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404 Initial biomarker and clinical data of a phase 2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab: cohort of subjects with checkpoint inhibitor-naïve advanced MSS-colorectal cancer
  1. Richard Kim1,
  2. Minal Barve2,
  3. Hirva Mamdani3,
  4. Melissa Johnson4,
  5. Byung Ha Lee5,
  6. Sara Ferrando-Martinez5,
  7. Marya Chaney6,
  8. Jean Fan5,
  9. NgocDiep Le5 and
  10. Aung Naing7
  1. 1Moffitt Cancer Center, Tampa, FL, USA
  2. 2Mary Crowley Cancer Research, Dallas, TX, USA
  3. 3Karmanos Cancer Institute, Detroit, USA
  4. 4Sarah Cannon/Tennessee Oncology, PLLC, Nashville, TN, USA
  5. 5NeoImmuneTech, Inc, Rockville, MD, USA
  6. 6Merck and Co, Inc, Kenilworth, NJ, USA
  7. 7MD Anderson Cancer Center, Houston, TX, USA


Background Checkpoint inhibitor (CPI) monotherapy is ineffective for microsatellite stable colorectal cancer (MSS-CRC). NT-I7 (efineptakin alfa) is the first-in-class long-acting IL-7 that can increase T-cell infiltration in the tumor microenvironment (TME). We hypothesize that NT-I7 may create a favorable immune-reactive TME to enhance the efficacy of CPI when combined with pembrolizumab (pembro).

Methods This is an open-label, phase 2a study in subjects with relapsed/refractory (R/R) tumors, including CPI-naïve R/R MSS-CRC. Subjects received the recommended-phase-2-dose of NT-I7 intramuscularly at 1200 µg/kg every 6 weeks (Q6W) plus pembro 200 mg intravenously Q3W. Preliminary anti-tumor activity based on Overall Response Rate (ORR) was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a primary objective and by iRECIST as an exploratory objective. Biomarker analyses in peripheral blood and tumor biopsies were performed.

Results As of 15-July-2021, 19 subjects were enrolled in the CPI-naïve R/R MSS-CRC cohort. Six subjects are ongoing. Median age 58 years [37–81], ECOG PS 0 (26%), 1 (74%). Sixteen (84%) subjects received ≥ 2 prior therapies. All subjects had metastatic or locally advanced disease at enrollment. The median duration of follow-up was 4.64 months. Among 15 evaluable subjects, disease-control rate (DCR) based on RECIST1.1 was 47% and 1 subject achieved partial response per iRECIST (iPR) with 33% tumor reduction. Treatment-related adverse events (AEs) occurred in 14 (73.7%) subjects, 9 (47.4%) G1–2 events and 5 (26.3%) G3 events; no G4 or G5 AEs were reported. No subjects discontinued from the study due to AE. NT-I7 + pembro elicited a significant increase in the absolute lymphocyte count that peaked at week 3 (>3X from baseline, p<0.0001) and was sustained at least until week 18. CD4+/CD8+ T-cell subsets followed the same response pattern. Importantly, Stem-Cell Memory CD8+ T-cells (TSCM), the potential target for CPIs that differentiate into effectors, were remarkably increased post-study treatment (>25X from baseline, p<0.01). Plasmatic chemokines (CXCL9, CXCL10, CXCL11 and CCL9) were significantly increased after the first dose. The iPR subject had an enhanced T-cell infiltration in the TME at week 5. Subject’s follow-up continues and more updated data will be presented.

Conclusions The chemo-free combination of NT-I7 + pembro was well tolerated and showed encouraging anti-tumor activity in subjects with CPI-naïve R/R MSS-CRC. Increased TSCM and CD8+ T-cell infiltration in TME may be the underlying mechanisms of action for the observed efficacy. These results support continued evaluation of NT-I7 + pembro in CPI-naïve subjects with R/R MSS-CRC.

Acknowledgements The authors thank ICON for their partnership in conducting this trial.

Trial Registration NCT04332653

Ethics Approval The trial was approved by MD Anderson IRB (#2020–0008_MOD001), Mary Crowley IRB (#20–13) and Advarra IRB (#Pro00042639)All participant gave informed consent prior to study enrollment.

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