Study of ART0380 in Patients With Biologically Selected Solid Tumors

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.

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.