Study of JK06 in Patients With Unresectable Locally Advanced or Metastatic Cancer

This Phase 1/2, open label, dose escalation and cohort expansion study is designed to evaluate and characterize the safety, tolerability, PK, immunogenicity, and preliminary anti-tumor activity of JK06 administered intravenously (IV) in patients with unresectable, locally advanced, or metastatic cancer. The study consists of a Dose Escalation phase to determine the MTD/recommended phase 2 dose (RP2D) of JK06, followed by a Cohort Expansion phase to further define the safety and initial efficacy of JK06 in tumor specific cohorts.

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 histologically diagnosed unresectable, locally advanced, or metastatic solid tumors.
• Dose expansion solid tumor groups.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Life expectancy ≥ 12 weeks.
• Measurable disease as per RECIST 1.1 criteria and documented by CT and/or 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 ≥ 100, 000.
• Hemoglobin ≥ 9.0 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 ≤ 1.5 ULN for patients with total bilirubin > 1.5 ULN.
• Creatinine ≤ 1.8 mg/dL. -Or calculated/measured creatinine clearance > 30 mL/minute.
• 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-treatment fresh tumor biopsy for patients enrolled in the back-fill part of Dose Escalation and all eligible patients enrolled in Cohort Expansion.
• 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 and be willing to use 2 forms of effective contraception throughout the study starting with screening through 217 days after the last dose of JK06.
• Male patients with partners of childbearing potential, even if surgically sterilized (i.e., status post-vasectomy) must agree to contraceptive use from the time of consent through 217 days after treatment discontinuation.
• Central nervous system (CNS) metastases must have been treated, be asymptomatic for ≥ 14 days, and meet certain criteria 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 inhibitors 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.
• Major surgery within 6 weeks from treatment initiation.
• Clinically significant cardiovascular/vascular disease ≤ 6 months before first dose.
• Clinically significant gastrointestinal disorders.
• Clinically significant pulmonary compromise requiring supplemental oxygen use.
• Grade 2 or greater peripheral neuropathy at time of study entry.
• Vaccination with any live virus vaccine within 4 weeks prior to the initiation of study drug administration. Inactivated annual influenza vaccination is allowed.
• Known hypersensitivity to JK06 or any excipient.
• 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.
• Prior systemic anti-cancer treatment:

• 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.
• 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.
• Active pneumonitis/interstitial lung disease (ILD) or history of drug-induced or radiation-induced pneumonitis/ILD that requires ongoing systemic corticosteroid treatment or has not fully resolved at study entry.