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EP-4741016-A2 - A PHARMACEUTICAL COMBINATION FOR THE TREATMENT OF A CANCER

EP4741016A2EP 4741016 A2EP4741016 A2EP 4741016A2EP-4741016-A2

Abstract

Use of ABTL0812 in the treatment of a cancer in a human patient, wherein the cancer treatment is related to chemotherapy, targeted therapy treatment, immunotherapy treatment or radiotherapy treatment.

Inventors

  • PÉREZ MONTOYO, Héctor
  • FESTUCCIA, CLAUDIO
  • YESTE-VELASCO, Marc
  • MUÑOZ GUARDIOLA, Pau
  • ALFÓN CORIAT, José Alberto
  • DOMÈNECH GARCIA, Carles
  • YOLDI SALINAS, Guillermo
  • LIZCANO DE LA VEGA, Jose Miguel
  • SEGURA GUINARD, Miguel Francisco
  • PARIS-CODERCH, Laia

Assignees

  • Ability Pharmaceuticals S.A.

Dates

Publication Date
20260513
Application Date
20210210

Claims (15)

  1. A pharmaceutical combination comprising: (A): a compound which is a polyunsaturated fatty acid of formula COO R 1 -CH R 2 -(CH 2 ) a- (CH=CHCH 2 ) b -(CH 2 ) c -CH 3 , a pharmaceutically acceptable salt thereof, or a combination thereof, wherein (i) a can be any integer value between 0 and 7, (ii) b can be any integer value between 2 and 7, (iii) c can be any integer value between 0 to 7, (iv) R 1 is H, Na, K, CH 3 , CH 3 -CH 2 , or PO(O-CH 2 -CH 3 ) 2 , and (v) R 2 is OH, OCH 3 , O-CH 2 COOH, CH 3 , Cl, CH 2 OH, OPO(O-CH 2 -CH 3 ) 2 , N(OH) 2 , F, HCOO or N(OCH 2 CH 3 ) 2 ; and (B1): a chemotherapeutic agent compound for the simultaneous, separate or sequential use in the treatment of a cancer in a human patient, wherein Compound (B1) is at least one chemotherapeutic agent compound selected from the group consisting of: Temozolomide; Topotecan; Irinotecan; Cyclophosphamide; Fluorouracil; Oxaliplatin; Leucovorin; and Doxorubicin.
  2. The pharmaceutical combination of claim 1, wherein (i) a can be any integer value between 5 and 7, (ii) b can be any integer value between 2 and 4, and (iii) c can be any integer value between 1 to 5.
  3. The pharmaceutical combination of any of the preceding claims, wherein R 1 is H and R 2 is OH.
  4. The pharmaceutical combination of any of the preceding claims, wherein Compound (A) is at least one compound or a pharmaceutically acceptable salt thereof selected from the group consisting of: COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 2 -(CH 2 ) 3 -CH 3 (ABTL0812), COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 3 -CH 3 (183A1), COOH-CHOH-(CH 2 ) 3 -(CH=CH-CH 2 ) 3 -(CH 2 ) 3 -CH 3 (183A2), COOH-CHOH-(CH 2 ) 2 -(CH=CH-CH 2 ) 4 -(CH 2 ) 3 -CH 3 (204A1), COOH-CHOH-(CH 2 ) 2 -(CH=CH-CH 2 ) 5 -CH 3 (205A1) and COOH-CHOH-CH 2 -(CH=CH-CH 2 ) 6 -CH 3 (226A1).
  5. The pharmaceutical combination of any of the preceding claims, wherein Compound (A) is COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 2 -(CH 2 ) 3 -CH 3 (ABTL0812) or a pharmaceutically acceptable salt thereof.
  6. The pharmaceutical combination of claim 5, wherein Compound (A) is a sodium salt of COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 2 -(CH 2 ) 3 -CH 3 (ABTL0812).
