Aldoxorubicin
Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate in development by CytRx. Specifically, it is the (6-maleimidocaproyl) hydrazone of doxorubicin. Essentially, this chemical name describes doxorubicin attached to an acid sensitive linker (N-ε-maleimidocaproic acid hydrazide, or EMCH).
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| ECHA InfoCard | 100.244.879  |
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| Formula | C37H42N4O13 |
| Molar mass | 750.758 g·mol−1 |
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The proposed mechanism of action is as follows:
- After administration, aldoxorubicin rapidly binds endogenous circulating albumin through the EMCH linker.
- Circulating albumin preferentially accumulates in tumors, bypassing uptake by other non-specific sites including heart, bone marrow and gastrointestinal tract.
- Once albumin-bound aldoxorubicin reaches the tumor, the acidic environment of the tumor causes cleavage of the acid sensitive linker.
- Free doxorubicin is released at the site of the tumor.
Clinical trials
Five phase I trials for safety characterization have been completed. Several phase II and III trials are underway.
Phase II
As of January 2017, there are 6 phase II clinical trials in progress:
- Second-line therapy for patients with glioblastoma[1]
- Treatment of HIV-positive patients with Kaposi's sarcoma[2]
- Combination therapy of ifosfamide and aldoxorubicin for treatment of metastatic or locally advanced sarcoma[3]
- Comparison of aldoxorubicin to the gold-standard treatment, topotecan, for metastatic small cell lung cancer[4]
- Treatment of advanced or metastatic pancreatic ductal adenocarcinoma[5]
- Comparison of aldoxorubicin and doxorubicin for patients with metastatic or locally advanced carcinoma[6]
References
- Clinical trial number NCT02014844 for "Phase 2 Study to Investigate the Efficacy and Safety of Aldoxorubicin in Subjects With Glioblastoma" at ClinicalTrials.gov
- Clinical trial number NCT02029430 for "A Study to Investigate ALDOXORUBICIN in HIV-infected Subjects With Kaposi's Sarcoma" at ClinicalTrials.gov
- Clinical trial number NCT02235701 for "Study to Investigate the Safety and Activity of Aldoxorubicin Plus Ifosfamide/Mesna in Subjects With Metastatic Soft Tissue Sarcoma" at ClinicalTrials.gov
- Clinical trial number NCT02200757 for "Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer" at ClinicalTrials.gov
- Clinical trial number NCT01580397 for "Pilot Phase 2 Study to Investigate the Preliminary Efficacy and Safety of INNO-206 in Advanced Pancreatic Cancer" at ClinicalTrials.gov
- Clinical trial number NCT01514188 for "Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma" at ClinicalTrials.gov
- Clinical trial number NCT02049905 for "Phase 3 Study to Treat Patients With Soft Tissue Sarcomas" at ClinicalTrials.gov
- "CytRx (CYTR) Announces Statistically Significant Data from Aldoxorubicin Phase 3 in r/r STS". 29 November 2016.
Further reading
- Kratz F, Azab S, Zeisig R, Fichtner I, Warnecke A (January 2013). "Evaluation of combination therapy schedules of doxorubicin and an acid-sensitive albumin-binding prodrug of doxorubicin in the MIA PaCa-2 pancreatic xenograft model". International Journal of Pharmaceutics. 441 (1–2): 499–506. doi:10.1016/j.ijpharm.2012.11.003. PMID 23149257.
- Walker L, Perkins E, Kratz F, Raucher D (October 2012). "Cell penetrating peptides fused to a thermally targeted biopolymer drug carrier improve the delivery and antitumor efficacy of an acid-sensitive doxorubicin derivative". International Journal of Pharmaceutics. 436 (1–2): 825–32. doi:10.1016/j.ijpharm.2012.07.043. PMC 3465682. PMID 22850291.
- Kratz F, Warnecke A (December 2012). "Finding the optimal balance: challenges of improving conventional cancer chemotherapy using suitable combinations with nano-sized drug delivery systems". Journal of Controlled Release. 164 (2): 221–35. doi:10.1016/j.jconrel.2012.05.045. PMID 22705248.
- Sanchez E, Li M, Wang C, Nichols CM, Li J, Chen H, Berenson JR (July 2012). "Anti-myeloma effects of the novel anthracycline derivative INNO-206". Clinical Cancer Research. 18 (14): 3856–67. doi:10.1158/1078-0432.CCR-11-3130. PMID 22619306.
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