A Study of HS-20089 in Patients With Advanced Solid Tumors

Официальное название

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20089 in Patients With Advanced Solid Tumors

Обзор

HS-20089 is a novel DAR-6 antibody-drug conjugate （ADC） targeting B7-H4. In preclinical studies, it inhibited tumor cell growth expressing B7-H4 in vitro and in vivo. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-20089 in Patients With Advanced Solid Tumors.

Подробное описание

This is a Phase 1a/1b open-label, multicenter study with dose escalation and dose expansion cohorts to evaluate the safety, tolerability, PK and preliminary efficacy of HS-20089 in patients with advanced solid tumors.

The Dose Escalation will include an initial accelerated titration design followed by a Bayesian optimal interval (BOIN) design. Enrollment into Dose Expansion will begin after identification of the MTD and/or MAD in Phase 1a. In Phase 1b, preliminary efficacy will be evaluated in planned expansion cohorts that include patients with specific tumor types that are B7-H4+ advanced solid tumors.

Вмешательства

• Препарат HS-20089 (Phase Ia：Dose escalation )
  Participants will receive HS-20089 in 21 day dosing cycles. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and unequivocal disease progression.
• Препарат HS-20089 (Phase Ib: Dose expansion)
  IV administration of HS-20089 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.

Первичные конечные точки

• Maximum Tolerated Dose of HS-20089 [Срок оценки: 3 weeks after initiation of treatment]

Вторичные конечные точки (9)

• Incidence and severity of treatment-emergent adverse events [Срок оценки: Baseline through study completion(90 days after last dose)]
• Observed maximum plasma concentration (Cmax) after single dose of HS-20089 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-20089 [Срок оценки: From pre-dose to 24 hours after the dose on Day 1 of the 21-Day cycle of therapy]
• Apparent terminal half-life (t1/2) after single dose of HS-20089 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-20089 [Срок оценки: From pre-dose to 24 hours after single dose on Day 1]
• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-20089 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-20089 [Срок оценки: From pre-dose to 120 hours after single dose on Day 1]
• To further evaluation of the anti-tumor activity of HS-20089 by assessment of objective response rate (ORR) [Срок оценки: From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study，up to 2 years]
• Anti-drug Antibodies (ADA) of HS-20089 [Срок оценки: Baseline through study completion(90 days after last dose)]

Критерии участия

Критерии включения

• Men or women aged more than or equal to (≥) 18 years
• Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
• Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)
• ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
• Estimated life expectancy greater than (>) 12 weeks
• Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential
• Sign Informed Consent Form

Критерии исключения

• Treatment with any of the following:

• Previous or current treatment with drugs targeting B7-H4
• Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
• Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
• Known and untreated, or active central nervous system metastases.
• Existing abnormal CTCAE≥grade 2 resulted from previous treatment
• History of other malignancy
• Inadequate bone marrow reserve or organ function
• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
• History of hypersensitivity to any active or inactive ingredient of HS-20089.
• Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.

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 · 1 центр

• Fudan University Cancer Hospital — Шанхай

Идентификаторы

NCT: NCT05263479 · HS-20089-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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