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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат MOMA-313
  MOMA-313 administered orally
• Препарат Olaparib
  Olaparib administered orally

Первичные конечные точки

• Number of participants with AEs, dose-limiting toxicities (DLTs), serious AEs (SAEs), and/or AEs leading to discontinuation [Срок оценки: From screening until treatment discontinuation (up to 35 months)]

Вторичные конечные точки (12)

• Identify the recommended phase 2 dose (RP2D) [Срок оценки: From screening until treatment discontinuation (up to 35 months)]
• PK parameter: area under curve (AUC) of MOMA-313 [Срок оценки: Up to 6 weeks with sparse sampling up to 35 months]
• PK parameter: maximum concentration (Cmax) of MOMA-313 [Срок оценки: Up to 6 weeks with sparse sampling up to 35 months]
• PK parameter: time to maximum concentration of MOMA-313 [Срок оценки: Up to 6 weeks with sparse sampling up to 35 months]
• PK parameter: half-life of MOMA-313 [Срок оценки: Up to 6 weeks with sparse sampling up to 35 months]
• Plasma concentration of olaparib [Срок оценки: Up to 6 weeks with sparse sampling up to 35 months]
• Objective response rate (ORR) [Срок оценки: Up to 35 months]
• Duration of response (DOR) [Срок оценки: Up to 35 months]
• Time to response (TTR) [Срок оценки: Up to 35 months]
• Progression free survival (PFS) [Срок оценки: Up to 35 months]
• Disease control rate (DCR) [Срок оценки: Up to 35 months]
• Overall survival (OS) [Срок оценки: Up to 35 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 12 центров

• Investigative Site #108 — Goodyear
• Investigative Site #101 — La Jolla
• Investigative Site #111 — San Francisco
• Investigative Site #104 — Lake Mary
• Investigative Site #110 — St Louis
• Investigative Site #103 — New York
• Investigative Site #106 — New York
• Investigative Site #109 — Philadelphia
• … и ещё 4 центра

Испания · 3 центра

• Investigative Site #114 — Barcelona
• Investigative Site #116 — Barcelona
• Investigative Site #115 — Madrid

Великобритания · 3 центра

• Investigative Site #113 — London
• Investigative Site #117 — Manchester
• Investigative Site #118 — Newcastle upon Tyne

Идентификаторы

NCT: NCT06545942 · MOMA-313-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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