Novel Antibody Combo Demonstrates Safety and Efficacy in NK/T-Cell Lymphoma

A phase II trial (NCT04763616) assessing the combined therapy of antibodies cemiplimab and isatuximab demonstrated sound responses and competent levels of safety in relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R ENKTL) patients.

Investigators of the study hypothesized that a CD38 blockade through isatuximab could enhance the antitumor activity of programmed death ligand 1 (PD-L1) inhibitors in combination with cemiplimab, providing synergistic activity in the two antibodies beyond what a PD-1 inhibitor could accomplish alone.

The study consisted of 37 enrolled patients who received 250 mg of cemiplimab on days 1 and 15 of the trial, and 10 mg/kg of isatuximab on days 2 and 16 intravenously every 4 weeks for six cycles. Responding patients then received 350 mg of cemiplimab and 10 mg/kg of isatuximab every 3 weeks for up to 24 months.

The primary endpoint of the study was the complete response rate (CR) based on the best individual patient response. Of the patients enrolled, the CR rate was 51% (19/37), which exceeded the primary endpoint of 40%, and the objective response rate was 65% (24/37).

The median follow-up time for each patient was 30.2 months (95% confidence interval [CI], 25.6-34.8 months), and the median progression-free survival rate was 9.5 months (95% CI, 1.4-17.6 months). However, the median overall survival rate (OS) had not yet been reached at the time of data collection.

Patients who achieved CR within the study received a median of 28 treatment cycles (within a range of 4-33 cycles), and the median duration for (n=24) responders was 29.4 months (95% CI, and a range of 15.4-43.4 months).

Professor Kim and his team did note that there was high PD-L1 expression as well as structural variations that disrupted the 3’-untranslated region of PD-L1 present in the study. The researchers believe that these were related in response to the trial’s combination therapy. Most adverse events (AEs) were mild at grade 1-2; however, 32% experienced events that were grade 3 or higher. No treatment-related deaths were observed.

Overall, the study produced promising results for new potential treatment opportunities for R/R ENKTL patients. The combined therapy of cemiplimab and isatuximab exhibited sustained antitumor activity within a manageable safety profile, providing confident results for treatment involving this new combination of antibodies.