Abstract CT078: Cyfi: Results from a Phase Ib expansion cohort of anti-hepatocyte growth factor and cytarabine in relapsed and refractory AML

Abstract

Abstract Objective: Patients with AML who are refractory to induction therapy or relapse within 1 year have poor outcomes. Elevated serum hepatocyte growth factor (HGF) level is an adverse prognostic factor. Pre-clinical models have shown that myeloid blasts produce HGF in an autocrine fashion and pharmacologic blockade of the HGF/c-Met axis sensitizes blasts to cell death. We initiated a Phase Ib study with dose expansion cohort study to assess the safety and tolerability of the anti-HGF antibody ficlatuzumab with cytarabine in AML patients who are refractory to 7+3 or have relapsed within 1 year of induction. Methodology: The 3 x 3 design was used for the Phase I with an expansion cohort of an additional 13 patients accrued and treated at the MTD. Ficlatuzumab was administered in escalated dosing of 10, 15, or 20 mg/Kg for 4 doses every 2 weeks starting on day 1. 20 mg/Kg dose was used for the expansion cohort. Cytarabine was administered at a fIxed dose of 2 g/m2 on days 2-7. PBMCs were collected at defined time points. Differential expression from multiplexed single cell RNA sequencing (scRNAseq) was used to assess biomarkers predictive of response. Results: Of the total 18 patients accrued thus far, 16 are evaluable. 5 had progressive disease, and 11 responded, all complete responses. Most frequent grade 3/4 TEAEs were febrile neutropenia, LFT abnormalities, and electrolyte disturbance. There was 1 death from sepsis and multi-organ failure on day 23, following ANC recovery, from the disease, and 1 patient who withdrew from the study due to grade 4 gastrointestinal bleed, likely ficlatuzumab related, both prior to response assessment. scRNA sequencing identified a TNF alpha and IFN gamma inflammatory signature that correlates with response to ficlatuzumab at count recovery. Conclusion: Cytarabine and ficlatuzumab is a safe combination with promising efficacy in high risk relapsed and refractory AML. This combination is warranted in further Phase II studies. scRNAseq may be used to identify biomarkers of response. Citation Format: Victoria E. Wang, Charalambos Andreadis. Cyfi: Results from a Phase Ib expansion cohort of anti-hepatocyte growth factor and cytarabine in relapsed and refractory AML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT078.