172P Phase I study of JTX-8064, a LILRB2 (ILT4) inhibitor, as monotherapy and combination with pimivalimab (pimi), a PD-1 inhibitor (PD-1i), in patients (pts) with advanced solid tumors

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oregon; portland; chiles


Background JTX-8064, a highly selective and potent IgG4 inhibitor of myeloid-specific Leukocyte Immunoglobulin Like Receptor B2 (LILRB2), leads to macrophage reprogramming from an immunosuppressive to an immune activated state, resulting in T cell activation. INNATE (NCT04669899) is a phase (P) 1/2 dose escalation/expansion study of two investigational agents, JTX-8064 monotherapy (mono) and combination (combo) with pimi. P1 data defining Recommended P2 Dose (RP2D) are presented. Methods Pts with advanced solid tumors who progressed after all available therapy were treated at 7 dose levels of JTX-8064 mono IV q3w (50, 150, 300, 450, 600, 900, 1200 mg) and 2 dose levels of JTX-8064 (700, 1200 mg) + pimi 500 mg IV q3w using Bayesian design. 1o objectives: safety, tolerability, RP2D. 2 o objectives: receptor occupancy (RO), PK, immunogenicity. Objective response rate (RECIST 1.1) was exploratory. Results 31 pts were treated in dose escalation, 22 JTX-8064 mono, 9 JTX-8064 + pimi. No dose limiting toxicities; maximum tolerated dose not reached. Safety: Mono: Median age 67. Eleven pts (50%) had treatment-related adverse events (TRAE). Most common were fatigue (n= 5), upper abdominal pain, arthralgia, flushing, nausea, and pyrexia (n= 2 each). The only Grade 3 (G3) TRAE and only serious related AE (SRAE) was tumor flare at 1200 mg. Combo: Median age 63. Six pts (66.7%) had TRAE, most common fatigue (n=4) and pyrexia (n=2). No ≥ G3 TRAEs, no SRAEs. PK was linear. Full RO thru 21 days was achieved at ≥ 300 mg. RP2D of 700 mg q3w was selected for JTX-8064 +/- pimi to optimize RO in tumor, with Cmin at steady state 63.4 (26.0-139.7) ug/mL. Treatment induced antibodies to JTX-8064 occurred in 1 mono and no combo pts. P1 Efficacy: Mono: 0 PR, 7 SD with 2 durable SD (appendiceal cancer 8.3, ovarian cancer 12.2 mo). Combo: 1 PR (6.2 mo) at 700 mg in PD-1i resistant cholangiocarcinoma with resolution of both bone pain and cachexia, 3 SD with 1 durable SD (post-PD-1i NSCLC 6 mo). Conclusions JTX-8064 was well-tolerated as mono and with pimi, with 700 mg q3w selected as the preliminary RP2D. Enrollment is ongoing in P2, including cohorts in renal and ovarian cancer that have met Simon’s 2-stage response criteria to expand.

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Papadopoulos KP, Li T, Lakhani N, Powderly J, George T, Teoh D, Kilari D, Giaccone G, Sanborn R, Ghamande S, LoRusso P, Gibney G, Ma VT, Yalamanchili K, Brown J, Mota N, TasilloKadra C, Umiker B, Xiao X, Trehu E. ESMO Immuno-Oncology Congress; December 7-9; Geneva Switzerland. 2022: 172P.

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