Key Points
- 01AstraZeneca (AZN) is discontinuing the Phase III eVOLVE-Lung02 trial
- 02Review found volrustomig plus chemo unlikely to meet PFS and OS goals
- 03Trial enrolled 895 metastatic non-small cell lung cancer patients
- 04Other Phase III volrustomig studies in solid tumors continue
AstraZeneca ends Phase III eVOLVE-Lung02 trial
AstraZeneca (AZN) is discontinuing the eVOLVE-Lung02 Phase III clinical trial testing volrustomig in combination with chemotherapy as a first-line treatment for metastatic non-small cell lung cancer. The move follows a planned review by an Independent Data Monitoring Committee, which concluded that the volrustomig regimen was unlikely to meet the study’s dual primary endpoints of progression-free survival and overall survival in the primary analysis population.
The primary analysis population in eVOLVE-Lung02 consisted of patients with PD-L1 negative tumours, defined as less than 1% PD-L1 expression. Based on the committee’s assessment, continuing the study to its planned completion was not expected to demonstrate sufficient benefit on these key efficacy measures in this group.
Trial design and patient enrollment
The eVOLVE-Lung02 trial was a global study that enrolled 895 patients with metastatic non-small cell lung cancer across 25 countries. Participants were randomized in a 1:1 ratio to receive either volrustomig plus chemotherapy or pembrolizumab plus chemotherapy as first-line treatment.
Patients in the volrustomig arm received 750 mg of intravenous volrustomig in combination with chemotherapy every three weeks for four cycles, followed by volrustomig every three weeks as maintenance. In the comparator arm, patients received 200 mg of pembrolizumab plus chemotherapy every three weeks for four cycles, followed by pembrolizumab every three weeks for up to 24 months or until disease progression.
Safety profile and patient management
AstraZeneca reported that the safety profile observed for the volrustomig plus chemotherapy combination in eVOLVE-Lung02 was consistent with the known safety profiles of the individual medicines used in the regimen. No new safety signals were identified during the course of the study.
Following the decision to discontinue the trial, AstraZeneca said it will work with trial investigators to ensure continuity of care for all patients who participated in eVOLVE-Lung02. The company also plans to ensure appropriate follow-up for these patients as treatment is adjusted in light of the trial’s early termination.
Ongoing development of volrustomig
While the eVOLVE-Lung02 lung cancer trial is being discontinued, AstraZeneca stated that other Phase III studies of volrustomig remain ongoing. These continuing trials are evaluating the medicine in cervical cancer, head and neck squamous cell carcinoma and mesothelioma.
The continuation of these additional Phase III programmes indicates that the decision to stop eVOLVE-Lung02 is specific to the metastatic non-small cell lung cancer setting evaluated in this study, rather than a blanket halt to volrustomig’s broader clinical development. Data from these trials are still in progress and were not detailed alongside the eVOLVE-Lung02 announcement.
Key Takeaways
- 01The eVOLVE-Lung02 halt reflects a lack of expected efficacy benefit for volrustomig plus chemotherapy in PD-L1 negative metastatic lung cancer patients.
- 02Safety did not drive the decision, as no new safety signals were observed and the profile matched known characteristics of the component medicines.
- 03Volrustomig remains in late-stage development for several other solid tumors, so its potential will now be tested primarily outside the metastatic lung cancer setting.