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

Artios Pharma

Status and phase: Enrolling; Phase 2

Conditions: Metastatic Cancer; Recurrent Endometrial Cancer; Advanced Solid Tumor

Treatments: Drug: ART0380

Study type: Interventional

Funder types: Industry

Identifiers

NCT05798611

ART0380C004

2023-504153-12 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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.

  1. P-glycoprotein or breast cancer resistance protein (BCRP) inhibitors
  2. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Arm 1 [ART0380 monotherapy (endometrial cancer patients)]

Experimental group

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.

Treatment:

Drug: ART0380

Arm 2 [ART0380 monotherapy (solid tumors patients)]

Experimental group

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.

Treatment:

Drug: ART0380