Administration of karenitecin for the treatment of platinum and/or taxane chemotherapy-resistant or -refractory advanced ovarian cancer
Inventors
Assignees
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Publication Number
US-10413538-B2
Publication Date
2019-09-17
Expiration Date
Abstract
The present invention discloses and claims methods and compositions for the treatment of subjects having advanced ovarian cancer, including platinum and/or taxane chemotherapy resistant or refractory sub-populations, with the administration to the subject having advanced ovarian cancer of the silicon-containing highly lipophilic camptothecin derivative (HLCD), Karenitecin (also known as BNP1350; cositecan; 7-[(2′-trimethylsilyl)ethyl]-20(S) camptothecin) in an amount sufficient to provide a therapeutic benefit. The administration of Karenitecin by intravenous (i.v.) and/or oral methodologies are also disclosed and claimed. Methods for the administration of Karenitecin to increase Progression Free Survival (PFS) are also disclosed and claimed herein.
Core Innovation
The patent discloses Karenitecin (BNP1350/cositecan), described as a silicon-containing highly lipophilic camptothecin derivative, for treating advanced epithelial ovarian cancer that is platinum/taxane resistant or refractory. It provides methods of treatment based on i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit.
The patent addresses the problem of limited efficacy and clinically relevant toxicity associated with other camptothecins and Topotecan in platinum/taxane-resistant or refractory settings, where myelosuppression and adverse effects limit treatment outcomes. Background rationale is given for Karenitecin’s HLCD properties, including lactone stability, long plasma half-life, and protein binding.
In the Phase III study overview, Progression Free Survival (PFS) is assessed using RECIST by an independent radiologic committee, with Overall Survival (OS) and grade ≥3 hematologic toxicities including anemia, neutropenia, and thrombocytopenia. The patent reports an overall PFS advantage favoring Karenitecin and also reports findings in a mucinous adenocarcinoma subtype.
Claims Coverage
The provided independent claims cover Karenitecin-based methods centered on the mucinous adenocarcinoma subtype of ovarian cancer in platinum and/or taxane resistant or not sensitive disease, with inventive features specifying increasing PFS, improving OS, reducing occurrence and/or grade of chemotherapy-induced adverse effects, and second-line single-agent use.
Increasing PFS in platinum/taxane-insensitive mucinous adenocarcinoma subtype
A method for increasing the time period of Progression Free Survival (PFS) in a subject having the mucinous adenocarcinoma-subtype of ovarian cancer that is not sensitive to treatment with platinum and/or taxane cancer treating agents, comprising i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit.
Increasing PFS while reducing chemotherapy-induced adverse effects in platinum/taxane-failed mucinous adenocarcinoma
A method for increasing the time period of Progression Free Survival (PFS) while concomitantly reducing the occurrence and/or the grade of occurrence of chemotherapy-induced adverse effects in a subject having the mucinous adenocarcinoma-subtype of ovarian cancer, where the subject has previously failed to respond to platinum and/or taxane cancer treating agent(s) for a time of 180 days or more, or whose tumor(s) relapsed or progressed within 180 days of completion of platinum and/or taxane treatment, comprising i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit.
Second-line single-agent Karenitecin for platinum/taxane-insensitive mucinous adenocarcinoma
A method for second line, single agent treatment of a subject having the mucinous adenocarcinoma subtype of ovarian cancer where the subject's cancer is not sensitive to treatment with platinum and/or taxane cancer treating agents, comprising i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit.
Treating advanced platinum/taxane-resistant ovarian cancer while reducing chemotherapy-induced adverse effects
A method for the treatment of a subject having advanced ovarian cancer that is resistant or not sensitive to treatment with platinum and/or taxane chemotherapeutic agents while concomitantly reducing the occurrence and/or the grade of occurrence of chemotherapy-induced adverse effects in said subject, comprising i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit, including the mucinous adenocarcinoma-subtype of ovarian cancer.
Increasing OS while reducing chemotherapy-induced adverse effects in platinum/taxane-insensitive mucinous adenocarcinoma
A method for increasing the overall survival (OS) while concomitantly reducing the occurrence and/or the grade of occurrence of chemotherapy-induced adverse effects in a subject having the mucinous adenocarcinoma-subtype of ovarian cancer, where the subject's cancer is resistant or not sensitive to treatment with platinum and/or taxane cancer treating agents, comprising i.v. and/or oral administration of Karenitecin in an amount sufficient to provide a therapeutic benefit.
Across the independent claims, Karenitecin i.v. and/or oral administration is used as a therapeutic intervention for mucinous adenocarcinoma-subtype ovarian cancer that is resistant or not sensitive to platinum and/or taxane agents, with inventive coverage directed to increasing PFS, optionally increasing OS, and concomitantly reducing the occurrence and/or grade of chemotherapy-induced adverse effects; one claim additionally specifies second-line single-agent treatment and one claim specifies an advanced ovarian cancer framing that includes the mucinous adenocarcinoma subtype.
Stated Advantages
Increasing the time period of Progression Free Survival (PFS).
Increasing overall survival (OS).
Concomitantly reducing the occurrence and/or the grade of occurrence of chemotherapy-induced adverse effects.
Reduced occurrence/grade of chemotherapy-induced hematologic toxicities is described in the patent context (e.g., reduced grade 3/4 anemia and thrombocytopenia and reduced grade 4 neutropenia).
More treatment cycles are described as possible in the patent context.
Documented Applications
Treatment of advanced epithelial ovarian cancer, including stage III/IV platinum/taxane-resistant or refractory patients, using i.v. and/or oral Karenitecin administered as a Phase III randomized open-label active-controlled study.
Subgroup-oriented treatment application in the mucinous adenocarcinoma subtype of ovarian cancer within platinum/taxane-resistant or refractory disease.
Second line, single agent treatment of mucinous adenocarcinoma subtype ovarian cancer that is not sensitive to platinum and/or taxane cancer treating agents.
Treatment of advanced ovarian cancer resistant or not sensitive to platinum and/or taxane chemotherapeutic agents while reducing chemotherapy-induced adverse effects.
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