A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study of ADG126 in Combination With Pembrolizumab (Anti PD-1 Antibody) in Patients With Advanced/Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- Adagene Inc
- 入组人数
- 186
- 试验地点
- 30
- 主要终点
- Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.
研究概览
简要总结
This is a Phase 1b/2, open-label, dose escalation, dose expansion and dose optimization study to evaluate the safety, tolerability, PK, and immunogenicity of ADG126-pembrolizumab combination regimens in patients with advanced/metastatic solid tumors.
The study drug ADG126 is an anti-CTLA-4 fully human monoclonal antibody that specifically binds to human CTLA-4. Pembrolizumab is a PD-1 receptor-blocking antibody (a humanized IgG4 monoclonal antibody).
详细描述
This is a Phase 1b/2, open-label, multicenter, dose escalation, dose expansion and dose optimization study to evaluate the safety, tolerability, PK, and preliminary efficacy of ADG126-Pembrolizumab or ADG126-Pembrolizumab in combination with trifluridine/tipiracil-bevacizumab or fruquintinib in patients with advanced/metastatic solid tumors, with a focus on MSS CRC.
In Phase 2, the study will use a randomized design to evaluate the dose optimization regimen in patients with MSS CRC for ADG126- Pembrolizumab doublet only.
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
- •≥18 years of age at the time of informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Wash out period from previous antitumor therapies
- •At least 1 measurable lesion at baseline according to the definition of RECIST v1.
- •Adequate organ function.
- •An archival tumor biopsy is required and should be taken within 2 years of enrollment. If not available, a fresh tumor biopsy is acceptable.
- •For Dose Escalation Phase Only: Patients with histologically or cytologically confirmed, locally advanced or metastatic solid tumors, who have progressed after all standard therapies, or for whom no further standard therapy exists.
- •Dose Expansion Phase Only: Tumor tissues (archived tissue) before treatment are required for all patients.
排除标准
- •Pregnant or breastfeeding females.
- •Childbearing potential who does not agree to the use of contraception during the treatment period.
- •Treatment with any investigational drug within washout period.
- •Prior treatment with a PD-1, PD-L1 targeting agent or a next-generation anti-CTLA-4 therapy with enhanced ADCC function.
- •History of significant irAEs or irAE.
- •Central nervous system (CNS) disease involvement.
- •History or risk of autoimmune disease.
- •Patients requiring systemic treatment with corticosteroids or other immunosuppressive medications (>10 mg/day prednisone or equivalent).
- •Any uncontrolled active infections requiring systemic antimicrobial treatment (viral, bacterial, or other), or uncontrolled or poorly controlled, asthma, chronic obstructive pulmonary disease (COPD).
- •Major surgery within 4 weeks prior to the first dose of the study drug.
- •Has had an allogeneic tissue/solid organ transplant.
- •Has received a COVID-19 vaccine within 7 days prior to the first dose of study treatment. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed.
- •A positive COVID-19 test within 14 days of Cycle 1 Day
- •History of Hypersensitivity or known to be allergic to protein drugs or recombinant protein.
- •Active hemoptysis or central airway invasion by metastatic tumor.
