreal, Quebec, Canada
    9. 9Instituto de Investigación en Ciencias Médicas (ICIMED), San José, Costa Rica
    10. 10Department of OB/GYN, Taichung Veterans General Hospital, Taichung, Taiwan
    11. 11Department of Medical Oncology, Aix-Marseille University, CRCM, Inserm, CNRS, Institut Paoli-Calmettes, Marseille, France
    12. 12Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy
    13. 13Gynecologic Oncology Program, European Institute of Oncology IRCCS, Milan, Italy
    14. 14F. Hoffmann-La Roche Ltd, Basel, Switzerland
    15. 15Genentech, Inc, South San Francisco, California, USA
    16. 16Department of Oncology, HonorHealth University of Arizona College of Medicine and Creighton University School of Medicine, Phoenix, Arizona, USA
    1. Correspondence to Dr Ritu Salani, Department of Obstetrics and Gynecology, University of California Los Angeles, Los Angeles, California, USA; rsalani{at}mednet.ucla.edu
    • Present affiliation The present affiliation of Bradley J Monk is: Florida Cancer Specialists and Research Institute, West Palm Beach, Florida, USA

    Abstract

    Objective To evaluate tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) as second- or third-line therapy for PD-L1-positive persistent/recurrent cervical cancer.

    Methods In the open-label, non-comparative, randomized phase II SKYSCRAPER-04 trial (NCT04300647), patients with PD-L1-positive (SP263 tumor area positivity ≥5%) recurrent/persistent cervical cancer after 1–2 chemotherapy lines (≥1 platinum-based) were randomized 3:1 to atezolizumab 1200 mg with/without tiragolumab 600 mg every 3 weeks until disease progression or unacceptable toxicity. Stratification factors were performance status, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee-assessed confirmed objective response rate per RECIST v1.1 in patients receiving tiragolumab plus atezolizumab. An objective response rate ≥21% (one-sample z-test p≤0.0245) was required for statistical significance versus a historical reference.

    Results Protocol-defined independent review committee-assessed objective response rates were 19.0% (95% CI 12.6 to 27.0) in 126 patients receiving tiragolumab plus atezolizumab (p=0.0787 vs historical reference) and 15.6% (95% CI 6.5 to 29.5) in 45 atezolizumab-treated patients. Response rates were higher in PD-L1high (tumor area positivity ≥10%) than PD-L1low (tumor area positivity 5%–9%) subgroups with both regimens. At 8.5 months’ median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus atezolizumab and 1.9 months (95% CI 1.5 to 3.0) with atezolizumab. In post hoc analyses (10.4 months’ median follow-up), median overall survival was 11.1 months (95% CI 9.6 to 14.5) with the combination and 10.6 months (95% CI 6.9 to 13.8) with atezolizumab (crossover permitted). In the combination group, 3% of patients had adverse events requiring treatment discontinuation and 8% had grade ≥3 adverse events of special interest; corresponding values in the single-agent arm were 4% and 11%. There were no treatment-related deaths or new safety findings.

    Conclusion The objective response rate with the tiragolumab-plus-atezolizumab combination was numerically higher than the historical reference but did not reach statistical significance.

    • Cervical Cancer
    • Immunotherapy

    Data availability statement

    Data are available upon reasonable request. Qualified researchers may request access to individual patient-level clinical data through a data request platform. At the time of writing this request platform is Vivli (https://vivli.org/ourmember/roche/). For up-to-date details of Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see https://go.roche.com/data_sharing. Anonymized records for individual patients across more than one data source external to Roche cannot, and should not, be linked due to a potential increase in risk of patient re-identification.

    Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    Data availability statement

    Data are available upon reasonable request. Qualified researchers may request access to individual patient-level clinical data through a data request platform. At the time of writing this request platform is Vivli (https://vivli.org/ourmember/roche/). For up-to-date details of Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see https://go.roche.com/data_sharing. Anonymized records for individual patients across more than one data source external to Roche cannot, and should not, be linked due to a potential increase in risk of patient re-identification.

    View Full Text

    Footnotes

    • Contributors Study design: RSal, MM, Y-MK, SG, SLH, DL, VK, YGL, BJM. Data collection: RSal, MM, Y-MK, SG, DL, LB, LG, AGR, C-HL, RSab, NC, BJM. Data analysis: YH, VK, LM. All authors participated in data interpretation, review, and approval of the manuscript. RSal acted as guarantor.

    • Funding This study was funded by F. Hoffmann-La Roche Ltd.

    • Competing interests Medical writing support and article processing charges were funded by F. Hoffmann-La Roche Ltd. RSal reports personal consulting fees from Merck, Eisai, Regeneron, GSK, ImmunoGen, Karyopharm, Genentech, Clovis, AstraZeneca, and Mersana. Y-MK reports clinical study grants (to institution) from MSD, AstraZeneca, ImmunoGen, Zentalis, and BeiGene, and unpaid leadership roles for KGOG and EAGOT. SG reports consulting fees from GSK, Eisai, and Seagen; speaker honoraria from GSK; research contracts (with institution) from GSK, Merck, Takeda, BMS, Sutro, Jounce, AstraZeneca, and Eisai; and an unpaid leadership role with the GOG Foundation. DL reports personal fees for consulting from AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, MSD, PharmaMar, Seagen, and Novartis; speaker honoraria from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; research grants to institution from AstraZeneca, Clovis Oncology, Genmab, GSK, ImmunoGen, Incyte, MSD, Novartis, PharmaMar, Seagen, and Roche; participation on data safety monitoring or advisory boards for AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, ImmunoGen, MSD, Oncoinvest, PharmaMar, Seagen, and Sutro; and support for meeting attendance/travel from GSK, AstraZeneca, Clovis Oncology, and MSD. LG reports grants (to institution) from IMV, Pfizer, Sutro Biopharma, MSD, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group Beta, Inc., GOG Foundation, GSK, AstraZeneca, Oncquest Laboratories, Novocure GmbH, Alkermes Inc., Esperas, and Mersana; consulting fees from GSK and Merck; meeting support/travel from GSK, Merck, Genentech, and Zentalis Pharma; and advisory board participation for GSK, Merck, Eisai, Novocure, Kora Healthcare, Corcept Therapeutics, ImmunoGen, and Canaribio Inc. AGR reports speaker honoraria from Roche, Pfizer, and Janssen; support for attending meetings/travel from Novartis, Roche, and Pfizer; and participation in data safety monitoring or advisory boards for Roche and Novartis. RSab reports consulting/advisory roles for Eisai, and GSK; speaker honoraria from Clovis, GSK, MSD, Seagen, Eisai, and Novartis; research funding to institution from AstraZeneca; and travel/accommodation support from MSD, GSK, and Novartis. NC reports honoraria from AstraZeneca, Novartis, Clovis Ocology, GSK, MSD/Merck, and Eisai; consulting/advisory roles for AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Mersana, MSD/Merck, Nuvation Bio, Onxerna, Pfizer, Pieris, Roche, Novocure, and Eisai; research funding (to institution) from GSK, Roche, and AstraZeneca; leadership for ACTO onlus - Chair, Scientific Committee, and travel/accommodation/expenses from AstraZeneca. YH, VK, LM, YF, NK, MC, and YGL are employees of Roche/Genentech and hold shares in Roche. BJM reports consulting fees from Acrivon, Adaptimmune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Eisai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, Tesaro/GSK, US Oncology Research, VBL, Verastem, and Zentalis; and speaker honoraria from AstraZeneca, Eisai, Myriad, Roche/Genentech, and Tesaro/GSK. All remaining authors report no conflict of interest.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.