A Study of HG381 Administered to Patients With Advanced Solid Tumors
- Registration Number
- NCT04998422
- Lead Sponsor
- HitGen Inc.
- Brief Summary
This is a Phase I, first in human, open-label, non-randomized, multicenter study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and establish a recommended dose of HG381 administered intravenously (IV) alone in subjects with advanced solid tumors.
- Detailed Description
The trial consists of a dose escalation phase and a cohort expansion phase.In dose escalation phase, escalating doses of HG381 will be evaluated as guided by the traditional 3+3 design . In cohort expansion phase, subjects will receive HG381 alone at a single dose level determined based on the data form dose escalation phase. In total, approximately 57 subjects will participate in the study, approximately 42 in the dose-escalation cohort, and approximately 15 in the expansion cohort.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 57
- Capable of giving signed informed consent.
- Life expectancy of at least 3 months.
- Histological or cytological documentation of an advanced solid tumor，subjects with advanced/recurrent solid tumors, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
- Measurable disease per RECIST version 1.1, there is at least one measurable lesion during the screening period.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
- Adequate organ function : Hematologic system: Hemoglobin ≥9 g/dL, Absolute neutrophil count [ANC] ≥1.5x10^9/L, Platelets ≥100x10^9/L, INR ≤ 1.5 and APTT ≤1.5 x ULN; Hepatic system: Total bilirubin ≤1.5 x ULN, ALT and AST ≤ 2.5 x ULN; Renal system: serum creatinine ≤1.5×ULN or creatinine clearance ≥50 mL/min (calculated by the Cockcroft-Gault formula); Cardiac system: left ventricular ejection fraction (LVEF) ≥50% ; QT interval (QTcF) ≤470 ms for women, and ≤450 ms for men; Endocrine system: Thyroid-stimulating hormone (TSH) is within the normal limits.
- Subjects with fertility must agree to take medically approved effective contraceptive measures during the entire trial period and at least 3 months after the last medication.
- Chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy and other anticancer therapy within 4 weeks.
- Concurrent medical condition requiring the use of other systemic immunosuppressive treatment within 4 weeks before the first dose of study treatment.
- Receipt of any live vaccine within 4 weeks of the start of study treatment.
- Receipt of unmarketed clinical trial drugs or treatments within 4 weeks of the start of study treatment.
- Receipt of surgery or interventional treatment (excluding tumor biopsy, puncture, etc.) within 4 weeks of the start of study treatment.
- History or evidence of cardiovascular and cerebrovascular diseases risk.
- Subjects with uncontrolled diabetes.
- Symptomatic central nervous system (CNS) metastases or asymptomatic CNS metastases that have required steroids within 2 weeks prior to first dose of study treatment.
- Currently or in the past suffering from malignant tumors.
- Uncontrollable pleural effusion, pericardial effusion or ascites still need to be drained frequently after appropriate intervention.
- Active or suspected autoimmune disease.
- History of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia, or evidence of active, non-infectious pneumonitis.
- Toxicity from previous treatment including: Toxicity Grade ≥3 related to prior immunotherapy and that led to study treatment discontinuation; Toxicity related to prior treatment that has not resolved to Grade ≤ 1.
- Subjects who have acute bacterial, viral or fungal infections and require systemic anti-infective treatment.
- Positive test for syphilis antibodies or human immunodeficiency virus (HIV) antibodies.
- Subjects who are allergic to test drugs and excipients.
- Women who are pregnant or breastfeeding.
- Known drug or alcohol abuse.
- Patients with mental or neurological diseases.
- Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
- Subjects who have a history of serious systemic disease or any other reason are not suitable to participate in this trial as judged by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: HG381 Monotherapy Dose Escalation Cohort HG381 Subjects will receive HG381 IV at every one week intervals (Q1W). Escalating doses of HG381 will be evaluated by the traditional 3+3 design. Part B: HG381 Monotherapy Dose Expansion Cohort HG381 Subjects will be administered the recommended Phase 2 dose of HG381 IV Q1W established in Part A of the study.
- Primary Outcome Measures
Name Time Method Number of subjects with adverse events (AEs) and serious adverse events (SAEs) Up to 24 months An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or requires medical judgement.
Maximum Tolerated Dose (MTD) Up to 12 months The maximum tolerated dose (MTD) is defined as the maximum dose where the number of cases of DLT ≤ 1/6 of the total number of cases during the DLT observation period. At least 6 evaluable subjects are required to determine MTD.
Severity of AEs Up to 24 months The severity of AEs will be graded utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.
Number of subjects achieving Dose-limiting toxicity (DLT) Up to Day 21 DLT is defined as an adverse event (AE) that meets protocol defined DLT criteria during cycle 1 and is at least possibly related to study drug.
- Secondary Outcome Measures
Name Time Method Best objective response based on RECIST 1.1 Up to 24 months Best objective response rate is defined as the percentage of subjects with a best overall confirmed CR or PR at any time as per disease-specific criteria.
Maximum observed concentration (Cmax) following administration of HG381 alone Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) Blood samples will be collected at indicated time points for plasma PK analysis following administration of HG381 monotherapy.
Recommended Phase 2 Dose (RP2D) of HG381 Up to 12 months Up to 42 patients with advanced/metastatic solid tumors will be enrolled in Dose Escalation to determine the RP2D of HG381 as monotherapy.
HG381 concentrations in plasma following administration of HG381 alone Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) Blood samples will be collected at indicated time points for plasma pharmacokinetic (PK) analysis of HG381.
Apparent terminal phase half-life (t½) following administration of HG381 alone Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) Blood samples will be collected at indicated time points for plasma PK analysis following administration of HG381 monotherapy.
Area under the concentration-time curve (AUC) following administration of HG381 alone Cycle 1 Days 1, Cycle 2 Days 1 and Cycle 3 Days 1: pre-infusion and at multiple time points (up to 24 hours) post-infusion (Cycle length=21 days) Blood samples will be collected at indicated time points for plasma PK analysis following administration of HG381 monotherapy.
Trial Locations
- Locations (1)
HitGen Inc.
🇨🇳Chengdu, Sichuan, China