AzTrials
AzTrials

Advanced Solid TumorPhase 1/2NCT05898399

Study of ART6043 in Advanced/Metastatic Solid Tumors Patients (POLKA)

A Phase 1/2 study testing ART6043 and Olaparib in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by Artios Pharma Ltd at 27 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This interventional study will evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ART6043 as monotherapy or in combination with olaparib. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumor, Metastatic Solid Tumor
What is being tested?
ART6043 and Olaparib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
181 participants
Where
27 sitesin 3 countries
Study dates
30 Jun 2023to 30 Sep 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 15Show fewer
  • 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.

Who cannot join

  • 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.
Show all 9Show fewer
  • 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.
  • Inflammatory breast cancer.

Trial locations and contacts

27 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Artios Pharma contact

+44 (0)1223 867 900

info@artios.com

27 sites in 3 countries

Spain18 sites, 18 recruiting

  • Complejo Hospitalario Universitario A Coruña CHUAC

    A Coruña

    Recruiting

  • Instituto Valenciano de Oncologia-IVO

    Bàguena

    Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona, Catalonia, 08025

    Recruiting

  • Hospital San Pedro de Alcántara

    Cáceres, Extremadura, 10003

    Recruiting

  • Hospital Universitario de Jerez de la Frontera

    Cadiz, 11407

    Recruiting

  • Hospital Universitario de Canarias

    Canara

    Recruiting

  • Hospital Universitario Clínico San Cecilio

    Granada, Andalusia, 18007

    Recruiting

  • Hospital Universitario de Jaen

    Jaén

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, Madrid, 28041

    Recruiting

  • Hospital General Universitario Gregorio Marañon

    Madrid

    Recruiting

  • Hospital Universitario Virgen de la Victoria

    Málaga

    Recruiting

  • Hospital Clinico Universitario Virgen de la Arrixaca

    Murcia, 30120

    Recruiting

  • Hospital Clinico San Carlos

    San Carlos, Madrid, 28040

    Recruiting

  • Hospital Universitario Virgen del Rocio

    Seville, 41001

    Recruiting

  • Hospital Universitario Virgen Macarena

    Seville

    Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

    Recruiting

  • Hospital Clínico Universitario de Valladolid

    Valladolid, Castille and León, 47003

    Recruiting

  • Hospital Clinico Universitario Lozano Blesa

    Zaragoza, 50009

    Recruiting

Other trials in Spain

United States7 sites

  • Mary Crowley Cancer Center - Clinic

    Dallas, Texas, 75251

    Completed

  • South Texas Accelerated Research Therapeutics (START) - Midwest

    Grand Rapids, Michigan, 49546

    Active, not recruiting

  • The University of Texas - MD Anderson Cancer Center

    Houston, Texas, 77030

    Active, not recruiting

  • SCRI oncology partners

    Nashville, Tennessee, 37203

    Completed

  • Memorial Sloan-Kettering Cancer Center (MSKCC)

    New York, New York, 10065-6800

    Active, not recruiting

  • Stephenson Cancer Center - Oncology

    Oklahoma City, Oklahoma, 73104

    Active, not recruiting

  • Jefferson University Hospitals - Kimmel Cancer Center

    Philadelphia, Pennsylvania, 17107

    Active, not recruiting

Other trials in United States

United Kingdom2 sites, 2 recruiting

  • University College London

    London

    Recruiting

  • The Christie

    Manchester, M20 4BX

    Recruiting

Other trials in United Kingdom

About this study

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

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

Read the 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 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.

Being tested
ART6043, Olaparib
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, BRCA
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ART6043Drug

    ART6043 will be given orally.

  • OlaparibDrug

    Olaparib will be given orally.

Study groups in NCT05898399
Study groupRoleWhat they receive
Part A1 (ART6043 as monotherapy)ExperimentalPatients with advanced or metastatic cancer will receive ART6043 administered in 21-day cycles.
Receives: Drug: ART6043
Part A2 (ART6043 in combination with olaparib)ExperimentalPatients with advanced or metastatic cancer and with PARPi as an appropriate treatment option will receive ART6043 in combination with olaparib twice daily (BID) in 21-day cycles.
Receives: Drug: ART6043; Drug: Olaparib
Part B2 (ART6043 in combination with olaparib)ExperimentalPatients with gBRCA-m, HER2-ve locally advanced or metastatic breast cancer will be randomly assigned to receive ART6043 in combination with olaparib or olaparib alone.
Receives: Drug: ART6043; Drug: Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part A: Number of participants with Dose Limiting Toxicities (DLTs)

    Severity of adverse events as assessed by the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days)

  2. Part B2: Progression free survival (PFS)

    PFS is defined as the time from randomization until objective disease progression as defined by Response evaluation criteria in solid tumors (RECIST) v1.1 or death by any cause in the absence of progression, regardless of whether the patient withdraws from study medication or receives another anti-cancer therapy prior to progression.

