2019 ASCO Annual Meeting!
Session: Developmental Therapeutics and Tumor Biology (Nonimmuno)
Type: Poster Session
Time: Saturday June 1, 8:00 AM to 11:00 AM
Location: Hall A
Anticancer activity in patients with advanced ovarian and biliary tract cancers treated with NUC-1031 and a platinum agent.
Developmental Therapeutics and Tumor Biology (Nonimmuno)
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #22)
J Clin Oncol 37, 2019 (suppl; abstr 3030)
Author(s): Sarah Patricia Blagden, Jennifer Bré, Peter Mullen, Chathunissa Gnanaranjan, Essam Ahmed Ghazaly, Mairead Geraldine McNamara, Juan W. Valle; University of Oxford, Oxford, United Kingdom; School of Medicine, University of St Andrews, St Andrews, United Kingdom; University of St. Andrews, St. Andrews, United Kingdom; Barts Cancer Institute, London, United Kingdom; The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom; University of Manchester/The Christie, Manchester, United Kingdom
Background: The inhibition of cellular nucleotide metabolism to promote apoptosis is a key principle of cancer therapy. This, in combination with platinum-induced DNA-damage, is key to promoting anti-cancer activity in a variety of tumors, including ovarian, biliary tract, lung, breast and bladder. NUC-1031, a phosphoramidate transformation of gemcitabine is designed to overcome resistance mechanisms that limit the efficacy of this nucleoside analog. NUC-1031 has shown broad clinical activity across multiple solid tumors as both a single agent and in combination with platinum agents. We show potential synergism between NUC-1031 and a platinum agent in advanced ovarian (OC) and biliary tract (BTC) cancers. Methods:PRO-002 was a phase Ib study; 25 patients (pts) with recurrent OC who had exhausted all other therapy options received NUC-1031 + carboplatin. 17 pts were considered platinum resistant (10) or platinum refractory (7). ABC-08 is a phase Ib study, 14 pts with advanced BTC treated in the first-line setting with NUC-1031 + cisplatin. Results: In PRO-002, strong efficacy signals were observed in non-platinum-responsive patients. Of the 17 response-evaluable platinum-resistant or refractory pts, 5 partial responses (PRs) and 11 stable diseases (SDs) were achieved, resulting in an ORR of 29% and a DCR of 94%. NUC-1031 + carboplatin was well-tolerated with no unexpected AEs; DLTs were myelosuppression and fatigue. Encouraging response rates were also observed in ABC-08 compared to historical standard of care (ABC-02). One CR (7%), 6 PRs (43%) and 1 SD (7%) were observed, resulting in an ORR of 50%. NUC-1031 + cisplatin was well-tolerated, with no unexpected AEs or DLTs. Complementary in vitro evidence suggests that the beneficial interaction occurs whereby platinum treatment sensitizes cells to NUC-1031. Conclusions: Increasing evidence suggests that NUC-1031 in combination with a platinum agent may have synergistic properties, leading to enhanced anti-cancer activity. In both OC and BTC, durable tumor shrinkage was observed. This was particularly encouraging in a platinum resistant/refractory OC population. Future studies utilizing both NUC-1031 plus a platinum agent will further elucidate the potential of this therapeutic combination.