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NCT Number: NCT05898399

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

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

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Key information

Conditions

Advanced Solid Tumor Metastatic Solid Tumor Neoplasm Metastasis Neoplasms Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hospital Universitario Clínico San Cecilio, Granada, Andalusia, Spain

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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:

  • 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.
  • 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

ART6043

Drug

ART6043 will be given orally.

Olaparib

Drug

Olaparib will be given orally.

Primary outcomes

  1. 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)

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

  2. Part B2: Progression free survival (PFS)

    Time frame: Until disease progression (Upto 3.7 years).

    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.

Secondary outcomes

  1. Part B2: Number of participants with Adverse events

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

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

  2. Best overall response (BOR)

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

    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.

  3. Objective Response Rate (ORR)

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

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

  4. Disease control rate (DCR)

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

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

  5. Duration of response (DOR)

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

    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.

  6. Change in tumor size

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

    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.

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

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

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

  8. Part A: Progression free survival (PFS)

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

    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.

  9. Overall survival (OS)

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

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

  10. Plasma concentration

    Time frame: 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)

    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.

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

    Time frame: At Screening (≤28 days)

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

Study contacts

Contact information is provided by the study sponsor or research team.

Artios Pharma

CONTACT

[email protected]

+44 (0)1223 867 900

Sponsors and collaborators

Lead sponsor

Artios Pharma Ltd

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2028
Study completion
2028
First posted
Jun 12, 2023
Registry last updated
May 1, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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