Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
About
This is a Phase 1/2, open-label, multi-center, first-in-human, dose escalation and cohort expansion study evaluating multiple doses and schedules of subcutaneously administered JK08 in patients with unresectable locally, advanced or metastatic cancer.
Full description
This Phase 1/2, open label, dose escalation and cohort expansion study is designed to evaluate and characterize the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary antitumor activity of JK08 administered subcutaneously (SC) on a once weekly (QW) schedule in patients with unresectable locally, advanced or metastatic cancer.
The study consists of a Dose Escalation phase to determine the MTD/OBD of JK08, followed by a Cohort Expansion phase to further define the safety and initial efficacy of JK08 monotherapy or in combinations.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Age ≥ 18 years old.
Signed informed consent and willing and able to comply with study procedures and scheduled visits.
For Dose Escalation, patients with one of the following histologically diagnosed unresectable, locally advanced, or metastatic tumor types:
Expansion Combination Cohorts
A. Non-Small Cell Lung Cancer [limited to squamous and non-squamous carcinoma histology only]: (Combination with Pembrolizumab) patients must have received no more than 2 prior lines of therapy, including PD-(L)1 therapy and platinum-based chemotherapy. Patients must have been tested for relevant tumor mutations, translocation or other genomic aberrations for which an approved targeted therapy is available; if present, patients must have progressed on or be intolerant to mutation specific treatment.
B. Colorectal Cancer: (Combination with Pembrolizumab) Patients must have disease burden outside of liver; i.e., absence of liver metastasis. Previously treated liver metastasis would be permitted. Patients must also have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior standard regimens (containing a fluoropyrimidine plus a platinum analogue and/or irinotecan) for metastatic disease.
C. Hepatocellular Cancer: (Combination with Lenvatinib) histologically confirmed adenocarcinoma diagnosis of advanced unresectable and/or metastatic HCC. Patients must have had only one prior line of therapy, which should be inclusive of anti-PD-(L)1 therapy and must have Childs Pugh A or B7.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Life expectancy ≥ 12 weeks.
Measurable disease as per RECIST 1.1 criteria and documented by computed tomography (CT) and/or magnetic resonance imaging (MRI).
Note: lesions treated previously with radiation must demonstrate clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment.
Acceptable laboratory parameters:
Albumin ≥ 2.8 g/dL.
Platelet count ≥ 75,000.
Hemoglobin ≥ 8.0 g/dL.
Absolute neutrophil count ≥ 1,500/µL.
ALT/AST ≤ 3.0 times ULN.
Total bilirubin ≤ 1.5 ULN or ≤ 3 x ULN for patients with Gilbert's disease.
Creatinine ≤ 1.8 mg/dL.
Identification of an archival tumor sample (i.e., tissue block (formalin-fixed paraffin-embedded [FFPE]) or a series of approximately 10-15 slides).
Consent to pre- and on- treatment fresh tumor biopsy for all patients enrolled as back fill in Dose Escalation or for at least 6 additional patients per expansion cohort in Cohort Expansion in Simon Stage 2. Note: Biopsies are not required for the Basket Cohort.
Women of childbearing potential (WOCBP) not surgically sterilized and between menarche and 1 year post menopause must:
Male patients with partners of childbearing potential, even if surgically sterilized (i.e., status post-vasectomy) must agree to:
Central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥14 days, and meet the following at the time of enrollment:
Must be willing and able to comply with clinic visits and procedures outlined in the study protocol.
Concurrent use of hormones for breast cancer or for non cancer related conditions (e.g., insulin for diabetes, hormone replacement therapy) is acceptable. Bisphosphonates or RANK-L inhibitor or analogues are permitted for supportive care of patients with bone metastases.
Exclusion criteria
Patients with symptomatic or unstable CNS primary tumor or metastases and/or carcinomatous meningitis. Patients with documented treated CNS metastases stable for at least 4 weeks may be enrolled at the discretion of the investigator.
Patients with active, or history of, severe autoimmune disease who in the opinion of the investigator and/or the Sponsor or Sponsor's designee would be exposed to unacceptable risk by participating in the study.
Major surgery within 6 weeks from treatment initiation.
Clinically significant cardiovascular/vascular disease ≤ 6 months before first dose:
Clinically significant gastrointestinal disorders including:
Clinically significant pulmonary compromise requiring supplemental oxygen use.
History of Grade 3 or greater drug-related immune-mediated AE during treatment with CPIs such as anti-PD-(L)1 or anti-CTLA-4 antibodies.
Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed. At least 2 doses of COVID-19 vaccination must have been completed prior to enrollment (see Section 8.2 for further details).
Known hypersensitivity to JK08 or any excipient (histidine/histidine-HCl, sucrose, glycine, PS-80).
Second primary invasive malignancy not in remission for ≥ 1 year. Exceptions include non melanoma skin cancer, cervical carcinoma in situ, resected melanoma in situ, or any malignancy considered to be indolent and never required therapy.
Any serious underlying medical or psychiatric condition that would preclude understanding and rendering of informed consent or impair the ability of the patient to receive or tolerate the planned treatment.
Recent or ongoing serious infection including the following:
Use of systemic corticosteroids within 15 days or other immunosuppressive drugs within 30 days prior to start of the study, with the exception of corticosteroids as replacement therapy up to an equivalent of prednisone 10 mg/day which is allowed. Inhaled, topical, or intraarticular steroids are allowed.
Prior systemic anti-cancer treatment as follows:
Ascites or pleural effusions requiring large volume para- or pleurocentesis within 4 weeks of treatment initiation.
Pregnant or nursing.
Therapeutic anticoagulation for a thromboembolic event that occurred within 3 months of dosing; prophylactic anticoagulation is permitted.
Primary purpose
Allocation
Interventional model
Masking
263 participants in 4 patient groups
Loading...
Central trial contact
Naimish Pandya, MD
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal