Combinations of BCL-2/BCL-XL inhibitors and related uses
A technology of inhibitors and uses, which can be used in drug combinations, medical preparations containing active ingredients, organic active ingredients, etc., and can solve the problem of low objective response rate
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment approach
[0396] In some aspects, the invention provides a combination comprising:
[0397] (i) a pharmaceutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof; and
[0398] (ii) A pharmaceutically effective amount of osimertinib or a pharmaceutically acceptable salt thereof.
[0399] In some aspects, the invention provides a method of treating or preventing cancer in a subject comprising administering to the subject:
[0400] (i) a pharmaceutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereof; and
[0401] (ii) A pharmaceutically effective amount of osimertinib or a pharmaceutically acceptable salt thereof (eg, the mesylate salt of osimertinib).
[0402] In some aspects, the present invention provides a method of treating or preventing EGFR-TKI resistant NSCLC in a subject, comprising administering to the subject:
[0403] (i) a pharmaceutically effective amount of Compound 1 or a pharmaceutically acceptable salt thereo...
Embodiment 1
[0696] Example 1. Study of the combination of compound 1 and paclitaxel in patients with relapsed / refractory small cell lung cancer.
[0697] A multicenter, open-label, phase I / II study of compound 1 plus paclitaxel combination therapy was conducted in patients with relapsed SCLC.
[0698] The Phase I portion was performed using the TITE-CRM approach to determine the MTD of Compound 1 with fixed dose paclitaxel. The Phase II portion uses Simon's two-stage design to determine the efficacy of the combination therapy with response rate as the primary endpoint. After enrollment, patients underwent a comprehensive medical history and physical examination as well as baseline laboratory evaluations. Baseline CT imaging was required within 4 weeks prior to study entry. Biopsies of primary tumors or metastatic lesions should be performed at baseline for relevant biomarker and pharmacodynamic studies prior to initiating therapy.
[0699] In the Phase I portion, eligible patients rece...
Embodiment 2
[0735] Example 2. The study of the combination of compound 1 and osimertinib in EGFR-TKI resistant non-small cell lung cancer patients.
[0736] A multicenter, open-label phase 1b study was conducted to evaluate the adverse effects and optimal doses of osimertinib versus compound 1 in EGFR-TKI-resistant NSCLC patients.
[0737] In the exploratory phase, a 3+3 design was used to determine the MTD / RP2D of the combination of osimertinib and compound 1; the dose of osimertinib was fixed at 80 mg QD. The dose of compound 1 was started at 240 mg per week and then gradually increased to 320 mg per week and 400 mg per week, or decreased to 160 mg per week and 80 mg per week if the patient could not tolerate the 240 mg per week dose.
[0738] In the expansion phase, IF 1-confirmed PR or CR was observed in NSCLC patients who failed third-generation EGFR TKIs, and the combination of osimertinib and compound 1 in third-generation EGFR TKI-naïve NSCLC patients began to be explored. Patien...
PUM
| Property | Measurement | Unit |
|---|---|---|
| Platelet count | aaaaa | aaaaa |
| Platelet count | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More