A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors

Официальное название

A Phase Ib Study Evaluating the Safety, Tolerability , Pharmacokinetics and Activity of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors

Обзор

This is a Phase Ib study that will evaluate the Safety, Tolerability , Pharmacokinetics and Activity of HS-10370 in Combination With Other Anti-cancer Therapies in patients with KRAS G12C mutation advanced or metastatic solid tumors, especially in non-Small cell lung cancer (NSCLC) .

Вмешательства

• Препарат HS-10370
  HS-10370 administered orally every day
• Препарат Adebrelimab
  Administered intravenously every 21 days; dose by label.
• Препарат Cisplatin
  Administered intravenously every 21 days; dose by label.
• Препарат Carboplatin
  Administered intravenously every 21 days; dose by label.
• Препарат Pemetrexed
  Administered intravenously every 21 days; dose by label.

Первичные конечные точки

• Number of Participants with Adverse Event(s) (AEs) [Срок оценки: From Cycle 1 Day 1 to first documented progression of disease or death from any cause, approximately 2 years.]

Вторичные конечные точки (9)

• Overall Response Rate (ORR) [Срок оценки: From Cycle 1 Day 1 (C1D1) to disease progression or death, approximately 2 years.]
• Disease Control Rate (DCR) [Срок оценки: From C1D1 to disease progression or death, approximately 2 years.]
• Time to Response (TTR) [Срок оценки: Time from C1D1 until the date that measurement criteria for CR or PR (whichever is first recorded) are first met, approximately 2 years.]
• Duration of Response (DOR) [Срок оценки: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.]
• Progression-Free Survival (PFS) [Срок оценки: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.]
• Overall survival (OS) [Срок оценки: C1D1 to date of death from any cause, approximately 5 years.]
• Plasma Concentrations of HS-10370 [Срок оценки: C1D1 to date of death from any cause. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation, approximately 2 years.]
• Maximum plasma concentration (Cmax) [Срок оценки: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation.]
• Time of maximum concentration (Tmax) [Срок оценки: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation]

Критерии участия

Критерии включения

• Men or women greater than or equal to 18 years
• At least one measurable lesion in accordance with RECIST 1.1
• Must have an ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
• Documentation of the presence of a KRAS G12C mutation
• Must provide tumor tissue sample
• No history of systemic anticancer therapy in metastatic/non-curable settings
• Estimated life expectancy ≥12 weeks.
• Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose.
• Females must have the evidence of non-childbearing potential; Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Signed and dated Informed Consent Form.
• The subjects are able to comply with the process of the protocol.

Критерии исключения

• Treatment with any of the following:

• Previous or current treatment with other KRAS G12C inhibitors
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of study treatment; Any investigational agents and large molecule antibodies within 28 days of the first dose of study treatment.
• Local radiotherapy within 2 weeks prior to the first dose of study drug, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of study drug.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose
• Active brain metastases.
• Patients with uncontrolled pleural, ascites or pericardial effusion
• Spinal cord compression
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• Subjects with tumors known to harbor molecular alterations for which targeted therapy is locally approved, except for KRAS G12C.
• History of other primary malignancies.
• Inadequate bone marrow reserve or organ functions.
• Abnormal cardiac examination results.
• Severe, uncontrolled or active cardiovascular disorders.
• Diabetes ketoacidosis or hyperglycemia hyperosmolality
• Uncontrolled hypertension.
• Severe bleeding symptoms or bleeding tendencies.
• Severe arteriovenous thrombosis occurred
• Serious infection.
• Continuous use of glucocorticoids
• Active infectious diseases.
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
• Hepatic encephalopathy, hepatorenal syndrome, or ≥ Child Pugh B-grade cirrhosis.
• Interstitial lung disease (ILD).
• Serious neurological or mental disorders.
• Active autoimmune diseases

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT06594874 · HS-10370-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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