Advanced Solid Tumor, Breast Cancer, Homologous Recombination Deficiency, Metastatic Solid Tumor, Ovarian Cancer, Pancreas Cancer, Prostate Cancer
Conditions
Keywords
Phase 1, MOMA-313, Polymerase theta, MOMA Therapeutics, Advanced Solid Tumor, Metastatic Solid Tumor, Prostate Cancer, Pancreas Cancer, Breast Cancer, Ovarian Cancer, Homologous Recombination Deficiency, HRD Mutation, Advanced (including locally)
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 (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.
Interventions
DRUGMOMA-313
MOMA-313 administered orally
DRUGOlaparib
Olaparib administered orally
Sponsors
MOMA Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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 (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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: 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) | 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). |
| 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 |
| 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. |
| 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 |
| 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 |
Countries
Spain, United Kingdom, United States
Contacts
CONTACTMOMA Clinical Trials
Outcome results
None listed