Efficacy and safety of NT-I7, long-acting interleukin-7, plus pembrolizumab in patients with advanced solid tumors: Results from the phase 2a study.
Authors: Naing Aung , Mamdani Hirva , Barve Minal A. , Johnson Melissa Lynne , Morgensztern Daniel , Olszanski Anthony J. , Wolff Robert A. , Pant Shubham , Chaney Marya F. , Adebanjo Tolani , Fan Jean , Kim Richard D. , Kopetz Scott 
Published: June 2022

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Background: Checkpoint inhibitors (CPIs) are usually ineffective in patients (pts) with immune-cold microsatellite stable colorectal cancer (MSS-CRC) or pancreatic cancer (PDAC) and in those who progressed on previously treated with antibodies against PD1 or PD-L1. Here, we report the combination of NT-I7 plus pembrolizumab (pembro) on CPI-naïve MSS-CRC and PDAC cohorts, and patients (pts) with CPI-treated triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) cohorts of this ongoing phase 2a trial. Methods: Pts with CPI-naïve relapsed/refractory (R/R) MSS-CRC and PDAC, and CPI-treated R/R TNBC, NSCLC, and SCLC, were enrolled. NT-I7 (efineptakin alfa) 1200 µg/kg intramuscularly every 6 weeks and 200 mg pembro intravenously every 3 weeks were administered until disease progression/unacceptable toxicity. The primary endpoint of the Phase 2a is the objective response rate (ORR), assessed by RECIST v1.1 and iRECIST. The secondary endpoints are duration of response (DoR), disease control rate, progression-free survival, and overall survival. Results: As of 14 Jan 2022, 92 pts with metastatic or locally advanced cancer who had received a median of 3 prior treatments were enrolled in the study; 32 in PDAC, 28 in MSS-CRC, 22 in NSCLC, 6 in TNBC, and 4 in SCLC. The median age was 62 years [29-81], ECOG PS 0 in 23 (25%), 1 in 68 (74%) and 2 in 1 (1%). Among 71 evaluable pts, the median follow up (months) was 7.7, 5.3, 5.0, 3.7, and 2.4 in TNBC, MSS-CRC, NSCLC, PDAC and SCLC, respectively. The ORR was 50% (1/2) in SCLC, 12% (3/25) in MSS CRC, 8% (2/26) in PDAC 6% (1/16) in NSCLC and 0% (0/2) in TNBC per iRECIST; and 50% (1/2) in SCLC, 4% (1/25) in MSS CRC, and 4% (1/26) in PDAC per RECIST 1.1. All 7 responders are ongoing. The two PDAC pts had DoR over 1.35 months (mos) and 6.64 mos with the best tumor reduction 100% and 72% respectively. The one SCLC pt had DoR over 1.5 mos with the tumor reduction 67%. The one NSCLC pt had DoR over 2.73 mos with the tumor reduction 60%, and the three MSS-CRC pts had DoR 6.34, 2.96, and 0.03 mos with the tumor reduction 60%, 56%, and 43% respectively. A sustained and significant (approximate 3X from baseline) increase of peripheral lymphocytes in all arms was observed as shown in our previous report. Among 92 treated pts, NT-I7-related adverse events (AEs) occurred in 67 (72.8%) pts, including 52 (56.5%) Grade (G)1-2, 13 (14.1%) G3, and 2 (2.2%) G4. There were no NT-I7 related G5 AEs. Additional updated efficacy, safety and biomarker data will be presented. Conclusions: The combination of NT-I7 and pembro demonstrated antitumor activity and manageable toxicity profile in heavily pretreated pts with CPI-naïve MSS-CRC and PDAC and CPI-treated TNBC, NSCLC, and SCLC, suggesting that the addition of NT-I7 to CPI can overcome the primary resistance to CPI in the former group and acquired resistance in the latter. Clinical trial information: NCT04332653.