Study of ATR Kinase Inhibitor ART0380 as Monotherapy in Biologically Selected Advanced/Metastatic Solid Tumors Patients

• Status: Not yet recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Artios Pharma Ltd

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 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

3. warfarin. Note: Factor Xa inhibitors are permitted

• Patients who plan to father a child while in the study or within 16 weeks after the last administration of study treatment.