ORB-021 In Patients With Advanced Solid Tumors

Inclusion Criteria

• •All patients must meet the following criteria for inclusion:
• •1. Age 18 years or older
• •2. Patients with evidence of recurrent or refractory solid tumors deemed medically safe to undergo serial biopsies.
• •3. Must have received or be ineligible for all standard of care therapies as deemed appropriate by the treating physician.
• •4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• •5. Adequate organ and marrow function as defined below:
• •* Hemoglobin ≥ 9.0 g/dL
• •* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (\> 1500 per mm3)
• •* Platelet count ≥ 75 × 109/L (\> 75,000 per mm\^3)
• •* Serum bilirubin less than or equal to 1.5 × institutional upper limit of normal (ULN).
• •* AST (SGOT)/ALT (SGPT) less than or equal to 2.5 × institutional ULN for patients without known liver metastases and up to 5 x institutional ULN for patients with known liver metastases.
• •* Creatinine clearance (CL) \> 40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)
• •* Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 3 days prior to treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause)
• •6. Patients and their partners must practice approved forms of contraception. Sexually active WCBP must agree to use a highly effective method of contraception prior to study entry and continuing for 30 days after ORB-021 administration. Highly effective methods of contraception are highly effective birth control methods with a failure rate of \< 1% per year when used consistently and correctly. Additionally, male patients should refrain from donating sperm for 3 months following the last dose of study drug.
• •7. Ability to understand and willingness to sign an Institutional Review Board (IRB)-approved written informed consent document.
• •* HIV: Patients living with HIV infection are ineligible only if they have a CD4 count less than 350 cells/µL and a history of an AIDS-defining infection within the last 12 months. Patients with a CD4 count greater than 350 cells/µL or who have not had an AIDS-defining infection within the last 12 months are eligible. Eligible patients living with HIV should maintain effective anti-retroviral therapy.
• •* SARS-COV2 (PCR positive)
• •15. Receipt of live attenuated vaccination within 28 days prior to the study treatment
• •16. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results.
• •17. Patients with uncontrolled seizures
• •19. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ORB-021 may be included only after consultation with the Principal Investigator
• •20. Patients with QTcF \> 480 ms
• •21. Patients with prior grade 3 irAE or any irAE that resulted in discontinuation of PD-1 or PD-L1 ICI treatment.