Clinical trial NCT05798611: Study of ART0380 in Patients With Biologically Selected Solid Tumors
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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Advanced Solid Tumor
Recurrent Endometrial Cancer
Metastatic Cancer
Keywords: Solid Tumors
Monotherapy
Cancer cell
Oral anti-cancer
Lead sponsor: Artios Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2023-04-04
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Until disease progression (Every 6 weeks from randomization Upto 2 Years)
Secondary outcomes:
measure: Number of patients with adverse events
timeFrame: From Cycle 1 (each Cycle is 21-day) Day 1 until 30-day follow-up visit (Upto 2 Years)
measure: Progression free survival (PFS)
timeFrame: Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
measure: Best overall response (BOR)
timeFrame: Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
measure: Disease control rate (DCR)
timeFrame: Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
measure: Duration of response (DOR)
timeFrame: Screening (≤28 days) Until disease progression or death (Every 6 weeks from randomization Upto 2 Years)
measure: Change in tumor size
timeFrame: Screening (≤28 days) Until disease progression (Every 6 weeks from randomization Upto 2 Years)
measure: Overall survival (OS)
timeFrame: Screening (≤28 days) Until overall survival follow-up (Every 12 weeks until data cut-off)
measure: Maximum plasma concentration (Cmax)
timeFrame: 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)
measure: Half life (t1/2)
timeFrame: 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)
measure: Area under the plasma concentration-time curve from zero to infinity (AUC0-inf)
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles (UCLA)
state: California
city: Chicago
country: United States
facility: The University of Chicago
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Lake Success
country: United States
facility: Northwell Health R.J. Zuckerberg Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center (MSKCC) - Memorial Hospital - Oncology
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma/Sarah Cannon Research Institute
state: Oklahoma
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: Providence
country: United States
facility: Women and Infants Hospital
state: Rhode Island
city: Angers
country: France
facility: Institut de Cancérologie de l'Ouest
state: NAP
city: Caen
country: France
facility: Centre Francois Baclesse - Service d'Oncologie médicale
state: NAP
city: Paris
country: France
facility: Hopital Cochin Saint Vincent De Paul
state: NAP
city: Pierre-Benite
country: France
facility: Hopital Lyon Sud
state: NAP
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire De Poitiers
state: NAP
city: Jaén
country: Spain
facility: Hospital Universitario De Jaén
state: Andalucía
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano De Oncología
Study officials:
References: