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
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
NCT #
NCT05898399
Condition(s)
Breast, Solid Tumors
Molecular Target(s)
Polθ
Drug Classification(s)
Small Molecule
Agents(s)
Phase I, Open-Label, Multinational, Multicenter, Dose Escalation and Expansion Study of BH3120 in Patients with Advanced or Metastatic Solid Tumors
Phase(s)
I/Iia
Mechanism of Action
ART6043 is a Polθ inhibitor
Purpose
- How much of the study drug can be given alone and in combination with Olaparib or Talazoparib with an acceptable level of side effects
- The effects of the study drug alone and in combination with Olaparib or Talazoparib (good and bad)
- How much of the study drug is absorbed into the blood and how fast it is removed
- How the study drug is acting on your body, on tumors and the substances in your body that can be used to monitor how your disease is doing
- If research tests can be used in the future to predict who will benefit from the study drug when given alone or in combination with Olaparib or Talazoparib
- 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 longer. Endocrine and hormonal therapies for the treatment of cancer must have been discontinued 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.
- Radiologically evaluable and measurable and/or non-measurable (prostate cancer patients only) disease.
- Inclusion Criteria specific to Part A1 (ART6043 as Monotherapy)
- Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes.
- Inclusion criteria specific to Part A2/A3 (ART6043 in combination with Olaparib/Talazoparib)
- Advanced or metastatic cancer with genetic lesions known to cause loss of function of known DDR genes.
- 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 a PARPi or a PARPi 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.
- 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 aabsorption of ART6043, Talazoparib 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.
- 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.
Location
MCD
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