HF158K1 in Patients With HER-2 Expressing Advanced Solid Tumors

Официальное название

A Phase 1 Clinical Study to Investigate the Safety, Tolerability, and Preliminary Efficacy of HF158K1 in Participants With HER-2 Expressing Advanced Solid Tumors

Обзор

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.

Подробное описание

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 bridging) will be conducted in Chinese patients to bridge the safety and pharmacokinetic data between different ethnic populations.

Phase 1c(Dose expansion) will assess safety and preliminary efficacy of HF158K1 in participants with specific tumor types in selected dose groups.

Вмешательства

• Препарат HF158K1 / 1.4 g lipid dose
  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.
• Препарат HF158K1 / 2.2 g lipid dose
  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.
• Препарат HF158K1 / 2.9 g lipid dose
  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.

Первичные конечные точки

• Incidence of Adverse Events [Срок оценки: The period of AE collection starts after the participant receives the investigational drug, until 28±3 days after the EOT/early withdrawal or before the participant starts another anti-tumor treatment (whichever occurs first).]
• Incidence of dose-limiting toxicities(DLT) [Срок оценки: The DLT evaluation period is from the first administration of the investigational drug to the end of the first treatment cycle, lasting for 21 days.（only Ia）]
• Red blood cell count in whole blood sample [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• White blood cell in whole blood sample [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Hematocrit in whole blood sample [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Neutrophil count in whole blood sample [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Hemoglobin concentration in whole blood sample [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Percentage of lymphocytes (LYM%) [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Lymphocyte count [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]
• Percentage of neutrophils (NEU%) Percentage of neutrophils (NEU%) [Срок оценки: Baseline, Day 1 of each 21-day cycle, and at the End of Treatment (EOT) visit (up to 1 year)]

Вторичные конечные точки (11)

• HF158K1 pharmacokinetic parameters with Cmax [Срок оценки: Within 336 hours after the first and second administration]
• AUC by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• Tmax by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• T1/2 by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• CL by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• Vd by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• AUClast by plasma concentration of whole blood sample [Срок оценки: Within 336 hours after the first and second administration]
• The objective response rate(ORR) of HF158K1 [Срок оценки: ORR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.]
• disease control rate (DCR) of HF158K1 [Срок оценки: DCR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.]
• duration of response(DOR) of HF158K1 [Срок оценки: DOR will be calculated for all participants who have received the investigational drug at least once and have undergone at least one tumor evaluation after administration, assessed up to 51 weeks.]
• Analysis of immunogenicity [Срок оценки: On the first day of the first cycle, on the first day of the fourth cycle, on the 21st day of the eighth cycle]

Критерии участия

Критерии включения

• Voluntary to participate and sign ICF.
• Age ≥ 18 and ≤ 75 years.
• Unresectable or metastatic advanced solid tumors with HER-2 expression (IHC 3+, 2+, or 1+).
• ECOG score 0-1.
• Expected survival ≥ 6 months.
• At least one measurable lesion per RECIST v1.1.
• Adequate organ function: ANC ≥ 1.5×10⁹/L, LYM ≥ 1.0×10⁹/L, PLT ≥ 90×10⁹/L, HGB ≥ 8.0 g/dL; APTT ≤ 1.5×ULN, INR ≤ 1.5; TBIL ≤ 1.5×ULN, ALT/AST ≤ 2.5×ULN (≤ 5×ULN if liver metastases); CrCl ≥ 30 mL/min; LVEF ≥ 50%.
• Agreement to use effective contraception.

Критерии исключения

• Cumulative doxorubicin dose ≥ 350 mg/m² or prior anthracycline-induced cardiotoxicity.
• Current use of immunosuppressants or systemic corticosteroids (> 10 mg/day prednisone).
• Prior anti-tumor therapy < 2 weeks (4 weeks for nitrosourea/mitomycin C).
• Symptomatic CNS metastases.
• Unresolved AEs from prior therapy > Grade 1.
• Serious cardiovascular diseases (thromboembolic events within 3 months, NYHA III-IV, ACS within 6 months, or uncontrolled hypertension).
• Active infection or unexplained fever > 38.5°C.
• HIV, active HBV or HCV.
• Pregnant or breastfeeding.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Mary Crowley Cancer Research — Dallas

Китай · 1 центр

• Sun Yat-sen University Cancer Center — Гуанчжоу

Идентификаторы

NCT: NCT05861895 · HF158K1-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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