A phase 2 study of ART0380 in combination with gemcitabine for the treatment of platinum-resistant ovarian cancer has been initiated (NCT04657068).1
ART0380 is a potential best-in-class oral, highly potent, and selective ATR inhibitor. ATR inhibition can regulate DNA replication stress response, promoting apoptosis. The agent is being evaluated as monotherapy and in combination with other agents for the treatment of solid tumors.
About the Phase 2 Study of ART0380/Gemcitabine
Trial Name: A Phase I/IIa, Open-label, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the ATR Kinase Inhibitor ART0380 Administered Orally as Monotherapy and in Combination to Patients With Advanced or Metastatic Solid Tumors
ClinicalTrials.gov Identifier: NCT04657068
Sponsor: Artios Pharma Ltd
Recruitment Contact: Sarah Cannon Development Innovations, 844-710-6157, CANN.InnovationsMedical@sarahcannon.com
Completion Date: December 2023
Antonio Gonzalez-Martin, MD, PhD, president and founding member of the Spanish Ovarian Cancer Research Group (GEICO) and principal investigator for the trial, said, in a press release, “Ovarian cancer continues to be a difficult to treat cancer that ultimately leads to relapse. We are excited to collaborate with Artios to help bring an ATR targeted therapy with the potential to be highly effective in patients with platinum-resistant disease who are in much need of innovative treatment options. The favorable pharmacokinetic profile enabling combination with DNA damaging agents offers the potential of a new treatment option for patients with platinum resistant ovarian cancer. We at GEICO are looking forward to offering this novel treatment approach to our patients in the trial.”
The open-label, multi-center phase 2 study will assess the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of ART0380 in combination with gemcitabine. It follows encouraging phase 1 results.2
In the phase 1 dose-escalation portion of the study ART0380 and gemcitabine showed an expected safety profile. Although hematological toxicities occurred, the toxicities were all predictable, manageable, and reversible. There was no evidence of off-target toxicity. ART0380 also demonstrated good pharmacodynamic and PK profiles.3
The phase 2 portion of the study will include approximately 232 patients with platinum-resistant ovarian cancer. The primary end point to be explored in the study is progression-free survival by RECISTs v1.1. The secondary end points of the study include the number of patients with adverse events, objective response rate, duration of response, PFS, PK, and the assessment of tumor biopsies by immunohistochemistry to detect ATM mutations.2
To be eligible for inclusion, patients must not previously have received a therapy that targets the ATR/CHK1 pathway, and have discontinued all prior cancer treatments for at least 21 days. Patients with BRCA mutations who are eligible for treatment with a PARP inhibitor must have received their PARP inhibitor prior to be enrolled in the study.
Patients are also required to have at least 1 radiographically evaluable lesion and a non-irradiated tumor tissue sample. Acceptable hematologic, renal, hepatic, and coagulation functions are required by potential enrollees, and they must have an estimated life expectancy of at least 12 weeks.
“This is the first of 3 proof of concept phase 2 studies planned to evaluate our potentially best-in-class ATR inhibitor, ART0380, that has demonstrated a favorable safety and tolerability profile and clinical activity in the phase 1 dose escalation. We are delighted to be collaborating with ovarian cancer experts at GEICO in Spain on this important study that will help bolster our understanding of the therapeutic potential of ART0380 and further inform our clinical development strategy. We look forward to initial phase 2 data expected in the first half of 2025,” said Niall Martin, PhD, chief executive officer of Artios, in the press release.1
1. Artios announces initiation of phase 2 randomized trial for ATR Inhibitor ART0380 plus gemcitabine in patients with platinum resistant ovarian cancer. News release. February 10, 2023. Accessed February 10, 2023. https://bit.ly/3xfdH4k
2. Artios announces ATR inhibitor, ART0380, development on track and progressing into phase 1b evaluation. News release. April 5 2022. Accessed February 10, 2023. https://bit.ly/40QfFWb
3. A study of ART0380 for the treatment of advanced or metastatic solid tumors. ClinicalTrials.gov. Updated July 7, 2022. Accessed February 10, 2023. https://clinicaltrials.gov/ct2/show/NCT04657068