ATG-008/Toripalimab Yields Promising Responses in Relapsed/Metastatic Cervical Cancer

Preliminary results from the phase 1/2 TORCH-2 study (NCT04337463) highlighted the promising responses produced from ATG-008 (onatasertib) and toripalimab (Tuoyi) in patients with relapsed/metastatic cervical cancer, according to a press release from Antengene.

Preliminary data from the trial indicated that ATG-008 and toripalimab yielded an objective response rate (ORR) of 52.4% regardless of PD-L1 status in a population of 21 patients. Additionally, 10 patients had a partial response (PR), and 1 patient achieved a complete response. Of the responders, 5 are still responding and 2 achieved stable disease and are continuing with treatment. The ORR among patients with PD-L1–positive cancer was 77.8% (n = 7/9), and 1 of 2 patients exposed to checkpoint inhibitors also reached PR. The median progression-free survival (PFS) was 5.5 months. Moreover, treatment with ATG-008 on its own and in combination with toripalimab yielded a manageable safety profile that was comparable with previously reported global studies.

Initial results from the study were presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

“The…ORR from the TORCH-2 study with ATG-008 and toripalimab in patients with relapsed/metastatic cervical cancer, coupled with a manageable safety profile, is an exciting result that provides a potential guide to a registration program for ATG-008,” Jay Mei, MD, founder, chairman, and chief executive officer of Antengene, said in the press release. “Antengene intends to review the data with the Chinese [Center for Drug Evaluation] and move forward into pivotal studies as quickly as possible.”

The open-label, single-arm phase 1/2 TORCH-2 study was designed to assess the efficacy and safety of mTORC 1/2 inhibitor ATG-008 combined with PD-1 antibody toripalimab in patients with advanced solid tumors. Patients received oral ATG-008 tablets with intravenous infusions of toripalimab, including 9 patients (42.9%) who had PD-L1–positive tumors.

Primary end points of the TORCH-2 study included determining the maximum tolerated dose and recommended phase 2 dose, as well as ORR. Secondary end points included duration of response (DOR), disease control rate, PFS, and overall survival.

Patients 18 to 70 years in age with at least 1 measurable lesion according to RESIST 1.1 criteria were eligible to enroll on the study. Additional inclusion criteria included having an ECOG performance status of 0 or 1, adequate bone marrow function, and a life expectancy longer than 3 months. Patients with a history of hepatic encephalopathy or a thyroid disorder with clinically significant thyroid dysfunction were unsuitable for enrollment.

The pharmacokinetics, safety, tolerability, and efficacy of oral ATG-008 were also evaluated as part of the a multi-regional, open-label phase 2 TORCH trial (NCT03591965) in patients with hepatitis B positive hepatocellular carcinoma for whom at least 1 prior line of systemic therapy had failed. In the 45 mg per day monotherapy dosing cohort, the agent demonstrated an ORR of 16.7% including 3 confirmed PRs in a population of 18 patients. Two of 3 patients with PRs were previously treated with a PD-1/PD-L1 antibody. Additionally, the median DOR for patients in the monotherapy cohort was 4.3 months.

Reference

Antengene highlights encouraging ATG-008 efficacy results from TORCH-2 study in combination with PD-1 antibody in relapsed/metastatic cervical cancer. News release. Antengene. November 15, 2022. Accessed November 16, 2022. yhoo.it/3VjaIBZ