A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of the DNA Polymerase Theta Inhibitor ART6043 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors

Study Identifier:
ART6043C001
CT.gov Identifier:
NCT05898399
EudraCT Identifier:
202351000000
EU Trial (CTIS) Number:
2023-509220-17-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

This interventional study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043 as monotherapy or in combination with Olaparib or Talazoparib. Part A (Dose-escalation phase): Part A will evaluate ART6043 as monotherapy (Part A1) in patients with advanced or metastatic cancer and in combination with olaparib (Part A2), in patients with advanced or metastatic cancer with genetic lesions that cause loss of function of known DNA Damage Response (DDR) genes. Olaparib is also referred as PARPi. Part B (dose-expansion phase): To further confirm the safety of ART6043 in combination with olaparib (Part B1) and to assess initial effectiveness of ART6043 in combination compared to olaparib alone (Part B2) in patients with certain types of breast cancer.

To assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ART6043 as monotherapy and in combination with ola in pts with advanced solid tumors

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Part A1 (ART6043 as monotherapy)
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  • Drug: Experimental: Part A2 (ART6043 in combination with olaparib)
  • Drug: Drug: Olaparib
  • Drug: Experimental: Part B1 (ART6043 in combination with olaparib)
  • Drug: Experimental: Part B2 (ART6043 in combination with olaparib)
  • Drug: Patients may continue to receive ART6043 and/or PARPi as long as they may be continuing to derive clinical benefit as assessed by the investigator and/or until disease progression, withdrawal of consent or until they experience unacceptable drug-related toxicity.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Patients who have discontinued all previous chemotherapeutic agents, non-hormonal targeted therapy, or investigational drugs for at least 21 days or 5 half-lives (not including palliative radiotherapy at focal sites), whichever is shorter. Endocrine and hormonal therapies for the treatment of cancer must have been discontinued (unless for the treatment of Prostate Cancer) at least 7 days before receiving study medication. Palliative radiotherapy must have completed prior to start of study treatment.
    • Resolution of all toxicities of prior therapy or surgical procedures.
    • Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale.
    • Have adequate organ function.
    • Patients of childbearing potential and patients with partners of childbearing potential are required to use highly effective contraception.
    • Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.
    • Inclusion Criteria specific to Part A1 (ART6043 as Monotherapy)
    • • Advanced or metastatic cancer. Tumors with genetic lesions known to cause loss of function of known DDR genes based on available pre-existing testing are encouraged.
    • Inclusion criteria specific to Part A2 (ART6043 in combination with olaparib)
    • Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes based on available, pre-existing testing.
    • Patients for whom a PARPi is an appropriate treatment option. Patients may have received prior treatment with a PARPi.
    • Inclusion criteria specific to Part B (ART6043 in combination with olaparib or olaparib alone)
    • Histologically or cytologically confirmed HER2-ve locally advanced or metastatic carcinoma of the breast.
    • Documentation of a deleterious or suspected deleterious g/sBRCA mutation.
    • No more than 3 prior chemotherapy-inclusive schedules (including antibody conjugates) for locally advanced and/or metastatic disease.
    • Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, or metastatic setting unless medically contraindicated.
    • Patients must have received no or ≤1 month of prior treatment with a PARPi.
    Exclusion criteria
    • Patients who are pregnant.
    • Patients with Myelodysplastic syndrome (MDS)/Acute myeloid leukemia (AML) or with features suggestive of MDS/AML.
    • Have ongoing interstitial lung disease or pneumonitis.
    • Have any major gastrointestinal issues that could impact absorption of ART6043 or olaparib.
    • Patients with brain metastases (patients with treated brain metastases could be eligible if follow-up brain imaging after central nervous system-directed therapy shows no evidence of progression).
    • Have received a live vaccine within 30 days before the first dose of study treatment.
    • Recent major surgery within 4 weeks prior to entry into the study.
    • Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.
    • Have a history of allergy or hypersensitivity to study drug components.
    • Exclusion criteria specific to Part B
    • First-line locally advanced and/or metastatic breast cancer with no prior adjuvant chemotherapy.
    • Inflammatory breast cancer.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Nehal Lakhani
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor