Trial Title:
A Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of HF158K1 in Participants With HER-2 Positive or HER-2 Low Expression Advanced Solid Tumors
NCT ID:
NCT05861895
Condition:
Solid Tumors, Adult
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 2 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 2 mg/m²
Other name:
Infusion
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 6 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 6 mg/m²
Other name:
Infusion
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 15 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 15 mg/m²
Other name:
Infusion
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 30 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 30 mg/m²
Other name:
Infusion
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 45 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 45 mg/m²
Other name:
Infusion
Intervention type:
Drug
Intervention name:
HF158K1 /Arm 60 mg/m²
Description:
Duration of infusion: HF158K1 is diluted using 5% (50 mg/ml) glucose injection or 0.9%
sodium chloride injection (saline) to a total volume of 250 ml and is administered
through intravenous infusion for 90 ± 10 min.
Arm group label:
Dose escalation cohort 1: HF158K1 given Q3W at 60 mg/m²
Other name:
Infusion
Summary:
HF158K1 is an investigational liposome form of doxorubicin hydrochloride, an
anthracycline topoisomerase inhibitor, encapsulated by lipid membranes containing TL01, a
HER2-directed Trastuzumab Fab fragment conjugated lipid.
Detailed description:
This study is a multi-regional, open-label, multiple-dose administration dose-escalation
and dose-expansion study, including a Dose-Escalation Phase (Ia) and a Dose-Expansion
Phase (Ib).
HF158K1 contains multiple copies of the targeting antibody on liposome surface. It is
designed to bind and deliver the chemotherapeutic doxorubicin to tumor cells at even very
low HER2 expression levels. The study recruits patients with unresectable or metastatic
advanced solid tumors (HER-2 positive (IHC 3+, or IHC 2+ with ISH +) or HER-2 low
expression (IHC 2+ with ISH -, or IHC 1+)) who have failed or are intolerant (disease
progression, or intolerance to chemotherapy, targeted therapy, etc.) to standard
treatment, or currently have no available treatment regimen.
Phase 1a(Dose escalation) will assess the safety，tolerability，pharmacokinetics of HF158K1
in participants to determine the maximum tolerated dose (MTD) of HF158K1 through the
incidence of dose-limiting toxicity (DLT).
Phase 1b(Dose expansion) will assess safety and preliminary efficacy of HF158K1 in
participants with specific tumor types in selected dose groups.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
-
1. Voluntary to participate in the clinical study, sign a written informed consent
form, and able to comply with clinical visits and study-related procedures.
2. Male or female participants at least 18 years old when signing the informed
consent form.
3. ECOG performance score of 0 to 1 point. 4. Study population: HER-2 positive
(IHC 3+, or IHC 2+ with ISH +) or HER-2 low expression (IHC 2+ with ISH -, or
IHC 1+) participants with unresectable or metastatic advanced solid tumors
(confirmed by histopathology or cytology analysis) who have failed or are
intolerant (disease progression, or intolerance to chemotherapy, targeted
therapy, etc.) to standard treatment, or currently have no available treatment
regimen.
5. Expected survival of at least 3 months. 6. According to the RECIST v1.1
criteria, there is at least one measurable lesion in the dose expansion stage.
7. The functional level of bone marrow reserve and organs must meet the following
requirements (without ongoing continuous supportive treatment): Bone marrow
reserve: neutrophil count (NE#) ≥ 1.5×109/L, platelet count (PLT) ≥ 90×109/L,
and hemoglobin (HGB) > 9.0 g/dL (no blood transfusion or hematopoietic
stimulating factor therapy within 14 days).
Coagulation function: activated partial prothrombin time (APTT) prolonged to ≤1.5×ULN,
and international normalized ratio (INR) ≤1.5.
Liver function: total bilirubin (TBIL) ≤ 1.5×ULN, and alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) ≤ 2.5×ULN, if there is liver metastasis, ALT and AST ≤
5×ULN and TBIL≤ 3×ULN.
Renal function: creatinine clearance ≥ 50 mL/min or serum creatinine ≤ 1.5×ULN. 8.
Eligible Participants with fertility (male and female) must agree to use reliable
contraceptive methods with their partners and have no plan to have baby during the study
period and at least 6 months after the last administration. female Participants of
childbearing age must have a negative serum or urine pregnancy test during screening
period and before the first dose.
9. Other participants that can potentially benefit from the investigational drug as
assessed by the investigator.
Exclusion Criteria:
-
1. Participants who are known to be allergic to doxorubicin and/or other similar
compounds, or to any of excipients of HF158K1, or participants with allergic
constitution (multiple drug and food allergies).
