Dr Kim on Data for NT-I7 Plus Pembrolizumab in Pretreated Advanced MSS CRC and PDAC

Richard Kim, MD, chief, Medical Gastrointestinal Oncology, senior member, Gastrointestinal Oncology Department, Moffitt Cancer Center, professor of oncology, University of South Florida College of Medicine, discusses an updated analysis from a phase 2a trial (NCT04332653) evaluating NT-I7 in combination with pembrolizumab (Keytruda) in patients with pretreated microsatellite stable (MSS) colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC).

NT-I7 is a long-acting interleukin-7, and preclinical studies showed that combining it with pembrolizumab led to increased intratumoral T-cell infiltration and improved tumor control in difficult-to-treat gastrointestinal tumors.

The study enrolled patients with relapsed/refractory and immune checkpoint inhibitor–naive MSS CRC or PDAC. All patients received NT-I7 at 1200 µg/kg intramuscularly once every 6 weeks, plus pembrolizumab at 200 mg intravenously once every three weeks. Antitumor activity was measured using RECIST 1.1 and iRECIST criteria.

Kim notes that response rates per RECIST 1.1 and iRECIST criteria were modest. Findings presented at the 2024 ASCO Annual Meeting showed that 3 patients in MSS CRC cohort (n = 50) and 3 patients in the PDAC cohort (n = 48) achieved a partial response (PR) per iRECIST criteria. A PR per RECIST 1.1 criteria was observed in 1 patient with MSS CRC and 2 patients with PDAC. The disease control rates (DCR) were 36.0% per RECIST 1.1 criteria and 38.0% per iRECIST criteria in the MSS CRC cohort. These respective rates were 25.0% and 27.1% in the PDAC cohort.

Despite the limited responses, Kim points to the overall survival data as the intriguing findings from this study. The median OS was 13.2 months (95% CI, 8.3-18.6) in the MSS CRC cohort and 11.1 months (95% CI, 3.9-26.2) in the PDAC cohort. These findings served as improvements for historical OS data in these patient populations when treated with standard of care, according to Kim. Although this was a small, nonrandomized study, these OS data point to a potential improvement over historical outcomes for these patient populations, Kim concludes.