Claims for Patent: 12,324,806

Summary for Patent: 12,324,806

Title:	Method of treating SCLC and managing hepatotoxicity
Abstract:	Provided are methods for the treatment of SCLC patients by administering therapeutic amounts of lurbinectedin by intravenous infusion. Also provided are methods of treating cancer by administering lurbinectedin in combination with other anticancer drugs, in particular topoisomerase inhibitors. The invention further relates to the administration of lurbinectedin in combination with anti-emetic agents for effective control of symptoms related to nausea and vomiting, reduced lurbinectedin dosages to achieve a safer administration and an increase in the number of treatment cycles. Stable lyophilized formulations of lurbinectedin are also provided.
Inventor(s):	Carmen Kahatt, José María Fernandez, Salvador Fudio, Arturo Soto, Pilar Lardelli, Cristian Fernandez
Assignee:	Pharmamar SA
Application Number:	US18/448,122
Patent Claims:	1. A method of treating metastatic small cell lung cancer (SCLC) in a patient with disease progression after platinum-based chemotherapy, said method comprising administering, within 35 days of receiving a dose of 3.2 mg/m2 of lurbinectedin by intravenous infusion as a monotherapy, a dose of 2.6 mg/m2 lurbinectedin by intravenous infusion as a monotherapy to a patient having at the time of the administration of the dose of 2.6 mg/m2 of lurbinectedin: a) metastatic SCLC with disease progression after platinum-based chemotherapy, b) a platelet count of at least 100,000/mm3, c) an absolute neutrophil count of at least 1500 cells/mm3, and d) ≤Grade 1 hepatotoxicity; wherein the patient previously experienced ≥Grade 3 hepatotoxicity subsequent to receiving the dose of 3.2 mg/m2 of lurbinectedin. 2. The method according to claim 1, wherein one dose of lurbinectedin is administered per a treatment cycle, wherein a treatment cycle is 21 to 35 days, and wherein the patient is administered lurbinectedin for 2 to 24 treatment cycles. 3. The method according to claim 2, wherein at least one treatment cycle of the 2 to 24 treatment cycles is 22 to 35 days. 4. The method according to claim 2, wherein at least one of the 2 to 24 treatment cycles is 21 days. 5. The method according to claim 1 further comprising: administering, within 35 days of receiving a dose of 2.6 mg/m2 of lurbinectedin by intravenous infusion as a monotherapy, a dose of 2.0 mg/m2 lurbinectedin by intravenous infusion as a monotherapy to the patient having at the time of the administration of the dose of 2.0 mg/m2 of lurbinectedin: (a) a platelet count of at least 100,000/mm3, (b) an absolute neutrophil count of at least 1500 cells/mm3, and (c) ≤Grade 1 hepatotoxicity; wherein the patient previously experienced ≥Grade 3 hepatotoxicity subsequent to receiving the dose of 2.6 mg/m2 of lurbinectedin. 6. The method according to claim 5, wherein one dose of lurbinectedin is administered per a treatment cycle, wherein a treatment cycle is 21 to 35 days, and wherein the patient is administered lurbinectedin for 3 to 24 cycles. 7. The method according to claim 6, wherein at least one treatment cycle of the 3 to 24 treatment cycles is 22 to 35 days. 8. The method according to claim 6, wherein at least one of the 3 to 24 treatment cycles is 21 days. 9. The method according to claim 2, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of 90 days or longer following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 6.2 months from the initial administration of the dose of 3.2 mg/m2. 10. The method according to claim 3, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of 90 days or longer following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 6.2 months from the initial administration of the dose of 3.2 mg/m2. 11. The method according to claim 4, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of 90 days or longer following a platinum-based chemotherapy treatment, wherein the patient has a duration of response that is at least 6.2 months from the initial administration of the dose of 3.2 mg/m2. 12. The method according to claim 6, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of 90 days or longer following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 6.2 months from the initial administration of the dose of 3.2 mg/m2. 