A Phase Ib/II, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administration of QLC5508 in Combination With Other Anti-tumor Agents in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 444
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) for combination-treatments (Phase Ib)
研究概览
简要总结
QLC5508 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents in patients with advanced solid tumor patients.
详细描述
This is a phase Ib/II, open-label, multi-center, dose-escalation and expansion in Chinese subjects with advanced solid tumors. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of QLC5508 in combination with other anti-cancer agents.
The target population of dose escalation part is patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.
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
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
- •At least 18 years of age at screening;
- •Histologically or cytologically confirmed advanced solid tumors:
- •Dose escalation part will enroll participants who have progressed on or are intolerant to available standard therapies.
- •Dose expansion part will enroll participants who have not received prior treatment for advanced/metastatic diseases.
- •At least one measurable target lesion according to RECIST v1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1
- •Life expectancy ≥12 weeks
- •Female or male participants should be willing to use appropriate contraceptive measures throughout the study;
- •Female participants should have a negative blood pregnancy test within 7 days prior to the first dose or have evidence of non-childbearing potential;
- •A signed written Informed Consent Form
排除标准
- •. Received or undergoing any of the following treatment:
- •Previous or current treatment with B7-H3 targeted therapy
- •Previous or current treatment with topoisomerase I inhibitors
- •Previous treatment with cytotoxic chemotherapy, investigational agents, traditional Chinese medicine with an anti-tumor indication and antitumor drugs within 14 days prior to the first dose
- •Previous treatment with macromolecular antitumor drugs within 28 days prior to the first dose
- •f. Radiotherapy with a limited field of radiation within 2 weeks prior to the first dose; or more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first dose e. Pleural effusion or ascites requiring clinical intervention; or presence of pericardial effusion f. Major surgery within 4 weeks prior to the first dose g. Brain metastases; leptomeningeal or brainstem metastases; or spinal cord compression
- •Unresolved AEs ≥ Grade 2 (CTCAE v5.0) from prior therapy except for alopecia and residual neuropathy
- •Previous or concurrent primary malignancies
- •Inadequate bone marrow reserve or organ dysfunction
- •Evidence of cardiovascular risk
- •Evidence of current severe or uncontrolled systemic diseases
- •Severe infection within 4 weeks prior to the first dose; or uncontrolled active infection at screening
- •Known or suspected interstitial lung disease; or other moderate to severe pulmonary diseases that significantly impair respiratory function and may interfere with the detection or management of drug-related pulmonary toxicity
- •High risk of gastrointestinal or abdominal bleeding
- •Gastrointestinal diseases of clinical significance within 3 months prior to the first dose
- •History of severe neuropathy or mental disorders
- •History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to QLC5508 or any of the components of QLC5508
- •Unlikely to comply with study procedures and requirements in the opinion of the investigator
- •Any disease or condition that, in the opinion of the investigator, would compromise participant safety or interfere with study assessments
研究组 & 干预措施
QLC5508, QL1706 and Cisplatin/ Carboplatin
干预措施: Cisplatin/ Carboplatin (Drug)
QLC5508 and QL1706
干预措施: QLC5508 (Drug)
QLC5508 and QL1706
干预措施: QL1706 (Drug)
QLC5508, QL1706 and Cisplatin/ Carboplatin
干预措施: QLC5508 (Drug)
QLC5508, QL1706 and Cisplatin/ Carboplatin
干预措施: QL1706 (Drug)
QLC5508 and QL2107
干预措施: QLC5508 (Drug)
QLC5508 and QL2107
干预措施: QL2107 (Drug)
QLC5508, QL2107 and 5-fluorouracil (5-FU)
干预措施: QLC5508 (Drug)
QLC5508, QL2107 and 5-fluorouracil (5-FU)
干预措施: QL2107 (Drug)
QLC5508, QL2107 and 5-fluorouracil (5-FU)
干预措施: 5-fluorouracil (5-FU) (Drug)
QLC5508, QL2107 and Paclitaxel
干预措施: QLC5508 (Drug)
QLC5508, QL2107 and Paclitaxel
干预措施: QL2107 (Drug)
QLC5508, QL2107 and Paclitaxel
干预措施: Paclitaxel (Drug)
QLC5508, Oxaliplatin, 5-fluorouracil (5-FU) and leucovorin
干预措施: QLC5508 (Drug)
QLC5508, Oxaliplatin, 5-fluorouracil (5-FU) and leucovorin
干预措施: 5-fluorouracil (5-FU) (Drug)
QLC5508, Oxaliplatin, 5-fluorouracil (5-FU) and leucovorin
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) for combination-treatments (Phase Ib)
时间窗: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose
To determine the MTD for further evaluation of QLC5508 with other anti-cancer agents in participants with advanced solid tumors
Recommended Phase II Dose (RP2D) for combination-treatments (Phase Ib)
时间窗: Up to day 21 (Q3W combination) or day 28 (Q2W combination) from the first dose
To determine the RP2D for further evaluation of QLC5508 with other anti-tumor agents in participants with advanced solid tumors
Objective response rate (ORR) determined by investigators (Phase II)
时间窗: Approximately 12 months
ORR is defined as proportion of participants with best overall response of complete response (CR) and partial response (PR) \[Confirmed CR/PR assessment require at least one repeat (4-6 weeks)\] evaluated by investigator according to RECIST v1.1
次要结局
- ORR determined by investigators (Phase Ib)(Approximately 12 months)
- Disease control rate (DCR) determined by investigators (Phase Ib and II)(Approximately 12 months)
- Duration of response (DOR) determined by investigators (Phase Ib and II)(Approximately 12 months)
- Progression-free survival (PFS) determined by investigators (Phase Ib and II)(Approximately 12 months)
- Overall survival (OS) (Phase Ib and II)(Approximately 24 months)
- Incidence and severity of adverse events (AEs) (Phase II)(From the first dose through 90 days post end of treatment)
- Observed maximum plasma concentration (Cmax) of QLC5508 in advanced solid tumor (Phase Ib and II)(From pre-dose to study completion, approximately 24 months)
- Time to reach maximum plasma concentration (Tmax) of QLC5508 (Phase Ib)(From pre-dose to study completion, approximately 24 months)
- Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) following the first dose of QLC5508 (Phase Ib)(From pre-dose to study completion, approximately 24 months])
- Observed maximum plasma concentration (Cmax) of QL1706 in advanced solid tumor (Phase Ib and II)(From pre-dose to study completion, approximately 24 months)
- Observed maximum plasma concentration (Cmax) of QL2107 in advanced solid tumor (Phase Ib and II)(From pre-dose to study completion, approximately 24 months)
- Percentage of participants with antibodies to QLC5508 in serum (Phase Ib and II)(From pre-dose to study completion, approximately 24 months)
- Percentage of participants with antibodies to QL1706 in serum (Phase Ib and II)(From pre-dose to study completion, approximately 24 months)