WILMINGTON, Del.– Results from the large, randomized COAST Phase II trial showed oleclumab, an anti-CD73 monoclonal antibody, or monalizumab, an anti-NKG2A monoclonal antibody, in combination with IMFINZI® (durvalumab) improved progression-free survival (PFS) and objective response rate (ORR) compared to IMFINZI alone in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiation therapy (CRT).
After a median follow-up of 11.5 months, the results of an interim analysis showed IMFINZI in combination with oleclumab reduced the risk of disease progression or death by 56% (hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.26-0.75), and in combination with monalizumab by 35% (HR of 0.65; 95% CI 0.49-0.85), when compared to IMFINZI alone in Stage III NSCLC patients following CRT. The 10-month PFS rate was 64.8% for the durvalumab plus oleclumab combination and 72.7% for durvalumab plus monalizumab, versus 39.2% with durvalumab alone.
The results, presented during the European Society for Medical Oncology (ESMO) Congress 2021 today, also showed an increase in the primary endpoint of confirmed ORR for IMFINZI plus oleclumab over IMFINZI alone (30% vs. 18%) and for IMFINZI plus monalizumab over IMFINZI alone (36% vs. 18%).
One in four patients with NSCLC are diagnosed at Stage III, where the majority of tumors are unresectable (cannot be removed with surgery).1,2 IMFINZI after CRT is the global standard of care for patients in this setting, based on the PACIFIC Phase III trial.3-5
Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and Chair of the COAST Steering Committee said: “IMFINZI is the established standard of care for patients with unresectable, Stage III NSCLC, but solutions are still needed for patients who do not benefit from currently available therapies. 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.”
Susan Galbraith, Executive Vice President, Oncology R&D, said: “IMFINZI has transformed the treatment of patients with unresectable, Stage III NSCLC, and we’re excited by the promise of extending its benefit through novel combinations with two potential first-in-class monoclonal antibodies demonstrating strong clinical activity. Based on the stand-out 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 cure in this setting.”
Safety was similar across treatment arms with no new safety signals identified for either IMFINZI combination. Incidence of Grade 3 or higher treatment-emergent adverse events (TEAE; all cause) were 39.4% with IMFINZI, 40.7% with IMFINZI plus oleclumab, and 27.9% with IMFINZI plus monalizumab.
The most common Grade 3/4 TEAE was dyspnea (reported in 3.0%, 1.7% and 1.6% of patients, respectively). Grade 3/4 pneumonitis was only reported for one patient (1.6%), who received IMFINZI plus monalizumab.
