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

Phase 1RecruitingNCT06974110

MOMA Therapeutics132 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

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

...and 3 more locations

Outcomes

Primary Outcomes

Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation

To assess the safety and tolerability of MOMA-341 given as a single-agent, and in combination with irinotecan, and in combination with immunotherapy

Time frame: From screening until treatment discontinuation (up to 35 months)

Secondary Outcomes

Identify the recommended phase 2 dose (RP2D)

Determine the RP2D of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy

Time frame: From screening until treatment discontinuation (up to 35 months)

PK parameter; area under curve (AUC) of MOMA-341

Determine the AUC of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy