Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company
focused on the discovery and development of novel cancer
immunotherapies and predictive biomarkers, today 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 (LILRB2, also known as ILT4) with the potential to
reverse PD-(L)1 inhibitor resistance. JTX-8064 is being studied in
the INNATE trial (NCT04669899), a Phase 1/2 dose
escalation/expansion trial of two investigational agents, JTX-8064
monotherapy (mono) and combination (combo) with pimi, Jounce’s
investigational PD-1 inhibitor. Vopra is an inducible T cell
costimulator (ICOS) 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 naïve,
2nd line non-small cell lung cancer (NSCLC) patients.
In the poster titled “Phase 1 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” Phase 1 data defining
the recommended Phase 2 dose (RP2D) 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 (PK), receptor
occupancy (RO), and immunogenicity, and exploratory objectives
include evaluation of anti-tumor activity including objective
response rate (ORR) 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 (50%) and six combination
patients (66.7%) had treatment-related adverse events (TRAE), 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 ≥ 300 mg resulting in selection of
an RP2D of 700 mg q3w for JTX-8064 +/- pimi. Phase 1 efficacy data
in the mono cohort (n=22): zero partial response (PR), seven (35%)
stable disease (SD) including two durable SD (appendiceal cancer
8.3, ovarian cancer 12.2 months). Phase 1 efficacy data in the
combo cohort (n=9): one confirmed PR (6.2 months) at 700 mg in a
PD-1i resistant cholangiocarcinoma patient (PD-L1 score of 0) and
resolution of both bone pain and cachexia, three (33%) SD with one
durable SD of 6 months (PD-1i resistant NSCLC). Enrollment into
multiple expansion cohorts is ongoing.
A poster titled “SELECT: A phase II
randomized trial evaluating 2 doses of vopratelimab (V) +
pimivalimab (P) vs P in TISvopra
selected patients (pts)” 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
(NCT04549025) evaluating vopra, Jounce’s ICOS agonist, in
combination with pimi versus pimi alone in 69 immunotherapy naïve,
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 (n=69) TISvopra positive patients
with metastatic NSCLC after one prior platinum-containing regimen
were randomized 2:1:1 to pimi monotherapy 1000 mg (n=36), vopra 0.1
mg/kg (n=18) plus pimi or vopra 0.03 mg/kg (n=15) 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 (percent change from baseline of all measurable lesions
averaged over 9 and 18 weeks), ORR, and progression free survival
(PFS). ORR was 40% (95% confidence intervals [CI]16.34, 67.71) for
low dose vopra combination cohort, 27.8% (CI 14.20, 45.19) for pimi
alone, and 16.7% (CI 3.58, 41.42) for high dose vopra combination
cohort. Six month landmark PFS was 80% (CI 50, 93) for low dose
vopra combination, 36% (CI 20, 53) for pimi monotherapy, and 31%
(CI 11, 52) for high dose vopra combination. Benchmarks for
approved PD-1 inhibitors in second line IO naïve 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 ≥3 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.
The posters will be available on the “Our
Pipeline” section of the Jounce Therapeutics website after
presentation 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’s
Annual Meeting and the 2019 and 2021 American Association for
Cancer Research Annual Meetings support the development of JTX-8064
as a novel immunotherapy to reprogram immune-suppressive
macrophages and enhance anti-tumor immunity. A Phase 1/2 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 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 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 completed enrollment of 69 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.
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 1/2 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.
About Jounce Therapeutics
Jounce Therapeutics, Inc. is a clinical-stage
immunotherapy company dedicated to transforming the treatment of
cancer by developing therapies that enable the immune system to
attack tumors and may provide long-lasting benefits to patients
through a biomarker-driven approach. Jounce currently has multiple
development stage programs ongoing while simultaneously advancing
additional early-stage assets from its robust discovery engine
based on its Translational Science Platform. Jounce’s highest
priority program, JTX-8064, is a LILRB2 (ILT4) receptor antagonist
shown to reprogram immune-suppressive tumor associated macrophages
to an anti-tumor state in preclinical studies. JTX-8064 is
currently being investigated alone and in combination with
pimivalimab (formerly JTX-4014), Jounce’s internal PD-1 inhibitor,
in one monotherapy and eight indication-specific combination
therapy cohorts in the Phase 1/2 INNATE trial and is currently
enrolling patients with advanced solid tumors in the Phase 2
portion of the study. Jounce’s most advanced product candidate,
vopratelimab, is a monoclonal antibody that binds to and activates
ICOS, and is currently being studied in the SELECT Phase 2 trial.
Pimivalimab is a PD-1 inhibitor intended for combination use in the
INNATE and SELECT trials and with Jounce’s broader pipeline.
Additionally, Jounce exclusively licensed worldwide rights to
GS-1811 (formerly JTX-1811), a monoclonal antibody targeting CCR8
and designed to selectively deplete T regulatory cells in the tumor
microenvironment, to Gilead Sciences, Inc. For more information,
please visit www.jouncetx.com.
Cautionary Note Regarding
Forward-Looking Statements
Various statements in this release concerning
Jounce’s future expectations, plans and prospects, including
without limitation, Jounce’s plans to pursue a partnership to
enable further development of vopratelimab in combination with a
PD-1 inhibitor may constitute forward-looking statements for the
purposes of the safe harbor provisions under The Private Securities
Litigation Reform Act of 1995 and other federal securities laws and
are subject to substantial risks, uncertainties and assumptions.
You should not place reliance on these forward-looking statements,
which often include words such as, “expect,” “plan,” or similar
terms, variations of such terms or the negative of those terms.
Although Jounce believes that the expectations reflected in the
forward-looking statements are reasonable, Jounce cannot guarantee
such outcomes. Actual results may differ materially from those
indicated by these forward-looking statements as a result of
various important factors, including, without limitation, Jounce’s
ability to successfully demonstrate the efficacy and safety of its
product candidates the preclinical and clinical results for its
product candidates, which may not support further development and
marketing approval; whether interim results or past results from a
clinical trial will be predictive of the final results of the trial
or the results of future trials; the potential advantages of
Jounce’s product candidates; Jounce’s ability to establish and
maintain a partnership on favorable terms, if at all and the
success of any such partnership that Jounce enters into; and those
risks more fully discussed in the section entitled “Risk Factors”
in Jounce’s most recent Annual Report on Form 10-K filed with the
Securities and Exchange Commission as well as discussions of
potential risks, uncertainties, and other important factors in
Jounce’s subsequent filings with the Securities and Exchange
Commission. All such statements speak only as of the date made, and
Jounce undertakes no obligation to update or revise publicly any
forward-looking statements, whether as a result of new information,
future events or otherwise.
Investor and Media Contact:Eric
LaubJounce Therapeutics, Inc.+1-857-259-3853elaub@jouncetx.com
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