A Phase I/IIa, First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Initial Efficacy of HX044 in Patients with Advanced Solid Tumor Malignancies
Overview
- Phase
- Phase 1
- Intervention
- HX044
- Conditions
- Advanced Solid Tumor Malignancies
- Sponsor
- Hanx Biopharmaceuticals Pty Ltd
- Enrollment
- 100
- Locations
- 3
- Primary Endpoint
- Number of participants experiencing Adverse Events (AEs)
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The study will consist of a dose-escalation and dose-expansion component to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and to evaluate the preliminary antitumor activity of HX044.
HX044 is an investigational drug that has not yet been approved by the Food and Drug Administration (FDA) or any other regulatory authorities for commercial purposes. This is the first study in which HX044 will be given to humans. The study drug has been tested in animals and was found to be well-tolerated with minimal side effects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must voluntarily agree to participate by providing written informed consent and agreeing to comply with protocol and scheduled visit;
- •Male or female subject aged 18-75 years, inclusive;
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
- •Histologically confirmed advanced malignant solid tumor that is refractory/relapsed to standard therapies, or for which no effective standard therapy is available, or the subject refuses standard therapy.
- •At least 1 measurable tumor (It is acceptable to allow patients with no measurable lesion but evaluable tumor lesion in the first 2 dose levels in Phase I and at least 1 measurable tumor lesion must be present in Phase IIa) according to RECIST v1.1
- •Life expectancy ≥ 12 weeks.
- •Adequate organ function, as indicated by the following laboratory values: •Hematology (no growth factor and blood transfusion are allowed within 14 days before start of first dose study treatment): Hemoglobin ≥90g/L Absolute neutrophil count ≥1.5×109/L Platelet count ≥100×109/L
- •Hepatic: Serum total bilirubin ≤1.5 × upper limit of normal (ULN); or direct bilirubin ≤ULN for patients with total bilirubin levels \>1.5 × ULN
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (ALT and AST ≤ 5 × ULN for subjects with liver metastases)
- •Renal:Serum creatinine ≤1.5 × ULN
Exclusion Criteria
- •Prior malignancy active within the previous 5 years except for the tumor for which a subject is enrolled in the study and locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
- •Receipt of any anticancer (chemotherapy, radiation therapy, investigational drugs including small molecular inhibitors, endocrine therapy, immunotherapy) therapy within 4 weeks prior to the first dose of study treatment or 5 half-lives of the therapy, whichever is shorter.
- •Severe cardiovascular disease including symptomatic congestive heart failure (New York Heart Association class III or IV), unstable angina, uncontrolled hypertension, cardiac arrhythmia, a history of myocardial infarction within 6 months or a history of arterial thromboembolic event and pulmonary embolism within 3 months of the first dose of investigational agent, as follows:
- •QT/QTc interval prolongation (using Fredericia's QT correction formula) at baseline, Female \> 470 ms, Male \> 450 ms;
- •Medications to prolong the QT/QTc interval are currently being taken;
- •Family history of long QT syndrome.
- •Patients with a history of or presently experiencing an active autoimmune disease within 2 years of initiating study drug, or those who are at high risk of relapse ; however, subjects with the following are allowed to enroll:
- •Type I diabetes that is stable after a fixed dose of insulin or other hypoglycemic;
- •Only requiring hormone replacement therapy for autoimmune hypothyroidism;
- •Skin disease that does not require systemic treatment such as eczema rash that accounts for \<10% of the body surface, psoriasis without ophthalmic symptoms.
Arms & Interventions
HX044
Conventional dose-escalation design with 3+3 cohort size. Patients received HX044 treatment at assigned dose level on a Q3 weekly basis.
Intervention: HX044
Outcomes
Primary Outcomes
Number of participants experiencing Adverse Events (AEs)
Time Frame: All AEs up to 90(±7）days after the last dose of study treatment
An AE is any untoward medical occurence in a patient or subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Number of Participants With Dose-Limiting Toxicities(DLT) of HX044
Time Frame: At the end of Cycle 2(each cycle is 21±3 days)
All AEs/toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events,Vesion5.0(NCI CTCAE v5.0);For the purpose of dose escalation, any of the following AEs occurring during the DLT observation period that were attributable to one or both study drugs were classified as DLTs.
Secondary Outcomes
- Objective response rate (ORR) per Investigator Assessment Using RECIST 1.1 and iRECIST(Approximately 2 years)
- Disease control rate(DCR) per Investigator Assessment Using RECIST 1.1 and iRECIST(Approximately 2 years)
- Number of participants with positive Anti-Drug Antibody(ADA) of HX044(Cycle 1,2,3,4,5,6,10,14,18 and then every 8 cycles,Day 1: with 60 minutes before the start of the infusion.)
- Time of Cmax(Tamx) of HX044(Approximately 2 years)
- Terminal Half life( t½) of HX044(Approximately 2 years)
- Area Under the serum concentration-time curve(AUC)(Approximately 2 years)