  7. The pharmaceutical combination of any of the preceding claims, wherein the cancer is at least one cancer selected from the group consisting of: Lung cancer; Non-small cell lung cancer; Squamous cell cancer; Adenocarcinoma; Endometrial cancer; Endometrial serous cancer; Endometroid cancer; Pancreatic cancer; Glioblastoma; Resistant-recurrent breast cancer; Head and neck cancer; Multiple myeloma cancer; Neuroblastoma and Cholangiocarcinoma.
  8. The pharmaceutical combination of any of the preceding claims, wherein Compound (B1) is at least one chemotherapeutic agent compound selected from the group consisting of: Temozolomide; Topotecan; Fluorouracil; Oxaliplatin; and Leucovorin.
  9. The pharmaceutical combination of claim 8, wherein Compound (A) is COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 2 -(CH 2 ) 3 -CH 3 (ABTL0812) or a pharmaceutically acceptable salt thereof.
  10. The pharmaceutical combination of claim 9, wherein - Compound (B1) is Temozolomide and the cancer is neuroblastoma; - Compound (B1) is Topotecan and the cancer is neuroblastoma; - Compound (B1) is Irinotecan and the cancer is neuroblastoma; - Compound (B1) is Cyclophosphamide and the cancer is neuroblastoma; - Compound (B1) is Irinotecan, Leucovorin, Oxaliplatin and Fluorouracil and the cancer is pancreatic cancer; - Compound (B1) is Doxorubicin and the cancer is endometrial cancer; or - Compound (B1) is Temozolomide and the cancer is glioblastoma.
  11. The pharmaceutical combination of any of the preceding claims, wherein the pharmaceutical combination is a single composition comprising both Compound (A) and Compound (B1).
  12. The pharmaceutical combination of any of the preceding claims, wherein Compound (A) is administrated orally.
  13. The pharmaceutical combination of any of the preceding claims, wherein the administrated dose of Compound (A) is a daily dose of from 200 mg to 7000 mg, more preferably a daily dose of from 1500 mg to 5000 mg, even more preferably a daily dose of from 3000 mg to 4700 mg and most preferably a daily dose of from 3500 mg to 4300 mg.
  14. The pharmaceutical combination of any of claims 12 to 13, wherein Compound (A) is COOH-CHOH-(CH 2 ) 6 -(CH=CH-CH 2 ) 2 -(CH 2 ) 3 -CH 3 (ABTL0812) or a pharmaceutically acceptable salt thereof.
  15. The pharmaceutical combination of claim 14, wherein Compound (B1) is Temozolomide and it is administrated via oral capsules or tablets; Compound (B1) is Topotecan and it is administrated intravenously via infusion solution; Compound (B1) is Irinotecan and it is administrated intravenously via infusion solution; Compound (B1) is Cyclophosphamide and it is administrated intravenously via infusion solution; Compound (B1) is Fluorouracil and it is administrated intravenously via infusion solution; Compound (B1) is Oxaliplatin and it is administrated intravenously via infusion solution; Compound (B1) is Leucovorin and it is administrated intravenously via infusion solution; or Compound (B1) is Doxorubicin and it is administrated intravenously via infusion solution.

