Durvalumab, Novel Immunotherapies Improve Clinical Outcomes in Unresectable, Stage III Non-Small Cell Lung Cancer

A phase 2 trial found that durvalumab (Imfinzi; AstraZeneca) in combination with oleclumab, an anti-CD73 monoclonal antibody, or monalizumab, an anti-NKG2A monoclonal antibody, significantly delayed disease progression and increased objective response rate in patients with stage 3 non-small cell lung cancer (NSCLC) who had not progressed following concurrent chemoradiation therapy.

An estimated 2.2 million people worldwide were diagnosed with lung cancer in 2020, with between 80% and 85% classified as NSCLC. Stage 3 NSCLC represents approximately 25% of all NSCLC incidence, according to an AstraZeneca press release.

With a median follow-up of 11.5 months, an interim analysis of the COAST trial found that durvalumab in combination with oleclumab reduced the risk of disease progression or death by 56%, whereas patients receiving durvalumab and monalizumab had a 35% reduction. The 10-month progression-free survival rate was 64.8% in the durvalumab plus oleclumab arm, and was 72.7% in the durvalumab plus monalizumab arm, compared to 39.2% for durvalumab alone.

In addition to these findings, the results showed an increase in the primary endpoint of confirmed overall response rate for durvalumab plus oleclumab compared to durvalumab alone (30% vs 18%) and for durvalumab plus monalizumab over durvalumab alone (36% vs 18%). These findings were presented during the European Society for Medical Oncology Congress 2021.

Earlier findings from the phase 3 PACIFIC trial set durvalumab after chemoradiation therapy as the global standard of care for patients in this setting, according to the press release.

“Imfinzi is the established standard of care for patients with unresectable, stage 3 NSCLC, but solutions are still needed for patients who do not benefit from currently available therapies,” said Roy S. Herbst, MD, PhD, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital, in the press release. “The remarkable improvement observed with the addition of oleclumab or monalizumab to Imfinzi, along with the strong safety profile, suggests these novel combinations could further redefine outcomes for these patients.”

Safety findings were similar across treatment arms and no new safety signals were identified for either combination. According to the press release, the incidence of grade 3 or higher treatment-emergent adverse events (TRAEs) were 39.4% with durvalumab, 40.7% with durvalumab plus oleclumab, and 27.9% with durvalumab plus monalizumab.

The most common grade 3 or 4 TRAE was dyspnea. Grade 3 or 4 pneumonitis was only reported for 1 patient, who was in the durvalumab plus monalizumab arm.

“Imfinzi has transformed the treatment of patients with unresectable, stage 3 NSCLC, and we’re excited by the promise of extending its benefit through novel combinations with 2 potential first-in-class monoclonal antibodies demonstrating strong clinical activity,” said Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, in the press release. “Based on the standout results from COAST, we plan to start a registrational trial with the hope of bringing these new treatment options to patients that further increase the potential for cures in this setting.”

REFERENCE

Imfinzi combined with novel immunotherapies improved clinical outcomes for patients with unresectable, stage III non-small cell lung cancer. News release. AstraZeneca; September 17, 2021. Accessed September 23, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/imfinzi-combined-with-novel-immunotherapies-improved-clinical-outcomes-for-patients-with-unresectable-stage-iii-non-small-cell-lung-cancer.html