Agent exhibits activity in leukemias, MDS


AML cells

The experimental agent prexigebersen (formerly BP1001) was considered well-tolerated and demonstrated early evidence of activity against relapsed/refractory hematologic disorders in a phase 1/1b trial.

The drug reduced blasts in the bone marrow and peripheral blood for patients with acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS).

When given in combination with low-dose cytarabine, prexigebersen produced complete responses (CRs) in patients with AML.

Researchers said that, overall, the toxic effects of prexigebersen were manageable.

There was 1 patient who had dose-limiting toxicities, 1 who discontinued treatment due to possible drug-related toxic effects, and 1 treatment-related death.

Still, the maximum tolerated dose of prexigebersen was not established.

These results were published in The Lancet Haematology. The study was sponsored by Bio-Path Holdings, Inc., the company developing prexigebersen.

Prexigebersen is an anti-sense oligodeoxynucleotide developed to block Grb2 expression and function. Researchers tested the drug in a single-center, dose-escalation, phase 1/1b trial that enrolled and treated 39 patients.

In the phase 1 portion of the trial, patients received prexigebersen monotherapy. In the phase 1b portion, they received the drug in combination with low-dose cytarabine.

There were 32 patients in the phase 1 portion of the trial. Most (n=23) had AML, 5 had CML in blast phase, and 4 had MDS. The patients’ median age was 63 (range, 56-73), and they had received a median of 4 prior therapies.

All 7 patients in the phase 1b portion had AML. They had a median age of 72 (range, 70-76) and had all received 1 prior therapy.

For phase 1, prexigebersen was administered intravenously, twice weekly for 28 days at doses of 5 mg/m² in cohort 1 (n=13), 10 mg/m² in cohort 2 (n=6), 20 mg/m² in cohort 3 (n=3), 40 mg/m² in cohort 4 (n=3), 60 mg/m² in cohort 5 (n=3), and 90 mg/m² in cohort 6 (n=4).

In the phase 1b portion, patients received prexigebersen at 60 mg/m² (n=4) or 90 mg/m² (n=3) in combination with 20 mg of cytarabine (twice-daily subcutaneous injections).


Twenty-seven patients were evaluable for dose-limiting toxicity—21 from phase 1 and 6 from 1b.

One patient in cohort 1 developed mucositis and hand-foot syndrome, which were considered possibly related to prexigebersen and deemed dose-limiting toxicities. The patient was also receiving hydroxyurea (3 g/day) for CML and had a history of hydroxyurea-induced mucositis.

There were no other dose-limiting toxicities, and the researchers did not identify a maximum tolerated dose of prexigebersen.

The most common grade 3-4 adverse events (AEs) were cardiopulmonary disorders and fevers (including neutropenic fevers and infections).

In the monotherapy group, 17% of patients had grade 3-4 cardiopulmonary AEs, and 11% had fevers. In the prexigebersen-cytarabine combination group, 8% had grade 3-4 cardiopulmonary AEs, and 6% had fevers.

There were 5 grade 5 AEs in 4 patients, all of whom received monotherapy. These included cardiopulmonary disorders (n=2), fevers (n=2), and multi-organ failure (n=1). One patient had both fever (sepsis) and multi-organ failure.


According to the researchers’ assessments, 22% of phase 1 patients (7/32) benefited from prexigebersen monotherapy and therefore received more than 1 cycle of treatment. Five of these patients had AML, and 2 had MDS.

Single-agent activity was observed in other patients as well.

Thirty-three percent (9/27) of patients who had peripheral blood blasts at baseline saw their blasts reduced by 50% or more while receiving monotherapy. One of these patients had CML, and the rest had AML.

Ten percent (3/29) of patients with bone marrow blasts at baseline had a reduction in blasts of 50% or more while receiving monotherapy. Two of these patients had AML, and 1 had MDS.

Of the 7 patients receiving prexigebersen with cytarabine, 2 achieved a CR, and 1 had a CR with incomplete hematological recovery.

Two of the patients had stable disease, and the remaining 2 patients progressed. One of the patients with progressive disease withdrew from the study, and the other died.


There were a total of 8 deaths.

One death was considered treatment-related. This patient had progressive CML in blast phase and died of multiple organ failure. This was the first patient treated on the trial, who also had the only dose-limiting toxicities.

Two patients with AML and 1 with MDS died of disease progression. Three AML patients died of sepsis, pneumonia, and cardiac arrest. And a CML patient died of respiratory distress.

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