NCT07244705招募中1 期
An Open-label, Multicenter, Phase 1/2 Study Exploring the Safety and Efficacy of ABT-301 in Combination With Tislelizumab and Bevacizumab in Participants With Proficient Mismatch Repair (pMMR)/Non-Microsatellite Instability-High (Non-MSI-H) Locally Advanced or Metastatic Colorectal Cancer (mCRC)
Anbogen Therapeutics, Inc.15 个研究点 分布在 2 个国家目标入组 66 人开始时间: 2025年11月1日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 66
- 试验地点
- 15
- 主要终点
- Part I - To evaluate the safety and tolerability of escalating doses of ABT-301 in combination with fixed doses of tislelizumab 200 mg IV infusion and bevacizumab 7.5 mg/kg IV infusion Q3W, in participants with pMMR/non-MSI-H CRC.
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and tolerability of escalating doses of ABT-301 in combination with fixed doses of tislelizumab 200 mg IV infusion and bevacizumab 7.5 mg/kg IV infusion Q3W, in participants with pMMR/non-MSI-H colorectal cancer (CRC). It will also determine the maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) of ABT-301.
Participants will receive ABT-301 administered once daily (QD ±3 hours) or twice daily (Q12H ±3 hours, at least 9 hours apart) with water in 21-day treatment cycles. Tislelizumab 200 mg IV and bevacizumab 7.5 mg/kg IV Q3W will be given in both parts of the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥18 years at the time of signing the informed consent.
- •Participant with pMMR/non-MSI-H advanced/recurrent histologically confirmed CRC with at least one measurable lesion, per RECIST version 1.
- •Participant must have received ≥2 lines of prior systemic therapy (including but not limited to chemotherapeutic agents of 5-fluorouracil, oxaliplatin, irinotecan; participant may or may not have received biologic agents such as cetuximab, panitumumab, aflibercept, ramucirumab, bevacizumab; tyrosine kinase inhibitors of regorafenib, fruquintinib).
- •NOTE: Participants with BRAF V600E, HER2 amplification/ mutation, KRAS G12C mutation, NTRK gene fusion, RET fusion, may or may not have received relevant targeted therapy and failed.
- •Participant must submit an archival formalin-fixed, paraffin-embedded tumor specimen collected within 5 years before screening. If archival specimens are unavailable, alternative samples, such as colon endoscopy biopsy, are acceptable.
- •NOTE: For participants who consent to join the exploratory biomarker study, a fresh biopsy sample is required during the screening and treatment periods. Exceptions may be granted if tumor tissue cannot be obtained due to specific circumstances.
- •Tumor tissues were identified as pMMR by immunohistochemistry (IHC) method or nonMSI-H by polymerase chain reaction (PCR) (Appendix 13).
- •ECOG Performance Status of 0 or
- •Adequate hematologic and end-organ function, defined by laboratory data obtained within 7 days prior to the first dose of study intervention:
- •Absolute neutrophil count ≥1.5 × 109/L (1500/μL) without granulocyte colony-stimulating factor support.
- •Lymphocyte count >0.5 × 109/L (500/µL).
- •Platelet count >100 × 109/L (100,000/μL), without transfusion.
- •Hemoglobin >90 g/L (9 g/dL), participants may be transfused to meet this criterion.
- •AST, ALT, and ALP <2.5 × ULN (must be ≤5 × ULN for participants with liver metastases).
- •Total serum bilirubin <1.5 × ULN (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases at baseline).
- •Creatinine clearance >60 mL/min.
- •Serum albumin ≥30 g/L (3 g/dL).
- •International normalized ratio (INR) or activated partial thromboplastic time (aPTT) <1.5 × ULN.
- •Urine dipstick for proteinuria ≤2+ (within seven days prior to the first dose of study intervention).
- •Resolution of any acute, clinically significant treatment-related toxicity from prior therapy to Grade ≤1 prior to study entry, with the exception of Grade ≤2 chemotherapy-related peripheral neuropathy or any Grade alopecia.
- •Participant must have a negative test for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.
- •NOTE: Participants with active hepatitis B virus (HBV) infection are eligible for the study if the following applies: HBV deoxyribonucleic acid (DNA) <500 IU/mL within 28 days prior to initiation of study intervention, and anti-HBV treatment (per local standard of care, e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study. Participants with positive hepatitis C virus (HCV) test are eligible for the study if they complete their antiviral therapy prior to study entry.
- •Contraceptive use by participants or participant partners must be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •NOTE: The reliability of sexual abstinence for male and/or female enrollment eligibility needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Male Participants:
- •A male participant must agree to use a highly effective contraception as detailed in Appendix 4 of this protocol during the intervention period and for at least 90 days after the last dose of study intervention and refrain from donating sperm during this period.
- •Female Participants:
- •A female participant is eligible to participate if she is not pregnant (see Appendix 4), not breastfeeding, and at least one of the following conditions applies:
- •o Not a CBP participant as defined in Appendix 4 and below: surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy as confirmed by review of the participant's medical records, medical examination, or medical history interview), or postmenopausal (defined as no menses for 12 months) without an alternative medical cause with follicle-stimulating hormone (FSH) level in the postmenopausal range ≥1 year.
- •o A CBP participant who agrees to follow the contraceptive guidance in Appendix 4 during the intervention period and for at least 180 days after the last dose of study intervention.
- •- Participant is capable of giving signed informed consent as described in Appendix 1, Section 10.1.3 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
排除标准
- •History of leptomeningeal disease.
- •Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, or ankylosing spondylitis.
- •EXCEPTIONS:
- •Participants with the following conditions are eligible for the study: autoimmune-related hypothyroidism on thyroid-replacement hormone are eligible for the study. Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
- •Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
- •Rash must cover <10% of body surface area
- •Disease is well controlled at baseline and requires only low-potency topical corticosteroids
- •No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months.
- •History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan.
- •EXCEPTIONS:
- •o History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- •Active tuberculosis.
- •Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within three months prior to initiation of study intervention, unstable arrhythmia, or unstable angina.
- •NOTE: Participants are not eligible for the study if they have or are
- •A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds).
- •A history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
- •Using concomitant medications that prolong the QT/QTc interval. - Major surgical procedure, other than for diagnosis, within four weeks prior to initiation of study intervention, or anticipation of need for a major surgical procedure during the study.
- •History of malignancy other than CRC within five years prior to screening.
- •EXCEPTIONS:
- •o Participants with malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate >90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer, are eligible for the study.
- •- Severe infection within four weeks prior to initiation of study intervention, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- •- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications.
- •- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
- •Known hypersensitivity to Chinese hamster ovary cell products or to any component of the tislelizumab or bevacizumab formulation.
- •Participant is breastfeeding, has a positive serum pregnancy test at the Screening Visit, or is planning to become pregnant during the study intervention or within at least 120 days after the last dose of study intervention.
- •Symptomatic, untreated, or actively progressing CNS metastases.
- •NOTE: Asymptomatic participants with treated CNS lesions are eligible, provided that all of the following criteria are met:
- •Measurable disease, per RECIST version 1.
- •Must be present outside the CNS.
- •The participant has no history of intracranial hemorrhage or spinal cord hemorrhage.
- •There is no evidence of interim progression between completion of CNS-directed therapy and initiation of study intervention.
- •The participant has not undergone stereotactic radiotherapy within seven days prior to initiation of study intervention, whole brain radiotherapy within 14 days prior to initiation of study intervention, neurosurgical resection within 28 days prior to initiation of study intervention.
- •The participant has no ongoing requirement for corticosteroids as therapy for CNS disease.
- •NOTE: Anticonvulsant therapy at a stable dose is permitted. Asymptomatic participants with CNS metastases newly detected at screening are eligible for the study after receiving radiotherapy or surgery, with no need to repeat the screening brain scan.
- •Uncontrolled tumor-related pain:
- •Participants requiring pain medication must be on a stable regimen at study entry.
- •Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Participants should recover from the effects of radiation. There is no required minimum recovery period.
- •Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
- •Treatment with any investigational therapy within 28 days prior to initiation of study intervention.
- •Treatment with the following pharmaceutical or herbal agents within 14 days prior to initiation of study intervention:
- •Known to be moderate or strong inhibitors or inducers of CYP3A4 (Appendix 9).
- •Known to be sensitive or narrow therapeutic index substrates of CYP3A4, CYP2C8, CYP2C9, or CYP2C19 (Appendix 10).
- •- Prior treatment with any immunotherapy agent, including CD137 agonists or immune checkpoint blockade therapies (such as anti-cytotoxic T-lymphocyte-associated antigen-4 [anti-CTLA-4], anti-PD-1, and anti-PD-L1 therapeutic antibodies) and has experienced disease progression.
- •Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor agents) within two weeks prior to initiation of study intervention, or anticipation of need for systemic immunosuppressive medication during study intervention.
- •NOTE: Participants who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor approval has been obtained.
- •- Inadequately controlled arterial hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), based on an average of three blood pressure readings on two sessions.
- •NOTE: Anti-hypertensive therapy to achieve these parameters is allowable.
- •- Prior history of hypertensive crisis or hypertensive encephalopathy.
- •- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within six months prior to initiation of study intervention.
- 另有 17 项未显示
研究组 & 干预措施
Part 1 (Dose Escalation Phase)
Experimental
干预措施: Tislelizumab (Drug)
Part 1 (Dose Escalation Phase)
Experimental
干预措施: ABT-301 (Drug)
Part 1 (Dose Escalation Phase)
Experimental
干预措施: Bevacizumab (Avastin) (Drug)
Part 2 (Dose Optimization Phase)
Experimental
干预措施: ABT-301 (Drug)
Part 2 (Dose Optimization Phase)
Experimental
干预措施: Tislelizumab (Drug)
Part 2 (Dose Optimization Phase)
Experimental
干预措施: Bevacizumab (Avastin) (Drug)
结局指标
主要结局
Part I - To evaluate the safety and tolerability of escalating doses of ABT-301 in combination with fixed doses of tislelizumab 200 mg IV infusion and bevacizumab 7.5 mg/kg IV infusion Q3W, in participants with pMMR/non-MSI-H CRC.
时间窗: From screening to 90 days after last dose
Endpoints include: Adverse Event will be graded using the NCI CTCAE V5.0.
Part I - To determine the Maximum tolerated dose (MTD) and select the recommended Phase 2 dose (RP2D) of ABT-301.
时间窗: From the first dose of ABT-301 to the completion of the first 21-day cycle of ABT-301 treatment in the last cohort.
Endpoints include: Incidence of DLTs during the first cycle of treatment.
Part II - To evaluate the efficacy of two dosages/schemes of ABT-301 in combination with tislelizumab and bevacizumab.
时间窗: From baseline until progression of disease or death, whichever occurs first. (up to 28 months)
Endpoint: ORR per Investigator assessment, according to RECIST version 1.1.
次要结局
- Part I - To characterize the PK of repeated doses of ABT-301 in participants with pMMR/non-MSI-H CRC.(From Cycle 1 Day 1 through Cycle 2 Day 1 (each cycle is 21 days))
- Part II - Objective Response Rate (ORR) per Investigator Assessment According to RECIST v1.1(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part II - Duration of Response (DOR) per Investigator Assessment According to RECIST v1.1(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part II - Progression-Free Survival (PFS) per Investigator Assessment According to RECIST v1.1(From baseline until disease progression or death, whichever occurs first. (up to 28 months))
- Part II - Overall Survival (OS)(From baseline until disease progression or death, whichever occurs first. (up to 28 months))
- Part I - Objective Response Rate (ORR) per Investigator Assessment According to RECIST v1.1(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part I - Duration of Response (DOR) per Investigator Assessment According to RECIST v1.1(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part I - Progression-Free Survival (PFS) per Investigator Assessment According to RECIST v1.1(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part I - Overall Survival (OS)(From baseline until progression of disease or death, whichever occurs first. (up to 28 months))
- Part II - To evaluate the safety and tolerability of ABT-301 in combination with tislelizumab and bevacizumab.(From screening to 90 days after last dose)
- Part II - To evaluate the PK of ABT-301 in steady state.(From Cycle 1 Day 1 through the last Cycle Day 2 (each cycle is 21 days))
- Part II - To evaluate the PD of ABT-301 in steady state.(From Cycle 1 Day 1 through the last Cycle Day 2 (each cycle is 21 days))
研究者
研究点 (15)
Loading locations...
相似试验
已完成
1 期
A Study of Polatuzumab Vedotin in Combination With Rituximab or Obinutuzumab, Cyclophosphamide, Doxorubicin, and Prednisone in Participants With B-Cell Non-Hodgkin's LymphomaLymphoma, Non HodgkinNCT01992653Genentech, Inc.85
撤回
1 期
A Study of Venetoclax and ABBV-838 Combination Therapy With Dexamethasone in Participants With Multiple Myeloma Whose Cancer Has Come Back or Had No Response to Recent Cancer TreatmentMultiple MyelomaNCT02951117AbbVie
已完成
1 期
A Study of Escalating Doses of DCDS0780A in Participants With Relapsed or Refractory B-Cell Non-Hodgkin's LymphomaNon-Hodgkin's LymphomaNCT02453087Hoffmann-La Roche66
已完成
1 期
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of PF-06649751 in Parkinson's DiseaseParkinson's DiseaseNCT02224664Pfizer50
招募中
1 期
A Study of Oral Nuvisertib (TP-3654) in Patients With MyelofibrosisMyelofibrosisNCT04176198Sumitomo Pharma America, Inc.240