Description

FIELD OF THE INVENTION The present invention relates to use of ABTL0812 in the treatment of a cancer in a human patient, wherein the cancer treatment is related to chemotherapy, targeted therapy treatment, immunotherapy treatment or radiotherapy treatment. BACKGROUND ART EP2409963B1 (Lipopharma - filed in 2010) describes use of 1,2-derivatives of polyunsaturated fatty acids (termed D-PUFAs) compounds for treatment of cancer. The described fatty acids derivative compounds have the following formula:         COOR1-CHR2-(CH2)a-(CH=CH-CH2)b-(CH2)c-CH3 An example of a preferred compound is:         COOH-CHOH-(CH2)6-(CH=CH-CH2)2-(CH2)3-CH3 (182A1) The article "Erazo, et al.; Clinical Cancer Research; 22(10) May 15, 2016" describes the above referred compound (182A1) in further details - in the article is this compound termed "ABTL0812" and this term is used herein. As known in the art - the pharmacological treatment of cancer is generally based in four main groups of drugs including chemotherapy, targeted therapy, hormone therapy and immunotherapy. In addition, radiotherapy is also at a cornerstone of cancer treatment that is many times administered together with pharmacotherapy. WO2018/210830A1 (Ability Pharmaceuticals) describes use of the ABTL0812 compound in combination with other chemotherapeutic agents in the treatment of a cancer - such as e.g. a pharmaceutical combination of ABTL0812 with the chemotherapeutic agents Docetaxel, Paclitaxel, Carboplatin or Cisplatin in relation to first-line therapy. SUMMARY OF THE INVENTION Starting with WO2018/210830A1 (Ability Pharmaceuticals) as most relevant prior art document (so-called closest prior art document) - the problem to be solved by the present invention may be seen as the provision of alternative uses of ABTL0812 that may give an improved treatment of cancer. As discussed above, the compound COOH-CHOH-(CH2)6-(CH=CH-CH2)2-(CH2)3-CH3 is herein termed ABTL0812. As discussed above, WO2018/210830A1 (Ability Pharmaceuticals) describes use of the ABTL0812 compound in combination with other chemotherapeutic agents in the treatment of a cancer - such as e.g. a pharmaceutical combination of ABTL0812 with the chemotherapeutic agents Docetaxel, Paclitaxel, Carboplatin or Cisplatin in relation to first-line therapy. WO2018/210830A1 (Ability Pharmaceuticals) does not directly and unambiguously describe use of ABTL0812 in second-line therapy for treatment of cancer - for instance are the terms "second-line" or "second line" in relation to second-line therapy not even mentioned in WO2018/210830A1. Working examples herein provides detailed experimental data plausible demonstrating a significant synergistic effect in relation to use of the above discussed ABTL0812 compound in combination with other chemotherapeutic agents for e.g. second-line therapy treatment of a cancer in a human patient. The ABTL0812 compound is structurally and functionally similar to the other 1,2-derivatives of polyunsaturated fatty acids (D-PUFAs) compounds as described in above discussed EP2409963B1. Accordingly, prima facie it is plausible that substantial all the fatty acids derivative compounds of EP2409963B1 would have a herein relevant synergistic effect in combination with a chemotherapeutic agent and/or other preferred cancer treatments as discussed herein. Accordingly, a first aspect of the invention relates to a pharmaceutical combination comprising: (A): a compound which is a polyunsaturated fatty acid of formula COOR1-CHR2-(CH2)a-(CH=CHCH2)b-(CH2)c-CH3, a pharmaceutically acceptable salt thereof, or a combination thereof, wherein (i) a can be any integer value between 0 and 7,(ii) b can be any integer value between 2 and 7,(iii) c can be any integer value between 0 to 7,(iv) R1 is H, Na, K, CH3, CH3-CH2, or PO(O-CH2-CH3)2, and(v) R2 is OH, OCH3, O-CH2COOH, CH3, Cl, CH2OH, OPO(O-CH2-CH3)2, N(OH)2, F, HCOO or N(OCH2CH3)2; and(B1): a chemotherapeutic agent compound for the simultaneous, separate or sequential use in the treatment of a cancer in a human patient, wherein the treatment is a second-line therapy treatment of a cancer. As known in the art, first-line therapy is the treatment regimen or regimens that are generally accepted by the medical establishment for initial treatment of a given type and stage of cancer. It is also called primary treatment or therapy. The intent of first-line therapy is to cure the cancer if possible. Also called induction therapy, this primary therapy is the first assault of chemotherapy drugs on the malignancy. In agreement with the common general knowledge of the skilled person - the term "second-line therapy" of the first aspect relates to second-line therapy treatment tried when the first-line therapy does not work adequately. The management of a cancer case requires regular evaluation of treatment and adjustment as needed. A break with the primary first-line therapy treatment and an adoption of a new regimen signals "second-line therapy" treatment. As