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BP1001 in combination with Ventoclax plus decitabine

BP1001 + decitabine combination in patients who are resistant or intolerant of venetoclax-based treatment, or considered not optimal candidates for a venetoclax-based therapy.

BP1001 plus decitabine in ventoclax intolerant or resistant subjects

BP1001 plus decitabine

Maro Ohanian, DO

Bruck Habtemariam

Rika Galias

Gary Schiller, MD

Vamsi Kota, MD

Kerry Hepler, RN

Jecinta Scott, MS

Tara Lin, MD

Mohammad Maher Abdul Hay, MD

Gail J Roboz, MD

Maro Ohanian, MD

The primary objectives of this study are to assess: (1) whether the combination of BP1001 plus venetoclax plus decitabine provides greater efficacy (Complete Remission \[CR\], Complete Remission with incomplete hematologic recovery \[CRi\], Complete Remission with partial hematologic recovery \[CRh\], than venetoclax plus decitabine alone (by historical comparison) in participants with untreated AML that cannot or elect not to be treated with more intensive chemotherapy; (2) whether BP1001-based treatment provides greater efficacy (CR, CRi, CRh) than intensive chemotherapy (by historical comparison) in participants with refractory/relapsed AML.

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.

There are 3 cohorts exploring three-drug combinations of BP1001, venetoclax and decitabine.

* Untreated AML patients will be treated with BP1001 plus venetoclax plus decitabine.
* Refractory/relapsed AML patients will also be treated with BP1001 plus venetoclax plus decitabine.
* A third cohort of BP1001 + decitabine is offered to refractory/relapsed AML patients who are venetoclax resistant or intolerant, or not considered by the investigator as optimal candidates for venetoclax-based therapy.

Each cohort will continue until approximately 19 evaluable participants have been investigated. At that point, enrollment will be placed on hold so that the Sponsor can perform an administrative review of the data to determine which treatment cohorts should continue with enrollment.

Should one or more cohorts continue with enrollment, the sample size will be increased up to 54 in the refractory/relapsed AML cohorts and 98 in the untreated AML cohort. These sample sizes for the study are based on the primary endpoint.

Clinical Trial of BP1001 in Combination With With Venetoclax Plus Decitabine in AML

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

Assess whether the combination of BP1001 and Ventoclax plus decitabine provides greater efficacy (Complete Remission \[CR\], Complete Remission with incomplete hematologic recovery \[CRi\], Complete Remission with partial hematologic recovery \[CRh\], than Ventoclax + decitabine alone (by historical comparison) with untreated AML that cannot or elect not to be treated with more intensive chemotherapy

Assess whether BP1001-based treatment provides greater efficacy (CR, CRi, CRh) than intensive chemotherapy (by historical comparison) in participants with refractory/relapsed AML.

Evaluate safety and toxicity of the combination of BP1001 with Ventoclax plus decitabine using non-hematologic and hematologic measures per NCI CTCAE criteria (with a safety run-in)

Evaluate the in vivo PK using plasma to compute half life and elimination.

Assess time to response from administration of BP1001-based treatment to CR, CRi, or CRh, negative MRD status as defined by the site and as available (Usually ≤ 0.1% by multi-parameter flow cytometry).

Assessment of Partial Remissions (per Cheson, 2003), and blast count reductions (per Williams, 2016)

To assess event-free survival, overall survival, time to response, and duration of response from date of study entry to study closure or death.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Clinical Trial of BP1001 in Combination With With Venetoclax Plus Decitabine in AML	NCT02781883	Acute Myeloid L...	BP1001 in combi... BP1001 plus dec...	18 Years -	Bio-Path Holdings, Inc.
Clinical Trial of BP1001 in Combination With With Venetoclax Plus Decitabine in AML	NCT02781883	Acute Myeloid L...	BP1001 in combi... BP1001 plus dec...	18 Years -	Bio-Path Holdings, Inc.

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