a study of ft-2102 in patients with advanced solid tumors and gliomas with an idh1 mutation

Conditions: Cohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme); Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas); Cohort 3a and 3b: Chondrosarcoma; Cohort 4a and 4b: Intrahepatic Cholangiocarcinoma; Cohort 5a: Other Non-Central Nervous System Solid Tumors With IDH1 Mutations

Summary: this phase 1/2 study will evaluate the safety, efficacy, pk, and pd of ft-2102 as a single agent and in combination with other anti-cancer drugs in patients with advanced solid tumors and gliomas. the study is divided into two parts: single agent ft-2102 followed by combination therapy. part 1: a single agent, open-label study in up to five cohorts (glioma, hepatobiliary tumors, chondrosarcoma, intrahepatic cholangiocarcinoma, and other idh1 mutant solid tumors) that will include a phase 1 dose confirmation followed by a phase 2 investigation of clinical activity in up to 4 cohorts. during the dose confirmation, additional doses or altered dose schedules may be explored. part 2: an open-label study of ft-2102 in combination with other anti-cancer agents. patients will be enrolled across 4 different disease cohorts, examining the effect of ft-2102 + azacitidine (glioma and chondrosarcoma), ft-2102 + nivolumab (hepatobiliary tumors), and ft-2102 + gemcitabine/cisplatin (intrahepatic cholangiocarcinoma). there will be a safety lead-in followed by a phase 2 evaluation in up to four cohorts of patients.


Eligibility criteria:
key inclusion criteria: * patients must have documented idh1-r132 gene-mutated disease as evaluated by site * glioma: advanced glioma that has recurred or progressed following standard therapy, or that has not responded to standard therapy. * hepatobiliary cancer that is relapsed/refractory or intolerant to approved standard-of-care therapy (including: hepatocellular carcinoma, bile duct carcinoma, intrahepatic cholangiocarcinoma or other hepatobiliary carcinomas) * chondrosarcoma that is relapsed or refractory and either locally advanced or metastatic and not amenable to complete surgical excision * intrahepatic cholangiocarcinoma that is advanced nonresectable or metastatic cholangiocarcinoma not eligible for curative resection or transplantation. phase 1b/safety lead-in of phase 2: relapsed or refractory disease. combination phase 2 (beyond safety lead-in): have received no more than 1 cycle of gemcitabine/cisplatin therapy * other solid tumors that have relapsed or refractory to standard-of-care therapy with no other available therapeutic options * good performance status * good kidney and liver function key exclusion criteria: * prior solid organ or hematopoietic cell transplant * prior treatment with idh1 inhibitor (single agent cohorts only) * congestive heart failure (new york heart association class iii or iv) or unstable angina pectoris. previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias * unstable or severe, uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition, including pneumonitis and/or interstitial lung disease, and uncontrolled diabetes) * active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy * pd-1 only: active autoimmune disease

Keywords: olutasidenib