Oral MOMA-341 for advanced or metastatic MSI-H or dMMR solid tumors

A Phase 1 Study of MOMA-341 as Monotherapy or Combination Therapy in Participants With Advanced or Metastatic Solid Tumors

This trial will test whether the oral drug MOMA-341, alone or with irinotecan or immunotherapy, can be safe and show anti-tumor activity in adults with advanced or metastatic MSI-H/dMMR solid tumors who have progressed after prior PD-(L)1 therapy.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 132 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: MOMA Therapeutics (industry)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 14 sites (San Diego, California and 13 other locations)
• Trial ID: NCT06974110 on ClinicalTrials.gov

What this trial studies

MOMA-341 is a novel oral agent that targets Werner helicase (WRN) to exploit vulnerabilities in microsatellite instability-high (MSI-H) or mismatch repair–deficient (dMMR) cancers. This first-in-human, open-label Phase 1 study uses dose-escalation and dose-optimization cohorts to measure safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. The drug will be tested as a single agent and in combination with irinotecan or with immunotherapy across successive dose cohorts to identify presumptive optimal biologic doses. Safety, PK/PDx, and antitumor activity data will inform subsequent clinical development.

Who should consider this trial

Good fit: Adults (≥18) with unresectable advanced or metastatic histologically confirmed MSI-H or dMMR solid tumors, at least one lesion for imaging, ECOG performance status ≤2, adequate organ function, and prior progression on anti-PD-(L)1 therapy (unless ineligible) are the intended participants.

Not a fit: Patients without MSI-H/dMMR tumors, those with known Werner syndrome, uncontrolled or active other advanced-stage cancers, poor organ function, or ECOG >2 are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, MOMA-341 could become a new targeted oral treatment option for MSI-H/dMMR advanced tumors, potentially improving responses when used alone or with chemotherapy or immunotherapy.

How similar studies have performed: Preclinical studies show WRN inhibition selectively kills MSI-H/dMMR cancer cells, but clinical data for WRN-targeted therapies are very limited, making this a novel first-in-human effort.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years
2. 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
3. Have at least 1 lesion at baseline (measurable or non-measurable) suitable for repeat imaging evaluation by RECIST and/or PCWG-3
4. ECOG PS ≤ 2
5. Fully recovered from clinically relevant effects of prior therapy, radiotherapy, and/or surgery \*\*hormonal therapy allowed. Palliative radiotherapy allowed
6. Adequate organ function per local labs
7. Comply with contraception requirements
8. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Known Werner Syndrome
2. Active prior or concurrent advanced-stage malignancy (some exceptions allowed including early-stage cancers)
3. Clinically relevant cardiovascular disease
4. Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed)
5. Known active uncontrolled infection
6. Known allergy, hypersensitivity, and/or intolerance to MOMA-341
7. Impaired GI function that may impact absorption
8. Patient is pregnant or breastfeeding
9. Known to be HIV positive, unless all of the following criteria are met:

   1. Undetectable viral load or CD4+ count ≥300 cells/μL
   2. Receiving highly active antiretroviral therapy
   3. No AIDS-related illness within the past 12 months
10. Active liver disease (some exceptions are allowed)
11. 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

Where this trial is running

San Diego, California and 13 other locations

• Investigative Site #101 — San Diego, California, United States (RECRUITING)
• Investigative Site #128 — Tampa, Florida, United States (RECRUITING)
• Investigative Site #120 — Detroit, Michigan, United States (RECRUITING)
• Investigative Site #110 — St Louis, Missouri, United States (RECRUITING)
• Investigative Site #131 — Raleigh, North Carolina, United States (RECRUITING)
• Investigative Site #121 — Portland, Oregon, United States (RECRUITING)
• Investigative Site #127 — Dallas, Texas, United States (RECRUITING)
• Investigative Site #129 — Houston, Texas, United States (RECRUITING)
• Investigative Site #122 — Sydney, New South Wales, Australia (RECRUITING)
• Investigative Site #123 — Westmead, New South Wales, Australia (RECRUITING)
• Investigative Site #124 — Woolloongabba, Queensland, Australia (RECRUITING)
• Investigative Site #125 — Adelaide, South Australia, Australia (RECRUITING)
• Investigative Site #126 — Clayton, Victoria, Australia (RECRUITING)
• Investigative Site #119 — Perth, Western Australia, Australia (RECRUITING)

Study contacts

• Study coordinator: MOMA Clinical Trials

Conditions: Advanced Solid Tumor, Metastatic Solid Tumor, Endometrial Cancer, MSI-H Cancer, Colorectal Cancer, Gastric Cancer, dMMR Cancer, Phase 1