Study of ART6043 in Advanced/Metastatic Solid Tumors Patients

Trial Title: Study of ART6043 in Advanced/Metastatic Solid Tumors Patients

NCT ID: NCT05898399

Condition: Advanced Solid Tumor
Metastatic Solid Tumor

Conditions: Official terms:
Neoplasms
Olaparib
Niraparib

Conditions: Keywords:
Metastatic Cancer
HER2-negative Breast Cancer
Poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi)
Human epidermal growth factor receptor 2 negative (HER2-ve)
Oral anticancer
Sensitivity to Polymerase Theta Inhibitor

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ART6043
Description: ART6043 will be given orally.
Arm group label: Part A1 (ART6043 as monotherapy)
Arm group label: Part A2 (ART6043 in combination with Olaparib)
Arm group label: Part A3 (ART6043 in combination with Niraparib)
Arm group label: Part B1 (ART6043 in combination with a PARPi)
Arm group label: Part B2 (ART6043 in combination with a PARPi or a PARPi alone)

Intervention type: Drug
Intervention name: Olaparib
Description: Olaparib will be given orally.
Arm group label: Part A2 (ART6043 in combination with Olaparib)
Arm group label: Part B1 (ART6043 in combination with a PARPi)
Arm group label: Part B2 (ART6043 in combination with a PARPi or a PARPi alone)

Intervention type: Drug
Intervention name: Niraparib
Description: Niraparib will be given orally.
Arm group label: Part A3 (ART6043 in combination with Niraparib)
Arm group label: Part B1 (ART6043 in combination with a PARPi)
Arm group label: Part B2 (ART6043 in combination with a PARPi or a PARPi alone)

Summary: This interventional study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043 as monotherapy or in combination with Olaparib or Niraparib.

Detailed description: ART6043 is being developed as an oral anti-cancer agent in combination with a poly (adenosine diphosphate ribose) polymerase (PARP) inhibitor (PARPi) in patients with cancers that harbor defects in DNA repair. The study will consist of two parts: 1. 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 either Olaparib (Part A2) or Niraparib (Part A3), in patients with advanced or metastatic cancer with genetic lesions that cause loss of function of known DNA Damage Response (DDR) genes. Olaparib or Niraparib are collectively referred to as PARPi. 2. Part B (dose-expansion phase): Part B: To further confirm the safety of ART6043 in combination with PARPi (Part B1) and to assess initial effectiveness of ART6043 in combination compared to PARPi alone (Part B2) in patients with certain types of breast cancer. 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.

Criteria for eligibility:
Criteria:
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/A3 (ART6043 in combination with Olaparib/Niraparib) - 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 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. 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, Niraparib 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.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: South Texas Accelerated Research Therapeutics (START) - Midwest

Address:
City: Grand Rapids
Zip: 49546
Country: United States

Status: Recruiting

Facility:
Name: Stephenson Cancer Center - Oncology

Address:
City: Oklahoma City
Zip: 73104
Country: United States

Status: Recruiting

Facility:
Name: Jefferson University Hospitals - Kimmel Cancer Center

Address:
City: Philadelphia
Zip: 17107
Country: United States

Status: Recruiting

Facility:
Name: SCRI oncology partners

Address:
City: Nashville
Zip: 37203
Country: United States

Status: Recruiting

Facility:
Name: Mary Crowley Cancer Center - Clinic

Address:
City: Dallas
Zip: 75251
Country: United States

Status: Recruiting

Facility:
Name: The University of Texas - MD Anderson Cancer Center

Address:
City: Houston
Zip: 77030
Country: United States

Status: Recruiting

Start date: June 30, 2023

Completion date: December 14, 2026

Lead sponsor:
Agency: Artios Pharma Ltd
Agency class: Industry

Source: Artios Pharma Ltd

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05898399