Overview
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.
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.
Eligibility
Key Inclusion Criteria:
- Age ≥ 18 years
- Have histologically confirmed disease for each treatment arm as follows:
- Treatment Arm 1 (MOMA-313 Monotherapy)
- Advanced 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 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.
- Treatment Arm 1 (MOMA-313 Monotherapy)
- 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