NCT04328844进行中（未招募）1 期
First-in-Human Dose Study of IOA-244 in Patients With Advanced or Metastatic Cancers
iOnctura5 个研究点 分布在 2 个国家目标入组 210 人开始时间: 2020年2月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 210
- 试验地点
- 5
- 主要终点
- Numbers of participants with treatment-related adverse events as assessed by CTCAE v5.0
研究概览
简要总结
The objective of study IOA-244-101 is to determine whether IOA-244 is safe and tolerable in cancer patients (Part A). In addition, the study will assess whether IOA-244 can increase the anti-tumour immune response in patients both as monotherapy and in combination pemetrexed/cisplatin/avelumab (Part B Mesothelioma and NSCLC 1st line), in combination with avelumab (Part B Cutaneous Melanoma and NSCLC 2nd/3rd line) and ruxolitinib (Part B Primary Myelofibrosis)
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
- •≥18 years of age inclusive, at the time of signing the informed consent.
- •Capable of giving signed informed consent, which includes compliance with the requirements of this protocol.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •For patients with NHL, ECOG 2 will be allowed.
- •Patients with histologically or cytologically confirmed advanced or metastatic malignancies (including histologically confirmed, unresectable Stage III or IV melanoma); see following details for each malignancy:
- •For Patients with cutaneous and mucosal melanoma:
- •Baseline lactate dehydrogenase levels are available.
- •Disease progression is confirmed and they are eligible for second- or third-line treatment:
- •After first-line treatment and progression on approved programmed cell death-1 (PD-1) or cytotoxic T lymphocyte antigen-4 (CTLA-4) or combination of PD-1 and CTLA-4-pathway targeted agent.
- •After second-line treatment and progression on prior BRAF V600 mutation targeted agent followed by PD-1 or CTLA-4-pathway targeted agent (Note: There is no mandatory sequence of these approved treatments).
- •No clinically significant tumour-related symptoms.
- •For Patients with metastatic ocular/uveal melanoma:
- •Patients must have metastatic histologically or cytologically confirmed uveal melanoma.
- •For Patients with advanced or metastatic mesothelioma:
- •Histological confirmation of mesothelioma (any subtype).
- •Part A: They received at least one prior line of treatment (including patients who were re-challenged with pemetrexed-based therapy). Prior maintenance therapy is permitted but will not count as a line of treatment.
- •Part B: Considered for first-line treatment with pemetrexed/cisplatin and avelumab.
- •For Patients with Indolent Non-Hodgkin Lymphoma, type Follicular Lymphoma (FL):
- •Patients must have a past diagnosis of indolent Non-Hodgkin lymphoma, type Follicular Lymphoma, Grade 1-3A.(Dreyling et al., 2016)
- •Patients must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy, such as rituximab monotherapy, chemotherapy given with or without rituximab, radioimmunoconjugates (e.g., 90Y-ibritumomab tiuxetan and 131I-tositumomab).
- •Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose).
- •Patients with prior exposure to a PI3K inhibitor (e.g., idelalisib/GS-1101, duvelisib) or a Bruton's tyrosine kinase (BTK) inhibitor are eligible if they discontinued either inhibitors in the last 4 weeks prior entering study treatment.
- •Patients are not eligible for transplantation (autologous or any similar intervention, including CART-cell therapy).
- •For Patients with Non-Hodgkin Lymphoma, type Peripheral T cell lymphoma (PTCL):
- •Diagnosis of one of the following histologic subtypes of PTCL, pathologically-confirmed, as defined by the World Health Organization (other rare PTCL may be enrolled upon discussion with the medical monitor of this study):
- •Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS)
- •Angioimmunoblastic T-cell lymphomas (AITL)
- •Anaplastic large cell lymphoma (ALCL)
- •Natural-killer/T-cell lymphoma (NKTL)
- •Received at least 2 cycles of one prior regimen administered with curative intent and one of the following:
- •failed to achieve at least a partial response after 2 or more cycles;
- •failed to achieve a complete response after 6 or more cycles; and/or
- •progressed after an initial response.
- •For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin.
- •Measurable disease as defined by IWG for PTCL, i.e., at least 1 measurable disease lesion > 1.5 cm in at least one dimension by 18FDG-PET-CT, MRI, or diagnostic CT.
- •Patients with prior exposure to a PI3K inhibitor (e.g., idelalisib/GS-1101, duvelisib) or a Bruton's tyrosine kinase (BTK) inhibitor are eligible if they discontinued either inhibitors in the last 4 weeks prior entering study treatment.
- •For Patients with Non-Small Cell Lung Cancer (NSCLC) 1st line:
- •Histological diagnosis of locally advanced (primary or recurrent) NSCLC non-squamous not amenable for treatment with curative intent.
- •No prior systemic treatment for unresectable locally advanced or metastatic disease for NSCLC.
- •Non-squamous NSCLC, with no activating EGFR mutations, ALK or ROS1 translocations/rearrangements.
- •If monotherapy pembrolizumab is available as a standard of care treatment option, patients must have a tumour proportion score (TPS) <50% for PD-L1 (e.g., via the 22C3 pharmDx or the Ventana (SP263) PD-L1 IHC assay, or any other approved IHC assay.
- •For Patients with Non-Small Cell Lung Cancer (NSCLC) 2nd or 3rd line:
- •Histological confirmed Stage IIIb/IV or recurrent NSCLC who have experienced disease progression.
