Trial results for the Phase 2 study NCT03137771, investigating pembrolizumab (Keytruda) as part of maintenance chemotherapy with or without local consolidative therapy (LCT) in Stage IV non-small cell lung cancer, were posted on 2025-03-11. The study showed that while LCT numerically increased median progression-free survival to 13.7 months compared to 11.1 months without LCT, the hazard ratio for PFS was 0.98 (95% CI: 0.68 to 1.4) with a p-value of 0.66, indicating it did not meet the predefined threshold to proceed to a phase 3 component.
Background
Pembrolizumab (Keytruda) is an immunotherapy drug often used in the treatment of non-small cell lung cancer (NSCLC). This trial investigated its use as part of maintenance chemotherapy, with or without local consolidative therapy (LCT), for patients with Stage IV non-small cell lung cancer. Maintenance chemotherapy aims to prevent cancer recurrence or progression after initial treatment, while LCT, such as radiation or surgery, targets residual cancer cells locally.
Trial design
The study NCT03137771 was a Phase 2 randomized trial that enrolled 218 participants. It investigated maintenance chemotherapy with or without local consolidative therapy (LCT) in patients with recurrent non-small cell lung carcinoma and Stage IV non-small cell lung cancer. Participants received systemic maintenance chemotherapy, which included agents like docetaxel, gemcitabine, pemetrexed disodium, erlotinib hydrochloride, and pembrolizumab. The trial compared two arms: Arm 1 received systemic maintenance chemotherapy alone, while Arm 2 received LCT in addition to systemic maintenance chemotherapy. The primary objective for the phase II component was to assess progression-free survival to determine if the study should proceed to a phase III component, requiring a hazard ratio estimate of ≤ 0.83.
Key results
The trial results provided several key measurements for the Phase 2 component:
- Progression-free Survival (PFS):
- For Arm 1 (systemic maintenance chemotherapy), the median PFS was 11.1 months.
- For Arm 2 (LCT + systemic maintenance chemotherapy), the median PFS was 13.7 months.
- In-Field Local Failure:
- In Arm 1, in-field local failure was observed in 15.3 percentage of participants and 19.8 percentage of participants in two separate measurements.
- In Arm 2, in-field local failure was observed in 8.6 percentage of participants and 13.4 percentage of participants in two separate measurements.
- Development of New Lesions:
- In Arm 1, the development of new lesions was observed in 32.5 percentage of participants and 41.5 percentage of participants in two separate measurements.
- In Arm 2, the development of new lesions was observed in 28.1 percentage of participants and 30.5 percentage of participants in two separate measurements.
- Adverse Events:
- The number of participants by highest grade adverse event reported was 7 Participants in Arm 1 and 6 Participants in Arm 2.
Key analysis for progression-free survival indicated a Hazard Ratio (HR) of 0.98 (95.0% CI: 0.68 to 1.4) with a p-value of 0.66, using a Log Rank method. This HR did not meet the predefined threshold of ≤ 0.83 required for the study to proceed to its phase III component.
What this means
The Phase 2 results suggest that while adding local consolidative therapy (LCT) to systemic maintenance chemotherapy, including pembrolizumab, for Stage IV non-small cell lung cancer showed numerically longer median progression-free survival and lower rates of local failure and new lesion development, this improvement was not statistically significant enough to meet the predefined criteria for advancing to a Phase 3 study. The hazard ratio for PFS of 0.98 indicates no statistically significant benefit in PFS with the addition of LCT in this patient population, based on the trial's specific progression criteria.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT031337771, titled "Maintenance Chemotherapy With or Without Local Consolidative Therapy in Treating Patients With Stage IV Non-small Cell Lung Cancer," were posted on 2025-03-11 on clinicaltrials.gov.