CMF (Cyclophosphamide 600mg/m2 + Methotrexate 40mg/m2 + Fluorouracil 600mg/m2, IV, day 1 and 8, every 4 weeks) remains a chemotherapeutic modality effective for metastatic triple-negative breast cancer (mTNBC). A plasmid encoding p62/SQTM1 reduces chronic inflammation, changes the tumor microenvironment, and increases the number of tumor-infiltrating lymphocytes. Dosing of the plasmid preserved the lives of 10 out of 11 dogs with breast cancer. In a human phase I/IIa trial, it demonstrated an excellent safety profile and limited cancer progression.
This ongoing prospective randomized clinical study tests an adjuvant potency of p62-plasmid administered in combination with CMF in mTNBC patients. In this first interim report, we analyzed the treatment result of 11 mTNBC patients randomized into groups receiving CMF alone (n=5) or CMF in combination with the p62-plasmid (n=6). The plasmid was injected at 2.5 mg weekly IM. Efficacy was assessed in accordance with the RECIST 1.1 criteria. Progression free survival (PFS) was assessed from the date of randomization until the first indication of disease progression (to date no deaths in either group).
After multiple courses of CMF plus p62, two patients (33,3%) demonstrated complete response (CR) of tumor lesions, and 3 patients (50.0%) had a partial response (PR). To date, no patient in the p62 group has progressed. Afterward, both CR patients underwent surgery. One patient had pCR (pathologic complete response) and another – pCR in tumor and 1 metastasis (from 20 removed lymph nodes). In the CMF - only group, transient PR was observed in 2 patients (40,0%). The median of observation is 14.0 and 11.0 weeks for the p62 plus CMF and CMF-only group respectively. PFS difference between the p62 plus CMF and CMF only groups was statistically significant (р=0.028). No Grade 3-4 toxicities were observed according to CT CAE v.4.0.
A plasmid p62-encoding may be a safe and effective to CMF chemotherapy in mTNBC.
Clinical trial identification
The authors would like to thank Dr. Robert Devlin and Mr. Aaron Shneider for editorial assistance.
Legal entity responsible for the study
N.N. Alexandrov National Cancer Center of Belarus.
Has not received any funding.
V. Gabai, A. Shneider: Financial Interests, Institutional, Full or part-time Employment: CureLab Oncology. All other authors have declared no conflicts of interest.