First-in-Human, Phase I, Open-label, Multicenter, Dose Escalation Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of FL115 Monotherapy in Patients With Locally Advanced/Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- FL115
- Conditions
- Locally Advanced/Metastatic Solid Tumors
- Sponsor
- Suzhou Forlong Biotechnology Co., Ltd
- Enrollment
- 18
- Locations
- 4
- Primary Endpoint
- To evaluate the safety and tolerability of FL115 in approximately 26 patients with unresectable locally advanced or metastatic solid tumors
- Status
- Completed
- Last Updated
- 3 months ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female ≥ 18 years
- •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
- •Histologically or cytologically confirmed incurable, unresectable, locally advanced or metastatic cancer that is refractory to standard therapies
- •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
- •Patient has at least 1 measurable target lesion or evaluable disease according to RECIST version 1.1
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Patient's life expectancy ≥ 6 months
- •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).
Exclusion Criteria
- •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)
- •Prior allogeneic stem cell, bone marrow, or solid organ transplant.
- •Live virus vaccine within 30 days prior to study entry
- •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
- •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
- •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
- •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
- •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
- •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.
- •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
Arms & Interventions
A Single Arm
Intervention: FL115
Outcomes
Primary Outcomes
To evaluate the safety and tolerability of FL115 in approximately 26 patients with unresectable locally advanced or metastatic solid tumors
Time Frame: From screening to 30 days after last dose.
The study eligible 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. Adverse events (AEs) and serious adverse events (SAEs), other than those associated with CRS and related neurotoxicity events, will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.