5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)

Background

SFX-01 is a proprietary synthetic pharmaceutical product based upon a stabilised sulforaphane. In preclinical models SFX-01 inhibits the activity of cancer stem-like cells and reverses resistance to endocrine therapies (ET) tamoxifen (Tam) and fulvestrant (Fulv). The STEM study investigated the potential of SFX-01 to reverse acquired resistance to Tam, Fulv and third generation aromatase inhibitor (AI) therapy.

Methods

STEM is an open label parallel arm exploratory phase II trial. Patients were eligible if they had measurable (RECIST v1.1) estrogen receptor (ER) positive Her2- mBC that had developed acquired resistance to AI (arm A), Tam (arm B) or Fulv (arm C) therapy i.e. mBC was progressing having shown clinical benefit (stable disease (SD) for 6 months or objective response (OR)). SFX-01 300mg bd po was added to the current ET. The co-primary endpoints were clinical benefit rate (CBR) and safety/tolerability. Secondary endpoints included OR rate (ORR) and time to progression (TTP). Patients progression free at 24wks were enrolled into a compassionate use phase to continue SFX-01 and the same ET.

Results

Between January 2017 and July 2018 46 patients were recruited; arm A n = 31, arm B n = 8 and arm C n = 7. 33/46 (71.7%) had visceral involvement. Prior lines of ET were: 1= 17/46 (37.0%), 2= 17/46 (37.0%) and ≥3 = 12 (26%). 8 patients (17.4%) had received prior chemotherapy for mBC. The CBR overall was 12/46 (26.0%) with 2 objective responses (both partial). SFX-01 was well tolerated with grade 1/2 nausea (54.3%) and dyspepsia (32.6%) the most frequent adverse events (AEs). Only 2 grade 3 AEs were possibly drug related. There were no drug related serious AEs. There was no significant association between duration of prior ET and subsequent duration of ET+SFX-01 (Spearman r 0.17; p = 0.26).

Conclusions

SFX-01 300 mg BID was safe and well tolerated in patients with ER+ and HER2- mBC. SFX-01 in combination with ET demonstrated anti-tumour activity and prolonged disease stabilisation in pre-treated patients who were progressing on the background ET at study entry. Further development of SFX-01 in ER+ mBC is warranted.

Clinical trial identification

NCT02970682.

Editorial acknowledgement

Legal entity responsible for the study

Evgen Pharma PLC.

Funding

Evgen Pharma PLC.

Disclosure

S.J. Howell: Research grant / Funding (self), Travel / Accommodation / Expenses: Evgen Pharma PLC. S. Ross: Full / Part-time employment: Evgen Pharma PLC. T. Morris: Full / Part-time employment: Evgen Pharma PLC. S. Franklin: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Evgen Pharma PLC. All other authors have declared no conflicts of interest.