A Multicenter, Open Label, Phase I/II Clinical Study of CM350 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 248
- 试验地点
- 2
- 主要终点
- Dose escalation phase in phase I:Dose-Limiting Toxicity (DLT).
研究概览
简要总结
This is an open label, dose escalation and expansion Phase I/II study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of CM350 in patients with advanced solid tumors.
The phase I study consists of a dose escalation phase and a dose expansion phase The safety and tolerability of CM350 and the maximum tolerated dose (MTD) (if applicable) will be evaluated in dose escalation phase.
The recommended phase 2 dose (RP2D) of CM350 will be determined in dose expansion phase.
The phase II study is to evaluate the efficacy of CM350 at the recommended phase 2 dose (RP2D) for advanced glypican-3 (GPC3)-positive solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with histologically or cytologically confirmed advanced solid tumors that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
- •hepatocellular-cancer(HCC) participants must have a Barcelona Clinic Liver Cancer (BCLC) stage of B (ineligible for liver surgery and/or other locoregional treatments, or disease progression after locoregional therapy) or stage C , or a China National Liver Cancer (CNLC) stage of IIb or III (ineligible for liver surgery and/or other locoregional treatments, or disease progression after locoregional therapy).
- •HCC participants must have a Child-Pugh score of ≤
- •Phase I dose escalation phase: participants must have evaluable lesions based on RECIST version 1.1.Phase I dose expansion phase and phase II: participants must have at least one measurable lesion.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Patients who have received any cytotoxic chemotherapy, radiotherapy, biological therapy (oncologic vaccines, cytokines, or growth factors for cancer control), or any other investigational anticancer drug treatment (defined as treatments without regulatory approval for any indication) within 28 days before the first dose of CM
- •Note: For palliative radiotherapy to non-central nervous system lesions (total radiotherapy duration ≤14 days) to improve symptoms, a minimum washout period of 7 days before the first dose is required.
- •Patients who have received any immunotherapy (including but not limited to PD-1, PD-L1, anti-cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], chimeric antigen receptor T-cell [CAR-T] therapy, etc.) within 28 days or 5 half-lives (whichever is shorter) before the first dose of CM
- •Patients who have received targeted therapy within 28 days or 5 half-lives (whichever is shorter) before the first dose of CM
- •Patients who have previously received any therapy targeting GPC3, including but not limited to monoclonal antibodies, peptide vaccines, CAR-T, and bispecific antibodies.
- •Received chronic systemic corticosteroid therapy (daily intake of more than 10 mg prednisone or equivalent doses of other corticosteroids) or any other form of immunosuppressive treatment within 7 days before the first dose of CM
- •Known active central nervous system metastases. Note: Participants with previously treated brain metastases that have been stable for at least 14 days before the first dose (confirmed by repeat imaging at least 4 weeks apart, with the repeat imaging conducted during the screening period) may be considered for enrollment.
- •Participants with uncontrolled pleural effusion, ascites, or pericardial effusion as assessed by the investigator.
- •History of other malignancies within 5 years before the first dose of CM350, excluding cured basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, or ductal carcinoma in situ of the breast.
- •Presence of active infection at screening as assessed by the investigator.
研究组 & 干预措施
Dose escalation phase in phase I
There are 11 target dose levels in dose escalation phase.
干预措施: CM350 group1 (Biological)
Dose expansion phase in phase I
Three or four doses will be selected for further evaluation in dose expansion phase to determine the RP2D (recommended phase 2 dose).
干预措施: CM350 group2 (Biological)
Phase II
The efficacy of CM350 will be evaluated at RP2D (recommended phase 2 dose) for advanced GPC3-positive solid tumors.
干预措施: CM350 group3 (Biological)
结局指标
主要结局
Dose escalation phase in phase I:Dose-Limiting Toxicity (DLT).
时间窗: Up to 7 days after the first target dose
Dose-Limiting Toxicity (DLT).
Dose escalation phase in phase I:Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.
时间窗: Up to 5 years
Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.
Dose escalation phase in phase I:Maximum tolerated dose (MTD) (if applicable).
时间窗: Up to the end of dose escalation phase (3 years)
Maximum tolerated dose (MTD) (if applicable).
Dose expansion phase in phase I:To determine the recommended Phase 2 Dose (RP2D).
时间窗: Up to 5 years
the efficacy including objective response rate (ORR), disease control rate (DCR), etc., safety, pharmacokinetics (PK) and pharmacodynamics (PD) profile of CM350 will be assessed.
Phase II:To evaluate the efficacy of CM350 in advanced glypican-3-positive solid tumors.
时间窗: Up to 5 years
including objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Modified Response Evaluation Criteria in Solid Tumors \[mRECIST\] for liver cancer and RECIST v1.1) evaluated by investigator.
次要结局
- Phase I & Phase II:To evaluate the progression-free survival (PFS) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).(Up to 5 years)
- Phase I & Phase II: To assess the incidence of anti-drug antibody (ADA).(Up to 5 years)
- Phase I: To evaluate the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for liver cancer and RECIST v1.1].(Up to 5 years)
- Phase I & Phase II: To evaluate the duration of response (DOR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).(Up to 5 years)
- Phase I & Phase II:To evaluate the overall survival (OS)(Up to 5 years)
- Phase I & Phase II:To assess the cytokine interleukin-2 (IL-2).(Up to 5 years)
- Phase I & Phase II:Area Under the Curve over a dosing interval (AUC tau).(Up to 5 years)
- Phase I & Phase II:Peak Plasma Concentration (Cmax).(Up to 5 years)
- Phase I & Phase II:Observed concentration at the end of a dosing interval (Ctrough).(Up to 5 years)
- Phase I & Phase II:Time of Maximum Observed Concentration (Tmax).(Up to 5 years)
- Phase I & Phase II:To assess the cytokine interferon-gamma(IFN-γ).(Up to 5 years)
- Phase I & Phase II:To assess the cytokine interleukin-6 (IL-6).(Up to 5 years)
- Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 3 positive (CD3+).(Up to 5 years)
- Phase I & Phase II:To assess the cytokine tumor necrosis factor-alpha (TNF-α).(Up to 5 years)
- Phase I & Phase II: Area Under the Curve from 0 to the time of the last quantifiable concentration (AUC0-t).(Up to 5 years)
- Phase I & Phase II: To evaluate the disease control rate (DCR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).(Up to 5 years)
- Phase I & Phase II:To evaluate the time to response (TTR) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1.(Up to 5 years)
- Phase I & Phase II:To evaluate the time to progression (TTP) per RECIST v1.1(mRECIST for liver cancer and RECIST v1.1).(Up to 5 years)
- Phase II:Incidence of Adverse events（AEs）, including any abnormal physical examinations, abnormal vital signs, abnormal ECG, and abnormal lab testing.(Up to 5 years)
- Phase I & Phase II:To assess the cytokine interleukin-10 (IL-10).(Up to 5 years)
- Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 4 positive (CD4+).(Up to 5 years)
- Phase I & Phase II: To assess the Immunophenotyping cluster of differentiation 8 positive (CD8+).(Up to 5 years)