In an interim analysis of the phase II COAST trial reported in the Journal of Clinical Oncology, Roy S. Herbst, MD, PhD, FACP, FASCO, and colleagues found that consolidation durvalumab in combination with the anti-CD73 antibody oleclumab or anti-NKG2A antibody monalizumab both improved objective response rate and progression-free survival vs durvalumab alone among patients with unresectable stage III non–small cell lung cancer (NSCLC) without disease progression following definitive platinum-based concurrent chemoradiotherapy.

Roy S. Herbst, MD, PhD, FACP, FASCO

As stated by the investigators, “Durvalumab significantly improves overall survival for patients with unresectable stage III [NSCLC] and no [disease] progression after concurrent chemoradiotherapy. Building upon that standard of care, COAST is a phase II study of durvalumab alone or combined with…oleclumab or …monalizumab as consolidation therapy in this setting.”

Study Details

The international open-label trial enrolled 189 patients between January 2019 and July 2020. They were randomly assigned 1:1:1 to receive:

• Durvalumab alone at 1,500 mg once every 4 weeks on day 1 of each treatment cycle (n = 67)
• Durvalumab with oleclumab at 3,000 mg every 2 weeks on days 1 and 15 for cycles 1 and 2 and then every 4 weeks starting on day 1 of cycle 3 (n = 60)
• Durvalumab with monalizumab at 750 mg every 2 weeks on days 1 and 15 of each cycle (n = 62).

Treatment was continued for up to 12 months. The primary endpoint was investigator-assessed confirmed objective response rate.

Objective Response and Progression-Free Survival

At data cutoff for the interim analysis (in May 2021), median follow-up in all patients was 11.5 months (range = 0.4–23.4 months).

Confirmed objective response was observed in 12 patients in the durvalumab group (17.9%, 95% confidence interval [CI] = 9.6%–29.2%) vs 18 patients in the durvalumab/oleclumab group (30.0%, 95% CI = 18.8%–43.2%) and 22 patients in the durvalumab/monalizumab group (35.5%, 95% CI = 23.7%–48.7%), with complete response in 2, 1, and 3 patients, respectively. Median response durations were not reached in any group, with ranges of 1.9+ to 17.5+, 1.8+ to 16.9+, and 1.9+ to 18.4+ months, respectively.

Progression-free survival was significantly prolonged with both durvalumab/oleclumab (hazard ratio [HR] = 0.44, 95% CI = 0.26–0.75) and durvalumab/monalizumab (HR = 0.42, 95% CI = 0.24–0.72) vs durvalumab alone. Median progression-free survival was not reached and 15.1 months (95% CI = 13.6 months–not reached) vs 6.3 months (95% CI = 3.7–11.2 months), with 12-month rates of 62.6% and 72.7% vs 33.9%.

Adverse Events

Grade ≥ 3 adverse events occurred in 40.7% of patients in the durvalumab/oleclumab group, 27.9% of the durvalumab/monalizumab group, and 39.4% of the durvalumab group; the most common (> 5%) were pneumonia and decreased lymphocyte count (6.8% each) in the durvalumab/oleclumab group and pneumonia (9.1%) in the durvalumab group. Adverse events led to treatment discontinuation in 15.3%, 14.8%, and 16.7% of patients, respectively, most commonly due to pneumonitis (5.1%, 4.9%, and 6.1%, respectively). Overall, 6.8%, 4.9%, and 10.6% of patients, respectively, died within 90 days of last dose of study drug. A total of four deaths were considered treatment-related, consisting of two deaths due to pneumonitis and radiation pneumonitis in the durvalumab group, one due to pneumonitis in the durvalumab/oleclumab group, and one due to myocardial infarction in the durvalumab/monalizumab group.

The investigators concluded, “Both combinations increased objective response rate and prolonged progression-free survival vs 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.”

Dr. Herbst, of Yale Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by AstraZeneca. For full disclosures of the study authors, visit ascopubs.org.