Study of a PD-1 Inhibitor (JTX-4014) in Subjects With Solid Tumor Malignancies

JTX-4014-101 is a Phase 1, open label, dose escalation clinical study of JTX-4014 in adult subjects with advanced refractory solid tumor malignancies, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).

JTX-4014 is a fully human IgG4 monoclonal antibody designed to specifically bind to PD-1 and block its interaction with its ligands, PD-L1 and PD-L2, to augment anti-tumor T cell activity. This is a Phase 1, first in human, open label, multicenter, dose escalation clinical study to evaluate the safety, tolerability, and PK of JTX-4014 when administered as a single agent to adult subjects with advanced refractory solid tumor malignancies. The intent of this study will be to determine the MTD and RP2D.

Eligibility Criteria:
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 extracranial solid tumor malignancy that is recurrent, metastatic, or persistent after at least 1 line of standard therapy and with no further standard treatment options that are likely to provide meaningful clinical benefit;
3. Evaluable or measurable disease, according to the RECIST version 1.1, that has objectively progressed since (or on) previous treatment as assessed by the Investigator; while target lesions are not required, target lesions should be measured if present;
4. ≥ 18 years of age;
5. ECOG performance status 0 or 1;
6. Predicted life expectancy of ≥ 3 months;
7. Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance with the study protocol;
8. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72 hours prior to planned Cycle 1 Day 1 (C1D1) and a negative urine pregnancy test on 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;
10. Subjects with medical history of the following must be discussed with the Medical Monitor:

    1. Prior biliary tract disorders (as based on hepatobiliary system organ class high level terms of: obstructive bile duct disorders, hepatic vascular disorders, structural and other bile duct disorders).
    2. Portal hypertension and/or hepatic vascular disorders.

Exclusion Criteria:

1. Concurrent anticancer treatment, either FDA-approved, palliative, or investigational for the cancer being evaluated in this study or for other cancers (with protocol-specified exceptions);
2. Prior receipt of a PD-1 or PD-L1 inhibitor mAb, including JTX-4014;
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, with protocol-specified exceptions:

   1. Major surgery \< 4 weeks prior to planned C1D1;
   2. Biologic therapy, including non-PD-1/PD-L1 inhibitor immunotherapy, \< 28 days prior to planned C1D1;
   3. Chemotherapy \< 21 days prior to planned C1D1, or \< 42 days for mitomycin or nitrosoureas;
   4. Targeted small molecule therapy \< 14 days 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, with protocol-specified exceptions;
   6. Radiation therapy \< 21 days prior to planned C1D1, with protocol-specified exceptions;
   7. Any prior organ transplantation, including allogeneic or autologous stem cell transplantation;
4. History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events on prior non PD 1/PD L1 inhibitor immunotherapy;
5. Diagnosis of immunodeficiency, either primary or acquired, or treatment with immunosuppressive levels of systemic corticosteroids or any other form of immunosuppressive therapy within 7 days prior to planned C1D1, with protocol-specified exceptions;
6. Known severe intolerance or life-threatening hypersensitivity reactions to humanized mAbs or intravenous immunoglobulin preparations; any history of anaphylaxis; prior history of human anti-human antibody response; known allergy to any of the study medications, their analogues, or excipients;
7. Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord compression not definitively treated with surgery or radiation, with protocol-specified exceptions;
8. Active and clinically relevant bacterial, fungal, or viral infection, including known hepatitis A, B, C, or human immunodeficiency virus;
9. Receipt of live vaccines within 30 days of planned C1D1;
10. 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;
11. History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis);
12. Symptomatic ascites or pleural effusion;
13. History of acute diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or abdominal carcinomatosis;
14. Symptomatic cardiac or cerebrovascular disease that is unresponsive to surgical or medical management;
15. 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.