Date: 2016-11-02
Type of information: Treatment of the first patient
phase: 2
Announcement: treatment of the first patient
Company: Bio-Path Holdings (USA - TX)
Product: BP1001 (liposomal Grb2 antisense oligonucleotide)
Action
mechanism: antisense drug/antisense oligonucléotide. Liposomal Grb-2 is a liposomal P-ethoxy growth factor receptor-bound protein 2 antisense oligonucleotide. The adaptor protein Growth Receptor Bound protein-2 (Grb-2) is essential to cancer cell signaling because it is utilized by oncogenic tyrosine kinases to induce cancer progression. This adaptor protein links tyrosine kinases such as bcr-abl with their downstream signaling molecules, including MAPK and AKT, which are critical regulators of cancer proliferation and survival. Liposomal Grb-2 seeks to suppress the function or expression of Grb-2, interrupt the vital signaling function and have a therapeutic effect.
Disease: acute myeloid leukemia (AML)
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The trial is a single arm, open label, two-stage design to assess the safety profile, pharmacokinetics, pharmacodynamics, and efficacy of 60 mg/m2 of BP1001 in combination with low-dose cytarabine (LDAC) compared to historical response rates documented for LDAC alone. Evaluable patients will receive an initial dose intravenous (IV) infusion of BP1001 over 60 minutes and every three days thereafter, as eight doses per 28-day cycle of 60 mg/m2 BP1001, and will be administered LDAC as a subcutaneous (SQ) injection, twice daily for 20 consecutive
doses per 28-day cycle. The primary objective of this study is to assess whether the combination of BP1001 and LDAC provides greater efficacy (Complete Remission [CR], Complete Remission with incomplete hematologic recovery [CRi], Complete Remission with incomplete platelet recovery [CRp]) than LDAC alone (by historical comparison) in participants with AML that cannot or elect not to be treated with more intensive chemotherapy. Safety, pharmacokinetics, overall survival, time to response, and duration of response will also be studied.(NCT02781883)
Latest
news: * On November 2, 2016, Bio-Path Holdings announced the enrollment and dosing of the first patient in the efficacy portion of its Phase 2 clinical study of BP1001, a liposomal Grb2 antisense for the treatment of acute myeloid leukemia (AML). The objective of the Phase 2 study is to further assess the efficacy and safety of BP1001, Bio-Path’s lead development candidate. The Phase 2 clinical trial is a multicenter study of BP1001 in combination with low dose cytarabine (LDAC) in patients with previously untreated AML who are not otherwise eligible for standard or high-intensity chemotherapy regimens or who have elected a lowintensity regimen.
The full trial design includes approximately 54 evaluable patients with an interim analysis performed after 19 patients. In the event the interim results exceed the primary endpoint in a number of patients that meets or exceeds statistically determined thresholds, the Company may seek to convert the trial into a registration trial for accelerated approval. Among the sites registered to conduct the study are Weill Medical College of Cornell University, Baylor Scott & White Health, The University of Kansas and The University of Texas MD Anderson Cancer Center.
Patients in the safety segment of the trial treated with 60 mg/m2 and 90 mg/m2 of BP1001 twice a week over a four-week period, in combination with a standard regimen of frontline low-dose cytarabine (LDAC), showed BP1001 to be safe and well tolerated, with signs of significant anti-leukemia activity. Of the six evaluable patients included in both cohorts of the safety segment, three achieved complete remissions, while two others achieved partial remission. There were no attributable adverse events reported.
As previously reported, BP1001’s pharmacokinetics at a dose of 60 mg/m2 had a 30-hour half-life, significantly better than the half-life with a dose of 90 mg/m2. The final analysis of these data, along with the demonstrated reductions in bone marrow blasts, suggested that 60 mg/m2 is the appropriate dose for use in the Phase 2 trial. Administratively, this required Bio-Path to reformat documents for the Phase 2 trial with the 60 mg/m2 dose and
resubmit for approvals with the FDA and site Institutional Review Boards, requiring additional time prior to starting the Phase 2 trial.
