| Eligibility |
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.
Exclusion Criteria:
1. Prior major surgery, chemotherapy, immunotherapy, or radiation therapy within 14 days
prior to initiation of study treatment. No AE is evident from prior anticancer therapy
except Grade 2 alopecia, sensory neuropathy, lymphopenia, and endocrinopathies
controlled with hormone replacement. Palliative radiotherapy to a single area of
metastasis is allowed (consult with assigned Medical Monitor)
2. Prior allogeneic stem cell, bone marrow, or solid organ transplant.
3. Live virus vaccine within 30 days prior to study entry
4. Known active autoimmune disease or history of autoimmune disease requiring systemic
therapy within 2 years prior to entry; except hypothyroidism, vitiligo, Grave's
disease, Hashimoto's disease, or Type 1 diabetes mellitus
5. Use of systemic corticosteroids in a dose equivalent to > 10 mg/day of prednisone or
other immunosuppressive agent within 2 weeks prior to study entry. Use of inhaled,
topical, or ophthalmological steroids are allowed
6. Symptomatic CNS metastases. Patients with asymptomatic CNS metastases who are
radiologically and neurologically stable = 4 weeks following CNS directed therapy and
are on a stable or decreasing dose of corticosteroids (e.g., prednisone less than 10
mg/day or equivalent) are eligible for study entry
7. Uncontrolled hypertension (systolic blood pressure > 160 mmHg and diastolic blood
pressure > 99 mmHg), with symptoms or a known history of hypertension crisis, or
hypertensive encephalopathy
8. Severe cardiovascular disease, including cerebrovascular accident (CVA), transient
ischemic attack (TIA), myocardial infarction, or unstable angina within 6 months of
study entry; New York Heart Association (NYHA) class III or IV heart failure within 6
months of study entry; uncontrolled arrhythmia within 6 months of study entry
9. Resting QTcF interval > 470 msec on ECG at baseline; no concomitant medications that
would prolong the QT interval; known family history of long QT syndrome. Left
ventricular ejection fraction <40% at baseline.
10. Concurrent malignancy within 2 years except cervical carcinoma in situ, localized
squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active
surveillance, ductal carcinoma in situ of the breast, or = T1 urothelial carcinoma
11. Known active infection including HIV, hepatitis B or C, or tuberculosis, requiring
active therapy; exceptions are as follows:
- Patients infected with the HIV virus will be eligible if their CD4 count is > 350
cells/mm3 and the patient is on anti-retroviral therapy with an HIV viral load
that is below the level of detection.
- 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.
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