Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Methods: The objectives of this cohort are to evaluate the maximum tolerated dose, dose- limiting toxicity (DLT), safety, pharmacokinetic/pharmacodynamic profiles, and preliminary efficacy of CTX-712 and to determine the RD for the next phase in patients with hematologic malignancies. A 3+3 design is used for finding the RD. An initial CTX-712 dose of 105 mg twice a week was used based on the safety information of the preceding solid tumor dose escalation cohort.
Results: As of April 28, 2022, a total of 6 patients (5 AML and 1 MDS) were enrolled in the initial 105 mg twice-a-week dosing cohort. Three of the 6 patients were considered non-evaluable for DLT analysis (2 patients received less than 75% of the dose in cycle 1 due to tumor lysis syndrome, 1 patient discontinued treatment due to disease progression before completing cycle 1). A DLT of Grade 4 pneumonia was observed in 1 of 3 DLT-evaluable patients. Based on these safety profiles, the safety monitoring committee recommended to suspend the 105 mg twice-a-week dosing cohort and to initiate a 70 mg twice-a-week dosing cohort.
Among the safety analysis population (N=6), with a median treatment duration of 114 days (Range 15-609 days), the common any-grade adverse events (AEs) (≥30%) were nausea (100%), diarrhea, hypotension (66.7%), vomiting, blood creatinine increased, pyrexia, insomnia (50.0%), fatigue, malaise, amylase increased, tumour lysis syndrome, dysgeusia, nail discoloration, dry skin, rash, and oedema (33.3%). The most common Grade 3 or higher AE was tumour lysis syndrome (33.3%).
In the AML patients (N=5), complete remission (CR) was observed in two patients (40.0%), and CR with incomplete hematologic recovery (CRi) was observed in one patient (20.0%). The median time to remission is 56 days (Range 29-57 days), and the median duration of response is 56 days (Range 49+-532 days). In the MDS patient (N=1), CR was observed. Pharmacokinetic/pharmacodynamic profiles of the hematologic malignancies cohort were comparable with those of the solid tumor cohort in the same dosage.
Conclusions: Assessment of CTX-712 safety profile for hematologic malignancies is ongoing. CTX-712 showed preliminary anti-tumor efficacy for both AML and MDS.
Clinical trial information: JapicCTI-184188
Disclosures: Yokoyama: Astellas: Honoraria; BMS: Honoraria; Janssen: Honoraria; Sanofi: Honoraria. Fukuhara: Abbvie: Consultancy; Nippon Shinyaku: Honoraria; Kyowa kirin: Honoraria; Janssen: Honoraria; Eisai: Honoraria; Dainippon Sumitomo: Honoraria; Incyte: Research Funding; Genmab: Research Funding; BMS: Honoraria, Research Funding; Chugai pharma: Honoraria, Research Funding; Bayer: Research Funding; Novartis: Consultancy, Honoraria; HUYA: Consultancy; Eli Lilly: Consultancy; AstraZeneca: Consultancy, Honoraria; Sanofi: Honoraria; Ono pharma: Honoraria; Celgene: Honoraria, Research Funding; Symbio: Honoraria; Takeda: Honoraria. Iida: Chugai: Research Funding; Astellas: Honoraria; Novartis: Honoraria; Janssen: Honoraria; bristol myers squibb: Honoraria. Miyake: Takeda Pharmaceutical Company Ltd.: Current equity holder in publicly-traded company, Patents & Royalties: Chordia has royalty bearing rights to execute Takeda's CLK inhibitor etc. patent., Research Funding; Chordia Therapeutics Inc.: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees. Tanoue: Chordia Therapeutics Inc.: Current Employment; Eisai Inc.: Ended employment in the past 24 months. Tozaki: Honda Motor Co., Ltd.: Current equity holder in publicly-traded company; Kyowa Kirin Co., Ltd.: Current Employment, Patents & Royalties: Japanese Patent Application No.2002-078819; Chordia Therapeutics inc.: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties. Mizutani: Chordia Therapeutics inc.: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties. Morishita: Chordia Therapeutics lnc: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company, Patents & Royalties. Takeyama: Chordia Therapeutics Inc: Consultancy, Current equity holder in private company, Ended employment in the past 24 months. Shimizu: Eli Lilly: Honoraria, Research Funding, Speakers Bureau; LOXO Oncology: Research Funding; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi-Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Chordia Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Research Funding; Eisai: Research Funding; AstraZeneca: Research Funding; Takeda Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; 3D-Medicine: Research Funding; Symbio Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astellas Pharma: Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Honoraria, Speakers Bureau. Yamamoto: Astellas: Research Funding; Chugai: Research Funding; Eisai: Research Funding; Taiho: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Eli Lilly: Research Funding; AbbVie: Research Funding; Daiichi-Sankyo: Research Funding; Bayer: Research Funding; Boehringer Ingelheim: Research Funding; Kyowa Kirin: Research Funding; Takeda: Research Funding; ONO: Research Funding; Janssen Pharma: Research Funding; MSD: Research Funding; MERCK: Research Funding; GSK: Research Funding; Sumitomo Dainippon: Research Funding; Chiome Bioscience: Research Funding; Otsuka: Research Funding; Ciome Biosciences: Research Funding; Genmab: Research Funding; Shionogi: Research Funding; TORAY: Research Funding; Eisai: Consultancy; Takeda: Consultancy; Otsuka: Consultancy; Boehringer Ingelheim: Consultancy; Cimic: Consultancy; Chugai: Consultancy; AstraZeneca: Speakers Bureau; Eli Lilly: Speakers Bureau; ONO: Speakers Bureau; Chugai: Speakers Bureau; Sysmex: Speakers Bureau; Daiichi-Sankyo: Speakers Bureau; Eisai: Speakers Bureau.
OffLabel Disclosure: CTX-712 clinical trial compound