Onatasertib Plus Toripalimab Elicits Early Responses in Relapsed/Metastatic Cervical Cancer

Jai Mei, MD, PhD

Onatasertib (ATG-008) plus toripalimab elicited an objective response rate (ORR) of 52.4% in patients with relapsed or metastatic cervical cancer, irrespective of PD-L1 expression, according to preliminary data from the phase 2 TORCH trial (NCT03591965).¹

In 21 evaluable patients, 1 patient achieved a complete response (CR) to the combination and 10 patients experienced a partial response (PR). Five patients are still responding to treatment and 2 patients with stable disease are still receiving the regimen. The median progression-free survival with the doublet is 5.5 months in these patients.

For patients with PD-L1 positivity, onatasertib plus toripalimab induced an ORR of 77.8%. Moreover, 1 out of 2 patients who previously received checkpoint inhibitors also experienced a PR to treatment.

“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,” Jai Mei, MD, PhD, founder, chairman, and chief executive officer of Antengene Corporation Limited, stated in a press release. “Antengene intends to review the data with the Chinese CDE and move forward into pivotal studies as quickly as possible.”

TORCH-2 enrolled patients between the ages of 18 years and 70 years with at least 1 measurable lesion by RECIST v1.1 criteria and an ECOG performance status of 0 or 1.² To be eligible for enrollment, patients were required to have acceptable bone marrow function and a life expectancy of longer than 3 months.

If they had a history of hepatic encephalopathy; a thyroid disorder with a significant thyroid dysfunction; active or a history of upper gastrointestinal bleeding, ulcers, or esophageal varices; undergone a major surgery within 4 weeks before the first study dose; a history of organ transplantation; or poorly controlled pleural or pericardial effusion during the screening period, among other criteria, they were excluded.

The study is comprised of 2 parts. In the dose-escalation phase of the research, investigators set out to evaluate safety and tolerability of onatasertib plus toripalimab.³ Study participants were given oral onatasertib at a once daily dose of 15 mg, 20 mg, and 30 mg in combination with toripalimab at 240 mg once every 3 weeks.

The key objectives for the expansion phase of the trial includes evaluating antitumor activity and confirming the safety and tolerability of the regimen. The primary end points are to identify the maximum tolerated dose, the recommended phase 2 dose, and efficacy.

Prior data from the trial presented at the 2022 ASCO Annual Meeting showed that at a data cutoff date of December 20, 2021, the ORR among 21 patients evaluable for efficacy was 28.6%, and the disease control rate was 71.4%. Among the 5 evaluable patients with cervical cancer, 1 patient had a CR and 3 had a PR. One patient with cervical cancer who had PD-L1 negativity experienced a CR.³

Updated findings from TORCH-2 will be shared at upcoming medical meetings in 2023.

References

1. 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 Corporation Limited. November 15, 2022. Accessed November 16, 2022. http://bit.ly/3Grid5o
2. ATG-008 combined with toripalimab in advanced solid tumors. ClinicalTrials.gov. Updated May 17, 2021. Accessed November 16, 2022. https://clinicaltrials.gov/ct2/show/NCT04337463
3. Shu P, Li X, Yuan L, et al. A phase 1/2 study of onatasertib, a dual TORC1/2 inhibitor, combined with the PD-1 antibody toripalimab in patients with advanced solid tumors (TORCH-2). J Clin Oncol. 2022;40(suppl 16):2610. doi:10.1200/JCO.2022.40.16_suppl.2610