An Engineered Sirpα Fused to Anti-Pd-L1 And Tgf-β Fusion Protein (HCB301) in Subjects With Selected Advanced Tumors

Официальное название

A Phase 1, Open-label, Multicenter, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HCB301 in Subjects With Advanced Solid Tumors or Relapsed and Refractory cHL

Обзор

The purpose of this study is to find out whether IV injection of HCB301 is an effective treatment for different types of advanced solid tumors and relapsed and refractory classical Hodgkin lymphomas and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.

Подробное описание

This is a phase 1, open-label, multicenter, dose-escalation study. This study is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and identification of maximum tolerated dose (MTD) of HCB301 intravenous injection in adults with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.

Eligible subjects must have failed standard therapies, been intolerable, or been considered medically inappropriate by the investigator. Subjects will be treated until unacceptable AEs, radiographic or clinical documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study, whichever occurs first.

Вмешательства

• Препарат HCB301
  HCB301 administered via. intravenous (IV) infusion.

Первичные конечные точки

• Number/incidence and percentage of subjects with adverse events, including ADA. [Срок оценки: 12 months]
• Number of subjects with MTD and RDE of HCB301. [Срок оценки: 12 months]

Вторичные конечные точки (8)

• Overall Rate Response (ORR) [Срок оценки: 12 months]
• Duration of Response (DoR) [Срок оценки: 12 months]
• Disease Control Rate (DCR) [Срок оценки: 12 months]
• Progression-Free Survival (PFS) [Срок оценки: 12 months]
• Peak Plasma Concentration (Cmax) of HCB301 [Срок оценки: 12 months]
• Area under the plasma concentration versus time curve (AUC) of HCB301 [Срок оценки: 12 months]
• Time to maximum drug concentration in plasma (Tmax) of HCB301 [Срок оценки: 12 months]
• Terminal elimination half-life (t1/2) of HCB301 [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Able to understand and be willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor:

subjects confirmed advanced solid tumors who have relapsed or refractory and should have no options for standard or approved therapies known to potentially confer clinical benefit or classical Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of systemic therapy.

• For subjects with advanced solid tumors - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with classical Hodgkin lymphoma - must have classical Hodgkin lymphoma that is measurable or assessable for response.
• Must have ECOG performance status of 0 to 1 at Screening.
• Able to provide tumor tissue samples.
• Have a life expectancy of ≥12 weeks.

Критерии исключения

• With known history of hypersensitivity to any components of HCB301.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy within 28 days or palliative radiotherapy within 14 days or have used a radioactive drug within 56 days prior to the first dose of HCB301.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy administered within 21 days or 5 half-lives, whichever is shorter, before the first dose of the study drug.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 100 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB301.
• Have received any treatment targeting the SIRPα-CD47, PD-L1, or TGF-β pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB301.
• An investigational device used within 28 days prior to the first dose of HCB301.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.

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

Китай · 5 центров

• The First Affiliated Hospital, Zhejiang University School of Medicine — Ханчжоу
• Zhejiang Provincial Cancer Hospital — Ханчжоу
• Xuzhou Central Hospital — Xuzhou
• Yantai Yuhuangding Hospital — Yantai
• Southern Medical University Zhujiang Hospital — Zhujiang

США · 1 центр

• Prisma Health-Upstate — Greenville

Тайвань · 1 центр

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City

Идентификаторы

NCT: NCT06487624 · HCB301-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