Evaluating ART6043 for patients with advanced 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

This study is testing a new oral cancer drug called ART6043, alone or with other medications, to see how safe it is and if it can help people with advanced metastatic solid tumors, especially certain types of breast cancer.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 181 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Artios Pharma Ltd (industry)
• Drugs / interventions: chemotherapy
• Locations: 12 sites (Grand Rapids, Michigan and 11 other locations)
• Trial ID: NCT05898399 on ClinicalTrials.gov

What this trial studies

This interventional study aims to assess the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043, an oral anti-cancer agent, either alone or in combination with PARP inhibitors Olaparib or Niraparib. The study is divided into two parts: a dose-escalation phase to evaluate ART6043 as monotherapy and in combination with PARPi, and a dose-expansion phase to confirm safety and assess initial effectiveness in specific breast cancer types. Patients may continue treatment as long as they benefit clinically or until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced or metastatic solid tumors who have specific genetic lesions affecting DNA damage response and have discontinued prior therapies.

Not a fit: Patients with untreated or rapidly progressing cancers, or those who have not met the eligibility criteria, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced metastatic solid tumors, particularly those with DNA repair defects.

How similar studies have performed: Other studies have shown promise with PARP inhibitors in similar patient populations, indicating potential for success with this novel combination approach.

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 (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 gBRCA mutation.
* Previously treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting unless medically contraindicated.
* 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.

Where this trial is running

Grand Rapids, Michigan and 11 other locations

• South Texas Accelerated Research Therapeutics (START) - Midwest — Grand Rapids, Michigan, United States (ACTIVE_NOT_RECRUITING)
• Memorial Sloan-Kettering Cancer Center (MSKCC) — New York, New York, United States (ACTIVE_NOT_RECRUITING)
• Stephenson Cancer Center - Oncology — Oklahoma City, Oklahoma, United States (ACTIVE_NOT_RECRUITING)
• Jefferson University Hospitals - Kimmel Cancer Center — Philadelphia, Pennsylvania, United States (ACTIVE_NOT_RECRUITING)
• SCRI oncology partners — Nashville, Tennessee, United States (COMPLETED)
• Mary Crowley Cancer Center - Clinic — Dallas, Texas, United States (COMPLETED)
• The University of Texas - MD Anderson Cancer Center — Houston, Texas, United States (ACTIVE_NOT_RECRUITING)
• Hospital Universitario Clínico San Cecilio — Granada, Andalusia, Spain (RECRUITING)
• Hospital Clínico Universitario de Valladolid — Valladolid, Castille and León, Spain (RECRUITING)
• Hospital de la Santa Creu i Sant Pau — Barcelona, Catalonia, Spain (RECRUITING)
• Hospital San Pedro de Alcántara — Cáceres, Extremadura, Spain (RECRUITING)
• Hospital Universitario 12 de Octubre — Madrid, Madrid, Spain (RECRUITING)

Study contacts

• Study coordinator: Artios Pharma

Conditions: Advanced Solid Tumor, Metastatic Solid Tumor, Metastatic Cancer, HER2-negative Breast Cancer, Poly polymerase inhibitor, Human epidermal growth factor receptor 2 negative, Oral anticancer, Sensitivity to Polymerase Theta Inhibitor