ARTEMIS-002: HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas

Официальное название

ARTEMIS-002: A Phase 2, Multicenter, Open-label Study of Intravenous Administration of HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas

Обзор

HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20093 as a monotherapy in patients with relapsed or refractory osteosarcoma and other sarcomas.

Подробное описание

This is a phase 2, open-label, multi-center study consisting of two parts: Phase 2a and 2b.

Phase 2a: The study will be conducted in the following two cohorts: Cohort 1: Patients with advanced osteosarcoma upon disease progression after standard treatment. Cohort 2: Patients with other unresectable bone and soft tissue sarcomas, if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. Subjects will be randomly assigned in a 1:1 ratio to 8.0 mg/kg and 12.0 mg/kg of HS-20093 in cohort 1 and will receive 12.0 mg/kg in cohort 2.

Phase 2b: The study will be conducted in patients with advanced osteosarcoma upon disease progression after standard treatment. Subjects will receive HS-20093 at the recommended dose from Phase 2a.

All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of HS-20093. Subjects will be permitted to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists.

Вмешательства

• Препарат HS-20093
  IV administration of HS-20093 Q3W; Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression.

Первичные конечные точки

• Objective response rate (ORR) determined by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [Срок оценки: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.]

Вторичные конечные точки (12)

• Incidence and severity of adverse events (AEs) [Срок оценки: From the first dose through 90 days post end of treatment.]
• Observed maximum plasma concentration (Cmax) of HS-20093 [Срок оценки: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)]
• Time to reach maximum plasma concentration (Tmax) of HS-20093 following the first dose [Срок оценки: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)]
• Terminal half-life (T1/2) of HS-20093 following the first dose [Срок оценки: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)]
• Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of HS-20093 [Срок оценки: From pre-dose to 14 days after the first dose on Cycle 1 (each cycle is 21 days)]
• Percentage of participants with antibodies to HS-20093 in serum [Срок оценки: From pre-dose to 90 days post end of treatment]
• ORR determined by Independent review committee (IRC) according to RECIST 1.1 [Срок оценки: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.]
• Duration of response (DoR) determined by investigators and IRC according to RECIST 1.1 [Срок оценки: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.]
• Disease control rate (DCR) determined by investigators and IRC according to RECIST 1.1. [Срок оценки: From the first dose up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.]
• Progression-free survival (PFS) determined by investigators and IRC according to RECIST 1.1 [Срок оценки: From the first dose or random assignment up to disease progression or withdrawal from study, whichever came first, assessed up to 24 months.]
• 4-month PFS rate determined by investigators and IRC according to RECIST 1.1 [Срок оценки: 4 months.]
• Overall survival (OS) [Срок оценки: From the first dose or random assignment up to death or withdrawal from study, whichever came first, assessed up to 24 months.]

Критерии участия

Критерии включения

• At least age of 18 years at screening;
• Patients with histologically confirmed relapsed or refractory osteosarcoma or other sarcomas who have progressed upon first-line systemic treatment.
• At least one measurable lesion according to RECIST 1.1.
• Agree to provide fresh or archival tumor tissue and peripheral blood samples.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1
• Life expectancy >= 12 weeks
• Men or women should be using adequate contraceptive measures throughout the study;
• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential
• Signed and dated Informed Consent Form

Критерии исключения

• Treatment with any of the following:

• Previous or current treatment with B7-H3 targeted therapy
• Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093
• Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093
• Radiotherapy with a limited field of radiation for palliation within 2 weeks, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first scheduled dose of HS-20093
• Pleural or peritoneal effusion requiring clinical intervention. Pericardial effusion.
• Major surgery within 4 weeks of the first dose of HS-20093.
• Spinal cord compression or brain metastases.
• Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study.
• Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study.
• Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 with the exception of alopecia or neurotoxicity.
• History of other primary malignancies.
• Inadequate bone marrow reserve or organ dysfunction
• Evidence of cardiovascular risk.
• Severe, uncontrolled or active cardiovascular diseases.
• Diabetes ketoacidosis or hyperglycemia hypertonic occurring within 6 months before the first dose of the study drug, or the glycosylated hemoglobin value ≥ 7.5% in the screening period.
• Severe or poorly controlled hypertension.
• Bleeding symptoms with apparent clinical significance or obvious bleeding tendency within 1 months prior to the first dose of HS-20093
• Serious arteriovenous thrombosis events occurred within 3 months before the first dose.
• Severe infections occurred within 4 weeks before the first dose.
• Patients who have received continuous steroid treatment for more than 30 days within 30 days before the first dose, or need long-term (≥ 30 days) steroid treatment, or who have other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation
• The presence of active infectious diseases has been known before the first dose such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus HIV infection, etc.
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis.
• Other moderate or severe lung diseases that may interfere with the detection or treatment of drug-related pulmonary toxicity or may seriously affect respiratory function.
• Previous history of serious neurological or mental disorders, including epilepsy, dementia or severe depression and any other status that may interfere in assessment.
• Women who are breastfeeding or pregnant or planned to be pregnant during the study period.
• Vaccination or hypersensitivity of any level within 4 weeks prior to the first dose of HS-20093
• History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins.
• Hypersensitivity to any ingredient of HS-20093.
• Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator
• Any disease or condition that, in the opinion of the investigator, would compromise subject safety 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

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 11 центров

• Peking University People's Hospital — Пекин
• Hunan Cancer Hospital — Чанша
• First Affiliated Hospital, Sun Yat-Sen University — Гуанчжоу
• Sun Yat-sen University Cancer Center — Гуанчжоу
• Second Affiliated Hospital, School of Medicine, Zhejiang University — Ханчжоу
• Zhejiang Cancer Hospital — Ханчжоу
• Chinese PLA General Hospital of Eastern Theater Command — Нанкин
• Shanghai 6th People's Hospital — Шанхай
• … и ещё 3 центра

Идентификаторы

NCT: NCT05830123 · HS-20093-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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