Study of Orally Administered MOMA-341 in Participants With Advanced or Metastatic Solid Tumors
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.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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: 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
- 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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT06974110
Intervention or treatment
DRUG: MOMA-341
DRUG: Irinotecan
DRUG: Immunotherapy
Conditions
- Advanced Solid Tumor
- Metastatic Solid Tumor
- Endometrial Cancer
- MSI-H Cancer
- Colorectal Cancer
- Gastric Cancer
- dMMR Cancer
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Investigative Site #122
Select from list below to view details:
Investigative Site #122
Sydney, New South Wales, Australia
Investigative Site #123
Westmead, New South Wales, Australia
Investigative Site #124
Woolloongabba, Queensland, Australia
Investigative Site #125
Adelaide, South Australia, Australia
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Who is running the clinical trial?
MOMA Therapeutics
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: MOMA-341 Monotherapy (Treatment Arm 1)
| Drug: MOMA-341 |
EXPERIMENTAL: MOMA-341 in Combination with Irinotecan (Treatment Arm 2)
| Drug: MOMA-341, Drug: Irinotecan |
EXPERIMENTAL: MOMA-341 in Combination with Immunotherapy (Treatment Arm 3)
| Drug: MOMA-341, Drug: Immunotherapy |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 | From screening until treatment discontinuation (up to 35 months) |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | Up to 6 weeks with sparse sampling up to 35 months |
| PK parameter; maximum concentration (Cmax) of MOMA-341 | Determine the Cmax of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy | Up to 6 weeks with sparse sampling up to 35 months |
| PK parameter; time to maximum concentration (Tmax) of MOMA-341 | Determine the Tmax of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy | Up to 6 weeks with sparse sampling up to 35 months |
| PK parameter; half-life (T1/2) of MOMA-341 | Determine the T1/2 of MOMA-341 as a single-agent, and in combination with irinotecan, and in combination with immunotherapy | Up to 6 weeks with sparse sampling up to 35 months |
| PK parameter; plasma exposure of irinotecan | Determine the plasma exposure of irinotecan in combination with MOMA-341 | Up to 6 weeks with sparse sampling up to 35 months |
| Objective response rate (ORR) | 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) | Up to 35 months |
| Duration of response (DOR) | 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 | Up to 35 months |
| Time to response (TTR) | 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) | Up to 35 months |
| Progression free survival (PFS) | 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 | Up to 35 months |
| Disease control rate (DCR) | 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 | Up to 35 months |
| Overall survival (OS) | OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death | Up to 35 months |
References
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