On June 4, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported two trial in progress posters, on the Phase 1 INNATE clinical trial and the Phase 2 SELECT clinical trial, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting (Press release, Jounce Therapeutics, JUN 4, 2021, View Source [SID1234583507]). INNATE, a proof-of-concept (POC) trial, is evaluating Jounce’s lead macrophage program JTX-8064 (anti-LILRB2/ILT4 inhibitor) as a monotherapy and in combination with pimivalimab (anti-PD-1 inhibitor, formerly known as JTX-4014) in patients with a variety of advanced solid tumors. SELECT, Jounce’s second POC trial, is evaluating pimivalimab as a monotherapy and in combination with vopratelimab (ICOS agonist) in a novel biomarker selection paradigm in PD-(L)1 naïve non-small cell lung cancer patients.

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"Our INNATE trial is rapidly progressing through dose escalation and we are on-track to begin indication-specific, POC, monotherapy and pimivalimab combination expansion cohorts in the second half of this year," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "Furthermore, we are excited to announce the expansion cohort indications for INNATE, which were selected using our translational data-driven approach, linking JTX-8064’s mechanism to tumor types in three groups of patients including: PD-(L)1 inhibitor experienced and resistant, PD-(L)1 inhibitor naïve and historically resistant, and PD-(L)1 inhibitor and historically more sensitive. JTX-8064 is one of only two clinical-stage LILRB2 programs in development and we expect it to be the first program to initiate expansion cohorts in four of our chosen tumor types. We are also pleased to see TISvopra positivity rates tracking with expectations in our biomarker selection trial, SELECT, and we remain on-track to report data next year."

Poster Presentation Details:

Poster Title: Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid (INNATE)
Presenter: Kyriakos P. Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START), San Antonio, TX
Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: TPS2672
Date and Time: Friday, June 4, 2021; 9:00am ET
Highlights from the trial in progress poster include the selection criteria for expansion cohorts in the ongoing Phase 1 INNATE trial and an outline the future biomarker plan:

Expansion cohort selection was informed using human histoculture and gene signature analysis from Jounce’s Translational Science Platform and includes PD-(L)1 naïve and experienced patients as well as PD-(L)1 sensitive and resistant tumor types.
The INNATE trial is divided into 4 stages with indication-specific expansion cohorts intended to establish proof-of-concept for JTX-8064:
JTX-8064 monotherapy dose escalation in relapsed / refractory solid tumors
JTX-8064 plus pimivalimab dose escalation in relapsed / refractory solid tumors
JTX-8064 monotherapy expansion in PD-(L)1i naïve platinum resistant ovarian cancer
JTX-8064 plus pimivalimab expansions in:
PD-(L)1i naïve platinum resistant ovarian cancer
PD-(L)1i naïve head and neck squamous cell carcinoma (HNSCC)
PD-(L)1i naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS)
PD-(L)1i experienced non-small cell lung cancer (NSCLC)
PD-(L)1i experienced clear cell renal cell carcinoma (ccRCC)
PD-(L)1i experienced triple negative breast cancer (TNBC)
PD-(L)1i experienced cutaneous squamous cell carcinoma (cSCC).
The dose for expansion cohorts will be selected based on safety, pharmacokinetic and receptor occupancy data from the monotherapy dose escalation stage of INNATE.
Archival and pre-treatment tumor biopsies as well as pre- and post-treatment blood samples will be collected to evaluate a number of potential predictive and pharmacodynamic biomarkers using Jounce’s Translational Science Platform.
Poster Title: Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT)
Presenter: Oleh Kobziev, MD, Regional Center of Oncology, Kharkiv, 61070, Ukraine
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: TPS9137
Date and Time: Friday, June 4, 2021; 9:00am ET

The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker

TISvopra may serve as a unique biomarker for potential increased benefit for both pimivalimab monotherapy as well as pimivalimab in combination with vopratelimab.
Data from Jounce and a third-party ICOS agonist program support an ICOS-focused biomarker selection strategy to identify patients that may benefit from ICOS agonism.
Early screening data from SELECT support Jounce’s estimate that approximately 20% of PD-(L)1i naïve non-small cell lung cancer patients tested for TISvopra in the study would meet the TISvopra positivity threshold.
SELECT is on-track to report clinical data in 2022.
Both posters will be available on the "Our Pipeline" section of the Jounce Therapeutics website under "Publications" at www.jouncetx.com.

About JTX-8064

JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899) of JTX-8064 as a monotherapy and in combination with Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014) is currently enrolling patients with advanced solid tumors.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus pimivalimab compared to pimivalimab.