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

MOMA Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Breast Cancer; Homologous Recombination Deficiency; Advanced Solid Tumor; Pancreas Cancer; Ovarian Cancer; Prostate Cancer; Metastatic Solid Tumor

Treatments: Drug: MOMA-313; Drug: Olaparib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06545942

MOMA-313-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 158 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 or metastatic solid tumors that are not eligible for curative therapy, with any HR-deficient alteration, and have been previously exposed to a PARP inhibitor.

   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 significant toxicity or 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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158 participants in 2 patient groups

MOMA-313 Monotherapy (Treatment Arm 1)

Experimental group

Description:

MOMA-313 administered as a single-agent in 21-day cycles.

Treatment:

Drug: MOMA-313

MOMA-313 in Combination with Olaparib (Treatment Arm 2)

Experimental group

Description:

MOMA-313 administered together with twice daily (BID) olaparib in 28-day cycles.

Treatment:

Drug: Olaparib

Drug: MOMA-313