A Phase I, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated-Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, Promitil®) in Cancer Patients with Solid Tumors (completed and published, 2015)
Lipomedix has completed the clinical study Phase 1b/2a study in advanced colon cancer (June, 2018)
A Phase I, dose-escalating, study, designed to test the safety of intravenous administration of escalating doses of Promitil in patients with solid tumors was conducted in Israel at three medical sites (Sheba, Shaare Zedek and Ichilov), under the approval of the Israeli Ministry of Health. 27 patients diagnosed with inoperable, recurrent or metastatic malignant tumor that failed previous standard therapy were recruited.
The study primary objectives were:
- determination of the Maximal Tolerated Dose,
- determination of the Dose-Limiting Toxicity, and,
- characterization of the pharmacokinetics of Promitil.
The recommended dose of single agent Promitil was established as 3 mg/kg. The dose-limiting cumulative toxicity was thrombocytopenia. The maximal tolerated dose of Promitil® is ~3-fold greater than for free Mitomycin-C, confirming that toxicity is substantially reduced. Pharmacokinetic analysis indicates that Promitil® has a slow blood clearance, with a half-life of ~24 hours (in contrast to the reported short half-life, ~15 minutes, for mitomycin-C) which is characteristic of pegylated (“Stealth”) liposomes (Cancer Medicine, 2015).
This clinical study of Promitil was expanded to a Phase 1b/2a in patients with advanced colorectal cancer, receiving a 3rd or later line of therapy. The objectives of this expanded phase of the study are to evaluate the safety and disease control rate of Promitil® given either as a single agent, or in combination with Capecitabine, and/or Bevacizumab. Capecitabine, an oral fluopyrimidine, and Bevacizumab, an anti-VEGF monoclonal antibody, are part of the standard therapy of colon cancer. The expanded phase has taken place in 4 medical sites in Israel (Shaare Zedek, Sheba, Ichilov, and Rambam) and completed accrual in late 2017 of 61 patients in four successive cohorts.
Promitil dosing in 61 mCRC patients, as a single agent or in combination with capecitabine and/or bevacizumab, demonstrated its relative high safety profile with encouraging signs of antitumor activity. Thus, Promitil is an effective tool to safely achieve a high dose intensity with a prodrug of mitomycin c. These preliminary findings will require validation in randomized and large-scale studies.
Based on promising laboratory data and clinical observations suggesting synergistic activity of the combination of Promitil® with radiotherapy, Lipomedix will shortly start a phase 1B study to examine the safety and efficacy of Promitil-based chemo-radiotherapy.
For further details on the Promitil clinical study and participating centers, refer to: http://www.clinicaltrials.gov/ct2/show/NCT01705002?term=Promitil&rank=1