A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 4
- 主要终点
- Part III: To evaluate the incidence, severity and relationship of (S)AEs to further assess safety of Sym024 when administered alone or in combination with Sym021.
研究概览
简要总结
The primary purpose of this study is to see if Sym024 is safe and tolerable as monotherapy and in combination with Sym021 in patients with solid tumor malignancies.
详细描述
Part 1 of this study will assess the safety and tolerability to establish the maximum tolerated dose (MTD) (or the maximum administered dose [MAD]) and/or the selected dose(s) of Sym024 in patients with solid tumor malignancies.
Part 2 of this study will assess the safety and tolerability to establish the MTD (or the MAD) and/or the selected dose(s) of Sym024 when administered in combination with Sym021 in patients with solid tumor malignancies.
Part 2a of this study will assess the safety and tolerability of Sym024 when first administered as a single agent during Cycle 1 (safety lead-in) followed by administration in combination with Sym021 during Cycle 2 and subsequent cycles.
Part 3 of this study will assess the safety of Sym024 when administered alone or in combination with Sym021 in expanded cohorts of patients with solid tumor malignancies.
April 2024: The above was the study design at trial start. Per protocol, implementation of a part 3 would require an amendment. However, this was never done as it was decided not to include a part 3.
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
- •Male or female patients, ≥18 years.
- •Documented (histologically or cytologically proven), locally advanced or metastatic solid tumor malignancy (must be one of the following):
- •Squamous cell carcinoma of the head and neck
- •Non-small-cell lung carcinoma-adenocarcinoma histology subtype
- •Pancreatic ductal adenocarcinoma
- •Cholangiocarcinoma
- •Colorectal carcinoma (microsatellite stable [MSS] and microsatellite instability-high [MSI-H] phenotypes)
- •Gastric carcinoma (includes gastroesophageal carcinoma)
- •Esophageal carcinoma (includes squamous cell and adenocarcinoma)
- •Mesothelioma (pleural and peritoneal)
- •Cervical carcinoma (CC) (includes adeno, squamous and mixed adeno-squamous carcinoma histology subtypes)
- •Malignancy that is not currently amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor.
- •Measurable disease according to RECIST v1.
- •Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
- •Agreeing to mandatory tumor tissue biopsies (2 total).
- •ECOG PS of 0 or
- •Adequate organ function as indicated by the following laboratory values.
- •Adequate contraception required as appropriate.
排除标准
- •Central nervous system (CNS) malignancies.
- •Clinically significant cardiovascular disease or condition.
- •Active thrombosis, or a history of deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study drug(s).
- •Active uncontrolled bleeding or a known bleeding diathesis.
- •Significant ocular disease or condition.
- •Significant pulmonary disease or condition.
- •Current or recent (within 6 months) significant gastrointestinal disease or condition.
- •Active, known or suspected autoimmune disease.
- •History of organ transplantation (i.e., stem cell or solid organ transplant).
- •Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- •Any other serious/active/uncontrolled infection.
- •History of significant toxicities associated with previous administration of immune checkpoint inhibitors.
- •Known or suspected hypersensitivity to any of the excipients of formulated study drug.
- •Unresolved >Grade 1 toxicity associated with any prior antineoplastic therapy.
- •Inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to the first dose of study drug(s).
- •Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy).
- •Therapeutic Exclusions
- •Prior therapy with Sym024 or other inhibitors of CD73, CD39 or adenosine receptors ADORA2A, ADORA2B.
- •Part II and Part III, prior anti-PD-(L)1 therapy, except for indications where it is approved.
- •Any antineoplastic agent for the primary malignancy (standard or investigational) within 4 weeks or 5 elimination half-lives.
- •Any other investigational treatments within 2 weeks prior to the first dose of study drug(s).
- •Radiotherapy, with exceptions.
- •Live vaccines against infectious diseases 4 weeks prior to the first dose of study drug(s).
- •Immunosuppressive or systemic glucocorticoids therapy (>10 mg daily prednisone or equivalent) within 2 weeks prior to the first dose of study drug(s), with exceptions.
