A First-in-Human Phase 1 Dose Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of FID-022 as Monotherapy in Patients With Advanced Solid Tumors
Overview
- Phase
- Phase 1
- Intervention
- FID-022
- Conditions
- Advanced Solid Tumors
- Sponsor
- Fulgent Pharma LLC.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- MTD determination
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
The goal of this Phase I Clinical Trial is to evaluate the safety and tolerability of FID-022 in patients with advanced solid tumors.
Detailed Description
FID-022-001 is a Phase 1, multicenter, open label dose escalation clinical study of FID-022 as monotherapy. FID-022 is composed of topoisomerase inhibitors encapsulated with a polyethyloxazoline material. The study drug is administered through intravenous route. Patients with advanced solid tumor diagnosis without standard curative treatments are the target population (please see the eligibility section)
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and willingness to provide informed consent before the start of any study-specific procedures.
- •Age ≥18 years old.
- •Histologically- or cytologically confirmed malignant solid tumor that is metastatic, unresectable, progressive, or recurrent, and for which there are no standard curative measures, or for whom irinotecan is considered an appropriate palliative treatment option. Patients with known primary brain tumors will be excluded.
- •Measurable disease according to RECIST version 1.
- •Adequate treatment washout period of ≥21 days or 5 half-lives, whichever is shorter, for prior chemotherapy, radiotherapy, hormonal therapy, biological therapy, or immunotherapy before the first infusion of FID-
- •Note: Palliative radiation is permitted but not ≤14 days before the first infusion of FID-
- •ECOG PS of 0 or
- •Recovery from any toxic effects of previous chemotherapy, immunotherapy, targeted therapy, or radiotherapy, as judged by the investigator, to Grade ≤1 according to NCI-CTCAE version 5.0 with the following exceptions: alopecia any grade; and adequately controlled anorexia, fatigue, peripheral neuropathy, or hypothyroidism that must have recovered to Grade ≤
- •Adequate bone marrow and organ function defined as the following and these criteria need to be met:
- •Bone marrow function
Exclusion Criteria
- •Known hypersensitivity to irinotecan (also called camptothecin-11 \[CPT-11\]) and/or similar compounds (e.g., topotecan, Trodelvy®).
- •History of any secondary malignancy, with the exception of non-melanoma skin cancers and in situ cancers (such as the following: bladder, gastric, colon, cervical/dysplasia, melanoma, prostate, or breast), or has undergone potentially curative therapy with no evidence of disease recurrence for at least 2 years before the first FID-022 infusion and no additional therapy will be required during the study.
- •Patients with known symptomatic active brain metastases, gliomas, leptomeningeal carcinomatosis, or spinal cord compression or other primary brain tumors. Patients with adequately treated and asymptomatic brain metastases are eligible to participate in the study. Asymptomatic brain metastases are defined as having no neurological symptoms for at least 4 weeks before the first FID-022 infusion without evidence of radiographic progression after treatment, no requirements for corticosteroids within 7 days of the first FID-022 infusion, and no lesion ≥1.5 cm at time of screening. Patients with asymptomatic brain metastases may participate but will require regular imaging of the brain as a site of disease.
- •Received \>3 prior lines of chemotherapy for recurrent or metastatic disease unless otherwise discussed with the sponsor's medical monitor or delegate. Chemotherapy given as part of treatment for locally advanced disease in the adjuvant or neoadjuvant setting is not considered a line of prior therapy for recurrent/metastatic disease if completed at least 6 months before the start of FID-
- •Similarly, treatment with targeted agents or biologic agents such as naked antibodies as single agents or maintenance treatments will not count as a line of chemotherapy. Antibody drug conjugates are considered as lines of chemotherapy.
- •Medical history of interstitial pulmonary disease, intestinal obstructions, intestinal inflammatory disease and gastrointestinal bleeding, especially those developed from prior irinotecan treatments may not be enrolled.
- •Serious medical risk factors involving any of the major organ systems, or serious psychiatric disorders that, in the judgment of the investigator, could compromise the patient's safety or the study data integrity.
- •Known history of uncontrolled HIV infection defined as CD4+ cells \<350/mm
- •Patients with a positive viral load assay at time of screening for hepatitis C or hepatitis B. Patients with adequately treated viral hepatitis and a negative viral load assay are permitted.
- •Requirement of systemic steroids at daily doses \>10 mg prednisone equivalent systemic exposure daily, including for control of symptoms.
Arms & Interventions
Dose Escalation
Patients will be sequentially enrolled at progressively higher dose levels to receive FID-022 as monotherapy. According to the study design, maintaining the dose level or moving down a dose level will possibly happen when conditions are met. Intravenous Administration of FID-022, infusion on day 1 and 8 of each 21-day cycle: Dose level 1: 20 mg/m2. Dose level 2: 40 mg/m2. Dose level 3: 60 mg/m2. Dose level 4: 80 mg/m2. Dose level 5: 100 mg/m2. Dose level 6: 120 mg/m2.
Intervention: FID-022
Outcomes
Primary Outcomes
MTD determination
Time Frame: Through study completion, approximately 2.5 years
Determine the Maximum Tolerated Dose (MTD) of FID-022 in patients with advanced solid tumors
Number of participants with a treatment-related adverse events as assessed by NCI-CTCAE version 5.0.
Time Frame: Through study completion, approximately 2.5 years
Frequency and severity of abnormal clinical laboratory results, adverse events (AEs), severity of serious AEs (SAEs) and deaths graded according to the NCI-CTCAE version 5.0
Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 21 days of dosing)
Time Frame: 21 days
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0. Maximum tolerated dose (MTD) will be determined based on DLT per protocol.
Secondary Outcomes
- Pharmacokinetic (PK) parameters: Maximum observed plasma concentration (Cmax) of FID-022 and its components, major metabolites(Up to Day 22)
- Pharmacokinetic (PK) parameters: Time to the maximum observed plasma concentration (Tmax) of FID-022 and its components, major metabolites(Up to Day 22)
- Pharmacokinetic (PK) parameters: Area under the plasma concentration time curve (AUC0-t) of FID-022 and its components, major metabolites(Up to Day 22)
- Pharmacokinetic (PK) parameters: Area under the plasma concentration time curve (AUC0-∞) of FID-022 and its components, major metabolites(Up to Day 22)
- Tumor Response Assessment: Objective Response Rate (ORR) determined by the Investigator(Through study completion, approximately 2.5 years)
- Tumor Response Assessment: Disease control rate (DCR) determined by the Investigator(Through study completion, approximately 2.5 years)
- Tumor Response Assessment: Duration of response (DOR)(Through study completion, approximately 2.5 years)
- Tumor Response Assessment: Time to Response (TTR)(Through study completion, approximately 2.5 years)
- Tumor Response Assessment: Progression free survival (PFS)(Through study completion, approximately 2.5 years)