Clinical trial NCT06545942: Study of Orally Administered MOMA-313 in Participants With Advanced or Metastatic Solid Tumors
Official title: A Phase 1 Study of MOMA-313 Given as Monotherapy or in Combination With a PARP Inhibitor in Participants With Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Prostate Cancer
Pancreas Cancer
Breast Cancer
Ovarian Cancer
Homologous Recombination Deficiency
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
Lead sponsor: MOMA Therapeutics
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 158
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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.
   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

Primary outcomes:
measure: Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation
timeFrame: From screening until treatment discontinuation (up to 35 months)
Secondary outcomes:
measure: Identify the recommended phase 2 dose (RP2D)
timeFrame: From screening until treatment discontinuation (up to 35 months)
measure: PK parameter: area under curve (AUC) of MOMA-313
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter: maximum concentration (Cmax) of MOMA-313
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter: time to maximum concentration of MOMA-313
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: PK parameter: half-life of MOMA-313
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: Plasma concentration of olaparib
timeFrame: Up to 6 weeks with sparse sampling up to 35 months
measure: Objective response rate (ORR)
timeFrame: Up to 35 months
measure: Duration of response (DOR)
timeFrame: Up to 35 months
measure: Time to response (TTR)
timeFrame: Up to 35 months
measure: Progression free survival (PFS)
timeFrame: Up to 35 months
measure: Disease control rate (DCR)
timeFrame: Up to 35 months
measure: Overall survival (OS)
timeFrame: Up to 35 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Investigative Site #101
state: California
city: San Francisco
country: United States
facility: Investigative Site #111
state: California
city: Lake Mary
country: United States
facility: Investigative Site #104
state: Florida
city: Saint Louis
country: United States
facility: Investigative Site #110
state: Missouri
city: New York
country: United States
facility: Investigative Site #103
state: New York
city: New York
country: United States
facility: Investigative Site #106
state: New York
city: Philadelphia
country: United States
facility: Investigative Site #109
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Investigative Site #107
state: South Carolina
city: Nashville
country: United States
facility: Investigative Site #102
state: Tennessee
city: San Antonio
country: United States
facility: Investigative Site #105
state: Texas
city: Fairfax
country: United States
facility: Investigative Site #112
state: Virginia
city: Barcelona
country: Spain
facility: Investigative Site #114
city: Madrid
country: Spain
facility: Investigative Site #115
city: London
country: United Kingdom
facility: Investigative Site #113
city: Manchester
country: United Kingdom
facility: Investigative Site #117
Study officials:
References: