Trial Title:
First-in-Human, Phase I, Open-label, Multicenter, Dose Escalation Clinical Study
NCT ID:
NCT06130722
Condition:
Locally Advanced/Metastatic Solid Tumors
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Open-label, Multicenter, Dose escalation Clinical Study
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
FL115
Description:
FL115 is a novel long-acting IL-15 agonist designed as a fusion protein with a mutated
IL-15 structure (IL-15[N72D]/IL-15Rα-sFc).
Arm group label:
A Single Arm
Summary:
First-in-Human, Phase I, open-label, multicenter, dose-escalation study to evaluate the
safety, tolerability, PK, pharmacodynamics, and preliminary antitumor activity of FL115
in patients with advanced solid tumors who have progressed or are intolerant to current
standard-of-care therapies, including immune check-point inhibitors administered in
single-agent or combination use.
Detailed description:
This is a First-in-Human, Phase I, open-label, multicenter, dose-escalation clinical
study to evaluate the safety, tolerability, PK, pharmacodynamics, and preliminary
antitumor activity of FL115 when administered IV to adult patients with locally
advanced/metastatic solid tumors who have progressed on, cannot tolerate, or do not have
a standard-of-care therapy. If a patient is intolerant to standard-of-care therapy, the
reason that the treatment could not be tolerated will be documented in the electronic
case report form (eCRF). Patients will receive the investigational drug FL115 on Days 1,
8, 15, and 22 of Cycle 1 for the observation of AEs/SAEs to assess dose-limiting toxicity
(DLT) in first 28 days. FL115 will be administered IV QW (on Days 1, 8, 15, and 22) in
Cycle 2 and beyond. All patients will be monitored in the clinic over 24-hours for the
C1D1 dose for monitoring potential cytokine release syndrome (CRS). If no CRS symptoms
are observed after first dose, patients will not be asked for 24-hour inpatient
monitoring for future injections (i.e. 2nd, 3rd and 4th dosing) based on the investigator
discretion.
Seven dosing cohorts are planned, with doses of 3, 10, 30, 60, 120, 180 and 240 µg/kg.
For ethical reasons, the first 2 dose cohorts (3 and 10 µg/kg) are planned to enroll 1
patient per cohort because these 2 doses are considered suboptimal treatment for
late-stage cancer patients. The first 2 dose level cohorts will each enroll 1 patient
using an accelerated titration dose escalation design. If no DLT is observed by the end
of the first cycle (28 days) of treatment, the dose will be escalated to the next dose
cohort. However, if 1 treatment-related National Cancer Institute (NCI) Common
Terminology Criteria for Adverse Events (CTCAE) or American Society for Transplantation
and Cellular Therapy (ASTCT) Consensus Grading ≥ Grade 2 toxicity occurs in the safety
evaluation window, the study will be converted to a 3 + 3 design. After the initial 2
cohorts are completed, the study will use modified Fibonacci 3 + 3 dose-escalation
design.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
HOAG Memorial Hospital Presbyterian
Address:
City:
Newport Beach
Zip:
92663
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ariel Klingfus, BSN,RN
Email:
Ariel.Klingfus@hoag.org
Investigator:
Last name:
Carlos Becerra, MD
Email:
Principal Investigator
Facility:
Name:
Moores Cancer Center at UCSD Health
Address:
City:
San Diego
Zip:
92037
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Galfo, MPH
Email:
agalfo@health.ucsd.edu
Investigator:
Last name:
Sandip Patel, MD
Email:
Principal Investigator
Facility:
Name:
Gabriel Cancer Center
Address:
City:
Canton
Zip:
44718
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Smith, RN
Phone:
330-417-8231
Email:
csmith@gabrailcancercenter.com
Investigator:
Last name:
Nashat Gabrail, MD
Email:
Principal Investigator
Start date:
October 30, 2023
Completion date:
September 30, 2025
Lead sponsor:
Agency:
Suzhou Forlong Biotechnology Co.,Ltd,
Agency class:
Industry
Source:
Suzhou Forlong Biotechnology Co.,Ltd,
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06130722
