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Study of ART0380 in Advanced/Metastatic Solid Tumors Patients (ARTIST)

Primary Purpose

Advanced Solid Tumor, Recurrent Endometrial Cancer, Metastatic Cancer

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ART0380
Sponsored by
Artios Pharma Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Solid Tumor focused on measuring Solid Tumors, Monotherapy, Cancer cell, Oral anti-cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 receiving potent inhibitors and inducers of CYP3A4 or CYP3A4 substrates which have a narrow therapeutic range or CYP3A4 sensitive substrates within 2 weeks before the first dose of study treatment will be excluded. Patients receiving the following within 2 weeks of the first dose will be excluded from study treatment. P-glycoprotein or breast cancer resistance protein (BCRP) inhibitors Statins 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.

Sites / Locations

  • Dana Farber Cancer CenterRecruiting
  • Northwell Health R.J. Zuckerberg Cancer CenterRecruiting
  • Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital - OncologyRecruiting
  • University of Oklahoma/Sarah Cannon Research InstituteRecruiting
  • Western Pennsylvania HospitalRecruiting
  • Women and Infants HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1 [ART0380 monotherapy (endometrial cancer patients)]

Arm 2 [ART0380 monotherapy (solid tumors patients)]

Arm Description

Patients with persistent or recurrent endometrial cancer (EC) will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Patients with advanced or metastatic solid tumors will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Number of patients with adverse events
To assess the safety and tolerability of ART0380 in patients with solid tumors.
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.
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.
Disease control rate (DCR)
To further explore the efficacy of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.
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.
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.
Overall survival (OS)
The OS is defined as the time from the randomization until death due to any cause.
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.
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.
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.

Full Information

First Posted
March 23, 2023
Last Updated
September 27, 2023
Sponsor
Artios Pharma Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05798611
Brief Title
Study of ART0380 in Advanced/Metastatic Solid Tumors Patients
Acronym
ARTIST
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 6, 2023 (Actual)
Primary Completion Date
March 2025 (Anticipated)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Artios Pharma Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor, Recurrent Endometrial Cancer, Metastatic Cancer
Keywords
Solid Tumors, Monotherapy, Cancer cell, Oral anti-cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 [ART0380 monotherapy (endometrial cancer patients)]
Arm Type
Experimental
Arm Description
Patients with persistent or recurrent endometrial cancer (EC) will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.
Arm Title
Arm 2 [ART0380 monotherapy (solid tumors patients)]
Arm Type
Experimental
Arm Description
Patients with advanced or metastatic solid tumors will receive ART0380 monotherapy on either a continuous daily dose or on an intermittent schedule for a 21-day cycle.
Intervention Type
Drug
Intervention Name(s)
ART0380
Intervention Description
Randomized patients will orally receive ART0380.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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).
Time Frame
Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Secondary Outcome Measure Information:
Title
Number of patients with adverse events
Description
To assess the safety and tolerability of ART0380 in patients with solid tumors.
Time Frame
From Cycle 1 (each Cycle is 21-day) Day 1 until 30-day follow-up visit (Upto 2 Years)
Title
Progression free survival (PFS)
Description
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.
Time Frame
Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Title
Best overall response (BOR)
Description
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.
Time Frame
Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Title
Disease control rate (DCR)
Description
To further explore the efficacy of ART0380 in patients with solid tumors enrolled in each of the biologically defined arms.
Time Frame
Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Title
Duration of response (DOR)
Description
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.
Time Frame
Screening (≤28 days) Until disease progression or death (Every 6 weeks from randomization Upto 2 Years)
Title
Change in tumor size
Description
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.
Time Frame
Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Title
Overall survival (OS)
Description
The OS is defined as the time from the randomization until death due to any cause.
Time Frame
Screening (≤28 days) Until overall survival follow-up (Every 12 weeks until data cut-off)
Title
Maximum plasma concentration (Cmax)
Description
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.
Time Frame
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)
Title
Half life (t1/2)
Description
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.
Time Frame
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)
Title
Area under the plasma concentration-time curve from zero to infinity (AUC0-inf)
Description
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.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 receiving potent inhibitors and inducers of CYP3A4 or CYP3A4 substrates which have a narrow therapeutic range or CYP3A4 sensitive substrates within 2 weeks before the first dose of study treatment will be excluded. Patients receiving the following within 2 weeks of the first dose will be excluded from study treatment. P-glycoprotein or breast cancer resistance protein (BCRP) inhibitors Statins 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Artios Pharma
Phone
+44 (0)1223 867 900
Email
info@artios.com
Facility Information:
Facility Name
Dana Farber Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwell Health R.J. Zuckerberg Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Individual Site Status
Recruiting
Facility Name
Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital - Oncology
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Oklahoma/Sarah Cannon Research Institute
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Name
Western Pennsylvania Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Individual Site Status
Recruiting
Facility Name
Women and Infants Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of ART0380 in Advanced/Metastatic Solid Tumors Patients

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