Abstract 5696
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.
Resources from the same session
1398 - Phase 1 study of liposomal formulation of eribulin (E7389-LF) in patients (pts) with advanced solid tumors: primary results of dose-escalation part
Presenter: Noboru Yamamoto
Session: Poster Display session 2
Resources:
Abstract
5818 - Polo-like Kinase 1 inhibitor onvansertib synergizes with paclitaxel in breast cancer carrying p53 mutation
Presenter: Antonio Giordano
Session: Poster Display session 2
Resources:
Abstract
5927 - Phase 1b study of heat shock protein 90 inhibitor, onalespib in combination with paclitaxel in patients with advanced, triple negative breast cancer (NCT02474173).
Presenter: Robert Wesolowski
Session: Poster Display session 2
Resources:
Abstract
1695 - Impact of pertuzumab and T-DM1 on prognosis of HER2-positive metastatic breast cancer (MBC) and factors affecting their efficacy: results from the AGMT_MBC-Registry
Presenter: Simon Peter Gampenrieder
Session: Poster Display session 2
Resources:
Abstract
1742 - Clinical profile and outcome of HER2 positive breast cancer patients with brain metastases treated with HER2 targeted therapy: Real world experience.
Presenter: Prabhat Bhargava
Session: Poster Display session 2
Resources:
Abstract
1846 - Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer: results of single arm phase IV COMACHI study
Presenter: Norikazu Masuda
Session: Poster Display session 2
Resources:
Abstract
5385 - Anti HER-2 Therapies and Left Ventricular Dysfunction The Renaissance Study
Presenter: ANDRES DANIELE
Session: Poster Display session 2
Resources:
Abstract
3320 - Safety and efficacy of T-DM1 in 128 patients with advanced HER2+ breast cancer: The Royal Marsden experience.
Presenter: Nicolò Battisti
Session: Poster Display session 2
Resources:
Abstract
4540 - Use of trastuzumab emtansine (T-DM1; K) after pertuzumab + trastuzumab (PH) in patients with HER2-positive metastatic breast cancer (mBC): challenges in assessing effectiveness of treatment sequencing in the real world (RW)
Presenter: Thibaut Sanglier
Session: Poster Display session 2
Resources:
Abstract
2376 - Patient Reported Outcomes (PRO) in patients (pts) with HER2- advanced breast cancer (ABC) and a germline BRCA1/2 mutation (gBRCAm) receiving talazoparib (TALA) vs physician’s choice chemotherapy (PCT) in the EMBRACA trial: A focus on subgroups with/ without visceral disease
Presenter: Johannes Ettl
Session: Poster Display session 2
Resources:
Abstract