Navitoclax pharmacokinetics and antitumor activity

2019-12-10 13:11

This study is an openlabel, multicenter, phase 1, dose escalation study with a phase 2 expansion cohort to determine the safety, pharmacokinetics and preliminary antitumor activity of intravenous TKM in subjects with advanced hepatocellular carcinoma (HCC).Nov 18, 2011  Conclusions: The combination of navitoclax with BR appears welltolerated and to have antitumor activity. The maximum tolerated dose of navitoclax has been reached at 250 mg for Arm B, but not for Arm A where escalation continues. To date, we have not observed unacceptable myelotoxicity when this bcl2 antagonist was used in combination with standard cytotoxic chemoimmunotherapy navitoclax pharmacokinetics and antitumor activity

Study M, a phase 1 doseescalation study, is employing a continuous reassessment method to assess ABT263 safety and antitumor activity of two dosing schedules in patients with relapsed or refractory CLL. Enrollment continues with 18 patients (15 on a

Nov 19, 2010  Abstract 3943 Background: Navitoclax (ABT263) is a novel, orally bioavailable, small molecule that binds with high affinity (Ki 1nM) to Bcl2, BclxL, and Bclw, promoting apoptosis. Navitoclax shows potent targeted cytotoxicity (EC50 1M) in vitro against T and B lymphoid malignancies that overexpress Bcl2. As monotherapy in phase 1 trials, oral navitoclax is well Navitoclax, a targeted highaffinity inhibitor of BCL2, in lymphoid malignancies: a phase 1 doseescalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity navitoclax pharmacokinetics and antitumor activity Early results show that the combination of navitoclax with BR is welltolerated, without DLTs of TCP or neutropenia, and show evidence of antitumor activity. Data are limited in the FCR portion of the study. The maximum tolerated dose of navitoclax has not been reached.

This phase I study (NCT ) evaluated the safety, pharmacokinetics, and preliminary antitumor activity of navitoclax combined with erlotinib in patients with advanced solid tumors. navitoclax pharmacokinetics and antitumor activity Navitoclax (ABT263), a novel, oral Bcl2 inhibitor, enhances the antitumor effects of chemotherapy in vitro by lowering the apoptotic threshold. This phase I study (NCT ) evaluated the safety, pharmacokinetics, and preliminary antitumor activity of navitoclax combined with erlotinib in patients with advanced solid tumors. Navitoclax is an orally active, synthetic small molecule and an antagonist of a subset of the Bcell leukemia 2 (Bcl2) family of proteins with potential antineoplastic activity. Navitoclax selectively binds to apoptosis suppressor proteins Bcl2, BclXL, and Bclw, which are frequently overexpressed in a wide variety of cancers, including The antitumor activity of navitoclax as a single agent against several tumor types, on the other hand, was not consistent. In SCLC and other nonhematologic cancers, navitoclax was minimally effective, as indicated by 23 partial response and 2325 stable disease [155, 156. Background BCL2 family proteins play a central role in regulating clonal selection and survival of lymphocytes and are frequently over expressed in lymphomas. Navitoclax (ABT263) is a targeted highaffinity small molecule that occupies the BH3 binding groove of BCL2 and BCLX L and inhibits their antiapoptotic activity.

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