Combination Immunotherapy Improves Outcomes for Patients with Non-small Cell Lung Cancer

Roy S. Herbst, MD, PhD

The phase 2 clinical trial of a multi-center study known as the COAST clinical trial (NCT03822351) has demonstrated improved outcomes using immunotherapy combinations for patients with unresectable stage III non–small cell lung cancer, according to researchers at Yale Cancer Center and participating organizations. The results are the first to demonstrate evidence of improved clinical outcomes with novel combinations of immunotherapy in this patient population. The results were published in the Journal of Clinical Oncology.

Despite progress with treatment using durvalumab, the current standard of care, additional research attention is needed to further improve outcomes for this patient population, researchers say. In the COAST trial, researchers explored immunotherapy combination strategies using oleclumab (a human monoclonal antibody targeting CD73) or monalizumab (a humanized anti-NKG2A blocking mAb) and building upon treatment with durvalumab to expand the number of patients who respond to treatment and remain progression-free.

Among all randomized patients, the objective response rate (ORR) was 30% with durvalumab plus oleclumab and 35.5% with durvalumab plus monalizumab. The response rate for durvalumab only was 17.9%. The secondary endpoint of disease control rate (DCR) at 16 weeks was 81.7% with durvalumab plus oleclumab, 77.4% with durvalumab plus monalizumab, and 58.2% with durvalumab only. The 12-month progression free survival (PFS) rate was higher with both combinations (62.6% with durvalumab plus oleclumab and 72.7% with durvalumab plus monalizumab compared with 33.9% with durvalumab alone).

“These new data have the potential to change the standard of care for patients with advanced non-small cell lung cancer, providing us with new treatment options with the ability to make a major impact on our patients’ lives,” said lead author Roy S. Herbst, MD, PhD, deputy director for Clinical Affairs at Yale Cancer Center and Smilow Cancer Hospital, ensign professor of Medicine (Medical Oncology) and Professor of Pharmacology. Dr. Herbst is also chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital and assistant dean for Translational Research at Yale School of Medicine.

“I look forward to seeing the launch of the phase 3 trial to help gather more insight on these combination therapies, and better determine which patients will benefit from each combination treatment to help personalize effective treatments.”

The COAST clinical trial was funded by AstraZeneca.