A Phase 1 Study of MOMA-341 as Monotherapy or Combination Therapy in Participants With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 132
- 试验地点
- 17
- 主要终点
- Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation
研究概览
简要总结
This Phase 1, multi-center, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and preliminary clinical activity of MOMA-341 administered orally as a single agent or combination therapy in patients with microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR) solid tumors.
详细描述
MOMA-341 is a novel therapeutic agent designed to target microsatellite instability high (MSI-H) or DNA mismatch repair deficiency (dMMR) cancers by inhibiting Werner helicase. MOMA-341 is being developed as a single agent and in combination with either chemotherapy or immunotherapy in patients with certain advanced or metastatic solid tumors.
This phase 1, first-in-human, open-label study of MOMA-341 is primarily intended to evaluate the safety and tolerability of MOMA-341 when administered orally as a single agent (Treatment Arm 1), in combination with irinotecan (Treatment Arm 2), or in combination with immunotherapy (Treatment Arm 3). Each treatment arm of the study includes a dose-escalation phase, which means successive cohorts of patients will receive increasing oral doses of MOMA-341 as a single agent or in combination with irinotecan or immunotherapy to determine the presumptive optimal biologic dose(s) (OBD) in this population. The study also includes a dose-optimization phase that will enroll additional patients to support the confirmation of the OBD.
The data from this study conducted in patients with MSI-H or dMMR advanced or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and antitumor activity, will form the basis for subsequent clinical development of MOMA-341 as a single-agent and in combination with irinotecan or immunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age ≥ 18 years
- •Participants have unresectable advanced or metastatic solid tumors with MSI-H or dMMR alterations and histologically confirmed disease. Participants must have previously received and progressed on an anti-PD-(L)1-based regimen, unless ineligible or in a region without access to anti-PD-(L)1 therapies
- •Have at least 1 lesion at baseline (measurable or non-measurable) suitable for repeat imaging evaluation by RECIST and/or PCWG-3
- •ECOG PS ≤ 2
- •Fully recovered from clinically relevant effects of prior therapy, radiotherapy, and/or surgery **hormonal therapy allowed. Palliative radiotherapy allowed
- •Adequate organ function per local labs
- •Comply with contraception requirements
- •Written informed consent must be obtained according to local guidelines
排除标准
- •Known Werner Syndrome
- •Active prior or concurrent advanced-stage malignancy (some exceptions allowed including early-stage cancers)
- •Clinically relevant cardiovascular disease
- •Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed)
- •Known active uncontrolled infection
- •Known allergy, hypersensitivity, and/or intolerance to MOMA-341
- •Impaired GI function that may impact absorption
- •Patient is pregnant or breastfeeding
- •Known to be HIV positive, unless all of the following criteria are met:
- •Undetectable viral load or CD4+ count ≥300 cells/μL
- •Receiving highly active antiretroviral therapy
- •No AIDS-related illness within the past 12 months
- •Active liver disease (some exceptions are allowed)
- •Prior or ongoing condition, therapy, or laboratory abnormality that, in the investigator's opinion, may affect safety of the patient, confound the results of the study, and/or interfere with the patients participation in the study
研究组 & 干预措施
MOMA-341 in Combination with Immunotherapy (Treatment Arm 3)
MOMA-341 administered together with immunotherapy in 21-day cycles
干预措施: Immunotherapy (Drug)
MOMA-341 Monotherapy (Treatment Arm 1)
MOMA-341 administered as a single agent in 21-day cycles
干预措施: MOMA-341 (Drug)
MOMA-341 in Combination with Irinotecan (Treatment Arm 2)
MOMA-341 administered together with irinotecan in 28-day cycles
干预措施: Irinotecan (Drug)
MOMA-341 in Combination with Immunotherapy (Treatment Arm 3)
MOMA-341 administered together with immunotherapy in 21-day cycles
干预措施: MOMA-341 (Drug)
MOMA-341 in Combination with Irinotecan (Treatment Arm 2)
MOMA-341 administered together with irinotecan in 28-day cycles
干预措施: MOMA-341 (Drug)
结局指标
主要结局
Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation
时间窗: From screening until treatment discontinuation (up to 35 months)
To assess the safety and tolerability of MOMA-341 given as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
次要结局
- Identify the recommended phase 2 dose (RP2D)(From screening until treatment discontinuation (up to 35 months))
- PK parameter; area under curve (AUC) of MOMA-341(Up to 6 weeks with sparse sampling up to 35 months)
- PK parameter; maximum concentration (Cmax) of MOMA-341(Up to 6 weeks with sparse sampling up to 35 months)
- PK parameter; time to maximum concentration (Tmax) of MOMA-341(Up to 6 weeks with sparse sampling up to 35 months)
- PK parameter; half-life (T1/2) of MOMA-341(Up to 6 weeks with sparse sampling up to 35 months)
- PK parameter; plasma exposure of irinotecan(Up to 6 weeks with sparse sampling up to 35 months)
- Objective response rate (ORR)(Up to 35 months)
- Duration of response (DOR)(Up to 35 months)
- Time to response (TTR)(Up to 35 months)
- Progression free survival (PFS)(Up to 35 months)
- Disease control rate (DCR)(Up to 35 months)
- Overall survival (OS)(Up to 35 months)