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PO002/#156  Efficacy and safety results from skyscraper-04: an open-label randomized phase 2 trial of tiragolumab plus atezolizumab for PD-L1-positive recurrent cervical cancer
  1. Ritu Salani1,
  2. Bradley Monk2,
  3. Yong-Man Kim3,
  4. Sharad Ghamande4,
  5. Shaundra Hall5,
  6. Domenica Lorusso6,
  7. Lisa Barraclough7,
  8. Lucy Gilbert8,
  9. Adrián Guzmán Ramírez9,
  10. Chien-Hsing Lu10,
  11. Dominique Berton11,
  12. Nicoletta Colombo12,
  13. Youyou Hu13,
  14. Venkatesh Krishnan14,
  15. Yuning Feng15,
  16. Nicole Kim16,
  17. Marcela Castro16,
  18. Yvonne Lin16 and
  19. Mary Mccormack17
  1. 1David Geffen School of Medicine, UCLA, Gynecology, Los Angeles, USA
  2. 2HonorHealth University of Arizona College of Medicine and Creighton University School of Medicine, Division of Gynecologic Oncology, Phoenix, USA
  3. 3Gynecologic Cancer Center, Asan Cancer Institute, Asan Medical Center, University of Ulsan, Dept. of Obstetrics and Gynecology, Seoul, Korea, Republic of
  4. 4Georgia Cancer Center, Augusta University, Gynecologic Oncology, Augusta, USA
  5. 5National Cervical Cancer Coalition, Patient Advocacy, Glendale, USA
  6. 6Fondazione Policlinico Gemelli and Catholic University of the Sacred Heart, Division of Gynecologic Oncology, Rome, Italy
  7. 7The Christie NHS Foundation Trust, -, Manchester, UK
  8. 8McGill University Health Centre, Department of Gynecologic Oncology, Montreal, Canada
  9. 9Instituto de Investigación en Ciencias Médicas (ICIMED), Oncology, San José, Costa Rica
  10. 10Taichung Veterans General Hospital, Department of Obstetrics and Gynecology, Taichung, Taiwan
  11. 11Institut de Cancérologie de l’Ouest, -, Saint Herblain, France
  12. 12University of Milan-Bicocca and Gynecologic Oncology Program, European Institute of Oncology IRCCS, Department of Medicine and Surgery, Milan, Italy
  13. 13F. Hoffmann-La Roche Ltd, Data Science, Basel, Switzerland
  14. 14Genentech, Oncology Biomarker Development, South San Francisco, USA
  15. 15Genentech, Product Development Safety, South San Francisco, USA
  16. 16Genentech, Product Development Oncology, South San Francisco, USA
  17. 17University College London Hospitals, Department of Oncology, London, UK


Introduction Immune checkpoint inhibitors are active in advanced cervical cancer. SKYSCRAPER-04 (NCT04300647) evaluated dual blockade with tiragolumab (anti-TIGIT) and atezolizumab (anti-PD-L1) (tira+atezo), an approach hypothesized to overcome immune suppression and restore immune response.

Methods Eligible patients had measurable (per investigator assessment) PD-L1-positive recurrent/persistent cervical cancer after 1–2 prior chemotherapy lines (including ≥1 platinum-based regimen). Patients were randomized 3:1 to atezolizumab 1200 mg with or without tiragolumab 600 mg q3w until unacceptable toxicity/progression. Crossover to tira+atezo was permitted after unequivocal progression during single-agent atezolizumab. Stratification factors were ECOG PS, prior (chemo)radiotherapy, and disease status. The primary endpoint was independent review committee (IRC)-assessed confirmed objective response rate (ORR) per RECIST v1.1 in all treated patients randomized to tira+atezo. An ORR ≥21% (1-sample z-test p≤0.0245) was required to demonstrate statistically significant improvement versus a 14.6% historical reference [Chung, 2019]. Secondary endpoints included IRC-assessed progression-free survival, overall survival, and pre-crossover safety.

Results Prior therapy in 171 treated patients included bevacizumab in 35%, (chemo)radiotherapy in 80%, and paclitaxel in 93%. IRC-assessed ORRs were 19.0% with tira+atezo and 15.6% with atezo alone (table 1). In post hoc exploratory analyses of patients with measurable disease per IRC assessment, ORRs were 21.6% (tira+atezo) and 15.8% (atezo). There were no new safety signals. In a post hoc follow-up analysis, 15% of patients remained on treatment and 15/45 initially randomized to atezo had crossed over to tira+atezo.

Abstract PO002/#156 Table 1

Outcomes for pts with PD-L1-positive (TAP ≥5%) recurrent cervical cancer receiving tiragolumab + atezolizumab or atezolizumab alone

Conclusion/Implications The ORR with tira+atezo was numerically but not significantly higher than the historical benchmark. This is the first reported phase 2 cervical cancer trial targeting TIGIT and PD-L1 concurrently.

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