Leukocyte immunoglobulin-like receptor (LILRB2)-targeted JTX-8064 plus the anti- PD1 inhibitor JTX-4014 (pimivalimab) in immune-checkpoint inhibitor (ICl) pretreated patients (pts) with advanced or metastatic renal cell cancer (mRCC): Results from the multi-stage phase 1-2 INNATE trial
Recommended Citation
Lara Jr. PN, Kroll S, Chatzkel JA, Gek Koon Teoh D, Ma VT, Kilari D, Hwang C, Sweis RF, Yalamanchili K, Peguero JA, Li T, Parikh M. Leukocyte immunoglobulin-like receptor (LILRB2)-targeted JTX-8064 plus the anti- PD1 inhibitor JTX-4014 (pimivalimab) in immune-checkpoint inhibitor (ICl) pretreated patients (pts) with advanced or metastatic renal cell cancer (mRCC): Results from the multi-stage phase 1-2 INNATE trial. J Clin Oncol 2024; 42(16).
Document Type
Conference Proceeding
Publication Date
5-29-2024
Publication Title
J Clin Oncol
Abstract
Background: Disease progression following treatment of mRCC pts with ICl-based therapy (tx) is nearly universal, warranting evaluation of novel immunotherapeutic approaches. LILRB2 is an immune checkpoint molecule expressed primarily in cells of myeloid origin (e.g., monocytes/macrophages). Inhibition of LILRB2 reprograms macrophages from an immunosuppressive (M2) to an immunostimulatory (M1) phenotype. JTX-8064 is a humanized monoclonal antibody that binds to LILRB2, blocking its interaction with MHC1 molecules. Preclinical studies suggest that JTX-8064 can overcome anti-PD(L)1 resistance mechanisms. Here we report the results of an expansion cohort of previously-treated mRCC pts in INNATE, a multistage phase 1-2 trial of JTX-8064 in combination with anti-PD1 agents in solid tumors. Methods: Pts with pathologically-confirmed clear cell mRCC progressing on or after anti- PD(L)1 tx in the most recent prior line, acceptable end-organ function, and ECOG PS 0-1 were treated with JTX-8064 700mgand JTX-4014 500mgIV q3 weeks. Primary endpoint was overall response rate (ORR); secondary endpoints were safety, disease control rate (DCR), progressionfree survival (PFS), & overall survival (OS). A Simon 2-stage design (n=10+19) was employed where ORR .= 20% was deemed to be of further interest versus null hypothesis of ORR ,= 5%, with alpha=0.05. Results: 31 pts were enrolled, with median age of 64 years (range 38-85); 84% males; 16% Hispanic; 93% White; 45% PS=0; 71% one prior tx line. Of 28 pts evaluable for response, 1 CR, 1 PR, 14 SD (± SD.= 6 months), and 11 PD were seen for an ORR of 7% & DCR of 54%.Median PFS was 4 months (95%CI: 2, 6.8); 12-month OS was 75% (95%CI: 55,88). Txrelated adverse events (AE) of all grades were reported in 11 pts (45%), most commonly fatigue (16%) & diarrhea (10%). Only 4 protocol-related G3-4 AEs were reported: thrombocytopenia (G4); diplopia, diarrhea, & bradycardia (all G3). Three on-study deaths (hypotension; cardiorespiratory arrest; & unknown) were deemed unrelated to protocol tx. Conclusions: While ORR did not meet the protocol-defined efficacy target, evidence of anti tumor activity was seen in ICI pre-treated mRCC pts with combination JTC-8064 + JTX-4014. Treatment was reasonably well-tolerated. Identification & evaluation of clinical and molecular phenotypes most likely to benefit from LILRB2-targeted therapies are warranted.
Volume
42
Issue
16
