Novel Dual IDH-Inhibitor Plus Chemotherapy Showed Promising Efficacy, Safety for Patients With Advanced IDH-Mutant Cholangiocarcinoma

First-In-Human Phase 1 Study of LY3410738

At the 2023 World Congress on Gastrointestinal Cancers, James Harding, MD, Memorial Sloan Kettering Cancer Center, New York, New York, the dual IDH1/2 inhibitor LY3410738 in combination with cisplatin-gemcitabine demonstrated preliminary efficacy among patients with locally advanced or metastatic IDH1/2 mutant cholangiocarcinoma.

Transcript:

Hi, I'm James Harding. I'm Assistant Attending at Memorial Sloan Kettering Cancer Center. I'm a member of the Gastrointestinal Oncology and Early Drug Development Service. And I'm really glad to be joining you here at the 2023 World Congress on GI Cancers. I presented data related to the treatment of IDH1 and IDH2 mutant cholangiocarcinomas. Intrahepatic cholangiocarcinoma is an uncommon disease and about 20% of patients harbor oncogenic mutations in IDH1, and about 1% to 2% harbor IDH2 alterations.

We assessed a novel compound, LY341 in these patients. This therapy is a small molecule, targeted therapy that's selective for IDH1 and IDH2. We treated 81 total patients, 44 with intrahepatic cholangiocarcinoma as monotherapy. In that cohort, we observed response rate of 6% for the IDH1-altered tumors, 9% for the IDH2-altered tumors. And meaningful extension of clinical benefit in a subset of patients.

Given those data, we expanded our study to look at patients that had been treatment-naive and added LY341 to cisplatin-gemcitabine. Here, we observed that the treatment was safe and tolerable, had favorable pharmacokinetics, and an objective response rate of 46% in 13 patients that were treated. This is really important evidence that this is a key target for the disease. We continue to enroll patients in this cohort, and will present updated data with longer follow up at an upcoming meeting.

Thank you so much. It's been great to be of the World Congress of Gastrointestinal Cancers, 2023. Look forward to seeing you next year at the meeting. Thank you.

Source:

Harding J, Ikeda M, Goyal L, et al. A first-in-human phase 1 study of LY3410738, a covalent inhibitor of mutant IDH1 and IDH2, as monotherapy and in combination with cisplatin and gemcitabine in advanced IDH-mutant cholangiocarcinoma. Presented at World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract SO-1