- •Prophylactic use of hematopoietic growth factors within 1 week prior to the first dose of study drug(s).
研究组 & 干预措施
Sym024 Dose Level 2
Part I, Sym024 monotherapy dose level 2
干预措施: Sym024 (Drug)
Sym024 Dose Level 3
Part I, Sym024 monotherapy dose level 3
干预措施: Sym024 (Drug)
Sym024 Dose Level 4
Part I, Sym024 monotherapy dose level 4
干预措施: Sym024 (Drug)
Sym024 Dose Level -1
Part I, Sym024 monotherapy dose level -1. Evaluate only if needed based on tolerability
干预措施: Sym024 (Drug)
Sym024 Dose Level 1
Part I, Sym024 monotherapy dose level 1
干预措施: Sym024 (Drug)
Sym021+Sym024 Dose Level 2
Part II, Sym021 in combination with dose level 2 of Sym024
干预措施: Sym021 (Drug)
Sym021+Sym024 Dose Level 2
Part II, Sym021 in combination with dose level 2 of Sym024
干预措施: Sym024 (Drug)
Sym021+Sym024 Dose Level 3
Part II, Sym021 in combination with dose level 3 of Sym024
干预措施: Sym021 (Drug)
Sym021+Sym024 Dose Level 3
Part II, Sym021 in combination with dose level 3 of Sym024
干预措施: Sym024 (Drug)
Sym021+Sym024 Dose Level 4
Part II, Sym021 in combination with dose level 4 of Sym024
干预措施: Sym021 (Drug)
Sym021+Sym024 Dose Level 4
Part II, Sym021 in combination with dose level 4 of Sym024
干预措施: Sym024 (Drug)
Sym021+Sym024 Dose Level 5
Part IIa, Sym024 monotherapy and in combination with Sym021
干预措施: Sym021 (Drug)
Sym021+Sym024 Dose Level 5
Part IIa, Sym024 monotherapy and in combination with Sym021
干预措施: Sym024 (Drug)
Sym021+Sym024 Dose Level 1
Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
干预措施: Sym021 (Drug)
Sym021+Sym024 Dose Level 1
Part II, Sym021 in combination with dose level 1 of Sym024. Evaluate only if needed based on tolerability
干预措施: Sym024 (Drug)
Dose Expansion Sym021 (+Sym024)
Part III, dose expansion Sym024 and/or Sym021+Sym024
干预措施: Sym021 (Drug)
Dose Expansion Sym021 (+Sym024)
Part III, dose expansion Sym024 and/or Sym021+Sym024
干预措施: Sym024 (Drug)
结局指标
主要结局
Part III: To evaluate the incidence, severity and relationship of (S)AEs to further assess safety of Sym024 when administered alone or in combination with Sym021.
时间窗: 12 months
Assess the safety and tolerability of Sym024 and/or Sym021+Sym024 on a Q2W schedule. Assessment based on the occurrence of AEs
Part I: To evaluate the incidence, severity and relationship of (S)AEs to establish the MTD/MAD of Sym024 monotherapy.
时间窗: 28 days
Assess the safety and tolerability of Sym024 monotherapy on a Q2W schedule (every two weeks). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1
Part II: To evaluate the incidence, severity and relationship of (S)AEs to establish MTD/MAD of Sym024 in combination with Sym021.
时间窗: 28 days
Assess the safety and tolerability of the sequential escalating doses of Sym024 in combination with Sym021 on a Q2W schedule. Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1
次要结局
- Time to progression (TTP) of disease(24 months)
- Evaluation of the immunogenicity of Sym024 as a single agent and in combination with Sym024(24 months)
- Evaluation of objective response (OR) or stable disease (SD)(24 months)
- Trough concentration (Ctrough)(24 months)
- Terminal elimination half-life (T½)(24 months)
- Clearance (CL)(24 months)
- Maximum concentration (Cmax)(24 months)
- Time to reach maximum concentration (Tmax)(24 months)
- Area under the concentration-time curve in a dosing interval (AUC)(24 months)