Dose Escalation and Dose Expansion Study of CPO-100 in Patients With Advanced Solid Tumors

Summary

This is a Phase 1, multicenter, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary evidence of antitumor activity of CPO-100 administered intravenously in cycles of 3 weekly doses with 1 week rest (1 cycle = 4 weeks) in adult patients with advanced solid tumors.

Timeline

Start

2021-03-24

Primary completion

2024-08-26

Completion

2024-08-26

Outcome

Outcome not reported

Stopped (Business): “Business Decision”

Publications

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• Background Aston WJ, Hope DE, Cook AM, Boon L, Dick I, Nowak AK, Lake RA, Lesterhuis WJ. Dexamethasone differentially depletes tumour and peripheral blood lymphocytes and can impact the efficacy of chemotherapy/checkpoint blockade combination treatment. Oncoimmunology. 2019 Jul 13;8(11):e1641390. doi: 10.1080/2162402X.2019.1641390. eCollection 2019.
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• Background de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wulfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdottir A, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. doi: 10.1056/NEJMoa1911206. Epub 2019 Sep 30.
• Background Gradishar WJ. Taxanes for the treatment of metastatic breast cancer. Breast Cancer (Auckl). 2012;6:159-71. doi: 10.4137/BCBCR.S8205. Epub 2012 Oct 25.
• Background Hardin C, Shum E, Singh AP, Perez-Soler R, Cheng H. Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer. Expert Opin Pharmacother. 2017 May;18(7):701-716. doi: 10.1080/14656566.2017.1316374. Epub 2017 Apr 17.
• Background Harvey V, Mouridsen H, Semiglazov V, Jakobsen E, Voznyi E, Robinson BA, Groult V, Murawsky M, Cold S. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol. 2006 Nov 1;24(31):4963-70. doi: 10.1200/JCO.2005.05.0294. Epub 2006 Oct 10.
• Background Minami H, Kawada K, Sasaki Y, Igarashi T, Saeki T, Tahara M, Itoh K, Fujii H. Pharmacokinetics and pharmacodynamics of protein-unbound docetaxel in cancer patients. Cancer Sci. 2006 Mar;97(3):235-41. doi: 10.1111/j.1349-7006.2006.00166.x.
• Background Ohbatake Y, Fushida S, Tsukada T, Kinoshita J, Oyama K, Hayashi H, Miyashita T, Tajima H, Takamura H, Ninomiya I, Yashiro M, Hirakawa K, Ohta T. Elevated alpha1-acid glycoprotein in gastric cancer patients inhibits the anticancer effects of paclitaxel, effects restored by co-administration of erythromycin. Clin Exp Med. 2016 Nov;16(4):585-592. doi: 10.1007/s10238-015-0387-9. Epub 2015 Sep 10.
• Background Palmeri L, Vaglica M, Palmeri S. Weekly docetaxel in the treatment of metastatic breast cancer. Ther Clin Risk Manag. 2008 Oct;4(5):1047-59. doi: 10.2147/tcrm.s3397.
• Background Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
• Background Socinski MA, Manikhas GM, Stroyakovsky DL, Makhson AN, Cheporov SV, Orlov SV, Yablonsky PK, Bhar P, Iglesias J. A dose finding study of weekly and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol. 2010 Jun;5(6):852-61. doi: 10.1097/jto.0b013e3181d5e39e.
• Background Urien S, Barre J, Morin C, Paccaly A, Montay G, Tillement JP. Docetaxel serum protein binding with high affinity to alpha 1-acid glycoprotein. Invest New Drugs. 1996;14(2):147-51. doi: 10.1007/BF00210785.
• Background American Cancer Society. https://www.cancer.org/cancer/pancreatic-cancer/about/key-statistics.html Accessed 17 May 2022
• Background Deeken JF, Slack R, Weiss GJ, Ramanathan RK, Pishvaian MJ, Hwang J, Lewandowski K, Subramaniam D, He AR, Cotarla I, Rahman A, Marshall JL. A phase I study of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. 2013 Mar;71(3):627-33. doi: 10.1007/s00280-012-2048-y. Epub 2012 Dec 30.
• Background Eheman C, Henley SJ, Ballard-Barbash R, Jacobs EJ, Schymura MJ, Noone AM, Pan L, Anderson RN, Fulton JE, Kohler BA, Jemal A, Ward E, Plescia M, Ries LA, Edwards BK. Annual Report to the Nation on the status of cancer, 1975-2008, featuring cancers associated with excess weight and lack of sufficient physical activity. Cancer. 2012 May 1;118(9):2338-66. doi: 10.1002/cncr.27514. Epub 2012 Mar 28.
• Background NCCN Guidelines Version 1.2022, Management of Neutropenia
• Background Pronk LC. Modulation of docetaxel treatment [dissertation], Rotterdam: Erasmus Universiteit; 1997
• Background Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012 Mar-Apr;62(2):118-28. doi: 10.3322/caac.20141. Epub 2012 Jan 4.
• Background Smith BD, Smith GL, Hurria A, Hortobagyi GN, Buchholz TA. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009 Jun 10;27(17):2758-65. doi: 10.1200/JCO.2008.20.8983. Epub 2009 Apr 29.
• Background StatBite. U.S. pancreatic cancer rates. J Natl Cancer Inst. 2010 Dec 15;102(24):1822. doi: 10.1093/jnci/djq517. Epub 2010 Dec 7. No abstract available.
• Background Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.
• Background Taxotere® US Package Insert (version 11/2021)
• Background Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, Smith LS, Wood TE, Korn RL, Desai N, Trieu V, Iglesias JL, Zhang H, Soon-Shiong P, Shi T, Rajeshkumar NV, Maitra A, Hidalgo M. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial. J Clin Oncol. 2011 Dec 1;29(34):4548-54. doi: 10.1200/JCO.2011.36.5742. Epub 2011 Oct 3.
• Background Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.
• Background Worni M, Guller U, White RR, Castleberry AW, Pietrobon R, Cerny T, Gloor B, Koeberle D. Modest improvement in overall survival for patients with metastatic pancreatic cancer: a trend analysis using the surveillance, epidemiology, and end results registry from 1988 to 2008. Pancreas. 2013 Oct;42(7):1157-63. doi: 10.1097/MPA.0b013e318291fbc5.

Drugs

Indications