Study of JTX-8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors

NCT ID: NCT04669899

Last Updated: 2024-04-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-12

Study Completion Date

2023-11-28

Brief Summary

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JTX-8064-101 is a Phase 1/2, open label, dose escalation and dose expansion clinical study to determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of JTX-8064 alone and in combination with a PD-1 inhibitor (PD-1i).

Detailed Description

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JTX-8064 is a humanized mAb designed to block the interaction of LILRB2 with its known ligands, endogenous major histocompatibility complex class I (MHC I) molecules. This is a Phase 1/2, first in human, open label, multicenter, dose escalation and dose expansion clinical trial to determine the safety, tolerability, maximum tolerated dose (MTD) and RP2D of JTX-8064 when administered as a single agent and in combination with a PD-1i in adult subjects with advanced refractory solid tumor malignancies. Additionally, the study will seek to evaluate the pharmacokinetics and immunogenicity of JTX-8064, and preliminary efficacy of JTX-8064 as a monotherapy and in combination with a PD-1i.

Conditions

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Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Stage 1, Dose Escalation: JTX-8064 monotherapy dose escalation

Dose Escalation, Stage 1: JTX-8064 Monotherapy. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

Stage 2, Dose Escalation: JTX-8064 in combination with pimivalimab

Dose Escalation, Stage 2: JTX-8064 in combination with pimivalimab. Cohorts will enroll subjects with histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancies.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 3 Expansion: JTX-8064 monotherapy (Ovarian)

Cohort will enroll subjects with advanced/metastatic PD-1/PD-L1 (PD-(L)1)-naïve, platinum-resistant ovarian cancer.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (ccRCC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced clear cell renal cell carcinoma (ccRCC).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (TNBC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1i-experienced triple negative breast cancer (TNBC).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (HNSCC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, PD-L1+ head and neck squamous cell carcinoma (HNSCC).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (Ovarian)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve, platinum-resistant ovarian cancer.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (NSCLC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced non-small cell lung cancer (NSCLC).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (cSCC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-experienced cutaneous squamous cell carcinoma (cSCC).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (UPS & LPS)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with advanced/metastatic PD-(L)1-naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS).

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (PD-(L)1i-experienced HNSCC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with PD-(L)1i-experienced HNSCC.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Stage 4, Expansion: JTX-8064 in combination with pimivalimab (BTC)

JTX-8064 in combination with pimivalimab. Cohort will enroll subjects with biliary tract cancer (BTC), including intra-and extra-hepatic biliary duct cancer and cancer of the gallbladder. All subjects must have progressed on or after gemcitabine/cisplatin (Gem/Cis) in the metastatic setting, must have PD-(L)1i resistance.

Group Type EXPERIMENTAL

JTX-8064

Intervention Type DRUG

Specified dose on specified days

pimivalimab

Intervention Type DRUG

Specified dose on specified days

Interventions

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JTX-8064

Specified dose on specified days

Intervention Type DRUG

pimivalimab

Specified dose on specified days

Intervention Type DRUG

Other Intervention Names

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Anti-LILRB2 Anti-ILT4 JTX-4014 Anti-PD-1

Eligibility Criteria

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Inclusion Criteria

1. Able and willing to participate and comply with all study requirements and provide signed and dated informed consent prior to initiation of any study procedures;
2. Histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy:

1. Stages 1 and 2: Subjects must have received, have been intolerant to, have been ineligible for, or have declined all treatment known to confer clinical benefit with the exception of subjects enrolled in combination cohorts with a PD-1i, where a PD-1i is approved by the local regulatory agencies;
2. Stage 3: This stage may enroll subjects with 3L/4L PD-(L)1-naïve, platinum-resistant ovarian cancer;
3. Stage 4: This stage may enroll subjects with the following cancers:

