1258MO - Low dose versus standard dose pembrolizumab for treatment of stage IV stage non-small cell lung carcinoma: Results of the pre-planned interim analysis of the NVALT-30 clinical trial

Background

Immune checkpoint inhibitors have shown to improve the overall survival for patients with metastasized non-small cell lung carcinoma (NSCLC) but the optimal dosing and patient selection are still a matter of discussion. We postulate that the standard dose of pembrolizumab (150-200 mg every three weeks [Q3W] or 400 mg every 6 weeks [Q6W]) can be decreased to a 300 mg dose Q6W or 100 mg Q3W without compromising efficacy.

Methods

We are performing an open label non-inferiority trial of reduced dose pembrolizumab (administered as 300 mg Q6W or 100 mg Q3W with or without chemotherapy) versus standard dose (400 mg Q6W or 150-200 mg Q3W in combination with chemotherapy), either as monotherapy or in combination with chemotherapy in NSCLC patients who are eligible for treatment with a pembrolizumab-based regimen. An interim analysis was preplanned after the first 250 patients were included and followed for a year. A difference of 10% between arms in one-year overall survival (OS) was considered clinically relevant and set as stopping criterion for the interim analysis.

Results

Data of 256 patients was used in the interim analysis. Of the 123 patients in the standard dose arm, 8 patients received the 150 mg Q3W pembrolizumab dose and 115 received the 400 mg Q6w dose. Of the 133 patients in the reduced dose arm, 5 received the 100 mg Q3W and 128 received the 300 mg Q6W dose, respectively. Pembrolizumab was administered together with chemotherapy in 49.2% of the patients. The one-year OS was 56.6% (95% CI: 48.3% − 66.4%) in the standard dose arm, and 53.4% (95% CI: 45.1% − 63.3%) in the reduced dose arm. Median OS was 15.9 (95% CI: 11.8 – 23.2) months in the standard dose arm and 13.1 (95% CI: 10.3 – 15.4) months in the reduced dose arm. OS did not differ significantly between arms (p = 0.45). Median progression free survival was 7.3 (95% CI: 6.3 – 9.8) and 7.3 (95% CI: 5.6 – 10.8) months in standard and reduced dose arms, respectively.

Conclusions

With an observed difference in one year survival of 3.2% the study meets the predetermined criterion for continuing inclusion.

Clinical trial identification

NCT04909684.

Editorial acknowledgement

Legal entity responsible for the study

Radboud University Medical Center.

Funding

Treatmeds Foundation.

Disclosure

M. van den Heuvel: Financial Interests, Institutional, Funding: Treatmeds Foundation; Other, Institutional, Advisory Board: AstraZeneca, BMS, Janssen Pharmaceutica, Novartis, MSD, PamGene, Pfizer, Roche, Lilly, AbbVie. R. Ter Heine: Financial Interests, Institutional, Funding: Treatmeds Foundation. All other authors have declared no conflicts of interest.