Clinical trial NCT06974110: Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors
Official title: A Phase 1 Study of MOMA-341 as Monotherapy or Combination Therapy in Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Endometrial Cancer
MSI-H Cancer
Colorectal Cancer
Gastric Cancer
dMMR Cancer
Keywords: Phase 1
MOMA-341
Werner helicase
WRN
Advanced Solid Tumor
Metastatic Solid Tumor
Gastric Cancer
Colorectal Cancer
Endometrial Cancer
MSI-H Cancer
dMMR Cancer
Lead sponsor: MOMA Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-05-15
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

   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)
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

Primary outcomes:
measure: Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation
timeFrame: From screening until treatment discontinuation (up to 35 months)
Secondary outcomes:
measure: Identify the recommended phase 2 dose (RP2D)
timeFrame: From screening until treatment discontinuation (up to 35 months)
measure: PK parameter; area under curve (AUC) of MOMA-341
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter; maximum concentration (Cmax) of MOMA-341
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter; time to maximum concentration (Tmax) of MOMA-341
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter; half-life (T1/2) of MOMA-341
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter; plasma exposure of irinotecan
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: Objective response rate (ORR)
timeFrame: Up to 35 months
measure: Duration of response (DOR)
timeFrame: Up to 35 months
measure: Time to response (TTR)
timeFrame: Up to 35 months
measure: Progression free survival (PFS)
timeFrame: Up to 35 months
measure: Disease control rate (DCR)
timeFrame: Up to 35 months
measure: Overall survival (OS)
timeFrame: Up to 35 months
Other outcomes:
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