Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2022

Neoadjuvant and Adjuvant Pembrolizumab plus standard of care (SOC) for the treatment of resectable locally advanced (LA) head and neck squamous cell carcinoma (HNSCC): phase 3 KEYNOTE-689 (#448)

Arkadiy Klochikhin 1 , Robert I. Haddad 2 , Amichay Meirovitz 3 , Sufia Safina 4 , Irene Brana 5 , Christophe Le Tourneau 6 , Ravindra Uppaluri 7 , Nancy Y. Lee 8 , Ezra E. W. Cohen 9 , Rebecca Chernock 10 , William Westra 11 , Hong Liu 12 , Burak Gumuscu 12 , Kimberly Benjamin 12 , Douglas Adkins 10 , Elani Bowers 13
  1. Yaroslavl Regional Clinical Oncology, Yaroslavl, Russia
  2. Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
  3. Hadassah University Medical Center, Jerusalem, Israel
  4. Republican Dispensary of Tatarstan MoH, Kazan, Russia
  5. Vall d’Hebron Institute of Oncology, Barcelona, Spain
  6. Institut Curie, Paris, France
  7. Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, USA
  8. Memorial Sloan Kettering Cancer Center, New York, NY, USA
  9. UC San Diego, La Jolla, CA, USA
  10. Washington University School of Medicine, St Louis, MO, USA
  11. Icahn School of Medicine, New York, NY, USA
  12. Merck & Co., Inc., Rahway, NJ, USA
  13. MSD, Melbourne, VIC, Australia

Aims: The randomized, open-label, phase 3 KEYNOTE-689 trial (NCT03765918) is designed to evaluate neoadjuvant pembrolizumab and adjuvant pembrolizumab plus SOC in previously untreated LA HNSCC.

Methods: Approximately, 704 patients with newly diagnosed, resectable, LA HNSCC (stage III oropharyngeal p16-positive disease [T4 (N0-N2), M0]; stage III/IVA oropharyngeal p16-negative; or stage III/IVA laryngeal or hypopharyngeal disease or disease of the oral cavity, independent of p16 status) will be randomly assigned 1:1 to arm A (200 mg Q3W neoadjuvant pembrolizumab [2 cycles], surgical resection, then 200 mg Q3W adjuvant pembrolizumab [15 cycles] plus SOC) or arm B (surgical resection then adjuvant SOC). SOC for low-risk disease is adjuvant radiotherapy, 60 Gy total, 30 fractions; SOC for high-risk disease is adjuvant chemoradiation, 3 cycles of 100 mg/m2 Q3W cisplatin plus 66 Gy total, 33 fractions; SOC for gross residual disease is adjuvant radiation, 70 Gy total, 35 fractions. Randomization will be stratified by primary tumor site (oropharynx/oral cavity vs larynx vs hypopharynx), tumor stage (III vs IVA), and PD-L1 status (tumor proportion score ≥50% vs <50%). Patients must have evaluable disease and ECOG PS 0/1 for eligibility. Postoperative imaging will occur Q12W after completion of SOC treatment, every 3 months until year 3, then every 6 months until year 5. Primary end points: major pathologic response and event-free survival per RECIST v1.1. Secondary end points: overall survival, pathologic complete response, health-related quality of life, and safety. End points except safety will be evaluated in PD-L1 combined positive score ≥1 tumors and regardless of PD-L1 status.

Results:  KEYNOTE-689 is enrolling patients in North America, South America, Europe, Asia, and Australia. Recruitment is ongoing globally.

Conclusion: Results of KEYNOTE-689 will provide clarity on safety and efficacy of pembrolizumab for patients with resectable LA HNSCC in the neoadjuvant and adjuvant setting.

Clinical trial registration: NCT03765918