AstraZeneca is discontinuing the Phase III eVOLVE-Lung02 trial, which evaluated volrustomig plus chemotherapy as first-line treatment compared with pembrolizumab plus chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 <50%.
The decision was based on a recommendation from the Independent Data Monitoring Committee (IDMC) following a planned review of trial data. The IDMC concluded that the volrustomig combination was unlikely to meet either of the dual primary endpoints of progression-free survival (PFS) or overall survival (OS) in the primary analysis population of patients with PD-L1-negative tumors (<1%) versus the comparator arm.
AstraZeneca reported that the safety profile of volrustomig plus chemotherapy was consistent with the known profiles of the individual medicines, with no new safety signals identified.
Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, said the trial was initiated with the aim of improving outcomes for patients with lower PD-L1 expression and less durable responses to current immunotherapy regimens. She added:
“While we are disappointed, we will learn from this trial and are determined to continue pioneering new medicines from our industry-leading pipeline in our quest to improve outcomes for patients with lung cancer.”
AstraZeneca said it will work with investigators to ensure continuity of care and appropriate follow-up for patients participating in the trial. Other Phase III trials of volrustomig in cervical cancer, head and neck squamous cell carcinoma, and mesothelioma will continue as planned.
About eVOLVE-Lung02
eVOLVE-Lung02 (NCT05984277) is a randomized, open-label, multicenter, global Phase III trial evaluating volrustomig plus chemotherapy as first-line treatment for patients with metastatic NSCLC whose tumors express PD-L1 <50%. The trial enrolled 895 patients across 25 countries.
Patients were randomized 1:1 to receive 750 mg intravenous volrustomig plus chemotherapy every three weeks for four cycles, followed by volrustomig every three weeks, or 200 mg pembrolizumab plus chemotherapy every three weeks for four cycles, followed by pembrolizumab every three weeks. Treatment continued until completion of 24 months, disease progression, or another discontinuation criterion.
The dual primary endpoints were PFS and OS in patients with PD-L1 <1%, while secondary endpoints included PFS and OS in the intent-to-treat population with PD-L1 <50%.
Volrustomig is a dual checkpoint inhibitor bispecific antibody designed to deliver coordinated and targeted PD-1 and CTLA-4 blockade on the same T cell. AstraZeneca is evaluating volrustomig as monotherapy and in combinations across several tumor types with high unmet need.
Read further on OncoDaily: AstraZeneca and HUTCHMED’s Tagrisso-Orpathys Combination Improves PFS and OS in Phase III SAFFRON Trial
