Study of ART0380 in Patients With Biologically Selected Solid Tumors

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).

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.

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.