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BR-112019023944-B1 - Pharmaceutical combination for the treatment of cancer.

BR112019023944B1BR 112019023944 B1BR112019023944 B1BR 112019023944B1BR-112019023944-B1

Abstract

This is a pharmaceutical combination comprising (A): a polyunsaturated fatty acid and (B): a chemotherapeutic compound for simultaneous, separate or sequential use in the treatment of cancer in a human patient.

Inventors

  • Carles DOMÈNECH GARCIA
  • JOSÉ ALBERTO ALFÓN CORIAT
  • Héctor PÉREZ MONTOYO
  • MIGUEL FRANCISCO SEGURA GINARD
  • JOSE MIGUEL LIZCANO DE VEGA

Assignees

  • ABILITY PHARMACEUTICALS S.L

Dates

Publication Date
20260317
Application Date
20180515
Priority Date
20170516

Claims (15)

  1. 1. Pharmaceutical combination characterized in that it comprises: (A): a compound that is a polyunsaturated fatty acid of formula COOH-CHOH-(CH2)6-(CH=CH-CH2)2-(CH2)3-CH3 (ABTL0812), a pharmaceutically acceptable salt thereof or a combination thereof and (B): a chemotherapeutic agent compound, wherein Compound (B) is at least one chemotherapeutic agent compound selected from the group consisting of: Paclitaxel; Nab-paclitaxel; Carboplatin; Cisplatin; Oxaliplatin; and Retinoic acid.
  2. 2. Use of a pharmaceutical combination, as defined in claim 1, characterized in that it is for the manufacture of a medicament for the treatment of cancer in a human patient.
  3. 3. Use of a pharmaceutical combination, according to claim 2, characterized in that Compound (B) is at least one chemotherapeutic agent compound selected from the group consisting of: Paclitaxel; Carboplatin; and Cisplatin.
  4. 4. Use, of a pharmaceutical combination, according to any of the preceding claims, characterized in that Compound (A) is a sodium salt of COOH-CHOH-(CH2)6-(CH=CH-CH2)2-(CH2)3-CH3 (ABTL0812).
  5. 5. Use of a pharmaceutical combination, according to any of the preceding claims, characterized in that the cancer is at least one cancer selected from the group consisting of: lung cancer; non-small cell lung cancer; small cell lung cancer; squamous cell carcinoma; adenocarcinoma; endometrial cancer; pancreatic cancer; glioblastoma; breast cancer; head and neck cancer; neuroblastoma; cholangiocarcinoma.
  6. 6. Use of a pharmaceutical combination, according to any of the preceding claims, characterized in that the cancer is at least one cancer selected from the group consisting of: non-small cell lung cancer; squamous cell carcinoma; endometrial cancer; pancreatic cancer; glioblastoma; breast cancer; neuroblastoma; cholangiocarcinoma.
  7. 7. Use of a pharmaceutical combination, according to any of the preceding claims, characterized in that: - Compound (B) is Paclitaxel and the cancer is lung cancer, preferably non-small cell lung adenocarcinoma; - Compound (B) is Carboplatin and the cancer is endometrial; - Compound (B) is Paclitaxel and the cancer is breast cancer, preferably triple-negative breast cancer; - Compound (B) is Paclitaxel and Carboplatin and the cancer is squamous cell carcinoma, preferably non-small cell squamous lung cancer; - Compound (B) is Paclitaxel and Carboplatin and the cancer is non-small cell lung adenocarcinoma; - Compound (B) is Paclitaxel and the cancer is endometrial cancer; - Compound (B) is Paclitaxel and Carboplatin and the cancer is endometrial cancer; - Compound (B) is Paclitaxel and Gemcitabine and the cancer is pancreatic cancer; - Compound (B) is Cisplatin and Gemcitabine and the cancer is neuroblastoma; or - Compound (B) is Cisplatin and Gemcitabine and the cancer is cholangiocarcinoma.
  8. 8. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that: - Compound (B) is Carboplatin and the cancer is endometrial; - Compound (B) is Paclitaxel and the cancer is breast cancer, preferably triple-negative breast cancer; - Compound (B) is Paclitaxel and Carboplatin and the cancer is squamous cell carcinoma, preferably non-small cell squamous lung cancer; - Compound (B) is Paclitaxel and Carboplatin and the cancer is non-small cell lung adenocarcinoma; - Compound (B) is pemetrexed and Cisplatin and the cancer is non-small cell lung adenocarcinoma; - Compound (B) is Paclitaxel and Carboplatin and the cancer is endometrial cancer; - Compound (B) is Paclitaxel and Gemcitabine and the cancer is pancreatic cancer; or - Compound (B) is Cisplatin and Gemcitabine and the cancer is cholangiocarcinoma.
  9. 9. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that: - Compound (B) is Paclitaxel and Carboplatin and the cancer is advanced endometrial cancer; or - Compound (B) is Paclitaxel and Carboplatin and the cancer is squamous cell carcinoma.
  10. 10. Use of the pharmaceutical combination, according to claim 9, characterized in that Compound (A) is administered orally.
  11. 11. Use of the pharmaceutical combination, according to claim 10, characterized in that the administered dose of Compound (A) is a dose of 1,200 mg to 1,400 mg.
  12. 12. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that the pharmaceutical combination is a single composition comprising Compound (A) and Compound (B).
  13. 13. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that Compound (A) is administered orally.
  14. 14. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that the administered dose of Compound (A) is a total dose of 200 mg to 2,000 mg per day.
  15. 15. Use of the pharmaceutical combination, according to any of the preceding claims, characterized in that Compound (B) comprises: Paclitaxel and Carboplatin; Paclitaxel and Gemcitabine; Nab-Paclitaxel and Gemcitabine; Gemcitabine and Cisplatin; or Pemetrexed and Cisplatin.

