2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
TACTICAL: A phase I/II trial to assess the safety and efficacy of MSCTRAIL in the treatment of metastatic lung adenocarcinoma.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #438a)
J Clin Oncol 37, 2019 (suppl; abstr TPS9116)
Author(s): Alice Davies, Beth Sage, Krishna Kolluri, Doraid Alrifai, Rebecca Graham, Ben Weil, Rita Rego, Owen Bain, P. Stephen Patrick, Kim Champion, Alex Day, Bilyana Popova, Graham Wheeler, Dan Fullen, Tammy Kalbur, Martin Forster, Mark Lowdell, Sam Janes; Lungs for Living Research Centre, UCL Respiratory, University College London, London, United Kingdom; Raigmore Hospital, NHS Highlands, Inverness, United Kingdom; Centre for Cell Gene and Tissue Therapy, London, United Kingdom; Centre for Cell, Gene & Tissue Therapeutics, Royal Free London NHS Foundation Trust, London, United Kingdom; Centre for Cell, Gene and Tissue Therapeutics, London, United Kingdom; Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom; Cancer Research UK & UCL Cancer Trials Centre, London, United Kingdom; Cancer Research UK & University College London Cancer Trials Centre, London, United Kingdom; UCL Translational Research Office, London, United Kingdom; UCL Cancer Institute, UCLH, London, United Kingdom
Background: Mesenchymal stromal cells (MSCs) migrate to and incorporate into tumour stroma allowing them to act as vehicles for delivering anti-cancer therapies. TNF-related apoptosis inducing ligand (TRAIL) selectively induces apoptosis in malignant cells however short biological half-life has its limited therapeutic efficacy. We have transduced umbilical cord MSCs with a lentiviral vector to express TRAIL (MSCTRAIL). These cells trigger apoptosis selectively in cancer cells with evidence of synergistic activity with other systemic anti-cancer therapies. Given their immune-privileged nature we are delivering ex vivo pooled MSCTRAIL from third party donors without tissue matching or immunosuppression. Efficacy has been demonstrated using in vitro co-culture assays and in vivo in orthotopic lung metastasis murine model, showing regression of metastases following treatment with intravenous MSCTRAIL . Methods: TACTICAL is a phase I/II trial assessing safety and efficacy of MSCTRAIL in combination with first line standard of care (SOC); pemetrexed (500mg/m2) and cisplatin (75mg/m2) and/or pembrolizumab (200mg), in treatment naïve patients with stage IIIB/IV metastatic lung adenocarcinoma. Patients have no actionable driver mutations and ECOG performance status 0-1. Phase I is a dose de-escalation study, patients receive SOC on day 1 and 4x108 MSCTRAIL cells on day 2 of a 21 day cycle for 3 cycles. A Bayesian adaptive design will recommend dose reductions if excessive toxicities occur. Primary outcomes are to determine recommended phase II dose along with safety and tolerability of MSCTRAIL. 46 patients will then be randomised into a multi-centre phase II double blind, placebo-controlled trial to receive SOC and either MSCTRAIL or placebo (1:1). Primary outcome is tumour response rate by RECIST (v 1.1) criteria at 12 weeks. Secondary outcomes include, best overall response, duration of response, progression free survival and overall survival. TACTICAL is the first clinical trial of this novel cell and gene therapy and if successful will pave the way for future allogeneic MSC therapy in cancer. 1. Loebinger, M.R., et al., Mesenchymal stem cell delivery of TRAIL can eliminate metastatic cancer. Cancer Res, 2009. 69(10): p. 4134-42. Clinical trial information: NCT03298763