研究组 & 干预措施
ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)
An IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes after administration of pembrolizumab (KEYTRUDA®) infusion. A treatment cycle will consist of 21 days. ADG126 and Pembrolizumab (KEYTRUDA®) combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: ADG126 (Drug)
ADG126 in combination with Pembrolizumab (Trade name KEYTRUDA®)
An IV infusion of ADG126 over 60-90 minutes will be administered 30-60 minutes after administration of pembrolizumab (KEYTRUDA®) infusion. A treatment cycle will consist of 21 days. ADG126 and Pembrolizumab (KEYTRUDA®) combination treatment both will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Trifluridine/Tipiracil-Bevacizumab) while assessing safety and tolerability. Standard of care treatment will be administered according to the specifications outlined in the Investigational Brochure. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: ADG126 (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Trifluridine/Tipiracil-Bevacizumab) while assessing safety and tolerability. Standard of care treatment will be administered according to the specifications outlined in the Investigational Brochure. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with Trifluridine/Tipiracil-Bevacizumab
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Trifluridine/Tipiracil-Bevacizumab) while assessing safety and tolerability. Standard of care treatment will be administered according to the specifications outlined in the Investigational Brochure. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: Standard of Care (Trifluridine/Tipiracil-Bevacizumab) (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Fruquintinib) while assessing safety and tolerability. The dose strength for treatment will be based on the IB and protocol. Fruquintinib (Fruzaqla) is orally given once daily for the first 21 days of each 28-day cycle. Each treatment cycle consists of 14 days. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: ADG126 (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Fruquintinib) while assessing safety and tolerability. The dose strength for treatment will be based on the IB and protocol. Fruquintinib (Fruzaqla) is orally given once daily for the first 21 days of each 28-day cycle. Each treatment cycle consists of 14 days. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
ADG126 and pembrolizumab (KEYTRUDA®) in combination with fruquintinib
To evaluate the preliminary antitumor efficacy of ADG126 and Pembrolizumab (KEYTRUDA®) in combination with SOC (Fruquintinib) while assessing safety and tolerability. The dose strength for treatment will be based on the IB and protocol. Fruquintinib (Fruzaqla) is orally given once daily for the first 21 days of each 28-day cycle. Each treatment cycle consists of 14 days. Will be dosed until progressive disease (PD), intolerable toxicities, withdrawals of consent, or up to 35 cycles.
干预措施: Standard of care (Fruquintinib) (Drug)
Dose Optimization
The randomized phase 2 Dose Optimization arm is intended to test two dosing regimens of ADG126 in combination with pembrolizumab (KEYTRUDA®), which allows the selection of an optimal regimen. The study treatments may continue for up to 35 treatments for pembrolizumab (KEYTRUDA®) if given every 21 days and 18 treatments for pembrolizumab (KEYTRUDA®) if given every 42 days until PD, intolerable toxicities or withdrawal of consent.
干预措施: ADG126 (Drug)
Dose Optimization
The randomized phase 2 Dose Optimization arm is intended to test two dosing regimens of ADG126 in combination with pembrolizumab (KEYTRUDA®), which allows the selection of an optimal regimen. The study treatments may continue for up to 35 treatments for pembrolizumab (KEYTRUDA®) if given every 21 days and 18 treatments for pembrolizumab (KEYTRUDA®) if given every 42 days until PD, intolerable toxicities or withdrawal of consent.
干预措施: Pembrolizumab (KEYTRUDA®) (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) and RP2D for ADG126 in combination with pembrolizumab.
时间窗: 9 months
To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) for ADG126+ pembrolizumab in dose escalation levels
the safety and tolerability of ADG126 at escalating dose level in combination with pembrolizumab in adults with advanced metastatic solid tumors
时间窗: 9 months
Incidence rate of AEs as assessed by CTCAE v5.0
Access the preliminary antitumor activity of ADG126-pembrolizumab combination regimens
时间窗: 9 months
Number of Participants with preliminary antitumor activity
Maximum tolerated dose (MTD) and/or RP2D for ADG126 with Trifluridine/Tipiracil-Bevacizumab
时间窗: 6 months
To assess the safety and tolerability of ADG126 + pembrolizumab in combination with the following SOC therapies (Trifluridine/tipiracil-bevacizumab) in MSS CRC To determine the MTD and/or RP2D for ADG126 + pembrolizumab in combination with the following SOC therapies in MSS CRC:
Access the preliminary antitumor activity of ADG126 with Pembrolizumab in combination standard of care
时间窗: 6 months
To assess the preliminary antitumor activity of ADG126 + pembrolizumab in combination with the following SOC therapies in MSS CRC (Trifluridine/tipiracil-bevacizumab) SOC (Fruquintinib)
Access and characterize the optimal dose based on safety and efficacy parameters
时间窗: 9 months
To characterize the optimal dose based on safety and efficacy parameters
次要结局
- Pharmacokinetic (PK) profile/parameters(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- Maximum (peak) plasma concentration (Cmax)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- Time to maximum (peak) concentration (Tmax)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- Trough concentration (Ctrough)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- Incidence of ADAs(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- To assess the disease control rate (DCR)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- To assess the progression free survival (PFS)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- To assess the overall survival (OS)(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))
- To assess the efficacy outcomes in the defined patient population(From first dose (Cycle 1 Day 1,) until the last dose (up to 2 years))