2594 Background: NT-I7 (efineptakin alfa) is the first-in-class long-acting IL-7 which can increase the number and functionality of T cells in the peripheral blood (PB) of patients (pts). The combination of NT-I7 and pembrolizumab (pembro), a PD-1 Checkpoint Inhibitor (CPI), may augment and broaden the efficacy of CPIs. Methods: This is an open-label, phase 1b/2a study in pts with relapsed/refractory (R/R) advanced solid tumors. In the phase 1b (Dose Escalation), which followed the 3+3 design, pts received NT-I7 intramuscularly (IM) at 3 dose levels (DLs): 480, 960, and 1200 µg/kg every 6 weeks (Q6W) plus pembro 200 mg intravenously (IV) Q3W. The objectives of the phase 1b were to evaluate Dose Limiting Toxicity (DLT), determine the Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose (RP2D), and assess pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity. Results: As of 12 January 2021, 12 pts were enrolled in the phase 1b: DL1 (n=3), DL2 (n=3) and DL3 (n=6). Median age 58.0 years [43-77], ECOG PS 0 (50%), PS 1 (50%), median number of prior therapies 4 [1-8]. MTD was not reached. One DLT (Grade [G] 3 ALT increased) was reported in DL3. Treatment-related adverse events (AEs) occurred in 11 (91.7%) pts, 11 (91.7%) G1-2 and 4 (33.3%) G3; no G4 or G5 AEs reported. Common treatment-emergent AEs were injection site reaction (n=8, 66.7%), chills (n=7, 58.3%), nausea (n=6, 50%) and pyrexia (n=6, 50%). Preliminary PK analysis showed Tmax = 24 hours and T1/2 = 123 hours for NT-I7 at DL3. NT-I7 + pembro induced dose-dependent lymphocyte proliferation in the PB, with ̃ 3-fold increase at DL3, and a corresponding decrease in neutrophil to lymphocyte ratio at 14 days after the 1st treatment. Importantly, increased number of T cells in the tumor microenvironment (TME) was also observed (Table). One pt with metastatic mucosal melanoma who had not responded to prior combination of nivolumab and ipilimumab had a rapid, confirmed partial response with 46% tumor reduction. Patient follow-up continues and updated data will be presented. The combination of NT-I7 1200 µg/kg IM Q6W + pembro 200 mg IV Q3W has been selected as the RP2D. Conclusions: The combination of NT-I7 + pembro was well tolerated in pts with R/R advanced solid tumors. NT-I7 + pembro significantly increased T cell numbers in both the TME and the PB, and there was encouraging antitumor activity with the combination in this pt population. These results support continued evaluation of NT-I7 in combination with pembro in pts with R/R advanced solid tumors. The phase 2a of the study is enrolling pts with either CPI-pretreated or CPI-naïve solid tumors (NCT04332653). Clinical trial information: NCT04332653. [Table: see text]
Preparation, Characterization, and Pharmacokinetic Study of a Novel Long-Acting Targeted Paclitaxel Liposome with Antitumor Activity