Abstract 2773
Background
Etoposide toniribate (also known as EDO-S7.1, and previously known as CAP7.1), a novel topoisomerase II inhibitor, is activated in the presence of carboxylesterases. In specific tumor cell lines, it was found to be more active than etoposide, with in vivo activity demonstrated in several drug-resistant tumor models. Anti-tumor activity was confirmed in a Phase II randomized study in patients (pts) with relapsed BTC.
Methods
Pts with BTC and disease progression after ≥1 line of chemotherapy were randomized 1:1 to 3-week cycles of etoposide toniribate (200 or 150mg/m2; iv on days 1–5), or best supportive care (BSC). Pts who progressed on BSC crossed over to receive etoposide toniribate. Efficacy data collected after crossover were evaluated separately as part of this post-hoc exploratory analysis.
Results
The per protocol analysis set included 19 pts: 10 pts were randomized to BSC, and crossed over to etoposide toniribate after disease progression, 9 pts were randomized directly to the etoposide toniribate treatment arm. Treatment after crossover from BSC to etoposide toniribate was associated with a trend for improved disease control: n/N (%; 95% CI) 4/10 (40%; 12.2, 73.8) vs 2/10 (20%; 2.5, 55.6), with tumor control achieved in 4/10 patients (1 pt partial response, 3 pts stable disease). Risk of disease progression was 2.33 times higher during BSC treatment vs after crossover to etoposide toniribate. Crossover from BSC to etoposide toniribate was associated with a trend for prolonged median PFS (39 vs 50 days). Median OS for pooled etoposide toniribate and crossover pts was 145 (59, 243) days, estimated 1-year OS 14.1%. Median (95% CI) OS for etoposide toniribate vs crossover pts was 180 (43, 468) vs 83 (11, 243) days, HR 0.39 (0.13, 1.18), estimated 1-year OS 29.6% (5.2%, 60.7%) vs 0%.
Conclusions
This post-hoc analysis provides further evidence for the efficacy of etoposide toniribate and suggests that early initiation in pts with advanced BTC may offer a potential survival benefit. The efficacy of etoposide toniribate will be further investigated in a planned phase III study. Funding: CellAct Pharm GmbH and Mundipharma EDO GmbH.
Clinical trial identification
NCT02094560.
Editorial acknowledgement
Sarah Birch, PhD, at Makara Health Communications Ltd, UK, funded by Mundibiopharma Ltd.
Legal entity responsible for the study
CellAct Pharma GmbH.
Funding
CellAct Pharma GmbH, Mundipharma EDO GmbH.
Disclosure
U. Pape: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Shire; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Ipsen. S. Kasper: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Servier; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Research grant / Funding (self): Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: Lilly. J. Meiler: Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Sanofi/Aventis. M. Sinn: Honoraria (self): Amgen; Honoraria (self), Research grant / Funding (self): Leo Pharma; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Boston Biomedical; Research grant / Funding (self): Incyte; Research grant / Funding (self): Merck Sharp and Dohme; Research grant / Funding (self): Servier; Research grant / Funding (self): Taiho Pharmaceutical. H. Jansen: Advisory / Consultancy: CellAct Pharma. T. Mehrling: Leadership role, Full / Part-time employment: Mundipharma EDO. K. Hilgier: Advisory / Consultancy: Mundipharma EDO. I. Wagner: Full / Part-time employment: Mundipharma EDO. N. Utku: Honoraria (self), Advisory / Consultancy, Leadership role, Research grant / Funding (self), Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: CellAct Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Mundipharma EDO; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
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
4874 - Complete Responses in Patients With 2nd-Line or Greater Metastatic Triple-Negative Breast Cancer (TNBC) Following First-in-Human Immunotherapy Combining NK and T Cell Activation with Off-the-Shelf High-Affinity CD16 NK Cell Line (haNK)
Presenter: Chaitali Nangia
Session: Poster Display session 2
Resources:
Abstract
4362 - Reproducibility and concordance of 4 clinically developed programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) assays in triple-negative breast cancer (TNBC)
Presenter: Aurelia Noske
Session: Poster Display session 2
Resources:
Abstract
4528 - Systemic Therapy in 2nd-Line Metastatic Triple Negative Breast Cancer (mTNBC): A Systematic Literature Review (SLR) and Meta-Analysis (MA) of Efficacy
Presenter: Peter Kaufman
Session: Poster Display session 2
Resources:
Abstract
4112 - Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia
Presenter: Yang Chen
Session: Poster Display session 2
Resources:
Abstract
5699 - Patterns and predictors of first-line (1L) taxane use in US patients with metastatic triple-negative breast cancer (mTNBC)
Presenter: Joyce O’Shaughnessy
Session: Poster Display session 2
Resources:
Abstract
1931 - Maintenance Chemotherapy is effective in Patients with Metastatic Triple Negative Breast Cancer After First-line Platinum-based Chemotherapy
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract
4696 - Using the Patient-Reported Outcomes Measurement Information System (PROMIS) to investigate symptom burden enrichment in Stage IV patients at an academic center
Presenter: Madeline Matthys
Session: Poster Display session 2
Resources:
Abstract
4582 - Measures of functional status in adults aged ≥70 years with advanced breast cancer (ABC) receiving palbociclib (PAL) combination therapy in POLARIS
Presenter: Meghan Karuturi
Session: Poster Display session 2
Resources:
Abstract
3565 - Real-World 1-Year Survival Analysis of Patients with Metastatic Breast Cancer with Liver or Lung Metastasis Treated with Eribulin, Gemcitabine or Capecitabine
Presenter: Shayma Kazmi
Session: Poster Display session 2
Resources:
Abstract