Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors

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.

Inclusion criteria

• 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

Exclusion criteria

• 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