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

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.

Key Inclusion Criteria:

• Age ≥ 18 years
• Have histologically confirmed disease for each treatment arm as follows:

• 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.
• 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.
• 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

Key Exclusion Criteria:

• Active prior or concurrent malignancy (some exceptions allowed)
• Clinically relevant cardiovascular disease
• Known CNS metastasis associated with progressive neurological symptoms (stable doses of corticosteroids allowed)
• Known active infection
• Prior polymerase theta inhibitor exposure
• Known allergy, hypersensitivity, and/or intolerance to MOMA-313
• Olaparib exposed patients with known hypersensitivity to PARP inhibitors (for patients considered for olaparib only)
• 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:

• Undetectable viral load or CD4+ count ≥300 cells/μL
• Receiving highly active antiretroviral therapy
• 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