JSP191 conditioning for patients with AML or MDS: Preliminary results from a phase I clinical trial

During the 2021 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, positive preliminary data from a phase I trial (NCT04429191), evaluating JSP191 as a conditioning agent prior to hematopoietic stem cell transplantation (HSCT) in older patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), was presented as a late-breaking abstract by Lori Muffly, Stanford Medicine.^1,2

JSP191

JSP191 is a first-in-class, humanized, anti-CD117 monoclonal antibody that has demonstrated safe depletion of normal and diseased hematopoietic stem cells in preclinical studies. CD117 is a stem cell factor receptor integral to the survival of hematopoietic stem and progenitor cells. JSP191 perturbs crucial survival pathways, resulting in stem cell death, which allows for the engraftment of transplanted stem cells.¹

Study design

The multi-center, open-label, phase I dose escalation study is investigating the safety, tolerability, and efficacy of JSP191 plus low-dose radiation and fludarabine as a targeted conditioning regimen prior to HSCT in patients aged 65–74 with AML or MDS who are ineligible for full myeloablative conditioning. Primary outcomes of the study were safety and tolerability of JSP191 as a conditioning regimen.¹

Preliminary data

All six patients who received a single dose of JSP191 at 0.6 mg/kg as a conditioning agent experienced successful engraftment following transplantation. Five of the six patients achieved complete donor myeloid chimerism, which persisted in all three of the evaluable patients at Day 90. Of the five patients evaluable for measurable residual disease (MRD) at Day 28, three demonstrated complete MRD negativity by next-generation sequencing, and two patients exhibited considerable reductions in MRD. Across the six patients, no treatment-related serious adverse events were described.^1,2

Conclusion

JSP191 was designed with the aim to provide a well-tolerated and effective outpatient conditioning option for newborn and older patients. These early data show that JSP191, in combination with a standard non-myeloablative regimen, demonstrates encouraging tolerability and efficacy in elderly patients with AML and MDS.