Session: 616. Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Acute Myeloid Malignancies, AML, MDS, adult, Non-Biological therapies, Clinical Research, Chemotherapy, Chronic Myeloid Malignancies, Diseases, Therapies, Myeloid Malignancies, Study Population, Human
Study Design and Methods: This is a Phase 1 single center investigator-initiated trial of BXCL701 in patients with relapsed/refractory AML or relapsed/refractory MDS with blasts ≥10% (ClinicalTrials.gov Identifier: NCT05703542). In the lead-in stage, we will use a 3 + 3 design with 4 dose levels of BXCL701 (0.2 mg, 0.4 mg, 0.6 mg and 0.8 mg). Doses of BXCL701 will be given on Days 1-3, Days 8-10, Days 15-17, and Days 22-24 on a 28-day cycle. The primary objective is to evaluate the safety of BXCL701 in the AML or MDS with ≥ 10% blasts. Secondary objectives include determining the maximum tolerated dose or recommended phase 2 dose, pharmacokinetics, and to estimate response, duration of response and overall survival. Exploratory endpoints include: pharmacodynamic profiling, T-cell response, inhibitory effect on DPP8/9, and evaluation of potential biomarkers such as Copy Number Variants and mRNA levels of DPP8, DPP9, FAP, Caspase-1, Pro-caspase-1, NLRP1, and CARD8.
Major eligibility criteria include: ≥18 years of age, relapsed or refractory AML or relapsed or refractory MDS with ≥10%.refractory to at least 4 cycles of hypomethylating agent, ECOG performance status ≤2, adequate renal function (CrCl ≥30 mL/min), adequate liver function (total bilirubin ≤1.5 x ULN, ALT and AST ≤3 x ULN), WBC <25,000/µL on Day 1 Cycle 1 (hydroxyurea permitted), no symptomatic CNS disease, no active viral or bacterial infections, and >100 days from allogeneic bone marrow transplant with no active graft versus host disease. Patients on gliptin therapy are not permitted on the study due to drug interaction; patients are also excluded if they have a history of orthostatic hypotension or uncontrolled hypertension.
There will be a second phase of the study that will evaluate BXCL701 in combination with a hypomethylating agent (decitabine or azacytidine) and venetoclax. Dose selection of BXCL701 in the combination stage will be based on the data from the single agent study.
Conclusion: The trial is currently open and continuing to enroll.
Disclosures: Winer: Curis Inc: Consultancy; Abbvie: Consultancy. Garcia: Genentech: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; Prelude: Research Funding; Pfizer: Research Funding; AstraZeneca: Research Funding; Astellas: Consultancy; AbbVie: Consultancy, Research Funding; New Wave: Research Funding; Servier: Consultancy; Gilead: Consultancy. Stone: Amgen: Consultancy; Takeda: Other: DSMB; BerGenBio: Consultancy; AvenCell: Consultancy; Lava Therapeutics: Consultancy; Ligand Pharma: Consultancy; Rigel: Consultancy; Kura One: Consultancy; Jazz: Consultancy; Cellularity: Consultancy; Syntrix: Other: DSMB; Hermavant: Consultancy; GSK: Consultancy; Epizyme: Other: DSMB; Aptevo: Other: DSMB; CTI Biopharma: Consultancy; Abbvie: Consultancy. Luskin: Pfizer: Honoraria; Novartis: Honoraria, Research Funding; Jazz: Honoraria; AbbVie: Research Funding. Stahl: Sierra Oncology: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Kymera: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: GME activity ; Haymarket Media: Other: GME activity ; Boston Consulting: Consultancy; Curis Oncology: Other: GME activity ; Dedham group: Consultancy; Clinical care options: Other: GME activity . Chen: Rigel: Consultancy; Abbvie: Consultancy. Deshpande: BioXcel Therapeutics: Current Employment. Borderies: BioXcel Therapeutics: Current Employment. O'Neill: BioXcel Therapeutics: Current Employment. DeAngelo: Blueprint: Honoraria; Novartis: Research Funding; Amgen: Honoraria; Jazz: Honoraria; Kite: Honoraria; Novartis: Honoraria; AbbVie: Research Funding; Blueprint: Research Funding; Autolus: Honoraria; Incyte: Honoraria; Gilead: Honoraria; Servier: Honoraria; Takeda: Honoraria; GlycoMimetics: Research Funding; Pfizer: Honoraria.