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NCT06545942PHASE1Recruiting

Study of Orally Administered MOMA-313 in Participants With Advanced or Metastatic Solid Tumors

MOMA Therapeutics

Start Date

8/13/2024

Completion Date

11/30/2027

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-313 administered orally as a single agent or combination therapy in patients with homologous recombinant deficient solid tumors.

Detailed Description

MOMA-313 is a novel therapeutic agent designed to target homologous recombination (HR)-deficient cancers by inhibiting DNA polymerase theta. MOMA-313 is being developed as a single-agent and in combination with a poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors. This phase 1, first-in-human, open-label study of MOMA-313 is primarily intended to evaluate the safety and tolerability of MOMA-313 when administered orally as a single agent (Treatment Arm 1) or in combination with olaparib (Treatment Arm 2). Each treatment arm of the study includes a dose-escalation phase followed by a dose-optimization phase. In the dose-escalation phase of each treatment arm, successive cohorts of patients will receive increasing oral doses of MOMA-313 as a single agent or in combination with olaparib to determine the presumptive optimal biologic dose(s) (OBD) in this population. The dose-optimization phase of each arm will enroll additional patients to support the confirmation of the OBD. The data from this study conducted in patients with HR-deficient advanced (including locally), relapsed or metastatic solid tumors, including safety, tolerability, PK/PDx findings, and antitumor activity, will form the basis for subsequent clinical development of MOMA-313 as a single-agent and in combination with olaparib.

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: 1. Age ≥ 18 years 2. Have histologically confirmed disease for each treatment arm as follows: 1. Treatment Arm 1 (MOMA-313 Monotherapy) \- Advanced (including locally), relapsed or metastatic solid tumors that are not eligible for curative therapy, with any HR-deficient alteration. 2. Treatment Arm 2 (MOMA-313 in Combination with Olaparib): * Dose escalation: Advanced (including locally), relapsed or metastatic solid tumors that are not eligible for curative therapy, for which a PARP inhibitor is indicated, with select HR-deficient mutations. Patients may be PARP inhibitor naive or exposed. * Dose optimization: Advanced (including locally), relapsed or metastatic CRPC or pancreatic ductal adenocarcinoma (PDAC) with select HR-deficient mutations. Patients must be PARP inhibitor naive. 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 Key Exclusion Criteria: 1. Active prior or concurrent malignancy (some exceptions allowed) 2. Clinically relevant cardiovascular disease 3. Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed) 4. Known active infection 5. Prior polymerase theta inhibitor exposure 6. Known allergy, hypersensitivity, and/or intolerance to MOMA-313 7. Olaparib exposed patients with known hypersensitivity to PARP inhibitors (for patients considered for olaparib only) 8. Impaired GI function that may impact absorption. 9. Patient is pregnant or breastfeeding. 10. 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 11. Active liver disease (some exceptions are allowed) 12. 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

Interventions

DRUG

MOMA-313

DRUG

Olaparib

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Conditions

Advanced Solid TumorMetastatic Solid TumorProstate CancerPancreas CancerBreast CancerOvarian CancerHomologous Recombination Deficiency

Locations

Investigative Site #108

Goodyear, Arizona 85338

United States

Investigative Site #101

La Jolla, California 92093

United States

Investigative Site #111

San Francisco, California 94143

United States

Investigative Site #104

Lake Mary, Florida 32746

United States

Investigative Site #110

St Louis, Missouri 63110

United States

Investigative Site #103

New York, New York 10016

United States

Investigative Site #106

New York, New York 10065

United States

Investigative Site #109

Philadelphia, Pennsylvania 19104

United States

Investigative Site #107

Myrtle Beach, South Carolina 29572

United States

Investigative Site #102

Nashville, Tennessee 37203

United States

Investigative Site #105

San Antonio, Texas 78229

United States

Investigative Site #112

Fairfax, Virginia 22031

United States

Investigative Site #114

Barcelona,

Spain

Investigative Site #116

Barcelona,

Spain

Investigative Site #115

Madrid,

Spain

Investigative Site #113

London,

United Kingdom

Investigative Site #117

Manchester,

United Kingdom

Investigative Site #118

Newcastle upon Tyne,

United Kingdom