Abstract OT1-03-03: STEM: SFX-01 in the treatment and evaluation of metastatic breast cancer
Authors: Ross SL , Morris T , Campone M , Cortes J , Duhoux FP , Howell SJ 
Published: May 2019

Abstract
Background: Sulforaphane, a plant secondary metabolite, was first identified as an anti-cancer agent in 1992, although its inherent instability has thus far held back its clinical development. SFX-01 is a proprietary synthetic pharmaceutical development product based upon a stabilised sulforaphane. Preclinical data show sulforaphane and SFX-01 inhibit breast cancer stem cells1,2 and SFX-01 potently suppresses STAT3 in ER+ metastatic breast cancer (mBC) PDX tumours3. It is therefore hypothesised that SFX-01 could become a potential therapy for reducing resistance to hormone therapy in patients with mBC.
Trial Design: An open label trial with a maximum target of 60 patients with ER+, HER2-negative, mBC who are on a third generation AI, tamoxifen (Tam) or fulvestrant (Fulv) and have evidence of emerging secondary endocrine resistance. Participants remain on AI, Tam or Fulv and take this in combination with 300mg SFX-01 orally, twice-daily, and are scanned every 6 weeks (wks) until disease progression. Patients come off study at disease progression or at the full term of 24wks. Patients who are progression free as they approach 24wks can be enrolled in a compassionate use phase.
Key Eligibility Criteria
·Male or female patients 18yrs or older
·Histological confirmation of ER+ HER2-negative breast cancer
·Clinical or histological confirmation of metastatic or locally advanced disease not amenable to curative surgical resection
·At least 1 site of measurable disease
·Must be on a third generation AI, Tam or Fulv and have evidence of emerging secondary endocrine resistance as evidenced by either: a) Progressive disease while on adjuvant ET but after the first 2 years, or b) Progressive disease within 12 months of completing adjuvant ET, or c) Progressive disease while on ET, ≥6 months after initiating ET for metastatic breast cancer
·No more than 3 lines of endocrine therapy including the treatment at the time of study entry
·No more than 1 prior line of chemotherapy for metastatic/locally advanced breast cancer
Specific Aims: The primary objectives are to determine the safety & tolerability of SFX-01 in combination with AI, Tam or Fulv and to determine clinical benefit rate (CBR) at 24wks using RECIST v1.1. Time to response, objective response rate, progression free survival interval and the PK of SFX-01, AI, Tam & Fulv will also be assessed.
Statistical Methods: Demographic, baseline characteristics, safety and efficacy data will primarily be summarised descriptively. The sample size of 20 patients in each treatment cohort is such that if the observed CBR on any arm is 15%, it will provide a 90% exact binomial confidence interval (CI) for the true CBR of 4.2% to 34.4%. Duration of response will be compared to duration of response on prior ET.
Accrual: To date, 46 of the maximum target of 60 patients have been enrolled across 10 centres in UK, Belgium, France and Spain. Final study results are expected end of 2018.
References
1. Li et al, Clin Cancer Res 2010 May1;16(9):2580-2590
2. Simões et al, AACR 106th Annual Meeting 2015, Philadelphia
3. Simões et al, 1st UK Interdisciplinary Breast Cancer Symposium 2018; Manchester, UK
Citation Format: Ross SL, Morris T, Campone M, Cortes J, Duhoux FP, Howell SJ. STEM: SFX-01 in the treatment and evaluation of metastatic breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-03-03.