Dose Escalation and Expansion Study Evaluating ODC-IL2 in Adult Patients With Advanced or Metastatic Solid Tumors

Inclusion criteria

• Each patient must meet all the following criteria to participate in the study:
• Histologically or cytologically confirmed advanced or metastatic solid tumors, for which no other standard treatment is available or appropriate, or for which the Trutino Biosciences Protocol #: TRT-ODC-IL2-001 Version: 1.0 Date: 20 September 2024 standard of care is refused by the patient due to tolerability or the Investigator believes the patient will not tolerate standard-of-care therapy
• Advanced or metastatic tumors measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Life expectancy of at least 3 months;
• Age ≥ 18 years;
• Signed, written Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent
• Acceptable liver function:
• Bilirubin ≤ 1.5 times upper limit of normal (ULN) or ≤ 5 × institutional ULN for patients who have serum bilirubin increases due to underlying Gilbert's Syndrome (familial benign unconjugated hyperbilirubinemia).
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
• Acceptable renal function: • Calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation.
• Acceptable hematologic status:
• Absolute neutrophil count ≥ 1500 cells/mm3
• Platelet count ≥ 75,000 (plt/mm3)
• Hemoglobin ≥ 9 g/dL
• A negative serum pregnancy test (if a woman of childbearing potential);
• Women of childbearing potential (WOCBP) and men with WOCBP partners must agree to use adequate contraception (hormonal method of birth control; intrauterine devices or abstinence) prior to study entry, for the duration of study participation and for 4 months after the last dose of study drug. Should a female trial participant or a female partner of a male trial participant become pregnant or suspect she is pregnant during the study, the Investigator must be informed immediately.

Exclusion criteria

• New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \> 470 msec
• Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Known active brain metastases; patients with previously treated, clinically stable, radiologically stable brain metastases (without evidence of progression in 4 weeks) and without the requirement for treatment with corticosteroids in prior 3 weeks may be considered for enrollment after discussion with the Medical Monitor
• History of prior organ transplant
• Conditions requiring systemic treatment with corticosteroids or any other form of immunosuppressive therapy within 7 days prior to start of study drug.
• History of autoimmune diseases requiring systemic immunosuppressive therapy in the last 2 years
• Pregnant or nursing women.
• Treatment with radiation therapy, major surgery, chemotherapy, or investigational therapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C). Radiation for palliation of pain is allowed within 1 week prior to study entry, but the lesion should not be selected as a target lesion for RECIST analysis.
• Unwillingness or inability to comply with procedures required in this protocol
• Known active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus, type 1 (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus (HCV)
• Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable
• Active infection with HIV and CD4+ T-cell count \<350/μL. Patients not on established anti-retroviral therapy for at least 4 weeks and having a detectable HIV viral load
• Serious uncontrolled nonmalignant disease (e.g., renal failure, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
• Prior treatment with an IL-2 targeted treatment, unless given as a part of a tumor infiltrating lymphocyte treatment combination;
• Known sensitivity to IL-2 or any of the excipients in ODC-IL2;
• Active treatment with heparin or heparin-related therapies, unless the patient can be transitioned to a non-heparin treatment for the clinical condition with an adequate washout prior to enrollment in the study.