study of art0380 in patients with biologically selected solid tumors

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

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).

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.

Keywords: solid tumors monotherapy cancer cell oral anti-cancer