A Phase I Study of BIO-008 Injection for Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity in Patients With Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- 未指定
- 疾病 / 适应症
- Solid Tumor, Adult
- 发起方
- Shijiazhuang Yiling Pharmaceutical Co. Ltd
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Adverse events (AE)/severe adverse events (SAE)
- 状态
- 招募中
- 最后更新
- 2年前
概览
简要总结
Phase 1: Dose escalation study (Phase Ia)
Main purpose:
Evaluate the safety and tolerability of BIO-008 in patients with advanced solid tumors, and determine the maximum tolerable dose (MTD) and dose limiting toxicity (DLT) of BIO-008.
Secondary purpose:
Evaluate the pharmacokinetic (PK) characteristics of BIO-008;
Evaluate the immunogenicity of BIO-008.
Exploratory purposes:
Preliminary evaluation of the anti-tumor activity of BIO-008 (if available);
Detect the expression of CLDN18.2 in tumor tissue and explore its correlation with BIO-008 anti-tumor activity indicators (only applicable to subjects who can provide fresh or archived tumor tissue samples before the first administration).
Phase 2: Dose Extension Study (Phase Ib)
Main purpose:
• Preliminary evaluation of ORR of BIO-008 in patients with CLDN18.2 positive advanced gastric cancer or gastroesophageal junction cancer (GC/GEJ), pancreatic cancer (PC) and other solid tumors;
Determine the recommended dose for clinical phase II (RP2D).
Secondary purpose:
Evaluate the safety and tolerability of BIO-008;
Evaluate the PK characteristics of BIO-008;
Evaluate the immunogenicity of BIO-008;
• Evaluate other anti-tumor activity indicators of BIO-008 in patients with CLDN18.2 positive advanced gastric cancer or gastroesophageal junction cancer, pancreatic cancer and other solid tumors;
Evaluate the correlation between the anti-tumor activity of BIO-008 and the expression of CLDN18.2.
研究者
入排标准
入选标准
- •Voluntary signed informed consent (ICF) and follow protocol requirements
- •Age is 18\~75 years old (including the boundary value), gender is not limited
- •Patients with advanced solid tumors who have histologically or cytologically confirmed standard therapy failure (progressive treatment or intolerance), or no standard therapy regimen, or who are not suitable for standard therapy at this stage
- •Dose escalation study (Phase Ia): Participants agreed to provide fresh or archived tumor tissue samples for assessment of CLDN18.2 expression levels before the first dose (central laboratory), and subjects enrolled in Phase Ia did not require positive CLDN18.2 expression. If the subject cannot provide samples or a sufficient number of slices, he may be evaluated by the investigator if other entry criteria are met
- •Dose extension study (Phase Ib): The subject agreed to provide fresh or archived tumor tissue samples for the assessment of CLDN18.2 expression levels (before the central laboratory) and tested positive for CLDN18.2 by the central laboratory
- •According to RECIST v1.1 standard, dose escalation studies (Phase Ia) have at least evaluable lesions; Dose extension study (Phase Ib) with at least one measurable lesion;
- •The ECOG physical strength score is 0-1 point
- •The estimated survival time is not less than 3 months
- •The toxicity of previous anti-tumor therapy has recovered to grade 1 as defined by CTCAE v5.0 (except for asymptomatic laboratory abnormalities, such as elevated ALP test, hyperuricemia, elevated blood glucose, etc.
- •except for toxicity without safety risk judged by the investigator, such as hair loss, pigmentation, grade 2 peripheral neurotoxicity, thyrotoxicity after immune checkpoint inhibitor treatment, except for those who have been controlled after hormone replacement therapy)
排除标准
- •Allergic or hypersensitivity to similar products or excipients
- •Received other clinical trial drug or treatment within 28 days prior to the first dose
- •They had received anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, endocrine therapy and immunotherapy within 28 days before the first dose. Enrollment may be judged by the investigator if:
- •Small local palliative radiotherapy (bone metastasis radiotherapy for pain control), more than 14 days since the first dose 2)Use of oral drugs, including fluorouracil and small molecule targeted drugs, more than 14 days or more than 5 half-lives since the first drug administration (whichever is longer) 3) It has been more than 14 days since the first administration of traditional Chinese medicine with anti-tumor indications 4) Nitrosourea or mitomycin C was used more than 6 weeks from the first administration.
- •4: Have received antitumor drugs for the CLDN18.2 target
- •5: Vaccination of any live vaccine within 28 days before the first dose (e. g., vaccines against infectious diseases, such as influenza, varicella, or COVID-19, etc.)
- •6: Those who have received immunosuppressive agents or systemic corticosteroids (receiving more than 10mg of prednisone or equivalent glucocorticoids per day) within 14 days prior to the first dose
- •7: Major organ surgery or interventional therapy (excluding tumor biopsy, puncture, etc.) or significant trauma within 28 days before the first dose, or required elective surgery during the trial
- •8: Those who are using anticoagulants, vitamin K antagonists, or heparin treatment may receive prophylactic doses
- •9: Patients with gastrointestinal obstruction or persistent recurrent vomiting (defined as 3 vomiting at 24 hours) or uncontrolled / severe gastrointestinal bleeding or ulcer within 28 days prior to the first dose
结局指标
主要结局
Adverse events (AE)/severe adverse events (SAE)
时间窗: from the start of the medication to the end of the study or 28 days after cessation of medication
To evaluate the safety of Bio-008
Incidence of dose limiting toxicity (DLT)
时间窗: From day 1 to day 21 after the first dose
To collect dose limiting toxicities (DLTs) occurring within 21 days after the first dose
Maximum Tolerated Dose (MTD）
时间窗: From day 1 to day 21 after the first dose
The maximum tolerated dose (MTD) is commonly estimated to be the maximum dose that can be determined through DLT of two among 6 subjects administered with Bio-008 once every 3 weeks in 21 days cycles.
Recommended Phase 2 Dose (RP2D)
时间窗: From day 1 to day 21 after the first dose
The RP2D will be determined during the dose expansion stage of the study. RP2D will be determined using available safety and efficacy data.
Objective response rate (ORR) (RECIST 1.1)
时间窗: From date of randomization until the date of first documented progression, up to 3 months
These measure are defined as the proportion of subjects with complete response (CR) or partial response (PR)
次要结局
- Area under plasma concentration vs time curve (AUC)(from the start of the medication to the end of the study or 28 days after cessation of medication)
- Peak plasma concentration (Cmax)(from the start of the medication to the end of the study or 28 days after cessation of medication)
- Time to maximum observed plasma concentration(Tmax)(from the start of the medication to the end of the study or 28 days after cessation of medication)
- Terminal elimination half life (T1/2)(from the start of the medication to the end of the study or 28 days after cessation of medication)
- Immunogenicity(from the start of the medication to the end of the study or 28 days after cessation of medication)
- Duration of response (DOR) (RECIST 1.1)(From date of randomization until the date of first documented progression, up to 3 months)
- Disease control rate (DCR) (RECIST 1.1)(From date of randomization until the date of first documented progression, up to 3 months)
- Progression free survival (PFS) (RECIST 1.1)(From date of randomization until the date of first documented progression, up to 3 months)