Jounce Therapeutics presents INNATE Phase 1, SELECT trial data

Jounce Therapeutics reported new clinical data from the INNATE trial with JTX-8064 and pimi and the SELECT trial with vopra and pimi in two poster presentations at the ESMO-IO 2022 Annual Congress being held in Geneva, Switzerland. JTX-8064 is a highly selective and potent inhibitor of myeloid-specific Leukocyte Immunoglobulin Like Receptor B2 with the potential to reverse PD-(L)1 inhibitor resistance. JTX-8064 is being studied in the INNATE trial, a Phase 1/2 dose escalation/expansion trial of two investigational agents, JTX-8064 monotherapy and combination with pimi, Jounce’s investigational PD-1 inhibitor. Vopra is an inducible T cell costimulator agonist monoclonal antibody that stimulates CD4 T cells and may amplify anti-tumor activity. The SELECT trial is a randomized Phase 2 trial of vopra combined with pimi versus pimi monotherapy in TISvopra biomarker selected, immunotherapy naive, 2nd line non-small cell lung cancer patients. In the poster titled "Phase 1 Study of JTX-8064, a LILRB2 inhibitor, as monotherapy and combination with pimivalimab, a PD-1 inhibitor, in patients with advanced solid tumors" Phase 1 data defining the recommended Phase 2 dose were presented. Patients with advanced solid tumors who progressed after all available therapy were treated at seven dose levels of JTX-8064 mono and two dose levels of JTX-8064 plus pimi 500 mg q3w using a Bayesian design. The study’s primary objectives are safety and determination of the RP2D. Secondary objectives are pharmacokinetics, receptor occupancy, and immunogenicity, and exploratory objectives include evaluation of anti-tumor activity including objective response rate by RECIST 1.1 criteria. Thirty-one patients were treated in dose escalation, 22 JTX-8064 mono, and nine JTX-8064 plus pimi. There were no dose limiting toxicities and maximum tolerated dose was not reached. Eleven monotherapy patients and six combination patients had treatment-related adverse events, most of which were Grade 1 or 2, and there was only one serious TRAE, a tumor flare in the 1200 mg mono cohort. PK was linear. Full RO through 21 days was achieved at greater than or equal to 300 mg resulting in selection of an RP2D of 700 mg q3w for JTX-8064 +/- pimi. Phase 1 efficacy data in the mono cohort: zero partial response, seven stable disease including two durable SD. Phase 1 efficacy data in the combo cohort: one confirmed PR at 700 mg in a PD-1i resistant cholangiocarcinoma patient and resolution of both bone pain and cachexia, three SD with one durable SD of 6 months. Enrollment into multiple expansion cohorts is ongoing. A poster titled "SELECT: A phase II randomized trial evaluating 2 doses of vopratelimab + pimivalimab vs P in TISvopra selected patients" of the vopra plus pimi SELECT trial included an update to data previously announced on clinical endpoints, including additional durability data for patients who remain on study. SELECT is a randomized Phase 2 trial evaluating vopra, Jounce’s ICOS agonist, in combination with pimi versus pimi alone in 69 immunotherapy naive, second line, non-small cell lung cancer patients. Two hypotheses were tested in the study. First, two different doses were examined, both intended to result in different levels of pulsatile target engagement, which may optimize the dose of an agonist by reducing T cell exhaustion. Second, all patients in the study were selected by TISvopra, an 18 gene RNA tumor inflammation signature, previously associated with improved clinical outcomes in patients treated with vopra +/- nivolumab. Sixty nine TISvopra positive patients with metastatic NSCLC after one prior platinum-containing regimen were randomized 2:1:1 to pimi monotherapy 1000 mg, vopra 0.1 mg/kg plus pimi or vopra 0.03 mg/kg q6w plus pimi. Both doses of vopra demonstrated distinct patterns of pulsatile target engagement while vopra 0.03 mg/kg achieved a shorter duration of target engagement and a meaningful rest period from receptor saturation and signaling was observed. The low dose vopra combination trended favorably for the primary endpoint, ORR, and progression free survival. ORR was 40% for low dose vopra combination cohort, 27.8% for pimi alone, and 16.7% for high dose vopra combination cohort. Six month landmark PFS was 80% for low dose vopra combination, 36% for pimi monotherapy, and 31% for high dose vopra combination. Benchmarks for approved PD-1 inhibitors in second line IO naive NSCLC are ORR 18-20% and 6 month landmark PFS 30-38%. PD-L1 was evenly distributed across TISvopra patients and not associated with efficacy, suggesting TISvopra may select for patients who respond independent of PD-L1. Study treatment was well tolerated with 7.2% of patients reporting Grade greater than or equal to3 TRAEs. Most common TRAEs were Grade 1/2 hyperthyroidism and hypothyroidism. Preclinical data demonstrating that a shorter period of target engagement with vopra in vitro stimulates T cells without the exhaustion seen with longer treatment was also summarized in the poster. This data provides a scientific rationale that clinical outcomes obtained with lower doses of vopra may be improved relative to doses that result in continuous target engagement, as the SELECT clinical data suggests. Jounce plans to pursue a partnership to enable further development of vopra 0.03 mg/kg in combination with a PD-1 inhibitor.