Novel Immunotherapy Combos Show Promise in Stage III Non-Small Cell Lung Cancer

Adding oleclumab or monalizumab to consolidation with durvalumab can improve clinical outcomes in patients with unresectable stage III non-small cell lung cancer (NSCLC), a phase 2 trial suggests.

Combining durvalumab with oleclumab or monalizumab produced a numeric improvement in response rate and prolonged progression-free survival (PFS), when compared with durvalumab alone. 

These results, from the COAST trial, were published in the Journal of Clinical Oncology. 

The trial (ClinicalTrials.gov Identifier: NCT03822351) enrolled and treated 186 patients with unresectable stage III NSCLC who had not progressed after concurrent chemoradiotherapy (cCRT). 

At 42 days or less after cCRT, patients were randomly assigned to receive durvalumab alone (n=66), durvalumab plus oleclumab (n=59), or durvalumab plus monalizumab (n=61) for up to 12 months.

At baseline, the patients’ median age was 65 years (range, 37-87 years). Most (84.1%) were White, men (68.3%), and current or former smokers (93.1%). Less than half of patients (42.9%) had squamous cell histology and unresectable stage IIIA disease (45.5%). Most (89.9%) were randomly assigned to consolidation 14 days or more after radiotherapy, and 34.9% had prior cisplatin. 

At a median follow-up of 11.5 months, there was an improvement in PFS with oleclumab-durvalumab (hazard ratio [HR], 0.44; 95% CI, 0.26-0.75) and monalizumab-durvalumab (HR, 0.42; 95% CI, 0.24-0.72), compared with durvalumab alone. 

The median PFS was not reached in the oleclumab arm, 15.1 months in the monalizumab arm, and 6.3 months in the durvalumab monotherapy arm. The 1-year PFS rate was 62.6%, 72.7%, and 33.9%, respectively.  

The overall response rate was 35.5% with the monalizumab combination, 30.0% with the oleclumab combination, and 17.9% with durvalumab alone. The median duration of response was not reached in any arm.

All-cause grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 40.7% of patients in the oleclumab arm, 27.9% of patients in the monalizumab arm, and 39.4% of patients in the durvalumab-alone arm. 

Cough, dyspnea, pneumonitis, asthenia, and pruritus were the most common 

TEAEs in the combination arms. 

There were 4 treatment-related deaths — 2 due to pneumonitis and radiation pneumonitis in the durvalumab-alone arm, 1 due to pneumonitis in the oleclumab arm, and 1 due to myocardial infarction in the monalizumab arm.

“To our knowledge, COAST is the first randomized phase 2 study to show improved clinical outcomes with novel immunotherapy combinations in this setting,” the researchers concluded. 

The combinations are currently under investigation in the phase 3 PACIFIC-9 trial (ClinicalTrials.gov identifier: NCT05221840).  

Disclosures: This research was supported by AstraZeneca. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Herbst R, Majem M, Barlesi F, et al. COAST: An open-label, phase II, multidrug platform study of durvalumab alone or in combination with oleclumab or monalizumab in patients with unresectable, stage III non–small-cell lung cancer. J Clin Oncol. Published online April 22, 2022. doi:10.1200/JCO.22.00227

This article originally appeared on Cancer Therapy Advisor