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

NCT04669899 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: JTX-8064-101
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 45

Brief Summary

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).

Conditions

Cancer

Keywords

JTX-8064; LILRB2; ILT4; PD-1; JTX-4014; Immunotherapy; Immuno-oncology; Solid tumor Malignancies; Dose escalation; INNATE; Monotherapy; Combination Therapy; Antineoplastic Agents; Immunological

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of DLTs, treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuation due to adverse events (AEs) evaluated using National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) version 5.0

  up to 24 months

• Determination of a RP2D for JTX-8064 monotherapy and in combination with a PD-1i

  up to 24 months

Secondary Outcomes (16)

• Cmax (the maximum observed concentration) for JTX-8064 monotherapy and in combination with a PD-1i

  Cycles 1 through 12 (each cycle is 21 days)

• Tmax (time of maximum observed concentration) for JTX-8064 monotherapy and in combination with a PD-1i

  Cycles 1 through 12 (each cycle is 21 days)

• Cmin for JTX-8064 monotherapy and in combination with a PD-1i

  Cycles 1 through 12 (each cycle is 21 days)

• AUClast (area under the concentration-time curve from time 0 to the last measurable concentration) for JTX-8064 monotherapy and in combination with a PD-1i

  Cycles 1 and 3 (each cycle is 21 days)

• Cmax for PD-1i in combination with JTX-8064

  Cycles 1 through 12 (each cycle is 21 days)

Study Arms (12)

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

EXPERIMENTAL

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

Drug: JTX-8064

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

EXPERIMENTAL

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.

Drug: JTX-8064; Drug: pimivalimab

Stage 3 Expansion: JTX-8064 monotherapy (Ovarian)

EXPERIMENTAL

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

Drug: JTX-8064

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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).

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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

Drug: JTX-8064; Drug: pimivalimab

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

EXPERIMENTAL

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.

Drug: JTX-8064; Drug: pimivalimab

Interventions

JTX-8064 DRUG

Specified dose on specified days

Also known as: Anti-LILRB2, Anti-ILT4

Stage 1, Dose Escalation: JTX-8064 monotherapy dose escalation; Stage 2, Dose Escalation: JTX-8064 in combination with pimivalimab; Stage 3 Expansion: JTX-8064 monotherapy (Ovarian); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (BTC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (HNSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (NSCLC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (Ovarian); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (PD-(L)1i-experienced HNSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (TNBC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (UPS & LPS); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (cSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (ccRCC)

pimivalimab DRUG

Specified dose on specified days

Also known as: JTX-4014, Anti-PD-1

Stage 2, Dose Escalation: JTX-8064 in combination with pimivalimab; Stage 4, Expansion: JTX-8064 in combination with pimivalimab (BTC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (HNSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (NSCLC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (Ovarian); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (PD-(L)1i-experienced HNSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (TNBC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (UPS & LPS); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (cSCC); Stage 4, Expansion: JTX-8064 in combination with pimivalimab (ccRCC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Histologically or cytologically confirmed advanced/metastatic extracranial solid tumor malignancy:
• 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;
• Stage 3: This stage may enroll subjects with 3L/4L PD-(L)1-naïve, platinum-resistant ovarian cancer;
• Stage 4: This stage may enroll subjects with the following cancers:
• L/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;
• L-4L TNBC. Subjects must have progressed on or after treatment with a prior anti-PD-(L)1 therapy;
• L, PD-(L)1-naïve, PD-L1+; combined positive score (CPS) ≥1% HNSCC;
• L/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;
• L/4L, PD-(L)1-naïve, platinum-resistant ovarian cancer;
• L/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;
• L/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;
• L-4L PD-(L)1-naïve undifferentiated pleomorphic sarcoma (UPS) and liposarcoma (LPS);
• L/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;
• Measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator;

You may not qualify if:

• 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;
• Prior infusion of JTX-8064, LILRB2, or ILT4-directed therapy;
• 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:
• Major surgery (excluding minor procedures, for example, placement of vascular access, gastrointestinal/biliary stent, biopsy) \<4 weeks prior to planned C1D1;
• Immunotherapy or biologic therapy \<28 days prior to planned C1D1 or 5 half-lives, whichever is shorter;
• Chemotherapy \<21 days prior to planned C1D1, or \<42 days for mitomycin or nitrosoureas or 5 half-lives, whichever is shorter;
• Targeted small molecule therapy \<14 days or 5 half-lives, whichever is shorter, prior to planned C1D1;
• 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;
• 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;
• Any prior organ transplantation, including allogeneic or autologous stem cell transplantation;
• History of intolerance, hypersensitivity, or treatment discontinuation due to Grade 3 or greater irAEs (related to prior immunotherapy);
• 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;
• 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;
• 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);
• Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis A, B, or C, or HIV (testing not required);

Sponsors & Collaborators

• Jounce Therapeutics, Inc.: lead

Study Sites (45)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Arizona Clinical Research Center

Tucson, Arizona, 85258, United States

Location

University of Arkansas Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

California Cancer Associates for Research & Excellence, Inc.

La Jolla, California, 92037, United States

Location

University of California, San Diego

La Jolla, California, 92093, United States

Location

Cedars Sinai

Los Angeles, California, 90048, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

Yale University

New Haven, Connecticut, 06519, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20057, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Adventist Health System/Sunbelt, Inc.

Orlando, Florida, 32803, United States

Location

Tampa General Hospital

Tampa, Florida, 33606, United States

Location

Augusta Oncology Associates - Wheeler Road

Augusta, Georgia, 30909, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Cancer Care Center of Decatur

Decatur, Illinois, 62526, United States

Location

University of Kentucky Chandler Medical Center (UKCMC)

Lexington, Kentucky, 40536, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

START Midwest -Cancer & Hematology Center of Western Michigan

Grand Rapids, Michigan, 49546, United States

Location

Regents of the University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Weill Cornell

New York, New York, 10021, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center PRIME

New York, New York, 10461, United States

Location

Carolina BioOncology

Huntersville, North Carolina, 28708, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

UC Health, LLC

Cincinnati, Ohio, 45229, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Providence Portland Cancer Center

Portland, Oregon, 97213, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

Prisma Health

Greenville, South Carolina, 29605, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Oncology Consultants, P.A.

Houston, Texas, 77024, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

Location

START Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

START Mountain Region

West Valley City, Utah, 84119, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98331, United States

Location

The Board of Regents of the University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

spartalizumab

Study Officials

• Stew Kroll

  Jounce Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: December 17, 2020
• Study Start: January 12, 2021
• Primary Completion: November 28, 2023
• Study Completion: November 28, 2023
• Last Updated: April 9, 2024

Record last verified: 2024-04

Locations

US (45)