In September 2023, Lipomedix plans to initiate a Phase 2 Multi-Center, Open-Label Study of PROMITIL in Combination with Capecitabine for the Treatment of Patients with Pancreatic Cancer Associated with Deleterious Mutations who Have Progressed After First Line Therapy (PROM).
Study Population: Patients with advanced solid tumors of the pancreas who have progressed after first line therapy, and who have deleterious germline or somatic mutations in BRCA1, BRCA2, PALB2, FANC, ATM or CHEK2 genes. Thirty patients is planned to be recruited at approximately 5-10 Medical Centers.
Lipomedix has completed an open-label, Phase 1b study of intravenously administered pegylated liposomal mitomycin C lipidated prodrug (PROMITIL) in combination with external beam radiotherapy in patients with advanced cancer requiring palliative radiotherapy for inoperable primary tumors or metastatic disease
The Phase 1b clinical study (LIPORAD-2018) was approved by the Israel Ministry of Health, was conducted in three Medical Centers in Israel and was completed in August 2021.
This study was conducted following encouraging preclinical and clinical data suggesting synergistic activity of the combination of Promitil® with radiotherapy (Tian X et al., Int. J. Radiation Oncol. Biol. Phys., 96:547-555, 2016; Tahover E et al., Front. Oncol., 8:544, 2018).
Lipomedix completed LIPORAD-2018 (NCT03823989), a multi-center, open-label, single-arm, prospective study, in 19 patients requiring RT for metastatic disease or for an inoperable primary tumor with no definitive curative treatment option.
In this study it was shown that, Promitil®, in combination with RT can be safely administered at a dose of 1.8 mg/kg every 3 weeks and results in a high rate of tumor control in a variety of tumor types. Clearance of Promitil® is not affected by radiation administration. Promitil® is a novel and attractive option for radiosensitization that needs to be evaluated in future randomized studies in the palliative and possibly also in the curative setting (Sapir et al. International Journal of Radiation Oncology 2023).
Phase 1b study testing the safety, tolerability and efficacy of Promitil® delivered in combination with FOLFOX chemotherapy (PROMIFOX)
An investigator initiated, single center Phase 1b DLT-clearing study, testing the safety, tolerability and efficacy of Promitil® delivered in combination with the FOLFOX chemotherapy for the treatment of advanced gastrointestinal cancers is ongoing (NCT04729205- study PROMIFOX). Up to 9 evaluable patients, ages 18 or older, with inoperable, locally advanced or metastatic GI solid tumors have been recruited in the study. No further patients will be recruited.
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)
A Phase 1A clinical study with Promitil® in patients with advanced-stage solid tumors was completed in Nov 2014. The study took place at two medical centers in Israel under the approval of the Israeli Ministry of Health. A total of 27 patients received 102 Promitil® infusions. Dose-limiting toxicity was thrombocytopenia. The maximal tolerated dose of Promitil® was found to be ~3-fold greater than for MMC in mg-equivalents, confirming that toxicity is substantially reduced. Pharmacokinetic analysis indicates that Promitil® has a slow blood clearance, with a half-life of ~1 day which is characteristic of pegylated liposomes. Anti-tumor activity was observed in various cancer types (Golan et al., Cancer Medicine 4:1472–1483, 2015).
This clinical study of Promitil was expanded to a Phase 1B in patients with advanced colorectal cancer, receiving a 3rd or later line of therapy. The objectives of this expanded phase of the study were 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 was conducted in 4 medical sites in Israel (Shaare Zedek, Sheba, Ichilov, and Rambam) and completed accrual in mid-2017 of 61 patients in four cohorts, the final report was released in June 2018.
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 phase 2-3 studies.