Clinical trial NCT04998422: A Study of HG381 Administered to Patients With Advanced Solid Tumors
Official title: Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of HG381 as Monotherapy in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Lead sponsor: HitGen Inc.
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Number of subjects achieving Dose-limiting toxicity (DLT)
timeFrame: Up to Day 21
measure: Maximum Tolerated Dose (MTD)
timeFrame: Up to 12 months
measure: Number of subjects with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 24 months
measure: Severity of AEs
timeFrame: Up to 24 months
Secondary outcomes:
measure: Recommended Phase 2 Dose (RP2D) of HG381
timeFrame: Up to 12 months
measure: Best objective response based on RECIST 1.1
timeFrame: Up to 24 months
measure: HG381 concentrations in plasma following administration of HG381 alone
timeFrame: 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)
measure: Maximum observed concentration (Cmax) following administration of HG381 alone
timeFrame: 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)
measure: Area under the concentration-time curve (AUC) following administration of HG381 alone
timeFrame: 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)
measure: Apparent terminal phase half-life (t½) following administration of HG381 alone
timeFrame: 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)
Other outcomes:
Locations:
city: Chengdu
country: China
facility: HitGen Inc.
state: Sichuan
Study officials:
affiliation: Chinese PLA General Hospital
name: Jianming Xu, M.D
role: PRINCIPAL_INVESTIGATOR
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