A First-in-Human, Two-Part, Open-Label, Phase I/II Study of DSP107 in Subjects with Advanced Solid Tumors Including a Dose-escalation Safety Study (part 1) and Preliminary Efficacy Assessment of DSP107 As Monotherapy and in Combination with Atezolizumab (part 2)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 125
- 试验地点
- 7
- 主要终点
- Adverse Events (AEs)
研究概览
简要总结
Part 1: A first-in-human, open-label, Phase I dose escalation study of DSP107 monotherapy and combination therapy with atezolizumab in patients with advanced solid tumors.
Part 2: Preliminary efficacy assessment of DSP107 in combination with atezolizumab in second or third line treatment of non small cell lung cancer. Preliminary efficacy assessment of DSP107 as a single agent or in combination with atezolizumab in third line treatment of colorectal cancer.
详细描述
This study will be the first time that DSP107 is administered to human subjects. The aim of the study is to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of DSP107 monotherapy and combination therapy in a two-part design.
Part 1 will involve DSP107 monotherapy dose escalation in subjects with advanced solid tumors that are not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit. Additional dose finding cohorts will be enrolled to establish a safe dose of DSP107 when given in combination with atezolizumab.
Part 2 will comprise two expansion cohorts:
A) Expansion cohort A consisting of one treatment arm in which subjects will be treated with DSP107 in combination with atezolizumab. This expansion cohort will enroll subjects with non small cell lung cancer who have progressed following no more than 2 lines of prior systemic treatment including treatment with PD-1 or PD-L1 targeting agents.
B) Expansion cohort B consisting of two treatment arms in which subjects will be treated either with DSP107 monotherapy or DSP107 in combination with atezolizumab. This expansion cohort will enroll subjects with colorectal cancer who have progressed following two previous lines of therapy.
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
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Subject must have measurable disease per RECIST version 1.1
- •o Histologically confirmed advanced solid tumor that is not amenable to surgical resection or other approved therapeutic options that have demonstrated clinical benefit or subject is intolerant or has refused available therapies
- •Part 2, Expansion Cohort A:
- •Histologically confirmed, inoperable non-small cell lung cancer (Stage 3b or Stage 4). Squamous and non-squamous histologies are both acceptable
- •Wildtype for actionable oncogenic driver mutations (e.g., ALK, EGFR, ROS1, RET, NTRK). Driver mutations for KRAS, BRAF and c-METex14skip will be allowed.
- •Received no more than 2 lines of prior systemic treatment, including anti PD-1 or anti PD-L1 therapeutic agent ± chemotherapy. Targeted therapies for KRAS, BRAF and c-METex14skip will not be counted towards the previous lines of therapy.
- •Part 2, Expansion Cohort B:
- •Histologically confirmed, inoperable microsatellite stable colorectal carcinoma (Stage 3b or Stage 4)
- •Received two previous lines of therapy including standard chemotherapy and/or targeted antibodies
排除标准
- •Life expectancy of ≤ 3 months
- •Central nervous system (CNS) metastases
- •Life-threatening (grade 4) immune-mediated adverse event related to prior immunotherapy
- •Immune-mediated adverse reaction that required discontinuation of prior immunotherapy
- •Past or current history of autoimmune disease or immune deficiency
- •History of autoimmune hemolytic anemia or autoimmune thrombocytopenia
- •History of hematological malignancy
- •History of organ or stem cell transplantation
- •Clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease and inherited liver disease
- •Previously treatment with CAR-T cells
- •Treatment with systemic immunosuppressive medication within 2 weeks prior to first dose of study treatment
- •Received live, attenuated vaccine within 4 weeks prior to first dose of study treatment
- •Treatment with systemic immunostimulatory agents within 4 weeks prior to first dose of study treatment
- •Treatment with atezolizumab, any CD47/SIRPα targeting agent or immune agonists (e.g., anti-CD137, anti-CD40, anti-OX40)
- •Known allergy or hypersensitivity to any of the test compounds, materials or contraindication to test product
- •Clinically significant abnormal laboratory safety tests
- •Detection of anti DSP107 antibodies at screening
- •History of HIV infection or active Hepatitis B or C infection
- •Pregnant or breast feeding or planning to become pregnant while enrolled in the study
- •History or evidence of any other clinically unstable/uncontrolled disorder, condition, or disease
研究组 & 干预措施
DSP107 monotherapy in advanced solid tumors
DSP107 will be administered by intravenous infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle for up to 12 treatment cycles. Starting dose will be 0.01 mg/kg and maximum dose will not exceed 10 mg/kg.
干预措施: DSP107 (Biological)
DSP107 in combination with atezolizumab in advanced solid tumors
DSP107 will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: DSP107 (Biological)
DSP107 in combination with atezolizumab in non-small cell lung cancer
DSP107 10mg/kg will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: DSP107 (Biological)
DSP107 in combination with atezolizumab in advanced solid tumors
DSP107 will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: Atezolizumab (Biological)
DSP107 monotherapy in colorectal cancer
DSP107 10mg/kg will be administered by intravenous infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle for up to 12 treatment cycles..
干预措施: DSP107 (Biological)
DSP107 in combination with atezolizumab in non-small cell lung cancer
DSP107 10mg/kg will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: Atezolizumab (Biological)
DSP107 in combination with atezolizumab in colorectal cancer
DSP107 10mg/kg will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: DSP107 (Biological)
DSP107 in combination with atezolizumab in colorectal cancer
DSP107 10mg/kg will be administered by IV infusion over 1 hour on Days 1, 8 and 15 of each 21-day cycle. Subjects will receive atezolizumab 1200 mg by intravenous infusion over 30 mins (first infusion over 1 hour) on Day 1 of every treatment cycle. DSP107 infusion will commence 1 hour following completion of atezolizumab infusion. The study will include up to 12 treatment cycles.
干预措施: Atezolizumab (Biological)
结局指标
主要结局
Adverse Events (AEs)
时间窗: Duration of the study, estimated to be 9 months
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Dose Limiting Toxicities (DLT)
时间窗: At the end of Treatment Cycle 1 (each cycle is 21 days)
A DLT is defined as a clinically significant AE of laboratory abnormality that is related to DSP107 or the combination of DSP107 and atezolizumab, but is unrelated to disease progression, intercurrent illness or concomitant medications
DSP107 Serum Concentration
时间窗: At the end of Treatment Cycle 8 (each cycle is 21 days)
Serum samples will be collected to determine circulating levels and PK profile of DSP107
次要结局
- DSP107 Effect on Phenotypic and Activation Profiles of Peripheral Blood Mononuclear Cells(At the end of Treatment Cycle 8 (each cycle is 21 days))
- DSP107 and atezolizumab anti-drug antibody (ADA) formation(Duration of the study, estimated to be 9 months)
- Preliminary Efficacy (Part 2 only)(Duration of the study, estimated to be 12 months)