Patients with stage III non-small-cell lung cancer that was unresectable and who were still alive after concomitant chemotherapy (cCRT) and radiation treatment benefited considerably from the use of durvalumab. Building on that standard of treatment, COAST was a phase II investigation evaluating durvalumab as consolidation therapy in this scenario, either alone or in combination with the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A monoclonal antibody monalizumab.

Patients stratified by histology were randomly assigned 1:1:1, ≤ 42 days post-cCRT, to receive durvalumab alone or in combination with oleclumab or monalizumab for up to 12 months if they had unresectable stage III non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0/1, and no progression following cCRT. Investigator-assessed verified objective response rate (ORR; RECIST v1.1) served as the main endpoint.

A random assignment was made for 189 patients between January 2019 and July 2020. The median follow-up at the time of the interim study (data cutoff, May 17, 2021) was 11.5 months (range, 0.4-23.4 months; all patients). In comparison to durvalumab alone (17.9%; 95% CI, 9.6 to 29.2), confirmed ORR was numerically greater 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). 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), higher 12-month PFS rates were observed with both combinations compared to durvalumab (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]). Progression-free survival (PFS) was extended with both combinations versus durvalumab alone: 33.9% [95% CI, 21.2 to 47.1]). Durvalumab plus oleclumab, durvalumab plus monalizumab, and durvalumab, in that order, were associated with all-cause grade ≥3 treatment-emergent adverse events in 40.7%, 27.9%, and 39.4% of patients, respectively.

Comparing the two combinations to durvalumab alone, both improved ORR and extended PFS. There were no novel or noteworthy safety signals discovered with each combination, and safety was comparable across arms. These findings warrant a phase III experiment that will further examine them.

Reference: ascopubs.org/doi/full/10.1200/JCO.22.00227