RecruitingRecruiting
Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (POLKA)
NCT05898399 · Artios Pharma Ltd
In plain English
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Official title
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
About this study
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 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 \[Enrollment Complete\]
2. Part B (dose-expansion phase): To further confirm the safety of ART6043 and assess its initial effectiveness in combination compared to olaparib alone (Part B2) in patients with a germline BRCA mutation who have HER2-ve advanced or metastatic breast cancer
Patients may continue to receive ART6043 and/or olaparib 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.
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 14 days prior to randomization.
* 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.
* 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.
* 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
• Inflammatory breast cancer.
Study design
Enrollment target: 181 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-06-30
Estimated completion: 2028-09-30
Last updated: 2026-09-15
Interventions
Drug: ART6043Drug: Olaparib
Primary outcomes
- • Part A: Number of participants with Dose Limiting Toxicities (DLTs) (From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days))
- • Part B2: Progression free survival (PFS) (Until disease progression (Upto 3.7 years).)
Sponsor
Artios Pharma Ltd · industry
Contacts & investigators
ContactArtios Pharma · contact · info@artios.com · +44 (0)1223 867 900
All locations (18)
South Texas Accelerated Research Therapeutics (START) - MidwestActive Not Recruiting
Grand Rapids, Michigan, United States
Memorial Sloan-Kettering Cancer Center (MSKCC)Active Not Recruiting
New York, New York, United States
Stephenson Cancer Center - OncologyActive Not Recruiting
Oklahoma City, Oklahoma, United States
Jefferson University Hospitals - Kimmel Cancer CenterActive Not Recruiting
Philadelphia, Pennsylvania, United States
SCRI oncology partnersCompleted
Nashville, Tennessee, United States
Mary Crowley Cancer Center - ClinicCompleted
Dallas, Texas, United States
The University of Texas - MD Anderson Cancer CenterActive Not Recruiting
Houston, Texas, United States
Hospital Universitario Clínico San CecilioRecruiting
Granada, Andalusia, Spain
Hospital Clínico Universitario de ValladolidRecruiting
Valladolid, Castille and León, Spain
Hospital de la Santa Creu i Sant PauRecruiting
Barcelona, Catalonia, Spain
Hospital San Pedro de AlcántaraRecruiting
Cáceres, Extremadura, Spain
Hospital Clinico San CarlosRecruiting
San Carlos, Madrid, Spain
Hospital Universitario de Jerez de la FronteraRecruiting
Cadiz, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Clinico Universitario Virgen de la ArrixacaRecruiting
Murcia, Spain
Hospital Universitario Virgen del RocioRecruiting
Seville, Spain
Hospital Clinico Universitario de ValenciaRecruiting
Valencia, Spain
Hospital Clinico Universitario Lozano BlesaRecruiting
Zaragoza, Spain