Study of ART0380 in Patients With Biologically Selected Solid Tumors (ARTIST)

A Phase II, Open-label, Multi-center, Basket Study of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy to Patients With Biologically Selected Advanced or Metastatic Solid Tumors (ARTIST)

This interventional study will evaluate the efficacy and safety of ART0380 as monotherapy in patients whose tumors have a biology to predict for sensitivity to inhibition of Ataxia-Telangiectasia Mutated and Rad3-related protein kinase (ATR).

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Advanced Solid Tumor; Recurrent Endometrial Cancer
• Intervention / Treatment: Drug: ART0380

Detailed Description

ART0380 is being developed as an oral anti-cancer agent for the treatment of patients with cancers that have defects in deoxyribonucleic acid (DNA) repair.

The study will recruit selected patients with advanced or metastatic solid tumors, specifically:

• Patients with persistent or recurrent endometrial cancer (EC)
• Patients with advanced or metastatic solid tumors of any histology

Above patients will be randomized in a 1:1 ratio to one of two dose regimens of ART0380.

Safety will be evaluated on a quarterly basis, at a minimum. Patients may continue to receive ART0380 as long as they are continuing to derive benefit from treatment or until disease progression, withdrawal of consent, or until they experience unacceptable drug-related toxicity.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • NAP
    • Angers, NAP, France, 49055
      • Institut de Cancérologie de l'Ouest
    • Caen, NAP, France, 14076
      • Centre Francois Baclesse - Service d'Oncologie Medicale
    • Paris, NAP, France, 75014
      • Hopital Cochin Saint Vincent De Paul
    • Pierre-Bénite, NAP, France, 69310
      • Hôpital Lyon Sud
    • Poitiers, NAP, France, 86000
      • Centre Hospitalier Universitaire de Poitiers
• Spain
  • Valencia, Spain, 46009
    • Fundación Instituto Valenciano de Oncología
  • Andalusia
    • Jaén, Andalusia, Spain, 23007
      • Hospital Universitario de Jaen
• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • University of California Los Angeles (UCLA)
  • Illinois
    • Chicago, Illinois, United States, 60637-1447
      • The University of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Center
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health R.J. Zuckerberg Cancer Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital - Oncology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma/Sarah Cannon Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have discontinued all previous treatments for cancer for at least 21 days or 5 half-lives (not including palliative radiotherapy at focal sites), whichever is shorter. Palliative radiotherapy must have completed 1 week prior to start of study treatment.
• Resolution of all toxicities of prior therapy or surgical procedures to baseline or Grade 1 (except for hypothyroidism requiring medication, neuropathy, and alopecia, which must have resolved to Grade ≤2).
• 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.
• Performance status of 0-1 on the Eastern Cooperative Oncology Group scale.
• Have a non-irradiated tumor tissue sample (archival or newly obtained core biopsy of a tumor lesion) available.

Inclusion Criteria specific to each Arm

Inclusion Criteria for Arm 1 [ART0380 monotherapy (endometrial cancer patients)]

• Persistent or recurrent EC with biological selection.
• Patients should have received taxane/platinum chemotherapy unless contraindicated.
• Measurable disease.

Inclusion Criteria for Arm 2 [ART0380 monotherapy (solid tumors patients)]

• Advanced or metastatic solid cancers of any histology with biological selection.
• If a Programmed cell death protein-1 /Programmed death-ligand-1 inhibitor (e.g., pembrolizumab) is approved and available for the patient's cancer, the patient should have received such treatment before participating in this study.
• Radiologically evaluable disease.

Exclusion Criteria:

• Patients who are pregnant.
• Prior treatment with an inhibitor of ATR, WEE1, checkpoint kinase 1 or PKMYT1.
• Have a serious concomitant systemic disorder that would compromise the patient's ability to adhere to the protocol.
• Have ongoing interstitial lung disease or pneumonitis (whether symptomatic or asymptomatic).
• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS) directed therapy shows no evidence of progression.
• Have any major gastrointestinal issues that could impact absorption of ART0380.
• Have a history of allergy or hypersensitivity to study drug components.
• Have a significant bleeding disorder or vasculitis or had a Grade ≥3 bleeding episode within 12 weeks prior to enrollment.
• Patients who plan to father a child while in the study or within 16 weeks (5 months in France) after the last administration of study treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 [ART0380 monotherapy (endometrial cancer patients)]; Patients with persistent or recurrent endometrial cancer (EC) will receive ART0380 monotherapy in one of two dose regimens for a 21-day cycle.	Drug: ART0380; Randomized patients will orally receive ART0380.
Experimental: Arm 2 [ART0380 monotherapy (solid tumors patients)]; Patients with advanced or metastatic solid tumors will receive ART0380 monotherapy in one of two dose regimens for a 21-day cycle.	Drug: ART0380; Randomized patients will orally receive ART0380.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the proportion of patients with a complete response (CR) or partial response (PR) to treatment according to Response evaluation criteria in solid tumors (RECIST v1.1).	Until disease progression (Every 6 weeks from randomization Upto 2 Years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with adverse events	To assess the safety and tolerability of ART0380 in patients with solid tumors.	From Cycle 1 (each Cycle is 21-day) Day 1 until 30-day follow-up visit (Upto 2 Years)
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 Prostate Cancer Working Group 3 (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.	Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Best overall response (BOR)	The best overall response is the best response (complete response, and partial response) recorded from the date of randomization for each patient until the progression or censoring date in the absence of progression.	Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Disease control rate (DCR)	To further explore the efficacy of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.	Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Duration of response (DOR)	The DOR will be defined for patients with a BOR of CR/PR, as the time from the date of first documented response until date of documented progression (by RECIST v1.1) or death in the absence of disease progression.	Screening (≤28 days) Until disease progression or death (Every 6 weeks from randomization Upto 2 Years)
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.	Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Overall survival (OS)	The OS is defined as the time from the randomization until death due to any cause.	Screening (≤28 days) Until overall survival follow-up (Every 12 weeks until data cut-off)
Maximum plasma concentration (Cmax)	To determine the Cmax of ART0380 following single oral dosing of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.	Pre-dose Cycle 1 day 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days)
Half life (t1/2)	To determine the t1/2 of ART0380 following single oral dosing of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.	Pre-dose Cycle 1 days 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days)
Area under the plasma concentration-time curve from zero to infinity (AUC0-inf)	To determine the AUC0-inf of ART0380 following single oral dosing of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.	Pre-dose Cycle 1 days 1, 2, 15, 16, 17, 18, Cycle 2 day 1, Cycle 3 day 1 Upto 2 Years (Each Cycle is 21-days)

Collaborators and Investigators

• Sponsor: Artios Pharma Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2023
• Primary Completion (Actual): November 15, 2024
• Study Completion (Actual): May 27, 2025

Study Registration Dates

• First Submitted: March 23, 2023
• First Submitted That Met QC Criteria: March 23, 2023
• First Posted (Actual): April 4, 2023

Study Record Updates

• Last Update Posted (Estimated): November 6, 2025
• Last Update Submitted That Met QC Criteria: November 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Solid Tumors; Monotherapy; Cancer cell; Oral anti-cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Neoplastic Processes; Genital Neoplasms, Female; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Endometrial Neoplasms
• Other Study ID Numbers: ART0380C004; 2023-504153-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No