Trial results for the Phase 2 umbrella study NCT03334617, investigating novel anti-cancer agents in participants with non-small cell lung cancer (NSCLC), were posted on ClinicalTrials.gov on 2025-10-27. The study, which included several treatment arms, reported an objective response rate of 25.8% for the combination of durvalumab 1500 mg + AZD6738 240 mg in one cohort of participants.
Background
The study (NCT03334617) is an open-label, multi-centre, umbrella Phase 2 study. It is designed to assess the efficacy, safety, and tolerability of multiple treatment arms in participants with metastatic Non-Small Cell Lung Cancer who have progressed on an anti-PD-1/PD-L1 containing therapy. The study is modular, allowing for initial assessment of various treatment approaches.
Trial design
The Phase 2 umbrella study (NCT03334617) enrolled 528 participants diagnosed with Non-Small Cell Lung Cancer. The study investigated various interventions, including durvalumab, danvatirsen, ceralasertib (AZD6738), vistusertib, and olaparib. The primary outcome measure for the reported results was the Percentage of Participants with Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1).
Key results
The key outcome measured was the Percentage of Participants with Objective Response Per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1). The results for various modules and cohorts are as follows:
- Module 1 Cohort A.1.HRR (Durvalumab 1500 mg + Olaparib 300 mg): 9.5% Percentage of Participants
- Module 1 Cohort A.1.LKB (Durvalumab 1500 mg + Olaparib 300 mg): 4.8% Percentage of Participants
- Module 1 Cohort B.1.PRI (Durvalumab 1500 mg + Olaparib 300 mg): 0% Percentage of Participants
- Module 1 Cohort B.1.ACQ (Durvalumab 1500 mg + Olaparib 300 mg): 4.3% Percentage of Participants
- Module 2 Cohort B.2.PRI (Durvalumab 1500 mg + Danvatirsen 200 mg): 0% Percentage of Participants
- Module 2 Cohort B.2.ACQ (Durvalumab 1500 mg + Danvatirsen 200 mg): 0% Percentage of Participants
- Module 3 Cohort A.3.ATM (Durvalumab 1500 mg + AZD6738 240 mg): 25.8% Percentage of Participants
- Module 3 Cohort B.3.PRI (Durvalumab 1500 mg + AZD6738 240 mg): 8.1% Percentage of Participants
- Module 3 Cohort B.3.ACQ (Durvalumab 1500 mg + AZD6738 240 mg): 8.6% Percentage of Participants
- Module 4 Cohort A.4.RIC (Durvalumab 1500 mg + Vistusertib 125 mg): Data not available
- Module 5 Cohort A.5.73H (Durvalumab 1500 mg + Oleclumab 3000 mg): 4.3% Percentage of Participants
- Module 5 Cohort B.5.PRI (Durvalumab 1500 mg + Oleclumab 3000 mg): 0% Percentage of Participants
What this means
The results from this umbrella study provide initial efficacy data for several novel anti-cancer agent combinations in patients with previously treated metastatic NSCLC. Notably, the combination of durvalumab and AZD6738 demonstrated the highest objective response rate of 25.8% in the Module 3 Cohort A.3.ATM. These findings contribute to understanding potential treatment strategies for NSCLC patients who have progressed on prior immunotherapy.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03334617, titled "Phase II Umbrella Study of Novel Anti-cancer Agents in Participants With NSCLC Who Progressed on an Anti-PD-1/PD-L1 Containing Therapy," were posted on 2025-10-27 on clinicaltrials.gov.