First-in-Human, Phase I, Open-label, Multicenter, Dose Escalation Clinical Study

Inclusion Criteria

• •1. Male or female ≥ 18 years
• •2. Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures
• •3. Histologically or cytologically confirmed incurable, unresectable, locally advanced or metastatic cancer that is refractory to standard therapies
• •4. Prior therapy:
• •• Progressed on or are intolerant to all standard therapies including checkpoint inhibitors (such as PD-1, PDL-1, CTLA-4) as a single agent or in combination with oncolytic vaccine, antibody, or chemotherapeutic agents
• •5. Patient has at least 1 measurable target lesion or evaluable disease according to RECIST version 1.1
• •6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• •7. Patient's life expectancy ≥ 6 months
• •8. Adequate hepatic function as evidenced by meeting all of the following requirements:
• •* Total bilirubin ≤ 1.5 × institutional 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 (ALP) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present
• •9. Adequate renal function as serum creatinine \< 1.5 × ULN and calculated creatinine clearance (CrCL) ≥ 60 mL/min (Cockcroft-Gault Equation).
• •10. Hematological function defined as:
• •* Absolute neutrophil count ≥ 1,500/µL without growth factor support in the 2 weeks prior to study entry
• •* Hemoglobin \> 9 g/dL without transfusion in the 2 weeks prior to study entry
• •* Platelet count ≥ 100,000/µL without transfusion in the 2 weeks prior to study entry
• •11. Prothrombin (PT), international normalized ratio (INR), or activated partial thromboplastin time (aPTT) \< 1.5 × ULN; use of full dose anticoagulants is permitted. These laboratory test values should be maintained within the therapeutic range and closely monitored by the Investigator.
• •12. Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception during study treatment that results in a low failure rate of \< 1% per year when used consistently and correctly. Male patients must always use a condom. Female patients of reproductive potential must not be pregnant, breastfeeding, or planning to conceive children within the duration of the study, beginning at the Screening visit (Initial Visit) through 120 days or for an additional 5 half-lives after the last dose of study treatment, whichever is longer. For female patients of reproductive potential, confirmation that the patient is not pregnant must be obtained by a negative serum pregnancy test result obtained during Screening.
• •Note: Women will not be considered in the category of 'female patients of reproductive potential' if they have undergone surgical sterilization (including hysterectomy, bilateral oophorectomy or total hysterectomy), or who are postmenopausal (defined as no menses for more than 12 consecutive months without medical interference). Highly effective methods of contraception include combined (estrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion or vasectomized partner (on the understanding that this is the only 1 partner during the whole study duration), and sexual abstinence. Oral contraception should always be combined with an additional contraceptive method because of a potential interaction with the study drug.
• •13. Able to stay in a 24-hour inpatient unit after 1st infusion visit and subsequent dosing visits as needed.
• •* Active Hepatitis B or C. HBV carriers without active disease (HBV DNA titer \< 1000 cps/mL or 200 IU/mL), or inactive Hepatitis C (negative HCV RNA test) may be enrolled.
• •12. Known or suspected hypersensitivity to FL115 or its excipients; known history of a Grade 3 or 4 allergic reaction to IL treatment or another fusion protein.
• •13. Women of childbearing potential who do not consent to use 2 highly effective methods of birth control (including 1 barrier method) during treatment and for an additional 5 half-lives or 120 days after the last administration of study drug, whichever is longer.
• •14. Men with a partner of childbearing potential who do not consent to use 2 highly effective methods of birth control (including 1 barrier method) during treatment and for an additional 5 half-lives or 120 days after the last administration of study drug, whichever is longer.
• •15. Any condition that the Investigator or primary physician believes may not be appropriate for the patient's participation in the study.