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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 350
- 试验地点
- 1
- 主要终点
- Number of Participants with Adverse Event(s) (AEs)
研究概览
简要总结
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) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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
研究组 & 干预措施
Arm A: HS-10370 dose 1 + Adebrelimab
Participants will receive HS-10370 dose 1 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: HS-10370 (Drug)
Arm E: HS-10370+ Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with pemetrexed and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Carboplatin (Drug)
Arm A: HS-10370 dose 1 + Adebrelimab
Participants will receive HS-10370 dose 1 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Adebrelimab (Drug)
Arm B: HS-10370 dose 2 + Adebrelimab
Participants will receive HS-10370 dose 2 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: HS-10370 (Drug)
Arm B: HS-10370 dose 2 + Adebrelimab
Participants will receive HS-10370 dose 2 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Adebrelimab (Drug)
Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met
干预措施: HS-10370 (Drug)
Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met
干预措施: Adebrelimab (Drug)
Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met
干预措施: Cisplatin (Drug)
Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met
干预措施: Carboplatin (Drug)
Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met
干预措施: Pemetrexed (Drug)
Arm D: HS-10370+ Adebrelimab + Pemetrexed
Participants will receive HS-10370 administered orally in plus with Adebrelimab and pemetrexed administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: HS-10370 (Drug)
Arm D: HS-10370+ Adebrelimab + Pemetrexed
Participants will receive HS-10370 administered orally in plus with Adebrelimab and pemetrexed administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Adebrelimab (Drug)
Arm D: HS-10370+ Adebrelimab + Pemetrexed
Participants will receive HS-10370 administered orally in plus with Adebrelimab and pemetrexed administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Pemetrexed (Drug)
Arm E: HS-10370+ Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with pemetrexed and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: HS-10370 (Drug)
Arm E: HS-10370+ Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with pemetrexed and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Cisplatin (Drug)
Arm E: HS-10370+ Pemetrexed and Platinum
Participants will receive HS-10370 administered orally in plus with pemetrexed and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Number of Participants with Adverse Event(s) (AEs)
时间窗: From Cycle 1 Day 1 to first documented progression of disease or death from any cause, approximately 2 years.
An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
次要结局
- Overall survival (OS)(C1D1 to date of death from any cause, approximately 5 years.)
- Overall Response Rate (ORR)(From Cycle 1 Day 1 (C1D1) to disease progression or death, approximately 2 years.)
- Disease Control Rate (DCR)(From C1D1 to disease progression or death, approximately 2 years.)
- Time to Response (TTR)(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)(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)(Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.)
- Plasma Concentrations of HS-10370(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)(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)(C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation)