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临床试验/NCT06400160
NCT06400160尚未招募1 期

An Open-label, Multi-center, and Dose-escalation, Phase 1/2a Clinical Trial to Assess the Maximum Tolerated Dose(MTD), Safety, and the Anti-tumor Effect of TB511 Monotherapy in Patients With Advanced Solid Tumors Refractory or Intolerant to Standard of Care(SoC) and Pembrolizumab Combination Therapy in Patients With Advanced Solid Tumors Relapsed or Refractory

Twinpig Biolab, Inc.0 个研究点目标入组 12 人开始时间: 2026年3月1日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
尚未招募
入组人数
12
主要终点
Phase I Clinical trial-Maximum tolerated dose (MTD).
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

  1. Study population

[TB511 Monotherapy Cohort for Phase 1 and Phase 2a Clinical Trial] Patients with advanced solid tumors who are either refractory or intolerant to standard of care (SoC).

[Immune checkpoint inhibitors (ICIs) Combination Therapy Cohort for Phase 2a Clinical Trial] Patients with advanced solid tumors who are refractory to immune checkpoint inhibitors (ICIs) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 inhibitors or who have no available standard of care. 2. Objectives of the Clinical Trial

2.1 Primary Objectives [Phase 1 Clinical Trial]

  • To evaluate the safety and tolerability of TB511 monotherapy in patients with advanced solid tumors and to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D).

[Phase 2a Clinical Trial]

  • To evaluate the Objective Response Rate (ORR) of TB511 monotherapy and TB511 in combination with Pembrolizumab in patients with advanced solid tumors (based on Response Evaluation Criteria In Solid Tumors Version 1.1, RECIST v1.1).

2.2 Secondary Objectives [Phase 1 Clinical Trial]

  • To evaluate the safety of TB511 monotherapy.
  • To assess the Objective Response Rate (ORR) and anti-tumor activity of TB511 monotherapy (based on RECIST v1.1).
  • To characterize the pharmacokinetic (PK) profile of TB511 monotherapy.

[Phase 2a Clinical Trial]

  • To evaluate the Disease Control Rate (DCR), Duration of Response (DoR), and Progression-Free Survival (PFS) of TB511 monotherapy and TB511 in combination with Pembrolizumab.
  • To assess the safety and tolerability of TB511 monotherapy and TB511 in combination with Pembrolizumab.
  • To characterize the pharmacokinetic (PK) profile of TB511 monotherapy and TB511 in combination with Pembrolizumab.

2.3 Exploratory Objectives

  • To compare changes in biomarker levels of TB511 monotherapy.
  • To assess immunogenicity of TB511 by measuring anti-drug antibodies (ADA).

详细描述

  1. Number of participants

[Phase 1 Clinical Trial] 3 to 6 patients per dose group

[Phase 2a Clinical Trial] Approximately 20 patients per cohort (Cohort 1: Approximately 20 patients, Cohort 2: Approximately 20 patients) 2. Study Duration

  • Total clinical trial duration: Approximately 36 months from the date of IRB approval (however, this may be adjusted depending on the enrollment rate of participants.)
  • Participation duration for individual participants
  • Screening period: Up to 4 weeks (28 days)
  • Treatment period: Each cycle consists of 3 weeks (21 days), and administration will continue until a reason for discontinuation occurs.
  • Safety follow-up period: 6 weeks after the End of Treatment (EOT)
  1. Investigational Product

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

盲法说明

Open Label

入排标准

年龄范围
19 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Male and female adults who are 19 years old or older at the time of obtaining informed consent form.
  • •Patients with at least one measurable lesion by RECIST v1.
  • •Patients whose Eastern Cooperative Oncology Group Performance Status (ECOG PS) is 0 or
  • •Female patients of childbearing potential who have not undergone sterilization surgery must agree to use appropriate contraception* for 6 months after the end of administration of the investigational product and must satisfy one of the following conditions at the time of screening to establish that they are not pregnant.
  • •Women over the age of 50 who have had amenorrhea for at least 12 months after the termination of all exogenous hormone treatment.
  • •Documented irreversible surgical sterilization by hysterectomy, dual ovariectomy, or oophorectomy (tubal litigation does not satisfy this criteria)
  • •Women under the age of 50 who have had amenorrhea for at least 12 months after the termination of all exogenous hormone treatment and whose luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the post-menopause range determined by the clinical trial institution.
  • •Male patients who have not undergone vasectomy must agree to use a barrier method of contraception (i.e., condom) and agree that both they and their partners will use an appropriate method of contraception* through 6 months after the end of administration of the investigational product.
  • •*Appropriate methods of contraception include: complete abstinence, hormonal contraceptives not known to have drug interactions [levonorgestrel-releasing intrauterine system (IUS) (e.g., Mirena), medroxyprogesterone (e.g., Provera)], copper intrauterine device, and partner's vasectomy. Periodic abstinence (e.g., calendar-based, ovulation tracking, or basal body temperature methods) and withdrawal are not considered appropriate methods of contraception.
  • •Patients who have been provided with sufficient explanations on this clinical trial, have voluntarily decided to participate in this clinical trial and have agreed in writing to faithfully comply with the requirements of the clinical trial.
  • •[Cohort of TB511 Monotherapy in Phase 1 and Phase 2a Clinical Trials]
  • •1) Patients with cytologically or histologically confirmed advanced solid tumors who are either refractory or intolerant to standard of care (SoC).
  • •[Cohort of ICIs Combination Therapy in Phase 2a Clinical Trial] 1) Patients with advanced solid tumors who, at the time of screening, are refractory to or have experienced disease progression during treatment with immune checkpoint inhibitors (ICIs) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 agents within their approved indications, and for whom no standard therapy is available.
  • •- This includes: melanoma, non-small cell lung cancer, head and neck cancer, classical Hodgkin lymphoma, urothelial carcinoma, gastric cancer, esophageal cancer, renal cell carcinoma, endometrial cancer, microsatellite instability-high (MSI-H) cancer, MSI-H colorectal cancer, triple-negative breast cancer, cervical cancer, biliary tract cancer, and hepatocellular carcinoma.

排除标准

  • •[Common] Current Disease and Medical History
  • •Patients who have had other malignant tumors within 5 years prior to the screening (provided, however, that patients with basal cell carcinoma that requires only stable long-term follow-up without treatment can be enrolled).
  • •Patients who had been subject to chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to the screening.
  • •Patients who had undergone major surgery requiring general anesthesia within 4 weeks prior to the screening.
  • •Patients with brain metastasis who have symptoms or required treatment (provided, however, that patients with asymptomatic metastasis that does not require treatment [excluding anticonvulsants used in maintenance therapy] can be enrolled).
  • •Patients with systemic disease for which administration of anti-cancer drugs is deemed inappropriate by the investigator.
  • •Patients with the following cardiovascular disease at the screening
  • •Myocardial infarction, unstable angina, stroke, or transient ischemic within 6 months.
  • •QTc interval ≥ 480 msec or clinically significant electrocardiographic change.
  • •Congestive heart failure classified as New York Heart Association (NYHA) class III or above.
  • •Patients who are HIV-positive.
  • •Patients whose participation in the clinical trial is deemed inappropriate by the investigator based on their results of Hepatitis B virus and Hepatitis C virus test.(Not applicable to patients with hepatocellular carcinoma.)
  • •However, the following cases are allowed:
  • •For patients positive for HBsAg or HBcAb: HBV DNA must be ≤ 2000 IU/mL or undetectable.
  • •For patients positive for HCV Ab: HCV RNA must be negative or the patient must have completed antiviral treatment and be stabilized.
  • •Patients with acute or severe hepatitis.
  • •Patients with autoimmune disease or with history of chronic or recurrent autoimmune disease.
  • •Patients with history of organ transplantation.
  • •Patients with history of identical hematopoietic stem cell transplantation.
  • •Patients with history of interstitial pneumonia requiring steroid treatment.
  • •Patients with known hypersensitivity to recombinant drugs (drugs with active ingredients of peptide or protein).
  • •Patients with history of hypersensitivity to the components of TB
  • •Prohibited Drugs
  • •Patients who require continuous treatment with immunosuppressants or systemic corticosteroid administration (Note: Use of topical corticosteroids such as intra-articular, intranasal, ophthalmic, or inhaled formulations is permitted. Temporary use of systemic corticosteroids administration for the treatment or prevention of contrast agent allergies or adverse reactions is also allowed.)
  • •Patients who have received live or attenuated live vaccines within 4 weeks prior to the screening.
  • •Laboratory tests
  • •Patients with the following laboratory levels at the time of screening.
  • •ANC < 1,500/mm³
  • •Platelet count < 100,000/mm³ (for hepatocellular carcinoma: < 75,000/mm³)
  • •Hemoglobin < 9.0 g/dL (Patients can be enrolled if hemoglobin level is recovered to ≥ 9.0 g/dL during the screening period; however, blood transfusion within 7 days prior to the screening to fulfill this criterion is not allowed.)
  • •AST, ALT > 3 × ULN (provided, however, that if liver metastasis is involved, AST, ALT > 5 × ULN)
  • •Total bilirubin > 1.5 × ULN
  • •Serum creatinine > 1.5 × ULN
  • •Pregnant, breastfeeding women, or patients with a positive pregnancy test at the time of screening.
  • •Patients who, in the investigator's judgment, have an expected survival of less than 12 weeks.
  • •Patients who have received other investigational drugs within 4 weeks prior to screening (Patients who did not receive investigational products or who participated only in non-interventional observational studies can be eligible).
  • •Any patient deemed unsuitable for participation in this clinical trial at the discretion of the investigator.
  • •[Only applicable to the cohort of TB511 and ICIs combination therapy in Phase 2a Clinical Trial]
  • •Patients with thyroid-stimulating hormone (TSH) levels above the institutional upper limit of normal (ULN) at the time of screening (Note: patients with abnormal TSH levels may be eligible if free T4 and total T3 levels are within normal ranges).
  • •Patients with a history of hypersensitivity to any component of pembrolizumab.

研究组 & 干预措施

TB511

Experimental

  • Product name or code: TB511 Injection (8 mg)

  • Formulation and appearance: White or off-white color of lyophilized powder ③ Main ingredient: TB511 ④ Storage method: Store in a hermetic container in a freezer (-20℃); protect from light

干预措施: TB511 (Drug)

Concomitant drug

Other
  • Product name or code: Keytruda

② Formulation and appearance: An injection comprised of clear to slightly opalescent, colorless to slightly yellow liquid contained in a colorless and transparent vial.

③ Main ingredient: Pembrolizumab

  • Storage method: Store in a hermetic container, refrigerated at 2 to 8℃; protect from light; do not freeze

干预措施: Keytruda (Drug)

结局指标

主要结局

Phase I Clinical trial-Maximum tolerated dose (MTD).

时间窗: 1 year

1. Definition and Assessment of Dose Limiting Toxicity (DLT) DLT is an adverse event or abnormal laboratory level unrelated to the progress of the disease or intercurrent disease that limits dose escalation and is consistent with one or more of the following criteria: DLT assessment is conducted only at Cycle 1 after completion of Cycle 1. However, even during Cycle 1, DLT can be immediately evaluated if toxicity is determined to be DLT. DLT assessment is conducted in accordance with NCI-CTCAE v5.0 based on individual assessment items on hematological/non-hematological toxicity and other toxicities. 2. Definition and Determination of Maximum Tolerated Dose (MTD) When 2 out of 3 subjects or 2 out of 6 subjects experience DLTs, the dose is considered intolerable, the subsequent dose escalation is stopped, and a level lower than the dose is declared the maximum tolerable dose (MTD).

Phase I Clinical trial-Recommended Phase IIa dose (RP2D).

时间窗: 1 year

RP2D of Phase IIa clinical trial is determined through MTD and overall toxicity assessment.

Phase IIa Clinical trial-anti-tumor effect-to evaluate the Objective response rate (ORR) of TB511 monotherapy and combination therapy with Pembrolizumab in patients with advanced solid tumors (based on RECIST v1.1).

