Trial Title:
Study of JK08 in Patients with Unresectable Locally Advanced or Metastatic Cancer
NCT ID:
NCT05620134
Condition:
Cancer
Tumor, Solid
Advanced Solid Tumor
Metastatic Cancer
Melanoma
Colorectal Cancer
Non-small Cell Lung Cancer
Small-cell Lung Cancer
Urothelial Carcinoma
Squamous Cell Carcinoma of Head and Neck
Luminal Breast Cancer
Triple Negative Breast Cancer
Clear Cell Renal Cell Carcinoma
Papillary Renal Cell Carcinoma
Gastric Adenocarcinoma
GastroEsophageal Cancer
Squamous Cell Carcinoma Skin
Pancreatic Adenocarcinoma
Hepatocellular Carcinoma
Colorectal Adenocarcinoma
Epithelial Ovarian Cancer
Thyroid Cancer
Conditions: Official terms:
Carcinoma
Neoplasms
Breast Neoplasms
Lung Neoplasms
Carcinoma, Squamous Cell
Adenocarcinoma
Carcinoma, Renal Cell
Small Cell Lung Carcinoma
Triple Negative Breast Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Carcinoma, Ovarian Epithelial
Squamous Cell Carcinoma of Head and Neck
Pembrolizumab
Lenvatinib
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
JK08
Description:
Recombinant fusion protein consisting of two functional elements, which are a fully human
monoclonal antibody, directed against CTLA-4 and a protein complex formed by the human
IL-15 and the Sushi domain of human IL-15Rα.
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion Lenvatinib Combination Cohort - Hepatocellular Cancer
Arm group label:
Dose Expansion Pembrolizumab Combination Cohort - Colorectal Cancer
Arm group label:
Dose Expansion Pembrolizumab Combination Cohort - Non-Small Cell Lung Cancer
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Immune checkpoint inhibitor
Arm group label:
Dose Expansion Pembrolizumab Combination Cohort - Colorectal Cancer
Arm group label:
Dose Expansion Pembrolizumab Combination Cohort - Non-Small Cell Lung Cancer
Intervention type:
Drug
Intervention name:
Lenvatinib Pill
Description:
Multi-kinase inhibitor
Arm group label:
Dose Expansion Lenvatinib Combination Cohort - Hepatocellular Cancer
Summary:
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.
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age ≥ 18 years old.
2. Signed informed consent and willing and able to comply with study procedures and
scheduled visits.
3. For Dose Escalation, patients with one of the following histologically diagnosed
unresectable, locally advanced, or metastatic tumor types:
- Non-small cell lung cancer (NSCLC).
- Small cell lung cancer (SCLC).
- Melanoma.
- Clear cell or papillary renal cell carcinoma (RCC).
- Urothelial cancer (UC).
- Head and neck squamous cell cancer (HNSCC).
- Luminal B (ER+, PR-, any HER2 status) or triple-negative breast cancer.
- Gastric or gastro esophageal adenocarcinoma (GC/GEJ).
- Esophageal squamous cell cancer.
- Skin squamous cell carcinoma (SCC).
- Pancreatic adenocarcinoma.
- Hepatocellular carcinoma (Childs-Pugh A or B7 only).
- Colorectal adenocarcinoma (CRC).
- Epithelial ovarian cancer.
- Cervical cancer.
- Endometrial adenocarcinoma.
- Thyroid cancer (follicular or papillary).
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Life expectancy ≥ 12 weeks.
7. 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.
8. 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.
- ALT/AST ≤ 5 × ULN for patients with liver metastases.
- Total bilirubin ≤ 1.5 ULN or ≤ 3 x ULN for patients with Gilbert's disease.
- Direct bilirubin ≤ ULN for patients with total bilirubin > 1.5 ULN.
- Creatinine ≤ 1.8 mg/dL.
- Or calculated/measured creatinine clearance > 30 mL/minute.
9. Identification of an archival tumor sample (i.e., tissue block (formalin-fixed
paraffin-embedded [FFPE]) or a series of approximately 10-15 slides).
10. 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.
11. Women of childbearing potential (WOCBP) not surgically sterilized and between
menarche and 1 year post menopause must:
- Have a negative serum or urine pregnancy test performed within 72 hours prior
to the initiation of study drug administration.
- Be willing to use 2 forms of effective contraception throughout the study,
starting with the screening and through 90 days after the last dose of JK08.
- Abstinence is considered a highly effective method if this is the established
and preferred contraception method for the patient and is defined as refraining
from heterosexual intercourse during the entire period of risk associated with
the study treatments. Periodic abstinence [e.g., calendar, ovulation,
symptothermal, postovulation methods], withdrawal, spermicides only, and
lactational amenorrhea method are not acceptable methods of contraception.
Female and male condoms should not be used together.
12. Male patients with partners of childbearing potential, even if surgically sterilized
(i.e., status post-vasectomy) must agree to:
- Use effective barrier contraception from the time of consent through 90 days
after discontinuation; or
- Agree to practice true abstinence, if this is the established and preferred
contraception method by the patient and is defined as refraining from
heterosexual intercourse during the entire period of risk associated with the
study treatments. Periodic abstinence [e.g., calendar, symptothermal,
post-ovulation methods], withdrawal, spermicides only, and lactational
amenorrhea method are not acceptable methods of contraception. Female and male
condoms should not be used together.
- In addition, male patients should also have their partners use contraception
for the same period of time.
13. Central nervous system (CNS) metastases must have been treated, be asymptomatic for
≥14 days, and meet the following at the time of enrollment:
- No concurrent treatment for CNS disease (e.g., surgery, radiation,
corticosteroids ≥ 10 mg prednisone/day or equivalent).
- No concurrent or past history of leptomeningeal disease or cord compression.
14. Must be willing and able to comply with clinic visits and procedures outlined in the
study protocol.
15. 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:
1. 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.
2. 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.
3. Major surgery within 6 weeks from treatment initiation.
4. Clinically significant cardiovascular/vascular disease ≤ 6 months before first dose:
- Myocardial infarction or unstable angina.
- Clinically significant cardiac arrhythmias.
- Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic
blood pressure (DBP) > 100 mmHg.
- Pulmonary embolism, symptomatic cerebrovascular events or any other serious
cardiac condition (e.g., pericardial effusion or restrictive cardiomyopathy).
- QTcF prolongation > 480 msec.
- Congestive heart failure (New York Heart Association class III-IV).
- Myocarditis/clinically significant pericarditis.
5. Clinically significant gastrointestinal disorders including:
- Gastrointestinal perforation or unhealed ulcerations < 6 months prior to study
drug administration. Patients must have documented evidence (e.g., upper
endoscopy, colonoscopy) of completely healed area of prior perforation.
- Clinically significant gastrointestinal bleeding < 3 months prior to study drug
administration.
- Pancreatitis < 6 months prior to study drug administration.
- History of Crohn's disease or ulcerative colitis.
6. Clinically significant pulmonary compromise requiring supplemental oxygen use.
7. 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.
8. 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).
9. Known hypersensitivity to JK08 or any excipient (histidine/histidine-HCl, sucrose,
glycine, PS-80).
10. 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.
11. 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.
12. Recent or ongoing serious infection including the following:
- Any uncontrolled Grade 3 or higher (per CTCAE v5.0) viral, bacterial, or fungal
infection within 2 weeks prior to the first dose of JK08. Routine antimicrobial
prophylaxis is allowed.
- Uncontrolled infection with human immunodeficiency virus (HIV). Patients on
stable highly active antiretroviral therapy (HAART) therapy with undetectable
viral load and normal CD4 counts for at least 6 months prior to study entry are
eligible. Serological testing for HIV at screening is not required.
- Known to be positive for hepatitis B (HBV) surface antigen, or any other
positive test for hepatitis B indicating acute or chronic infection. Patients
who are or have received anti-HBV therapy and have undetectable HBV DNA for at
least 6 months prior to study entry are eligible. Serological testing for
hepatitis B at screening is not required.
- Known active hepatitis C (HCV) as determined by positive serology and confirmed
by polymerase chain reaction (PCR). Patients on or having received antiviral
therapy are eligible provided they are virus-free by PCR for at least 6 months
prior to study entry. Serological testing for hepatitis C at screening is not
required.
- Known active or latent tuberculosis (testing at screening not required).
13. 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.
14. Prior systemic anti-cancer treatment as follows:
- For cytotoxic chemotherapy, small molecule inhibitors, radiation, or similar
investigational treatments, ≤ 2 weeks or 5 half lives, whichever is shorter.
- For monoclonal antibodies or similar experimental therapies: ≤ 3 weeks or 5
half-lives, whichever is shorter.
- Antibody drug conjugates and radioimmunoconjugates or other similar
experimental therapies ≤ 6 weeks or 5 half-lives, whichever is shorter.
15. Ascites or pleural effusions requiring large volume para- or pleurocentesis within 4
weeks of treatment initiation.
16. Pregnant or nursing.
17. Therapeutic anticoagulation for a thromboembolic event that occurred within 3 months
of dosing; prophylactic anticoagulation is permitted.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Institut Jules Bordet
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Facility:
Name:
UZA
Address:
City:
Edegem
Country:
Belgium
Facility:
Name:
UZ Ghent
Address:
City:
Ghent
Zip:
9000
Country:
Belgium
Facility:
Name:
CHU UCL Namur - site Godinne
Address:
City:
Yvoir
Country:
Belgium
Facility:
Name:
NEXT Oncology Barcelona
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Vall d Hebron Institute of Oncology VHIO
Address:
City:
Barcelona
Country:
Spain
Facility:
Name:
Next Oncology Madrid Hospital Quironsalud Madrid
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
NEXT Oncology Madrid
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
START Madrid
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
University Hospital October 12
Address:
City:
Madrid
Country:
Spain
Facility:
Name:
Instituto de Investigación Sanitaria INCLIVA
Address:
City:
Valencia
Country:
Spain
Start date:
October 17, 2022
Completion date:
February 20, 2026
Lead sponsor:
Agency:
Salubris Biotherapeutics Inc
Agency class:
Industry
Source:
Salubris Biotherapeutics Inc
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05620134
