Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors
- Conditions
- Advanced Solid TumorMetastatic Solid TumorEndometrial CancerMSI-H CancerColorectal CancerGastric CancerdMMR Cancer
- Interventions
- Registration Number
- NCT06974110
- Lead Sponsor
- MOMA Therapeutics
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 132
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Age ≥ 18 years
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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
a. Prior anti-PD(L)1-based regimen is not required if participant is ineligible for anti-PD(L)1-based regimen (eg, due to autoimmune conditions)
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Have at least 1 lesion at baseline (measurable or non-measurable) suitable for repeat imaging evaluation by RECIST and/or PCWG-3
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ECOG PS ≤ 2
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Fully recovered from clinically relevant effects of prior therapy, radiotherapy, and/or surgery **hormonal therapy allowed. Palliative radiotherapy allowed
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Adequate organ function per local labs
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Comply with contraception requirements
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Written informed consent must be obtained according to local guidelines
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Known Werner Syndrome
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Active prior or concurrent advanced-stage malignancy (some exceptions allowed including early-stage cancers)
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Clinically relevant cardiovascular disease
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Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed)
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Known active uncontrolled infection
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Known allergy, hypersensitivity, and/or intolerance to MOMA-341
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Impaired GI function that may impact absorption
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Patient is pregnant or breastfeeding
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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
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Active liver disease (some exceptions are allowed)
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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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MOMA-341 Monotherapy (Treatment Arm 1) MOMA-341 MOMA-341 administered as a single agent in 21-day cycles MOMA-341 in Combination with Irinotecan (Treatment Arm 2) MOMA-341 MOMA-341 administered together with irinotecan in 28-day cycles MOMA-341 in Combination with Irinotecan (Treatment Arm 2) Irinotecan MOMA-341 administered together with irinotecan in 28-day cycles MOMA-341 in Combination with Immunotherapy (Treatment Arm 3) MOMA-341 MOMA-341 administered together with immunotherapy in 21-day cycles MOMA-341 in Combination with Immunotherapy (Treatment Arm 3) Immunotherapy MOMA-341 administered together with immunotherapy in 21-day cycles
- Primary Outcome Measures
Name Time Method Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation 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
- Secondary Outcome Measures
Name Time Method Identify the recommended phase 2 dose (RP2D) From screening until treatment discontinuation (up to 35 months) Determine the RP2D of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
PK parameter; area under curve (AUC) of MOMA-341 Up to 6 weeks with sparse sampling up to 35 months Determine the AUC of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
PK parameter; maximum concentration (Cmax) of MOMA-341 Up to 6 weeks with sparse sampling up to 35 months Determine the Cmax of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
PK parameter; time to maximum concentration (Tmax) of MOMA-341 Up to 6 weeks with sparse sampling up to 35 months Determine the Tmax of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
PK parameter; half-life (T1/2) of MOMA-341 Up to 6 weeks with sparse sampling up to 35 months Determine the T1/2 of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy
PK parameter; plasma exposure of irinotecan Up to 6 weeks with sparse sampling up to 35 months Determine the plasma exposure of irinotecan in combination with MOMA-341
Objective response rate (ORR) Up to 35 months ORR is defined as the percentage of subjects with evidence of a complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and/or Prostate Cancer Working Group-3 (PCWG-3)
Duration of response (DOR) Up to 35 months DOR is defined as time from first documented PR or better to disease progression (as assessed by RECIST v1.1 and/or PCWG-3 by Investigator assessment) or death, whichever is earlier, for participants who have achieved a CR or PR
Time to response (TTR) Up to 35 months TTR is defined as the period of time from the date of first dose of study treatment until the first objective documentation of a CR or PR per RECIST 1.1 and/or PCWG-3)
Progression free survival (PFS) Up to 35 months PFS is defined as the time from first dose of study treatment to progressive disease or death from any cause, whichever is earlier, as assessed by RECIST 1.1 and/or PCWG-3 by investigator assessment
Disease control rate (DCR) Up to 35 months DCR is defined as the proportion of subjects who achieved either CR, PR, or stable disease (SD) at the first scheduled disease assessment according to disease-specific response criteria
Overall survival (OS) Up to 35 months OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death