A Phase 1 Study of MOMA-313 Given as Monotherapy or in Combination With a PARP Inhibitor 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
- 220
- 试验地点
- 34
- 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-313 administered orally as a single agent or combination therapy in patients with homologous recombinant deficient solid tumors.
详细描述
MOMA-313 is a novel therapeutic agent designed to target homologous recombination (HR)-deficient cancers by inhibiting DNA polymerase theta. MOMA-313 is being developed as a single-agent and in combination with a poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors.
This phase 1, first-in-human, open-label study of MOMA-313 is primarily intended to evaluate the safety and tolerability of MOMA-313 when administered orally as a single agent (Treatment Arm 1) or in combination with olaparib (Treatment Arm 2). Each treatment arm of the study includes a dose-escalation phase followed by a dose-optimization phase. In the dose-escalation phase of each treatment arm, successive cohorts of patients will receive increasing oral doses of MOMA-313 as a single agent or in combination with olaparib to determine the presumptive optimal biologic dose(s) (OBD) in this population. The dose-optimization phase of each arm will enroll additional patients to support the confirmation of the OBD.
The data from this study conducted in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and antitumor activity, will form the basis for subsequent clinical development of MOMA-313 as a single-agent and in combination with olaparib.
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
- •Age ≥ 18 years
- •Have histologically confirmed disease for each treatment arm as follows:
- •Treatment Arm 1 (MOMA-313 Monotherapy)
- •- Advanced (including locally), relapsed or metastatic solid tumors that are not eligible for curative therapy, with any HR-deficient alteration.
- •Treatment Arm 2 (MOMA-313 in Combination with Olaparib):
- •Dose escalation: Advanced (including locally), relapsed or metastatic solid tumors that are not eligible for curative therapy, for which a PARP inhibitor is indicated, with select HR-deficient mutations. Patients may be PARP inhibitor naive or exposed.
- •Dose optimization: Advanced (including locally), relapsed or metastatic CRPC or pancreatic ductal adenocarcinoma (PDAC) with select HR-deficient mutations. Patients must be PARP inhibitor naive.
- •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
- •Active prior or concurrent malignancy (some exceptions allowed)
- •Clinically relevant cardiovascular disease
- •Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed)
- •Known active infection
- •Prior polymerase theta inhibitor exposure
- •Known allergy, hypersensitivity, and/or intolerance to MOMA-313
- •Olaparib exposed patients with known hypersensitivity to PARP inhibitors (for patients considered for olaparib only)
- •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-313 in Combination with Olaparib (Treatment Arm 2)
MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.
干预措施: Olaparib (Drug)
MOMA-313 in Combination with Olaparib (Treatment Arm 2)
MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.
干预措施: MOMA-313 (Drug)
MOMA-313 Monotherapy (Treatment Arm 1)
MOMA-313 administered as a single-agent in 21-day cycles.
干预措施: MOMA-313 (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-313 given as a single-agent or in combination with olaparib
次要结局
- PK parameter: area under curve (AUC) of MOMA-313(Up to 6 weeks with sparse sampling up to 35 months)
- PK parameter: maximum concentration (Cmax) of MOMA-313(Up to 6 weeks with sparse sampling up to 35 months)
- Identify the recommended phase 2 dose (RP2D)(From screening until treatment discontinuation (up to 35 months))
- PK parameter: time to maximum concentration of MOMA-313(Up to 6 weeks with sparse sampling up to 35 months)
- Plasma concentration of olaparib(Up to 6 weeks with sparse sampling up to 35 months)
- Objective response rate (ORR)(Up to 35 months)
- Disease control rate (DCR)(Up to 35 months)
- Overall survival (OS)(Up to 35 months)
- Duration of response (DOR)(Up to 35 months)
- Progression free survival (PFS)(Up to 35 months)
- PK parameter: half-life of MOMA-313(Up to 6 weeks with sparse sampling up to 35 months)
- Time to response (TTR)(Up to 35 months)