Trial results for a Phase 3 study (NCT04026412) investigating nivolumab and ipilimumab in untreated participants with Stage 3 Non-small Cell Lung Cancer (NSCLC) were posted on ClinicalTrials.gov on 2025-07-24. The study compared nivolumab-based regimens to durvalumab following concurrent chemoradiotherapy, showing varied outcomes in progression-free survival and overall survival.
Background
The study focused on untreated participants with Stage 3 Non-Small Cell Lung Cancer (NSCLC) that is unable or not planned to be removed by surgery.
Trial design
The study (NCT04026412) was a Phase 3 trial that enrolled 925 participants with Non-Small Cell Lung Cancer (NSCLC). The primary purpose was to compare the effectiveness of nivolumab plus concurrent chemoradiotherapy (CCRT) followed by nivolumab plus ipilimumab (Arm A) versus CCRT followed by durvalumab (Arm C) in participants with untreated Locally Advanced NSCLC. An additional arm (Arm B) investigated nivolumab plus CCRT followed by nivolumab.
Key results
The trial results presented several key outcomes:
- Progression-Free Survival (PFS) by RECIST 1.1 Per Blinded Independent Central Review (BICR):
- Participants in Arm A (nivolumab + CCRT/nivolumab + ipilimumab) had a median PFS of 16.69 months.
- Participants in Arm C (CCRT/durvalumab) had a median PFS of 15.64 months.
- The Hazard Ratio for Arm A versus Arm C was 0.95 (96.0% Confidence Interval: 0.77 to 1.19), with a p-value of 0.646.
- Progression-Free Survival (PFS) (Irrespective of Subsequent Therapy) by RECIST 1.1 Per Blinded Independent Central Review (BICR):
- Arm A (nivolumab + CCRT/nivolumab + ipilimumab) showed a median PFS of 16.82 months.
- Arm B (nivolumab + CCRT/nivolumab) showed a median PFS of 17.38 months.
- Arm C (CCRT/durvalumab) showed a median PFS of 15.67 months.
- The Hazard Ratio for Arm B versus Arm C was 0.85 (95.0% Confidence Interval: 0.69 to 1.05).
- The Hazard Ratio for Arm A versus Arm B was 1.15 (95.0% Confidence Interval: 0.93 to 1.42).
- Overall Survival (OS):
- Median OS for Arm A (nivolumab + CCRT/nivolumab + ipilimumab) was 34.60 months.
- Median OS for Arm B (nivolumab + CCRT/nivolumab) was 39.49 months.
- Median OS for Arm C (CCRT/durvalumab) was 39.79 months.
- The Hazard Ratio for Arm A versus Arm C was 1.1 (95.0% Confidence Interval: 0.87 to 1.41).
- The Hazard Ratio for Arm B versus Arm C was 0.96 (95.0% Confidence Interval: 0.75 to 1.22).
- The Hazard Ratio, log, for Arm A versus Arm B was 1.16 (95.0% Confidence Interval: 0.91 to 1.48).
- Objective Response Rate (ORR) by BICR:
- Arm A (nivolumab + CCRT/nivolumab + ipilimumab) achieved an ORR of 67.6% of participants.
- Arm B (nivolumab + CCRT/nivolumab) achieved an ORR of 72.2% of participants.
- Arm C (CCRT/durvalumab) achieved an ORR of 64.5% of participants.
- Duration of Response (DoR) by RECIST 1.1 Per BICR:
- Arm A (nivolumab + CCRT/nivolumab + ipilimumab) had a median DoR of 25.76 months.
What this means
The results from this Phase 3 trial indicate a complex efficacy profile for the nivolumab-based regimens compared to durvalumab in untreated Stage 3 NSCLC. While the nivolumab and ipilimumab combination (Arm A) showed a slightly longer median progression-free survival compared to durvalumab (Arm C) in some analyses, its median overall survival was shorter. The hazard ratios for the primary comparison of PFS between Arm A and Arm C, with a p-value of 0.646, suggest no statistically significant difference. Similarly, overall survival comparisons did not show a clear benefit for the nivolumab-based arms over durvalumab. These findings provide important data for clinicians evaluating treatment options for locally advanced NSCLC.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04026412, titled "A Study of Nivolumab and Ipilimumab in Untreated Participants With Stage 3 Non-small Cell Lung Cancer (NSCLC) That is Unable or Not Planned to be Removed by Surgery," were posted on 2025-07-24 on clinicaltrials.gov.