An objective response rate (ORR) of 52.4% was observed in relapsed or metastatic cervical cancer in Phase I/II TORCH-2 Study of ATG-008 (onatasertib) in combination with toripalimab, regardless of PD-L1 status Study builds on promising results of Phase II TORCH monotherapy study in HBV+ patients with unresectable hepatocellular carcinoma (HCC) which demonstrated an ORR of 16.7% in the 45 mg per day dosing cohort Activity also seen in patients with prior CPI treatment Antengene plans to meet with the Center for Drug Evaluation (CDE) of China and move forward to pivotal study in cervical cancer as soon as possible
SHANGHAI and HONG KONG, Nov. 15, 2022 /PRNewswire/ — Antengene Corporation Limited (“Antengene” SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, today highlighted preliminary positive results from the TORCH-2 study of ATG-008 (onatasertib) used in combination with toripalimab (PD-1 antibody) in relapsed/metastatic cervical cancer patients (NCT04337463). The combination therapy demonstrated an ORR of 52.4% (based on all treated patients) regardless of PD-L1 status. The results are based on early data from 21 patients, including 10 patients who reached partial response (PR) and 1 patient who achieved a complete response (CR). Five out of the ten responders are still responding, and two patients who are currently in stable disease (SD) still remain on treatment. The median progression free survival (PFS) for these patients is currently 5.5 months.
Notably, in the TORCH-2 study, the ORR for PD-L1 positive subjects was 77.8% (7/9). In addition, 1 out of 2 CPI-exposed patients also reached PR.
Antengene also highlighted data from the 45 milligram (mg) per day monotherapy dosing cohort of the open-label Phase II TORCH Trial in subjects with Hepatitis B positive (HBV+) unresectable HCC who have received at least one prior line of systemic therapy (NCT03591965). ATG-008 monotherapy demonstrated a 16.7% ORR based on 3 confirmed PRs out of 18 patients in this cohort. The median duration of response (DOR) for these patients is 4.3 months. In the TORCH study, 2 of the 3 patients with PRs were previously treated with a PD-1/PD-L1 antibody.
Treatment with ATG-008 monotherapy and in combination with toripalimab was associated with manageable side effects, similar to observations in previous global studies with ATG-008. ATG-008’s pharmacokinetic profiles were comparable between ATG-008 monotherapy and the combination with PD-1 antibody and across Asia Pacific (including Greater China) and the U.S. populations.
“The 52.4% 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. Antengene intends to review the data with the Chinese CDE and move forward into pivotal studies as quickly as possible.” said Dr. Jay Mei, Antengene’s Founder, Chairman and CEO.
Dr. Mei continued, “Data from the TORCH and TORCH-2 studies have also demonstrated activity of ATG-008 in patients who have failed previous CPI treatments. This is an important signal that warrants further investigation in a group of patients where there is a desperate need. Importantly, observation of a 16.7% ORR as a monotherapy in the TORCH study is a strong validation of ATG-008’s single agent activity.”
The updated and detailed study results of the TORCH and TORCH-2 will be presented at international scientific conferences in 2023.
About the TORCH-2 Trial
The TORCH-2 trial (NCT04337463) was designed to evaluate the safety and efficacy of ATG-008 combined with toripalimab (PD-1 antibody) in subjects with advanced solid tumors. Promising signals in several tumor types were observed, especially in advanced cervical cancer. As of the Oct 21, 2022 efficacy evaluation, 21 cervical cancer patients had been dosed with the ATG-008/toripalimab combination including 9 patients (42.9%) who were PD-L1 positive. Initial results of the TORCH-2 study were presented at the 2022 American Society of Clinical Oncology (ASCO 2022) Annual Meeting.
About the TORCH Trial
The TORCH trial was designed as a multi-regional clinical trial to evaluate the pharmacokinetics, safety, tolerability and efficacy of oral ATG-008 in hepatitis B positive (HBV+) hepatocellular carcinoma (HCC) who had failed at least one prior line of systemic therapy. ATG-008 was administered daily until radiological disease progression (according to RECIST 1.1 criteria) or intolerable toxicity. A total of 73 subjects from mainland China, Taiwan, and South Korea were enrolled in the trial in four dosing cohorts (15 mg per day, 30 mg per day, 20 mg twice a day and 45 mg per day).
In the 18 subjects of the 45 mg per day dosing cohort, ATG-008 demonstrated a 16.7% ORR, based on 3 confirmed partial responses (PRs), validating the single agent activity of ATG-008. Notably, 2 of the 3 confirmed PRs were previously treated with a PD-1/PD-L1 antibody.
ATG-008 (onatasertib) is an orally available mTORC 1/2 inhibitor. ATG-008 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, has an important role in the PI3K/AKT/mTOR signaling pathway, which is frequently dysregulated in human cancers. ATG-008 has been studied in clinical trials to treat a broad range of tumor types including multiple myeloma (MM), glioblastoma (GBM), hepatocellular carcinoma (HCC), non-small cell lung cancer (NSCLC), diffuse large B-cell lymphoma (DLBCL), etc.
Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, driven by its vision of “Treating Patients Beyond Borders”.
Since its founding in 2017, Antengene has built a broad and expanding pipeline of 15 clinical and preclinical assets, including 10 assets with global rights and 5 with rights for Asia Pacific markets including the Greater China region. To date, Antengene has obtained 26 investigational new drug (IND) approvals in Asia and the U.S., and submitted 6 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in mainland China, Taiwan, South Korea, Singapore and Australia.
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