* 2L/3L ccRCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy;
* 2L-4L TNBC. Subjects must have progressed on or after treatment with a prior anti-PD-(L)1 therapy;
* 1L, PD-(L)1-naïve, PD-L1+; combined positive score (CPS) ≥1% HNSCC;
* 2L/3L platinum-experienced HNSCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1-agent in their most recent prior line of therapy;
* 3L/4L, PD-(L)1-naïve, platinum-resistant ovarian cancer;
* 2L/3L NSCLC. Subjects must have progressed on or after treatment with platinum-based chemotherapy and an anti-PD-(L)1-containing therapy. The anti-PD-(L)1 agent must have been a part of the most recent prior line of therapy. Subjects with EGFR mutations and ALK rearrangements will be excluded. Subjects with other targetable genomic aberrations for which FDA approved therapies exist must have received appropriate FDA-approved targeted therapy;
* 2L/3L cSCC. Subjects must have progressed on or after treatment with an anti-PD-(L)1 agent in their most recent prior line of therapy;
* 2L-4L PD-(L)1-naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS);
* 2L/3L biliary tract cancer (BTC), including intra- and extra-hepatic biliary duct cancer and cancer of the gallbladder. Subjects must have progressed on or after gemcitabine/cisplatin (Gem/Cis) in the metastatic setting and must have PD-(L)1 inhibitor resistance. Subjects with FGFR and IDH1 mutations must have progressed on or after targeted therapies for these mutations;
3. Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator;
4. ≥18 years of age;
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
6. Predicted life expectancy of ≥3 months;
7. Have specified laboratory values (obtained ≤28 days prior to planned Cycle 1, Day 1 \[C1D1\]) in accordance with the study protocol;
8. For women of childbearing potential (WOCBP): negative serum pregnancy test during the Screening period and a negative urine pregnancy test up to 24 hours in advance of C1D1;
9. WOCBP and males whose partners are WOCBP must agree to use a highly effective method of birth control throughout their participation and for 5 months following the last study drug administration.

Exclusion Criteria

1. Concurrent anticancer treatment, either FDA approved or investigational, for the cancer being evaluated in this study or for prior malignancies. A past history of other malignancies is allowed as long as the subject is not receiving treatment other than hormonal therapy and, in the judgment of the Investigator, is unlikely to have a recurrence. Of note, concurrent malignancies that do not require treatment and are clinically stable are allowed;
2. Prior infusion of JTX-8064, LILRB2, or ILT4-directed therapy;
3. The therapies listed below within the specified timeframe or ongoing toxicity attributed to prior therapy that was \>Grade 1 according to the NCI CTCAE, version 5.0. Exceptions: \>Grade 1 toxicities that, in the opinion of the Investigator, should not exclude the subject (e.g., alopecia, Grade 2 neuropathy, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement) and are approved by the Medical Monitor:

