Abstract 3000
Background
High deoxyuridine triphosphatase (dUTPase) in tumor tissue, as a gatekeeper enzyme for 5-fluorouracil (5-FU), is associated with 5-FU resistance. TAS-114 is an oral dUTPase inhibitor which enhance antitumor activity with 5-FU or fluoropyrimidines. Phase I study of TAS-114 in combination with S-1 showed its tolerability and preliminary antitumor signals for patients (pts) with non-small cell lung cancer and advanced gastric cancer (AGC). This phase II study has been conducted to evaluate efficacy and safety of TAS-114 and S-1 combination in pts with AGC.
Methods
The main eligibility criteria is pts with AGC after two or more previous chemotherapy regimens containing fluoropyrimidines, platinum agents, and taxanes or irinotecan. The primary endpoint is objective response rate (ORR) by investigators’ judgement. Using Simon’s optimal two-stage design, 29 pts were required, with one-sided a = 5% and power=80%. The threshold and expected ORRs were 5% and 25%. Protein expression levels of dUTPase and BRCA1 in tumor samples were determined by immunohistochemistry.
Results
The accrual was terminated in June 2018. Of all 20 enrolled pts, the ORR and disease control rate were 5.0% (95% confidence interval [CI], 0.1-24.9%) and 70.0% (95% CI, 45.7-88.1%), respectively. The median progression-free survival (PFS) and overall survival were 2.4 months (95% CI, 1.2-3.3 months) and 7.1 months (95% CI, 5.2-9.4 months), respectively. The median PFS in the groups with high and low dUTPase protein expression in the cytoplasm was 2.8 months (95% CI, 1.4–3.9) and 1.6 months (95% CI, 0.6–2.4), respectively (hazard ratio, 0.40 [95% CI, 0.16–1.04], P = 0.047). Grade 3 or higher treatment-related adverse events were anemia (20%), leucopenia (15%), neutropenia (10%), rash (10%), thrombocytopenia (5%), and Iymphopenia (5%).
Conclusions
TAS-114 with S-1 showed modest antitumor activity with acceptable safety profiles for heavily pretreated pts with AGC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Taiho.
Disclosure
D. Takahari: Research grant / Funding (self): Taiho Pharmaceutical Co; Research grant / Funding (self): Ono Pharmaceutical Co; Honoraria (self): Eli Lilly Japan; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Yakult Honsha Co; Honoraria (self): Chugai Pharmaceutical Co., Ltd. A. Kawazoe: Honoraria (self), Research grant / Funding (institution): Taiho. K. Shitara: Honoraria (self): Novartis; Honoraria (self): AbbVie; Honoraria (self): Yakult; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Lilly; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Takeda; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Ono Pharmaceutical; Advisory / Consultancy: MSD; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (self): Lilly; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Taiho Pharmaceutical; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Medi Science. All other authors have declared no conflicts of interest.
Resources from the same session
1988 - Molecular profiling reveals novel targetable biomarkers in neuroendocrine carcinoma of the uterine cervix
Presenter: Semir Vranic
Session: Poster Display session 2
Resources:
Abstract
2672 - Changes in clinico-pathological characteristics of vulvar cancer in Japan: increasing oldest-old, stage-shifting, and decreasing cohort-level survival
Presenter: Shin Nishio
Session: Poster Display session 2
Resources:
Abstract
4306 - Tumor Treating Fields (200 kHz) concomitant with weekly paclitaxel for platinum-resistant ovarian cancer: Phase 3 INNOVATE-3/ENGOT-ov50 study
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
5136 - Randomized, phase 1b/2 study of M6620 + avelumab + carboplatin vs standard care (sc) in patients (pts) with platinum-sensitive poly (ADP-ribose) polymerase inhibitor-(PARPi)-resistant ovarian cancer
Presenter: Susana Banerjee
Session: Poster Display session 2
Resources:
Abstract
2296 - An umbrella study of biomarker-driven targeted therapy in patients with platinum-resistant recurrent ovarian cancer: A Korean Gynecologic Oncology Group study (KGOG 3045), AMBITION
Presenter: Jung-Yun Lee
Session: Poster Display session 2
Resources:
Abstract
2732 - A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer
Presenter: Ana Oaknin
Session: Poster Display session 2
Resources:
Abstract
4404 - ENGOT-EN9/LEAP-001: a phase 3, randomized, open-label study of pembrolizumab plus lenvatinib versus chemotherapy for first-line treatment of advanced or recurrent endometrial cancer
Presenter: Christian Marth
Session: Poster Display session 2
Resources:
Abstract
4564 - Phase 1/2 trial of tisotumab vedotin plus bevacizumab, pembrolizumab, or carboplatin in recurrent or metastatic cervical cancer (innovaTV 205/ENGOT-cx8)
Presenter: Ignace Vergote
Session: Poster Display session 2
Resources:
Abstract
4933 - Updated data of Epitopes-HPV02 trial and external validation of efficacy of DCF in prospective Epitopes-HPV01 study in advanced anal squamous cell carcinoma. Pooled analysis of 115 patients
Presenter: Stefano Kim
Session: Poster Display session 2
Resources:
Abstract
2301 - Pre-specified pilot analysis of a randomised pilot/phase II/III trial comparing standard dose vs dose-escalated concurrent chemoradiotherapy (CRT) in anal cancer (PLATO-ACT5)
Presenter: Alexandra Gilbert
Session: Poster Display session 2
Resources:
Abstract