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

Cancer Clinical Trial

Official title:

Phase 1/2 First-in-Human (FIH) Study of Leukocyte Immunoglobulin-Like Receptor B2 (LILRB2) Inhibitor Monoclonal Antibody (mAb) JTX-8064, as Monotherapy and in Combination With a Programmed Cell Death Receptor-1 (PD-1) Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumor Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04669899
• Other study ID #: JTX-8064-101
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 12, 2021
• Est. completion date: November 28, 2023

Study information

• Verified date: April 2024
• Source: Jounce Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: November 28, 2023
• Est. primary completion date: November 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• JTX-8064
Specified dose on specified days
• pimivalimab
Specified dose on specified days

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Augusta Oncology Associates - Wheeler Road	Augusta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Gabrail Cancer Center	Canton	Ohio
United States	University of Chicago	Chicago	Illinois
United States	UC Health, LLC	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Barbara Ann Karmanos Cancer Center	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	University of Florida	Gainesville	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	START Midwest -Cancer & Hematology Center of Western Michigan	Grand Rapids	Michigan
United States	Prisma Health	Greenville	South Carolina
United States	MD Anderson	Houston	Texas
United States	Oncology Consultants, P.A.	Houston	Texas
United States	Carolina BioOncology	Huntersville	North Carolina
United States	California Cancer Associates for Research & Excellence, Inc.	La Jolla	California
United States	University of California, San Diego	La Jolla	California
United States	University of Kentucky Chandler Medical Center (UKCMC)	Lexington	Kentucky
United States	University of Arkansas Medical Sciences	Little Rock	Arkansas
United States	Cedars Sinai	Los Angeles	California
United States	Joe Arrington Cancer Research & Treatment Center	Lubbock	Texas
United States	The Board of Regents of the University of Wisconsin	Madison	Wisconsin
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Regents of the University of Minnesota	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
United States	Montefiore Medical Center PRIME	New York	New York
United States	Mount Sinai	New York	New York
United States	Weill Cornell	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	UC Irvine Medical Center	Orange	California
United States	Adventist Health System/Sunbelt, Inc.	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Cancer Center	Portland	Oregon
United States	University of California, Davis	Sacramento	California
United States	START Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Tampa General Hospital	Tampa	Florida
United States	Arizona Clinical Research Center	Tucson	Arizona
United States	Georgetown University	Washington	District of Columbia
United States	START Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Jounce Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determination of a RP2D for JTX-8064 monotherapy and in combination with a PD-1i		up to 24 months
Secondary	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)
Secondary	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)
Secondary	Cmin for JTX-8064 monotherapy and in combination with a PD-1i		Cycles 1 through 12 (each cycle is 21 days)
Secondary	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)
Secondary	Cmax for PD-1i in combination with JTX-8064		Cycles 1 through 12 (each cycle is 21 days)
Secondary	Tmax for PD-1i in combination with JTX-8064		Cycles 1 through 12 (each cycle is 21 days)
Secondary	Cmin for PD-1i in combination with JTX-8064		Cycles 1 through 12 (each cycle is 21 days)
Secondary	Incidence of anti-drug antibodies (ADAs) to JTX-8064 and, as appropriate, to PD-1i		Baseline through Cycle 12 (each cycle is 21 days)
Secondary	Incidence of neutralizing antibodies (Nabs) to JTX-8064 and, as appropriate, to PD-1i		Baseline through Cycle 12 (each cycle is 21 days)
Secondary	For Stages 1 and 2: Receptor occupancy for LILRB2 on monocytes in whole blood		Baseline through Cycle 6 (each cycle is 21 days)
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Objective response rate (ORR; the proportion of subjects who have had a partial response [PR] or complete response [CR]) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		up to 36 months
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Disease control rate (DCR; the proportion of subjects who have a PR, CR, or stable disease [SD]), as per RECIST version 1.1		up to 36 months
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Progression-free survival (PFS; the interval from start of treatment to the earlier of first documentation of disease progression or death from any cause)		up to 36 months
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Overall survival (OS; the interval from start of treatment to death of any cause)		up to 36 months
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Duration of response (DOR; the time from documentation of tumor progression or death due to any cause, whichever comes first)		up to 36 months
Secondary	For Stages 3 and 4: Preliminary efficacy endpoints: Percentage of subjects with tumor reduction at any time		up to 36 months