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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor; Prostate Cancer; Pancreas Cancer; Ovarian Cancer; Breast Cancer; Homologous Recombination Deficiency
• Interventions: Drug: MOMA-313; Drug: Olaparib

• Registration Number: NCT06545942
• Lead Sponsor: MOMA Therapeutics

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-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 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 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 Timeline

• Study First Submitted: 2024-07-26
• Study First Submitted QC: 2024-08-05
• Study First Posted: 2024-08-09
• Study Start: 2024-08-13
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-29
• Last Update Posted: 2025-05-01
• Primary Completion: 2027-05-31
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 158

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 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 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: Metastatic prostate cancer, metastatic breast cancer, or metastatic pancreatic cancer 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
MOMA-313 Monotherapy (Treatment Arm 1)	MOMA-313	MOMA-313 administered as a single-agent in 21-day cycles.
MOMA-313 in Combination with Olaparib (Treatment Arm 2)	MOMA-313	MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.
MOMA-313 in Combination with Olaparib (Treatment Arm 2)	Olaparib	MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.

Primary Outcome Measures

Name	Time	Method
Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation	From screening until treatment discontinuation (up to 35 months)	To assess the safety and tolerability of MOMA-313 given as a single-agent or in combination with olaparib

Secondary Outcome Measures

Name	Time	Method
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
Identify the recommended phase 2 dose (RP2D)	From screening until treatment discontinuation (up to 35 months)	Determine the RP2D of MOMA-313 as a single-agent or in combination with olaparib
PK parameter: time to maximum concentration 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)	Up to 35 months	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).
Disease control rate (DCR)	Up to 35 months	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.
Overall survival (OS)	Up to 35 months	OS is defined as the time from first dose of study treatment to the date of death, irrespective of the cause of death
Duration of response (DOR)	Up to 35 months	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
Progression free survival (PFS)	Up to 35 months	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
PK parameter: half-life of MOMA-313	Up to 6 weeks with sparse sampling up to 35 months
Time to response (TTR)	Up to 35 months	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.

Trial Locations

Locations (15)

Investigative Site #109; 🇺🇸 Philadelphia, Pennsylvania, United States

Investigative Site #114; 🇪🇸 Barcelona, Spain

Investigative Site #115; 🇪🇸 Madrid, Spain

Investigative Site #117; 🇬🇧 Manchester, United Kingdom

Investigative Site #101; 🇺🇸 La Jolla, California, United States

Investigative Site #111; 🇺🇸 San Francisco, California, United States

Investigative Site #104; 🇺🇸 Lake Mary, Florida, United States

Investigative Site #110; 🇺🇸 Saint Louis, Missouri, United States

Investigative Site #103; 🇺🇸 New York, New York, United States

Investigative Site #106; 🇺🇸 New York, New York, United States

Investigative Site #107; 🇺🇸 Myrtle Beach, South Carolina, United States

Investigative Site #102; 🇺🇸 Nashville, Tennessee, United States

Investigative Site #105; 🇺🇸 San Antonio, Texas, United States

Investigative Site #112; 🇺🇸 Fairfax, Virginia, United States

Investigative Site #113; 🇬🇧 London, United Kingdom