NCT07392736招募中1 期
A Phase I/IIa Clinical Trial of AL8326 Tablets Combined With Toripalimab in the Treatment of Advanced Recurrent or Metastatic Solid Tumors
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 228
- 试验地点
- 15
- 主要终点
- The first part (Phase I): Phase II recommended dose (RP2D)
研究概览
简要总结
This trial is an open, non-randomized, phase I/IIa clinical trial, which will evaluate the preliminary effectiveness and safety of AL8326 tablets in patients with advanced solid tumors
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 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
- •Subjects must be able to understand and voluntarily sign a written informed consent form prior to the initiation of any study-related procedures.
- •Age ≥ 18 years.
- •Subjects with histologically confirmed advanced recurrent or metastatic solid tumors who meet one of the following conditions:
- •Failure of standard therapy (disease progression after treatment or intolerance to treatment toxicity);
- •no effective treatment available.
- •Toripalimab monotherapy as a second-line or later standard treatment.
- •Must have at least one measurable lesion as defined by RECIST 1.
- •Prior cytotoxic chemotherapy must have been completed at least 4 weeks before enrollment, and any toxicities must have recovered to ≤ Grade 1 (except alopecia).
- •Life expectancy of ≥ 12 weeks at the time of enrollment.
- •ECOG performance status of 0 or
- •Adequate organ function:
- •Bone marrow function: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L (1500/mm³); Platelets ≥ 100 × 10⁹/L; Hemoglobin ≥ 9.0 g/dL.
- •Renal function: Serum creatinine ≤ 1.5 × upper limit of normal (ULN) or calculated creatinine clearance (Cockcroft-Gault formula) ≥ 60 mL/min.
- •Hepatic function: Total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN for subjects with Gilbert's syndrome); AST and ALT ≤ 2.5 × ULN in subjects without liver metastases, or ≤ 5 × ULN in subjects with liver metastases.
- •Coagulation function: International normalized ratio (INR) ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
- •Left ventricular ejection fraction (LVEF) > 50% during screening.
- •Systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg (without medication or controlled with a single agent).
- •Females: Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment and must agree to use medically acceptable methods of contraception during the treatment period and for 3 months after the last dose; The patient must be non-lactating; Postmenopausal women (≥ 12 months of amenorrhea without other causes) or surgically sterilized (oophorectomy and/or hysterectomy) are not considered of childbearing potential. Their partners must use medically acceptable contraception during the treatment period and for 3 months after the last dose. Males: Surgically sterile or must agree to use medically acceptable contraception during the treatment period and for 3 months after the last dose; Their partners must use medically acceptable contraception during the same period.
- •Ability and willingness to comply with the study protocol for the duration of the study and with follow-up procedures.
排除标准
- •Received systemic cytotoxic therapy or investigational therapy within 28 days prior to initiation of study treatment, or non-cytotoxic, non-investigational therapy (e.g., radiotherapy, hormone therapy, targeted therapy, immunotherapy) within 14 days prior to initiation of study treatment.
- •Major surgery (defined as requiring general anesthesia within 28 days before initiation of study treatment, or minor surgery requiring general anesthesia within 7 days before initiation of study treatment).
- •Pregnant or lactating women.
- •History of prior or concurrent second primary malignancy that, in the opinion of the investigator or sponsor, may interfere with the assessment of safety or efficacy of the study treatment.
- •Subjects with active or untreated central nervous system (CNS) metastases; Subjects with stable brain metastases may be enrolled if they meet the following criteria: a) No radiological evidence of progression for ≥ 4 weeks after completion of treatment; b) Completion of treatment ≥ 28 days before the first dose of study drug; c) No requirement for systemic corticosteroids (>10 mg/day prednisone or equivalent) within ≤ 14 days prior to the first dose of study drug.
- •Active, known, or suspected autoimmune disease or interstitial lung disease.
- •Requirement for systemic therapy with corticosteroids or other immunosuppressive drugs within 14 days prior to initiation of study treatment.
- •Peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, or other gastrointestinal conditions with risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to initiation of study treatment.
- •Untreated deep vein thrombosis (DVT) within the past 6 months. Subjects with DVT treated with therapeutic anticoagulants (excluding therapeutic warfarin) for at least 14 days prior to initiation of study treatment are allowed.
- •Uncontrolled infection.
- •New York Heart Association (NYHA) Grade III or greater congestive heart failure.
