A phase 2a study of NT-I7 (efineptakin alfa), a long-acting IL-7, and pembrolizumab to evaluate efficacy, including overall survival, in hard-to-treat gastrointestinal tumors.

Abstract

2621 Background: Microsatellite-stable colorectal (MSS-CRC) and pancreatic cancer (PDAC) are immunologically cold tumors with null response to checkpoint inhibitors (CPI). NT-I7, a long-acting IL-7, in combination with pembrolizumab (pembro) has shown to significantly increase intratumoral T cell infiltration and elicit some tumor control in these hard-to-treat gastrointestinal indications. The original MSS-CRC and PDAC cohorts, enrolling 25 patients (pts) each, were expanded to 50 pts per indication. Here, we provide an updated analysis including the original and expansion cohorts. Methods: Open-label Phase 2a study in subjects with relapsed/refractory CPI-naïve MSS-CRC and PDAC; NT-I7 1200 µg/kg IM every 6 weeks (Q6W), pembro 200 mg IV Q3W. Antitumor activity assessed by RECIST v1.1/iRECIST. Results: As of 02OCT2023, 98 subjects were efficacy-evaluable (50 MSS-CRC, 48 PDAC); median age 61.0 years, all with baseline ECOG status 0-1. 95.9% (94/98) received study treatment ≥3rd line, with a median follow -up of 6.1 months. Safety profile for NT-I7 was similar to previous reports. In MSS-CRC pts, 1 pt and 3 pts achieved confirmed partial responses per RECIST and iRECIST, respectively; median duration of response (DOR/iDOR) was 13.1/13.0 months (mo) and 2 responders were alive with no progression at data cutoff. Disease control rate (DCR/iDCR) was 36.0% (18/50) / 38.0% (19/50), with a duration of response and stable disease (DORSD/iDORSD) of 3.2/14.5mo. Interestingly, iDCR was 71.4% (5/7) in MSS-CRC pts with primary tumor in the rectum, versus 30.8% (12/39) in pts with primary tumor in the colon. With 11 pts on follow up, progression free survival (PFS/iPFS) was 1.5/3.8 mo. Among PDAC pts, 2 and 3 pts achieved confirmed PR and iPR, with DOR/iDOR of NE/9.7 mo; 1 responder was alive with no progression at data cutoff. DCR/iDCR was 25.0% (12/48) / 27.1% (13/48), and DORSD/iDORSD was 2.9/9.8mo. With 11 pts on follow up, PFS/iPFS was 1.4/2.1 mo. Clinical benefit in MSS-CRC and PDAC was most evident by a notable median overall survival (mOS); 13.2 mo in MSS-CRC [95% CI 8.9 – 18.6 mo] and 11.1 mo in PDAC [95% CI 4.1 – 13.3 mo], compared to historical mOS for standard of care, 10.8 mo (MSS-CRC) and 6.1 mo (PDAC). Conclusions: NT-I7 and pembro treatment was associated with longer mOS relative to historical studies. Identification of predictive biomarkers that may define pts with higher likelihood of clinical benefit would be a promising step to maximizing potential of the NT-I7 + pembro treatment combination for pts with these indications. Research in this area is ongoing. Clinical trial information: NCT04332653 .