- •Considered for 2nd line or 3rd line treatment either after radiographic progression or on stable disease:
- •Participants must have progressed after a minimum of 2 cycles of 1 course of a platinum based combination therapy administered for the treatment of a metastatic disease.
- •For Patients with Primary Myelofibrosis (PMF):
- •Diagnosis of PMF, Post-Polycythemia Vera Myelofibrosis MF(PPV-MF), or post-essential thrombocythemia MF (PET-MF)
- •Dynamic International Prognostic Scoring System (DIPSS) risk category of intermediate-1, intermediate-2, or high.
- •Treated with ruxolitinib for ≥ 3 months with a stable dose for at least the last 8 weeks prior to Day 1 and no significant spleen reduction (e.g., less than 15% spleen size reduction, or corresponding lack of response in spleen volume).
- •Did not receive experimental drug therapy for MF or any other drug considered as an effective treatment for MF (eg, danazol, hydroxyurea, interferon products) within the last 2 months prior to starting study treatment.
- 另有 15 项未显示
排除标准
- 未提供
研究组 & 干预措施
Group 1: Cutaneous Melanoma
Experimental
IOA-244 in combination with avelumab
干预措施: Avelumab Injection (Drug)
Group 1: Cutaneous Melanoma
Experimental
IOA-244 in combination with avelumab
干预措施: IOA-244 (Drug)
Group 2: Uveal Melanoma
Experimental
IOA-244 as monotherapy
干预措施: IOA-244 (Drug)
Group 5: NSCLC 1st line
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: IOA-244 (Drug)
Group 4: Mesothelioma
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: IOA-244 (Drug)
Group 4: Mesothelioma
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Avelumab Injection (Drug)
Group 7: NHL-FL and NHL-PTCL
Experimental
IOA-244 as monotherapy
干预措施: IOA-244 (Drug)
Group 3: Myelofibrosis
Experimental
IOA-244 in combination with ruxolitinib
干预措施: IOA-244 (Drug)
Group 5: NSCLC 1st line
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Avelumab Injection (Drug)
Group 6: NSCLC 2nd/3rd line
Experimental
IOA-244 in combination with avelumab
干预措施: IOA-244 (Drug)
Group 6: NSCLC 2nd/3rd line
Experimental
IOA-244 in combination with avelumab
干预措施: Avelumab Injection (Drug)
Group 4: Mesothelioma
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Pemetrexed (Drug)
Group 3: Myelofibrosis
Experimental
IOA-244 in combination with ruxolitinib
干预措施: Ruxolitinib (Drug)
Group 4: Mesothelioma
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Cisplatin (Drug)
Group 5: NSCLC 1st line
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Pemetrexed (Drug)
Group 5: NSCLC 1st line
Experimental
IOA-244 in combination with pemetrexed/cisplatin/avelumab
干预措施: Cisplatin (Drug)
结局指标
主要结局
Numbers of participants with treatment-related adverse events as assessed by CTCAE v5.0
时间窗: From time of first drug administration to first documented progression, toxicity or death from any cause whichever occurs first, assessed at week 30
Adverse Events will be assessed by nondirective questioning of the participants during the screening process, at each visit during the study and during the safety follow up period
次要结局
- Cmax(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- Pharmacodynamic activity of IOA-244 by evaluating levels of Mesothelin(At Cycle 1, Day 1 and Day 15 (pre-dose) , From Cycle 2 to Cycle 6, Day 1 (pre-dose). Each cycle is 28 days)
- Overall Survival (OS)(From date of the first dose of study treatment until the date of death from any cause, assessed up to 150 weeks)
- t½(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- AUC0-∞(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- Pharmacodynamic activity of IOA-244 by determining changes in Lymphocytes counts(At Cycle 1 Day 1, Day 2, Day 15 (pre-dose), From Cycle 2 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- Cmin(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- Pharmacodynamic activity of IOA-244 by determining changes in LDH(At Screening (D-28 to D-1), Cycle 1 Day 1, Day 8, Day 15, Day 22 (pre-dose). Each cycle is 28 days)
- Duration of response (DOR)(From date of the first documented evidence of CR or PR until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 54 weeks)
- tmax(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- AUC0-t(At Cycle 1 Day 1: 0 hours (pre-dose),1 hour, 2 hours, 3-4 hours and 6-8 hours post dose. From Cycle 2 Day 1 to Cycle 6 Day 1 (pre-dose). Each cycle is 28 days)
- Objective Response Rate (ORR)(Up to 28 weeks)
- Progression Free Survival (PFS)(From date of the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 104 weeks)
研究者
研究点 (5)
Loading locations...
相似试验
已完成
1 期
Study to Evaluate the Safety and Anti-tumor Activity of SCC244Advanced Solid TumorNCT03466268Haihe Biopharma Co., Ltd.56
已完成
1 期
A Study to Evaluate the Safety and Tolerability of ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal DetachmentRhegmatogenous Retinal Detachment - Macula OffNCT03780972ONL Therapeutics14
终止
1 期
A Study to Find the Maximum Tolerated Dose of the Experimental Combination of the Drugs INC424 and BKM120 in Patients With Primary or Secondary MyelofibrosisMyelofibrosisNCT01730248Novartis Pharmaceuticals63
已完成
1 期
A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacology of ONO-4474 in Healthy VolunteersOsteoarthritisNCT02454387Ono Pharmaceutical Co. Ltd141
已完成
1 期
Study of IPH4102 in Patients With Relapsed/Refractory Cutaneous T-cell Lymphomas (CTCL)Cutaneous T-Cell LymphomaNCT02593045Innate Pharma44