Roy S Herbst1, Margarita Majem2, Fabrice Barlesi3, Enric Carcereny4, Quincy Chu5, Isabelle Monnet6, Alfredo Sanchez-Hernandez7, Shaker Dakhil8, D Ross Camidge9, Leanne Winzer10, Yee Soo-Hoo11, Zachary A Cooper11, Rakesh Kumar11, John Bothos11, Charu Aggarwal12, Alex Martinez-Marti13. 1. Yale Cancer Center, New Haven, CT. 2. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 3. Gustave Roussy, Villejuif, France. 4. Institut Català d'Oncologia, Badalona-Hospital Germans Trias i Pujol, Barcelona, Spain. 5. Cross Cancer Institute, Edmonton, AB, Canada. 6. Centre Hospitalier Intercommunal de Créteil, Créteil, France. 7. Consorcio Hospitalario Provincial de Castellón, Castellón, Spain. 8. Cancer Center of Kansas, Wichita, KS. 9. University of Colorado Anschutz Medical Campus, Aurora, CO. 10. AstraZeneca, Cambridge, United Kingdom. 11. AstraZeneca, Gaithersburg, MD. 12. Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA. 13. Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Abstract
PURPOSE: Durvalumab significantly improves overall survival for patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting. METHODS: Patients with unresectable stage III non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and no progression after cCRT were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to durvalumab alone or combined with oleclumab or monalizumab for up to 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1). RESULTS: Between January 2019 and July 2020, 189 patients were randomly assigned. At this interim analysis (data cutoff, May 17, 2021), median follow-up was 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR was numerically higher with durvalumab plus oleclumab (30.0%; 95% CI, 18.8 to 43.2) and durvalumab plus monalizumab (35.5%; 95% CI, 23.7 to 48.7) versus durvalumab (17.9%; 95% CI, 9.6 to 29.2). Progression-free survival (PFS) was prolonged with both combinations versus durvalumab (plus oleclumab: hazard ratio, 0.44; 95% CI, 0.26 to 0.75; and plus monalizumab: hazard ratio, 0.42; 95% CI, 0.24 to 0.72), with higher 12-month PFS rates (plus oleclumab: 62.6% [95% CI, 48.1 to 74.2] and plus monalizumab: 72.7% [95% CI, 58.8 to 82.6] v durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). All-cause grade ≥ 3 treatment-emergent adverse events occurred in 40.7%, 27.9%, and 39.4% with durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, respectively. CONCLUSION: Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial.
PURPOSE: Durvalumab significantly improves overall survival for patients with unresectable stage III non-small-cell lung cancer and no progression after concurrent chemoradiotherapy (cCRT). Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with the anti-CD73 monoclonal antibody oleclumab or anti-NKG2A monoclonal antibody monalizumab as consolidation therapy in this setting. METHODS: Patients with unresectable stage III non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and no progression after cCRT were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to durvalumab alone or combined with oleclumab or monalizumab for up to 12 months, stratified by histology. The primary end point was investigator-assessed confirmed objective response rate (ORR; RECIST v1.1). RESULTS: Between January 2019 and July 2020, 189 patients were randomly assigned. At this interim analysis (data cutoff, May 17, 2021), median follow-up was 11.5 months (range, 0.4-23.4 months; all patients). Confirmed ORR was numerically higher with durvalumab plus oleclumab (30.0%; 95% CI, 18.8 to 43.2) and durvalumab plus monalizumab (35.5%; 95% CI, 23.7 to 48.7) versus durvalumab (17.9%; 95% CI, 9.6 to 29.2). Progression-free survival (PFS) was prolonged with both combinations versus durvalumab (plus oleclumab: hazard ratio, 0.44; 95% CI, 0.26 to 0.75; and plus monalizumab: hazard ratio, 0.42; 95% CI, 0.24 to 0.72), with higher 12-month PFS rates (plus oleclumab: 62.6% [95% CI, 48.1 to 74.2] and plus monalizumab: 72.7% [95% CI, 58.8 to 82.6] v durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). All-cause grade ≥ 3 treatment-emergent adverse events occurred in 40.7%, 27.9%, and 39.4% with durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, respectively. CONCLUSION: Both combinations increased ORR and prolonged PFS versus durvalumab alone. Safety was similar across arms with no new or significant safety signals identified with either combination. These data support their further evaluation in a phase III trial.
Authors: Bérengère Salomé; John P Sfakianos; Daniel Ranti; Jorge Daza; Christine Bieber; Andrew Charap; Christian Hammer; Romain Banchereau; Adam M Farkas; Dan Fu Ruan; Sudeh Izadmehr; Daniel Geanon; Geoffrey Kelly; Ronaldo M de Real; Brian Lee; Kristin G Beaumont; Sanjana Shroff; Yuanshuo A Wang; Ying-Chih Wang; Tin Htwe Thin; Monica Garcia-Barros; Everardo Hegewisch-Solloa; Emily M Mace; Li Wang; Timothy O'Donnell; Diego Chowell; Ruben Fernandez-Rodriguez; Mihaela Skobe; Nicole Taylor; Seunghee Kim-Schulze; Robert P Sebra; Doug Palmer; Eleanor Clancy-Thompson; Scott Hammond; Alice O Kamphorst; Karl-Johan Malmberg; Emanuela Marcenaro; Pedro Romero; Rachel Brody; Mathias Viard; Yuko Yuki; Maureen Martin; Mary Carrington; Reza Mehrazin; Peter Wiklund; Ira Mellman; Sanjeev Mariathasan; Jun Zhu; Matthew D Galsky; Nina Bhardwaj; Amir Horowitz Journal: Cancer Cell Date: 2022-09-12 Impact factor: 38.585