    Measured: Until disease progression (Upto 3.7 years).

Secondary outcomes (11)

  1. Part B2: Number of participants with Adverse events

    To assess the safety and tolerability of ART6043 given orally in combination with olaparib at the Recommended Phase II dose(s) [RP2D(s)].

    Measured: Screening (≤28 days) Until follow-up visit (90 days after discontinuation)] (up to 3.7 years)

  2. Best overall response (BOR)

    The best overall response is the best response (complete response [CR] or partial response [PR]) recorded from the date of randomization for each patient until the progression or censoring date in the absence of progression.

    Measured: Screening (≤28 days) Until disease progression/recurrence (Upto 3.7 years)

  3. Objective Response Rate (ORR)

    Objective Response Rate (ORR) is defined as the proportion of patients with a CR or PR to treatment according to RECIST v1.1.

    Measured: Screening (≤28 days) Until disease progression/recurrence (Upto 3.7 years)

  4. Disease control rate (DCR)

    To assess preliminary signs of efficacy for ART6043 as monotherapy and in combination with olaparib.

    Measured: Screening (≤28 days) Until disease progression (Upto 3.7 years)

  5. Duration of response (DOR)

    The DOR will be defined for patients with a BOR of CR/PR (with a Prostate Cancer Working Group [3PCWG-3] response of non-PD/NE for patients with prostate cancer), as the time from the date of first documented response until date of documented progression (by RECIST v1.1 or PCWG-3) or death in the absence of disease progression.

    Measured: Screening (≤28 days) Until disease progression (Upto 3.7 years)

  6. Change in tumor size

    The best percentage change in tumor size from baseline will be determined for each patient, ie, the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction.

    Measured: Screening (≤28 days) Until disease progression (Upto 3.7 years)

  7. Change in level of cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA)

    To assess preliminary signs of efficacy for ART6043 as monotherapy and in combination with olaparib.

    Measured: Screening (≤28 days) Until follow-up visit (Upto 3.7 years)

  8. Part A: Progression free survival (PFS)

    The PFS is defined as the time from randomization until the earliest objective disease progression defined by RECIST v1.1 or PCWG-3 (for patients with prostate cancer in Arm 2) or death by any cause in the absence of progression, regardless of whether the patient withdraws from study medication or receives another anti-cancer therapy prior to progression.

    Measured: Screening (≤28 days) Until disease progression (Upto 3.7 years)

  9. Overall survival (OS)

    OS is defined as the time from the start of study treatment (Part A) or randomization (Part B) until death due to any cause.

    Measured: Screening (≤28 days) Until overall survival follow-up (Upto 3.7 years)

  10. Plasma concentration

    To determine the plasma concentration of ART6043 and its potential active metabolite ART7276 following both single and multiple oral dosing of ART6043 monotherapy and following multiple oral dosing of ART6043 in combination with olaparib.

    Measured: Pre-dose Cycle 0 Days -2, -1 , Cycle 1 Days 1, 8, 15, 16, Cycle 2 Days 1, 8, 15, Cycle 3 Day 1 Upto 3.7 Years (Each Cycle is 21-Days)

  11. Cancer antigen 125 levels in pre-dose tumor samples

    To assess CA-125 levels in pre-dose tumor samples that may be predictive of the activity of ART6043.

    Measured: At Screening (≤28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2023
  2. Study start30 Jun 2023
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Sep 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
181 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05898399
Sponsor's protocol ID
ART6043C001
Status last verified
Oct 2026
First submitted
15 May 2023
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Robinson HMR, Grinkevich V, Majithiya JB, Mann SE, McWhirter C, Rajendra E, Ranzani M, Stockley ML, Costales P, Davis OA, Elinati E, Galbiati A, Geo L, Toste Rego A, Mason B, Armstrong L, Grande D, Neves J, Roy Luzarraga M, Cooper H, Edwardes L, Konstantinou T, van de Ven M, Moises da Silva A, Moser SC, Charles MD, Finch H, Higgins GS, Boulton SJ, Jonkers J, Martin NMB, Heald RA, Smith GCM. The pharmacological profile of ART6043, a first-in-class clinical DNA polymerase theta polymerase domain inhibitor potentiating PARP inhibitor efficacy. Clin Cancer Res. 2026 Jul 13. doi: 10.1158/1078-0432.CCR-26-0493. Online ahead of print.

    PubMed 42440368

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ART6043 and Olaparib in people with Advanced Solid Tumor and Metastatic Solid Tumor, run by Artios Pharma Ltd at 27 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in Spain, United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Artios Pharma (+44 (0)1223 867 900, info@artios.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of participants with Dose Limiting Toxicities (DLTs) (time frame: From first dose of study treatment until the end of Cycle 1 (each cycle is 21-days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05898399, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in