Unresectable Locally Advanced or Metastatic Cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10041067 Term: Small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10053571 Term:
Conditions
Interventions
Product Code: JK08
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not applicable
Other descriptive name: JK08
Concentration unit: µg/kg microgram(s)/kilogram
Concentration type: ran
Sponsors
Salubris Biotherapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion 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 •Small cell lung cancer •Melanoma •Clear cell or papillary renal cell carcinoma •Urothelial cancer •Head and neck squamous cell cancer •Luminal B or triple-negative breast cancer •Gastric or gastro esophageal adenocarcinoma •Esophageal squamous cell cancer •Skin squamous cell carcinoma •Pancreatic adenocarcinoma •Hepatocellular carcinoma •Colorectal adenocarcinoma •Epithelial ovarian cancer •Cervical cancer •Endometrial adenocarcinoma •Thyroid cancer 4.For Cohort Expansion, 4 monotherapy and 4 combination tumor specific cohorts: Monotherapy Expansion Cohorts a.HPV+ Tumors Cohort b.Melanoma Cohort c.Cutaneous Squamous Cell Cancer d.Basket Cohort: patients with histologically diagnosed unresectable, locally advanced, or metastatic tumor types noted below. •SCLC •Clear cell or papillary RCC •Urothelial cancer •HPV(-) HNSCC •Gastric or GEJ cancer •Esophageal squamous cell cancer •Pancreatic adenocarcinoma •CRC with liver metastases •Epithelial ovarian cancer •Endometrial adenocarcinoma Pembrolizumab Combination Cohorts a.Non-Small Cell Lung Cancer [limited to squamous and non-squamous carcinoma histology only]: 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: Patients must have disease burden outside of liver. Patients must also have had recurrence, progression or intolerance to standard therapy consisting of at least 2 prior standard regimens for metastatic disease. Patients who are inappropriate candidates for or have refused treatment with these regimens are also eligible. Patients should have received no more than 3 prior lines of therapy in the metastatic setting c.Luminal B or Triple Negative Breast Cancer: histologically confirmed diagnosis of advanced and/or metastatic luminal B or triple-negative breast cancer. Patients must have had recurrence, progression or intolerance to standard therapy for metastatic disease consisting of at least 2 prior regimens, but no more than 3 standard chemotherapy regimens. Hormonal and CDK-specific targeted treatment regimens without concomitant chemotherapy will not be counted as lines of therapy. Luminal B breast cancer by histology will include ER(+) and either PR(-) or Ki67 > 20% or Grade 3 by IHC analysis; HER2 status can be either positive or negative Lenvatinib Combination Cohort a.Hepatocellular Cancer: 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.ECOG performance status = 1 6.Life expectancy = 12 weeks 7.Measurable disease as per RECIST 1.1 criteria and documented by CT and/or MRI 8.Acceptable laboratory parameters 9.Identification of an archival tumor sample 10.Consent to pre- and on- treatment fresh tumor biopsy for all patients enrolled as back fill in Dose Escalation
Exclusion criteria
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 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. 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: • 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. 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 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 r
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to characterize the safety, tolerability, MTD and/or DLTs of JK08, administered SC on a QW schedule, in patients with unresectable locally, advanced or metastatic cancer in the Dose Escalation phase, followed by selection and evaluation of OBD in planned expansion cohorts.;Secondary Objective: The main secondary objectives of the study are to: • Characterize the PK of JK08. • Assess the immunogenicity (ADA) of JK08. • Evaluate the preliminary anti-tumor activity of JK08 as measured by ORR according to standard Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria • Assess disease control rate (DCR) and progression-free survival (PFS) by RECIST 1.1 and OS.;Primary end point(s): Primary endpoint: • MTD and/or DLT after one cycle of treatment and all SAEs, AEs tabulated/reported by type, grade, and frequency for the entire study duration.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint: • PK (analysis of Cmax, AUC, tmax, and t½ following treatment completion). • ADA status (see Section 10.3.8 for details of the reportable outcomes). • ORR according to standard RECIST 1.1 criteria. • DCR and PFS by RECIST 1.1 and OS in patients with advanced solid tumors.;Timepoint(s) of evaluation of this end point: Throughout the study | — |
Countries
Belgium, France, Portugal, Spain, United Kingdom
Contacts
Public ContactClinical Program Lead
Salubris Biotherapeutics, Inc.
Outcome results
None listed