A Phase IIa, Open-label, Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Venetoclax Plus Decitabine in Patients With AML Who Are Ineligible for Intensive Induction Therapy

Improvement of clinical benefit in fragile AML patients while maintaining tolerability is an important area of further clinical development. Modern aggressive combination chemotherapy can induce CR in a significant proportion of patients with previously untreated AML, but relapse occurs in most unless patients undergo intensive allogeneic hematopoietic stem cell transplantation. Novel therapies are needed for these patients

The Grb2 gene has been mapped to the human chromosome region 17q22-qter, a region that is duplicated in leukemias and solid tumors, which may result in an increased copy number of the Grb2 gene product. As Grb2 is important for the transformation of murine hematopoietic cells, and the proliferation of human leukemia cells that express high levels of oncogenic tyrosine kinases, inhibition of Grb2 may have a significant impact on the natural history of leukemias. The study drug (BP1001) may be able to inhibit the cells from making Grb-2. Researchers hope that without this protein, the leukemia cells will die.

This represents an area in which targeted therapies might be of benefit to these patients. One such potential treatment is BP1001, liposomal anti-sense treatment directed against Growth Factor Receptor-Bound Protein 2 (Grb2). Decitabine is approved in Europe for the treatment of adult patients with newly diagnosed de novo or secondary acute myeloid leukemia (AML). In vitro studies in AML cells co-incubated with BP1001 and decitabine suggests that treatment of AML patients with decitabine followed by BP1001 may be a combination that could benefit patients with AML.

This Phase IIa, multicenter, study of BP1001 in combination with Ventoclax plus decitabine will enroll participants with AML who are not otherwise eligible for for intensive induction therapy.

This trial will utilize an open label design to assess the safety profile, PK, PD, and efficacy of of BP1001 in combination with Ventoclax plus decitabine to assess whether the combination of either provides greater efficacy than intensive chemotherapy alone.