Description

FIELD OF INVENTION [0001] The present invention relates to a pharmaceutical combination comprising (A): a polyunsaturated fatty acid and (B): a chemotherapeutic agent compound for simultaneous, separate or sequential use in the treatment of cancer in a human patient. PREVIOUS TECHNIQUE [0002] Document EP2409963B1 (Lipopharma - filed in 2010) describes the use of 1,2-derivatives of polyunsaturated fatty acid compounds (called D-PUFAs) for cancer treatment. [0003] The fatty acid-derived compounds described have the following formula: COOR1-CHR2-(CH2)a-(CH=CH-CH2)b-(CH2)c-CH3 [0004] An example of a preferred compound is: COOH-CHOH-(CH2)6-(CH=CH-CH2)2-(CH2)3-CH3(182A1) [0005] The article “Erazo, et al.; Clinical Cancer Research; 22(10) May 15, 2016” describes the above-mentioned compound (182A1) in more detail - in the article this compound is referred to as “ABTL0812” and this term is used in the present document. [0006] The article describes that ABTL0812 induces autophagy-mediated cancer cell death without activating cell apoptosis. The article states: [0007] [p2515]: [0008] “Most current anticancer treatments activate apoptosis and resistance to chemotherapy is a major challenge in cancer (24). Autophagy-mediated cell death has emerged as an alternative to kill cancer cells without inducing resistance to apoptosis-inducing drugs (25).” [0009] [p2517]: [0010] “On the other hand, mTORC1 activation is frequently associated with resistance to antitumor drugs (6). As ABTL0812 is a potent inhibitor of the Akt/mTORC1 geometric axis, its administration in combination with standard chemotherapeutic drugs may be effective in refractory tumors resistant to therapy or apoptosis.” [0011] On the date of filing of this application - the applicant's web page (AbilityPharma - www.abilitypharma.com) included a News section (all inventors in this application have assigned all relevant rights in this document to the applicant in this application and priority application EP17382282.6 dated May 16, 2017 - in other words, the publication of the applicant's web page discussed below can be considered a so-called "inventor-originated disclosure" - (i.e., the object of the public disclosure must be attributable to the inventor, to one or more co-inventors or to another who has obtained the object directly or indirectly from the inventor or a co-inventor). [0012] The News section of November 22, 2016 says: [0013] “The Catalan biopharmaceutical company AbilityPharmaceuticals, SL announced today the start of its first phase 2 clinical trial with its new targeted anticancer agent ABTL0812 to evaluate its efficacy and safety in combination with paclitaxel and carboplatin in 80 patients with advanced or recurrent endometrial cancer or squamous cell lung cancer as first-line therapy (...) [0014] In preclinical cancer models, ABTL0812 is effective as a single agent with an excellent safety profile across a broad spectrum of cancer types: lung, endometrial, pancreatic, and neuroblastoma. In these models, the compound also has a synergistic effect with chemotherapy (taxanes, platinum compounds, and gemcitabine) without increasing its toxicity. [0015] The News section dated December 14, 2016 says: [0016] “In preclinical studies, ABTL0812 demonstrated efficacy in pancreatic cancer as a single agent and a synergistic effect (8 to 90 times) in combination with taxanes, platinum compounds and gemcitabine, inducing tumor regression without increasing the toxicity associated with chemotherapy (...) [0017] Currently, ABTL0812 is in phase 2 as first-line therapy in combination with chemotherapy in patients with endometrial or squamous lung cancer. [0018] With regard to the use of compound ABTL0812 in combination with other chemotherapeutic agents - the aforementioned Erazo article and the News published by the applicant (AbilityPharma) do not disclose any significant experimental data - that is, the statements relating to the combination can be seen as mere statements that are not supported by any significant verifiable experimental data. [0019] The published news refers to phase II studies - as is known in the art, the fact that phase II studies are ongoing means that phase I studies are completed and, from this information, a person skilled in the art can only conclude that the results on safety and tolerability in humans, as well as pharmacokinetic studies, were positive - that is, this does not provide information on a possible therapeutic effect in human patients, in particular on any possible synergistic effect of the combination. A person skilled in the art only knows after the completion of phase II trials an assessment of the results as to whether the drug is therapeutically effective - at the date of filing of this application, no relevant experimental data derived from phase II trials have been published herein. SUMMARY OF THE INVENTION [0020] The problem to be solved by the present invention is to provide an improved treatment for cancer. [