13. The method according to claim 2, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of less than 90 days following a platinum-based chemotherapy, and the patient has a duration of response that is at least 4.7 months from the initial administration of the dose of 3.2 mg/m2. 14. The method according to claim 3, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of less than 90 days following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 4.7 months from the initial administration of the dose of 3.2 mg/m2. 15. The method according to claim 4, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of less than 90 days following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 4.7 months from the initial administration of the dose of 3.2 mg/m2. 16. The method according to claim 6, in which an initial administration of a dose of 3.2 mg/m2 had been administered to the patient after a chemotherapy-free interval of less than 90 days following a platinum-based chemotherapy treatment, and the patient has a duration of response that is at least 4.7 months from the initial administration of the dose of 3.2 mg/m2. 17. The method according to claim 2, in which the patient is administered lurbinectedin for at least 4 treatment cycles. 18. The method according to claim 2, in which the patient is administered lurbinectedin for at least 6 treatment cycles. 19. The method according to claim 2, in which the patient is administered lurbinectedin for at least 10 treatment cycles. 20. The method according to claim 4, in which the patient is administered lurbinectedin for at least 4 treatment cycles. 21. The method according to claim 4, in which the patient is administered lurbinectedin for at least 6 treatment cycles. 22. The method according to claim 4, in which the patient is administered lurbinectedin for at least 10 treatment cycles. 23. The method according to claim 6, in which the patient is administered lurbinectedin for at least 4 treatment cycles. 24. The method according to claim 6, in which the patient is administered lurbinectedin for at least 6 treatment cycles. 25. The method according to claim 6, in which the patient is administered lurbinectedin for at least 10 treatment cycles. 26. A method of treating metastatic small cell lung cancer (SCLC) in a patient with disease progression after platinum-based chemotherapy, said method comprising: (a) administering a dose of 3.2 mg/m2 of lurbinectedin by intravenous infusion as a monotherapy to a patient having, at the time of the administration of the dose of 3.2 mg/m2 of lurbinectedin: (i) metastatic SCLC with disease progression after platinum-based chemotherapy, (ii) an absolute neutrophil count of at least 1500 cells/mm3, (iii) a platelet count of at least 100,000/mm3, and (iv) ≤Grade 1 hepatotoxicity; wherein the patient experienced ≥Grade 3 hepatotoxicity subsequent to the administration of the dose of 3.2 mg/m2 of lurbinectedin and returns within 35 days of the administration of the dose of 3.2 mg/m2 of lurbinectedin to ≤Grade 1 hepatotoxicity after experiencing the ≥Grade 3 hepatotoxicity; and (b) administering by intravenous infusion as a monotherapy a dose of 2.6 mg/m2 of lurbinectedin to the patient after the patient returns to ≤Grade 1 hepatotoxicity and has a platelet count of at least 100,000/mm3 and an absolute neutrophil count of at least 1500 cells/mm3. 27. The method according to claim 26, wherein one dose of lurbinectedin is administered per a treatment cycle, wherein a treatment cycle is 21 to 35 days, and wherein the patient is administered lurbinectedin for 4 to 24 treatment cycles. 28. The method according to claim 26, wherein at least one of the 4 to 24 treatment cycles is 21 days. 29. The method according to claim 26 further comprising: administering, within 35 days of receiving a dose of 2.6 mg/m2 of lurbinectedin by intravenous infusion as a monotherapy, a dose of 2.0 mg/m2 lurbinectedin by intravenous infusion as a monotherapy to the patient having at the time of the administration of the dose of 2.0 mg/m2 of lurbinectedin: (a) a platelet count of at least 100,000/mm3, (b) an absolute neutrophil count of at least 1500 cells/mm3, and (c) ≤Grade 1 hepatotoxicity; wherein the patient previously experienced ≥Grade 3 hepatotoxicity subsequent to receiving the dose of 2.6 mg/m2 of lurbinectedin. 30. The method according to claim 29, wherein one dose of lurbinectedin is administered per a treatment cycle, wherein a treatment cycle is 21 to 35 days, and wherein the patient is administered lurbinectedin for 4 to 24 treatment cycles.