A Multicenter, Open-Label, Phase I/II Study of EOS884448 (EOS-448) in Combination With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 153
- 试验地点
- 42
- 主要终点
- Percentage of participants with DLT and Adverse Events
研究概览
简要总结
This is a multicenter, open-label, phase I/II basket study, evaluating the safety, tolerability, RP2D, pharmacokinetics, pharmacodynamics and antitumor activity of EOS-448 (also known as GSK4428859A or belrestotug) combined with standard of care and/or with investigational therapies in participants with advanced solid tumors.
详细描述
The combinations evaluated will be:
- EOS-448 combined with pembrolizumab, an anti-PD-1 antibody
- EOS-448 combined with inupadenant an investigational adenosine A2A receptor antagonist
- EOS-448 combined with dostarlimab an anti-PD-1 antibody
- inupadenant combined with dostarlimab
- EOS-448 combined with inupadenant and dostarlimab
- EOS-448 combined with dostarlimab and standard of care chemotherapies in participants with NSCLC
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Provide a signed written informed consent for the trial
- •Have measurable disease, per RECIST v1.1
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 or
- •Have adequate organ functions
- •Part 1A/1B/1C/1D/1E/1F: Have histologically or cytologically confirmed advanced or metastatic solid tumor for whom no standard treatment with survival benefit is available
- •Part 1G (NSCLC):
- •Have a histologically confirmed or cytologically confirmed previously untreated stage IV OR stage III not amenable to curative chemoradiotherapy or surgery (AJCC 8th edition) nonsquamous NSCLC OR squamous NSCLC.
- •Are eligible to receive anti-PD(L)1 therapy combined with chemotherapy in first line metastatic setting
- •Part 2 (H&N cancer)
- •Have histologically or cytologically confirmed recurrent advanced or metastatic head and neck squamous cell carcinoma considered incurable by local therapies
- •PD-L1 status positive
排除标准
- •Have received any anti-cancer therapy within 4 weeks prior to the first dose
- •Have received a live vaccine within 30 days prior to the first dose
- •Have known primary CNS cancer.
- •Have known CNS metastases unless previously treated and well controlled for at least 1 month
- •Have concomitant second malignancies unless a complete remission was achieved at least 2 years before study entry
- •Have a history of Grade ≥ 2 pneumonitis, active autoimmune disease, or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2
- •Have toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery unless the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
- •Have uncontrolled or significant cardiovascular disease
- •Part 1: major surgery within 3 weeks before initiating treatment
- •Part 1: Have received prior radiotherapy within 2 weeks of start of study treatment
- •Part 2 (H&N cancer):
- •Have received prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
- •Have received prior chemotherapy administered in the recurrent advanced or metastatic setting (except for systemic therapy completed > 6 months prior to screening if given as part of multimodal treatment for locally advanced disease)
研究组 & 干预措施
Part 1A - EOS-448 + pembrolizumab
Participants will receive EOS-448 and pembrolizumab at every cycle
干预措施: EOS-448 (Drug)
Part 1A - EOS-448 + pembrolizumab
Participants will receive EOS-448 and pembrolizumab at every cycle
干预措施: pembrolizumab (Drug)
Part 1B - EOS-448 + inupadenant
Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
干预措施: EOS-448 (Drug)
Part 1B - EOS-448 + inupadenant
Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
干预措施: inupadenant (Drug)
Part 1C - EOS-448 + inupadenant
Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
干预措施: EOS-448 (Drug)
Part 1C - EOS-448 + inupadenant
Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
干预措施: inupadenant (Drug)
Part 1D - EOS-448 + dostarlimab
Participants will receive EOS-448 and dostarlimab at every cycle
干预措施: EOS-448 (Drug)
Part 1D - EOS-448 + dostarlimab
Participants will receive EOS-448 and dostarlimab at every cycle
干预措施: Dostarlimab (Drug)
Part 1E - inupadenant HCl + dostarlimab
Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis
干预措施: inupadenant (Drug)
Part 1E - inupadenant HCl + dostarlimab
Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis
干预措施: Dostarlimab (Drug)
Part 1F - EOS-448 + dostarlimab + inupadenant HC
Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis
干预措施: EOS-448 (Drug)
Part 1F - EOS-448 + dostarlimab + inupadenant HC
Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis
干预措施: inupadenant (Drug)
Part 1F - EOS-448 + dostarlimab + inupadenant HC
Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis
干预措施: Dostarlimab (Drug)
Part 1G - EOS-448 + dostarlimab + chemotherapies
Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle
干预措施: EOS-448 (Drug)
Part 1G - EOS-448 + dostarlimab + chemotherapies
Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle
干预措施: Dostarlimab (Drug)
Part 1G - EOS-448 + dostarlimab + chemotherapies
Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle
干预措施: SOC chemotherapies (Drug)
Part 2C - EOS-448 + dostarlimab
Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle
干预措施: EOS-448 (Drug)
Part 2C - EOS-448 + dostarlimab
Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle
干预措施: Dostarlimab (Drug)
Part 2D - EOS-448 + dostarlimab
Participants with 1L mHNSCC 1 < CPS < 20 will receive EOS-448 and dostarlimab at every cycle
干预措施: EOS-448 (Drug)
Part 2D - EOS-448 + dostarlimab
Participants with 1L mHNSCC 1 < CPS < 20 will receive EOS-448 and dostarlimab at every cycle
干预措施: Dostarlimab (Drug)
结局指标
主要结局
Percentage of participants with DLT and Adverse Events
时间窗: From first study treatment administration through Day 21-28 for DLT / Up to 120 days after the last dose
Recommended Phase 2 dose (RP2D) of EOS884448 in participants with advanced solid tumors
时间窗: Up to 48 weeks
Percentage of participants with Objective Response as determined by Investigator
时间窗: Until disease progression - Approximately 48 months
次要结局
- Duration of Response (DOR)(Until disease progression or death - Approximately 48 months)
- Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level(Up to 48 weeks)
- Progression-free-survival (PFS)(Until disease progression or death - Approximately 48 months)
- Disease Control Rate (DCR)(Until disease progression or death - Approximately 48 months)
- Percentage of participants with anti-drug antibodies to EOS884448(Up to 48 weeks)