2. Participants who have used doxorubicin prior to screening with a total
cumulative dose > 350 mg/m2 (other anthracyclines converted by 1 mg doxorubicin
equivalence: 2 mg epirubicin, or 2 mg epirubicin, or 2 mg zolpidem, or 0.5 mg
demethoxyzolpidem), or who have received anthracyclines and suffered severe
cardiotoxicity, or who discontinued doxorubicin liposome therapy due to serious
adverse events.
3. Participants who received radiotherapy or chemotherapy (paclitaxel,
cyclosporine, dextropropylenol, cytarabine, streptozotocin, etc.) within 4
weeks prior to first dose administration, or received other antitumor therapy
such as endocrine therapy, herbal therapy, or local radiation therapy for pain
relief within 2 weeks prior to first dose administration, except for the
following: Nitrosourea or mitomycin C within 6 weeks prior to the first
administration of the investigational drug.
Oral fluorouracil-based and small-molecule targeted drugs for 2 weeks prior to the first
administration of the investigational drug or within 5 half-lives of the drug (whichever
is longer).
4. Participants with brain parenchymal metastases or meningeal metastases with clinical
symptoms that, in the judgment of the investigator, are not suitable for enrollment
(those who have received prior treatment (radiation or surgery) for systemic,
radical brain metastases, have maintained imaging- confirmed stability for at least
28 days, and have discontinued systemic steroid therapy for > 14 days without
clinical symptoms will be allowed for enrollment).
5. Participants who have not recovered to < Grade 1 (according to CTCAE 5.0) or to
pre-treatment baseline levels from all prior treatment-induced adverse events prior
to the first dose (except for adverse events without safety risks as judged by the
investigator, such as alopecia, Grade 2 peripheral neurotoxicity, and stabilized
hypothyroidism under hormone replacement therapy).
6. Participants who are taking (or are not able to discontinue until at least 1 week
before the first dose of the study) any drug known to strongly inhibit or strongly
induce CYP3A4, CYP2D6 or P-gp.
7. Participants with a history of serious cardiovascular and cerebrovascular diseases,
including but not limited to: Serious heart rhythm or conduction abnormalities, such
as ventricular arrhythmia that requires clinical intervention, degree II-III
atrioventricular block, etc.
Cardiac function: left ventricular ejection fraction (LVEF) ≤ 50%, corrected QT interval
(QTcF) > 470 ms.
Thromboembolic events requiring therapeutic anticoagulation within 3 months before the
first administration, or participants with venous filters.
Participants with Class III~IV cardiac insufficiency according to the New York Heart
Association (NYHA) criteria.
Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other
Grade 3 and above cardiovascular and cerebrovascular events within 6 months before the
first administration.
Clinically uncontrollable hypertension (systolic blood pressure > 160 mmHg or diastolic
blood pressure > 100 mmHg), and patients with a history of hypertension were allowed to
enroll as long as their blood pressure was controlled below this limitation through
antihypertensive therapy.
Any factors that increase the risk of QTc prolongation or arrhythmia, such as heart
failure, hypokalemia, congenital long QT syndrome, or use of any concomitant drug that
are known to or may prolong the QT interval.
8. Participants who have received last dose of any other investigational drug product
or treatments within 28 days prior to the first administration of the
investigational drug.
9. Participants who have undergone major organ surgery (excluding needle
biopsy，tracheotomy, gastrostomy, etc.) or had significant trauma within 28 days
before the first administration of investigational drug or need to undergo elective
surgery during the study period.
10. Participants with a serious unhealable wound/ulcer/fracture within 28 days before
the first administration of the investigational drug.
11. Participants with an active infection within 1 week prior to the first
administration of the investigational drug and currently require intravenous
anti-infection therapy.
12. Third space effusion that cannot be clinically controlled and is not suitable for
enrollment as judged by the investigator.
13. Known history of drug abuse. 14. Participants with mental disorders or poor
compliance. 15. HIV infection, active HBV infection (HBV DNA > ULN), or active HCV
infection (HCV RNA > ULN).
16. Women who are pregnant or breastfeeding. 17. Participants who cannot tolerate venous
blood sampling. 18. The investigator believes that the participant has a history of
other serious systemic diseases or is not suitable for participating in this
clinical study for other reasons.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mary Crowley Cancer Research
Address:
City:
Dallas
Zip:
75241
Country:
United States
Status:
Recruiting
Contact:
Last name:
MINAL BARVE
Phone:
972-566-3000
Email:
MBarve@MaryCrowley.org
Start date:
December 12, 2023
Completion date:
December 22, 2025
Lead sponsor:
Agency:
HighField Biopharmaceuticals Corporation
Agency class:
Industry
Source:
HighField Biopharmaceuticals Corporation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05861895