1. Major surgery (excluding minor procedures, for example, placement of vascular access, gastrointestinal/biliary stent, biopsy) \<4 weeks prior to planned C1D1;
2. Immunotherapy or biologic therapy \<28 days prior to planned C1D1 or 5 half-lives, whichever is shorter;
3. Chemotherapy \<21 days prior to planned C1D1, or \<42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter;
4. Targeted small molecule therapy \<14 days or 5 half-lives, whichever is shorter, prior to planned C1D1;
5. Hormonal or other adjunctive therapy for cancers other than the cancer under evaluation in this study that started \<14 days prior to planned C1D1 are not permitted; however, antiestrogen therapy, bisphosphonates, somatostatin analogues, leuprolide, and denosumab are permitted if started ≥14 days prior to C1D1. Other hormonal treatments and/or treatment for stable cancers (other than the cancer being treated on-study) may also be permitted 1) if these therapies would not be expected to have any positive or negative effect on the cancer being treated and 2) if discussed with and approved by the Medical Monitor;
6. Radiation therapy \<21 days prior to planned C1D1. Exception: Limited (e.g., pain palliation) radiation therapy is allowed prior to and during study drug administration as long as there are no acute toxicities, any AE due to prior radiation therapy has recovered to \<Grade 2, and the radiation is not administered to a target lesion;
7. Any prior organ transplantation, including allogeneic or autologous stem cell transplantation;
4. History of intolerance, hypersensitivity, or treatment discontinuation due to Grade 3 or greater irAEs (related to prior immunotherapy);
5. Diagnosis of immunodeficiency, either primary or acquired, or treatment with immunosuppressive levels of systemic corticosteroids (equivalent to ≥10 mg prednisone per day) or any other form of immunosuppressive therapy within 7 days prior to planned C1D1. Exception: Inhaled, intra-articular, topical, or systemic corticosteroids (systemic only at doses intended for adrenal replacement) and doses of immunosuppressive agents used prophylactically for contrast allergies are permitted in the absence of active autoimmune disease;
6. Known severe intolerance or life-threatening hypersensitivity reactions to humanized mAbs or IV immunoglobulin preparations; any history of anaphylaxis; known allergy to any of the study medications, their analogues, or excipients (sodium acetate, sucrose, sodium chloride and polysorbate 80) in the various formulations of any agent;
7. Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation (brain metastases that are stable and asymptomatic after prior treatment will be allowed);
8. Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis A, B, or C, or HIV (testing not required);
9. Women who are pregnant or breastfeeding or who plan to become pregnant/breastfeed while on study; men who plan to father children during the study;
10. History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or severe (≥Grade 3) radiation pneumonitis (excluding localized radiation pneumonitis);
11. History in the last 3 months of acute diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction, unless approved by Medical Monitor;
12. Symptomatic cardiac or cerebrovascular disease that is unresponsive to surgical or medical management;
13. Medical or social condition that, in the opinion of the Investigator, might place the subject at increased risk, adversely affect compliance, or confound safety or other clinical study data interpretation;
14. Active disease requiring systemic immunosuppressive therapy;
15. Live vaccines ≤30 days of C1D1;
16. Deep vein thrombosis, pulmonary embolism (including asymptomatic pulmonary embolism identified on imaging), or other thromboembolic event within the 6 months preceding C1D1 for JTX-8064 monotherapy cohorts only.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jounce Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stew Kroll

Role: STUDY_DIRECTOR

Jounce Therapeutics, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Arizona Clinical Research Center

Tucson, Arizona, United States

Site Status

University of Arkansas Medical Sciences

Little Rock, Arkansas, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

California Cancer Associates for Research & Excellence, Inc.

La Jolla, California, United States

Site Status

University of California, San Diego

La Jolla, California, United States

Site Status

Cedars Sinai

Los Angeles, California, United States

Site Status

UC Irvine Medical Center

Orange, California, United States

Site Status

University of California, Davis

Sacramento, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Adventist Health System/Sunbelt, Inc.

Orlando, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Augusta Oncology Associates - Wheeler Road

Augusta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Cancer Care Center of Decatur

Decatur, Illinois, United States

Site Status

University of Kentucky Chandler Medical Center (UKCMC)

Lexington, Kentucky, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

START Midwest -Cancer & Hematology Center of Western Michigan

Grand Rapids, Michigan, United States

Site Status

Regents of the University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Weill Cornell

New York, New York, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Montefiore Medical Center PRIME

New York, New York, United States

Site Status

Carolina BioOncology

Huntersville, North Carolina, United States

Site Status

Gabrail Cancer Center

Canton, Ohio, United States

Site Status

UC Health, LLC

Cincinnati, Ohio, United States

Site Status

Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Site Status

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status

Providence Portland Cancer Center

Portland, Oregon, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Prisma Health

Greenville, South Carolina, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

Oncology Consultants, P.A.

Houston, Texas, United States

Site Status

MD Anderson

Houston, Texas, United States

Site Status

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, United States

Site Status

START Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Site Status

START Mountain Region

West Valley City, Utah, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

The Board of Regents of the University of Wisconsin

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

Other Identifiers

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JTX-8064-101

Identifier Type: -

Identifier Source: org_study_id

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