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

A Phase 1 Study of MOMA-313 Given as Monotherapy or in Combination With a PARP Inhibitor 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-313 administered orally as a single agent or combination therapy in patients with homologous recombinant deficient solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Ovarian Cancer; Prostate Cancer; Advanced Solid Tumor; Metastatic Solid Tumor; Pancreas Cancer; Homologous Recombination Deficiency
• Intervention / Treatment: Drug: MOMA-313; Drug: Olaparib

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.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 1

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain
    • Investigative Site #114
  • Barcelona, Spain
    • Investigative Site #116
  • Madrid, Spain
    • Investigative Site #115
• United Kingdom
  • London, United Kingdom
    • Investigative Site #113
  • Manchester, United Kingdom
    • Investigative Site #117
  • Newcastle upon Tyne, United Kingdom
    • Investigative Site #118
• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Investigative Site #108
  • California
    • La Jolla, California, United States, 92093
      • Investigative Site #101
    • San Francisco, California, United States, 94143
      • Investigative Site #111
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Investigative Site #104
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Investigative Site #110
  • New York
    • New York, New York, United States, 10016
      • Investigative Site #103
    • New York, New York, United States, 10065
      • Investigative Site #106
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Investigative Site #109
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Investigative Site #107
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Investigative Site #102
  • Texas
    • San Antonio, Texas, United States, 78229
      • Investigative Site #105
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Investigative Site #112

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOMA-313 Monotherapy (Treatment Arm 1); MOMA-313 administered as a single-agent in 21-day cycles.	Drug: MOMA-313; MOMA-313 administered orally
Experimental: MOMA-313 in Combination with Olaparib (Treatment Arm 2); MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.	Drug: MOMA-313; MOMA-313 administered orally; Drug: Olaparib; Olaparib administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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-313 given as a single-agent or in combination with olaparib	From screening until treatment discontinuation (up to 35 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identify the recommended phase 2 dose (RP2D)	Determine the RP2D of MOMA-313 as a single-agent or in combination with olaparib	From screening until treatment discontinuation (up to 35 months)
PK parameter: area under curve (AUC) of MOMA-313		Up to 6 weeks with sparse sampling up to 35 months
PK parameter: maximum concentration (Cmax) of MOMA-313		Up to 6 weeks with sparse sampling up to 35 months
PK parameter: time to maximum concentration of MOMA-313		Up to 6 weeks with sparse sampling up to 35 months
PK parameter: half-life of MOMA-313		Up to 6 weeks with sparse sampling up to 35 months
Plasma concentration of olaparib		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 time from first dose of study treatment to progressive disease or death from any cause, whichever is earlier, as assessed via RECIST v1.1 and/or PCWG-3 by Investigator assessment	Up to 35 months
Disease control rate (DCR)	DCR defined by the proportion of subjects who achieved either a complete response (CR), partial response (PR), or stable disease (SD) at their 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

Collaborators and Investigators

• Sponsor: MOMA Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2024
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: July 26, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2026
• Last Update Submitted That Met QC Criteria: April 14, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Prostate Cancer; Phase 1; Ovarian Cancer; Advanced Solid Tumor; Metastatic Solid Tumor; Pancreas Cancer; Homologous Recombination Deficiency; MOMA-313; Polymerase theta; MOMA Therapeutics; HRD Mutation; Advanced (including locally)
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Pathologic Processes; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Digestive System Neoplasms; Digestive System Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplastic Processes; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Neoplasm Metastasis; Pancreatic Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; olaparib
• Other Study ID Numbers: MOMA-313-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No