时间窗: 2 years

Solid tumor response is evaluated in accordance with RECIST v1.1 and immune RECIST (iRECIST). Objective response rate (ORR): Fraction of subjects whose best overall response is Complete Response (CR) or Partial Response (PR)

次要结局

  • Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-the Objective response rate (ORR)(1 year)
  • Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Disease control rate (DCR)(1 year)
  • Phase I clinical trial-anti-tumor effects of TB511 Monotherapy-Duration of response (DoR)(1 year)
  • Phase I clinical trial-safety-adverse events of TB511 Monotherapy(1 year)
  • Phase I clinical trial-safety-vital signs of TB511 Monotherapy(1 year)
  • Phase I clinical trial-safety-physical examination and ECG of TB511 Monotherapy(1 year)
  • Phase I clinical trial-safety-laboatory test of TB511 Monotherapy(1 year)
  • PK parameters for TB511 (Area Under the Curve from 0 to 24 h (AUC)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (AUC to the Last Measurable Concentration from 0 to 24 h (AUClast)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h (AUCinf)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Peak Plasma Concentration from 0 to 24 h (Cmax)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Time to Obtain Maximum Plasma Concentration from 0 to 24 h (Tmax)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 from 0 to 24 h (half-life (t1/2)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Clearance from 0 to 24 h (CL/F)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Volume of distribution from 0 to 24 h (Vd/F)) [Time Frame: Day 1 of first 1 cycle](1 year)
  • PK parameters for TB511 (Area Under the Curve from 0 to 24 h at steady-state (AUCss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (AUC to the Last Measurable Concentration from 0 to 24 h at steady-state (AUClast ss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h at steady-state (AUCinf, ss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (Peak Plasma Concentration from 0 to 24 h at steady-state (Cmax ss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (Time to Obtain Maximum Plasma Concentration from 0 to 24 h at steady-state (Tmax, ss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (half-life from 0 to 24 h at steady-state (t1/2, ss)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (Clearance from 0 to 24 h at steady-state (CL, ss/F)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • PK parameters for TB511 (Volume of distribution from 0 to 24 h at steady-state (Vd, ss/F)) [Time Frame: Day 21 of first 1 cycle](1 year)
  • Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Disease control rate (DCR)(2 years)
  • Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Duration of response (DoR)(2 years)
  • Phase IIa-anti-tumor effects of TB511 Monotherapy and TB511 & pembronizumab compination therapy-Progression-free survival (PFS) period(2 years)
  • Phase IIa-the safety-adverse events of TB511 Monotherapy and TB511 & pembronizumab compination therapy(2 years)
  • Phase IIa-the safety-vital signs of TB511 Monotherapy and TB511 & pembronizumab compination therapy(2 years)
  • Phase IIa-the safety-Physical examination and ECG of TB511 Monotherapy and TB511 & pembronizumab compination therapy(2 years)
  • Phase IIa-the safety-Laboratory test of TB511 Monotherapy and TB511 & pembronizumab compination therapy(2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Area Under the Curve from 0 to 24 h (AUC)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (AUC to the Last Measurable Concentration from 0 to 24 h (AUClast)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h (AUCinf)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Peak Plasma Concentration from 0 to 24 h (Cmax)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Time to Obtain Maximum Plasma Concentration from 0 to 24 h (Tmax)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (half-life from 0 to 24 h (t1/2)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Clearance from 0 to 24 h (CL/F)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Volume of distribution from 0 to 24 h (Vd/F)) [Time Frame: Day 1 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Area Under the Curve from 0 to 24 h at steady-state (AUCss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (AUC to the Last Measurable Concentration from 0 to 24 h at steady-state (AUClast ss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Area under the plasma concentration-time curve extrapolated to infinity from 0 to 24 h at steady-state (AUCinf, ss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Peak Plasma Concentration from 0 to 24 h at steady-state (Cmax ss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Time to Obtain Maximum Plasma Concentration from 0 to 24 h at steady-state (Tmax, ss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (half-life from 0 to 24 h at steady-state (t1/2, ss)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Clearance from 0 to 24 h at steady-state (CL, ss/F)) [Time Frame: Day 21 of first 1 cycle](2 years)
  • PK parameters for TB511 and Pembrolizumab combination (Volume of distribution from 0 to 24 h at steady-state (Vd, ss/F)) [Time Frame: Day 21 of first 1 cycle](2 years)

研究者

申办方类型
Industry
责任方
Sponsor

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