- •History of any of the following cardiac conditions within 6 months prior to initiation of study treatment:
- •Cardiac angioplasty or stenting;
- •Myocardial infarction;
- •Unstable angina;
- •Cerebrovascular accident.
- •Presence of any unhealed wound, fracture, or ulcer, or symptomatic peripheral vascular disease.
- •Evidence of hemorrhagic diathesis, coagulation disorder, or clinically significant bleeding (e.g., severe hematuria, gastrointestinal bleeding, hemoptysis) within 6 months prior to initiation of study treatment.
- •QTcF ≥470 msec on screening ECG per Fridericia's formula.
- •Urinalysis showing urine protein ≥ ++ and 24-hour urine protein quantification > 1.0 g within 28 days prior to initiation of study treatment.
- •Positive hepatitis B surface antigen (HBsAg) with HBV-DNA above the lower limit of detection of the local laboratory; Positive hepatitis C antibody (anti-HCV) with HCV-RNA above the lower limit of detection of the local laboratory; Positive syphilis antibody; Positive human immunodeficiency virus (HIV) antibody test.
- •History of organ transplantation.
- •Clinical conditions affecting the intake or absorption of AL8326 (e.g., inability to swallow, chronic diarrhea, intestinal obstruction, malabsorption disorders, gastrectomy or small bowel resection).
- •Use of prohibited concomitant medications within 14 days prior to initiation of study treatment.
- •Receipt of red blood cell or platelet transfusion within 14 days prior to initiation of study treatment.
- •Known allergy, hypersensitivity, or intolerance to protein therapies, or history of any severe drug allergy (e.g., anaphylaxis, hepatotoxicity, immune-mediated thrombocytopenia or anemia).
- •Any severe and/or unstable pre-existing medical, psychiatric, or other condition that may jeopardize subject safety, obtaining informed consent, compliance with study procedures, or achievement of study objectives.
研究组 & 干预措施
AL8326 plus toripalimab
Experimental
Phase 1: Cohort 1 will initiate with AL8326 +Toripalimab 240mg multiple dose (28-Day cycles) After three subjects have completed the first cycle of therapy without a DLT, additional cohorts may be enrolled sequentially. After the first cohort has completed one full cycle of therapy without a DLT, further cohorts will be enrolled sequentially, following the same 28-day cycle regimen.
Phase 2a: Each subject will receive AL8326 +Toripalimab 240mg of this study for continuous 28-Day/21-Day cycles of therapy. AL8326 is orally administered daily at the RP2D found in Phase 1.
干预措施: AL8326 tablets (Drug)
AL8326 plus toripalimab
Experimental
Phase 1: Cohort 1 will initiate with AL8326 +Toripalimab 240mg multiple dose (28-Day cycles) After three subjects have completed the first cycle of therapy without a DLT, additional cohorts may be enrolled sequentially. After the first cohort has completed one full cycle of therapy without a DLT, further cohorts will be enrolled sequentially, following the same 28-day cycle regimen.
Phase 2a: Each subject will receive AL8326 +Toripalimab 240mg of this study for continuous 28-Day/21-Day cycles of therapy. AL8326 is orally administered daily at the RP2D found in Phase 1.
干预措施: Toripalimab (Drug)
结局指标
主要结局
The first part (Phase I): Phase II recommended dose (RP2D)
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Determine the Recommended Phase 2 Dose (RP2D) via evaluation of dose limiting toxicity (DLT) events.
The second part (Phase IIa):Objective remission rate (ORR)
时间窗: Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）
(ORR):The proportion of subjects achieving complete remission (CR) and partial remission (PR) with optimal efficacy according to RECIST 1.1.
次要结局
- The first part (Phase I): Objective remission rate (ORR)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The first part (Phase I): Duration of remission (DOR)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The first part (Phase I): Disease Control Rate (DCR)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The first part (Phase I): Duration of Disease Control (DDC)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The first part (Phase I): Progression Free Survival (PFS)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The first part (Phase I): Overall Survival (OS)(Every 2 cycles,up to 24 months (each cycle is 28 days))
- The second part (Phase IIa): Duration of remission (DOR)(Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）)
- The second part (Phase IIa): Disease Control Rate (DCR)(Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）)
- The second part (Phase IIa): Duration of Disease Control (DDC)(Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）)
- The second part (Phase IIa): Progression Free Survival (PFS)(Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）)
- The second part (Phase IIa): Overall Survival (OS)(Every 2/3/4 cycles,up to 24 month（each cycle is 21 days）)
研究者
研究点 (15)
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