CLINICAL TRIAL / NCT04669899
Study of JTX-8064, as Monotherapy and in Combination With a PD-1 Inhibitor, in Adult Subjects With Advanced Refractory Solid Tumors
- Interventional
- Recruiting
- NCT04669899
Contact Information
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
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).
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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.