Abstract 1465
Background
Canerpaturev (C-REV, former HF10) is an oncolytic, spontaneous mutant Herpes Simplex Virus type 1, and is one of immunotherapies that combine direct tumor cell killing with immune modulation. The purpose of this study is to evaluate the safety, tolerability and efficacy of C-REV with S-1 in patients with gemcitabine-refractory advanced pancreatic cancer, as well as to assess whether the immune modulation can work in pancreatic cancer by direct tumor cell killing. We report the safety and antitumor activity data of this study.
Methods
Aiming to assess C-REV as the immunostimulator, we randomly assigned patients to be injected to the primary tumor (Cohort 1) or to be injected to both the primary tumor and liver metastasis (Cohort 2). The pts received C-REV at 1x107 TCID50/mL (up to 2mL, depending on tumor size) intratumorally by EUS-guidance or by ultrasound-guidance at a 2-week interval in combination with oral 40 - 60 mg S-1 at twice daily for 4 weeks followed by 2 weeks rest. The study treatment could continue up to 1 year if eligible for injection. The primary endpoint was Adverse events (AEs) assessed per NCI-CTCAE v4.0; the secondary endpoints were best overall response rate (BORR) at 16-week by RECISTv1.1, progression-free survival and viral shedding in body fluids. The treatment regimen of either cohort will be selected for the subsequent stage.
Results
In Cohort 1, 9 patients (pts) were enrolled and treated at data cut-off 16 Apr 2019; 11% (1/9) pts had C-REV-related ≥G3 AE and 11% (1/9) pts had S-1-related ≥G3 AEs. Disease control rate was 56% (0 PR and 5 SDs), and 3 of 5 pts on-study are showing a decrease in lesion size in response to treatment, with 1 documented PRin. In Cohort 2, 8 pts were enrolled and treated. No pts had C-REV-related ≥G3 AE and 25% (2/8) pts had S-1-related ≥G3 AEs. Two of 4 efficacy evaluable pts had SD, and 5 pts are on-study. In both cohorts, C-REV was rapidly cleared from blood, saliva and urine.
Conclusions
Intratumoral C-REV serial injections are safe and well-tolerated in combination with S-1. The majority of S-1-related ≥G3 AEs were similar as the AEs previously reported in S-1 therapy. Assessment of C-REV plus S-1 as a potential new second-line treatment for stage IV pancreatic cancer is ongoing in this study.
Clinical trial identification
TBI1401-03.
Editorial acknowledgement
Legal entity responsible for the study
Takara Bio Inc.
Funding
Takara Bio Inc.
Disclosure
S. Hijioka: Honoraria (self): Novartis; Honoraria (self): Teijin Pharma; Honoraria (self): Olympus; Honoraria (self): Zeon medical; Shareholder / Stockholder / Stock options: CHUGAI; Honoraria (self): Norvel Pharma; Honoraria (self): Pfizer; Honoraria (self): Fujifilm medical. M. Ueno: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): Teijin Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Shire; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): NanoCarrier; Research grant / Funding (institution): Dainippon Sumitomo pharma; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Aslan Pharmaceuticals. T. Ioka: Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): AstraZeneca; Speaker Bureau / Expert testimony: Chugai Pharmaceutical; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Speaker Bureau / Expert testimony: Yakult Honsha; Advisory / Consultancy: Shire; Advisory / Consultancy, Speaker Bureau / Expert testimony: Daiichi Sankyo; Advisory / Consultancy, Speaker Bureau / Expert testimony: Otsuka; Research grant / Funding (institution): Baxalta/Shire; Research grant / Funding (institution): Incyte. T. Okusaka: Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Novartis Pharma K.K.; Research grant / Funding (self), Research grant / Funding (institution): Pfizer Japan Inc.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd.; Research grant / Funding (self), Research grant / Funding (institution): Kyowa Hakko Kirin Co., Ltd.; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Dainippon Sumitomo Pharma Co., Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Eisai Co., Ltd.; Honoraria (self), Research grant / Funding (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca K.K.; Research grant / Funding (self), Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers K.K.; Research grant / Funding (self), Research grant / Funding (institution): Nano Carrier Co., Ltd.; Research grant / Funding (self), Research grant / Funding (institution): Baxter; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Yakult Honsha Co., Ltd.; Honoraria (self): Teijin Pharma Ltd.; Honoraria (self): Shire; Honoraria (self): AbbVie Inc.; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo Co., Ltd.; Honoraria (self): Takeda Pharmaceutical Co., Ltd. S. Kobayashi: Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Boston Scientific; Honoraria (self): Merck Serono; Honoraria (self): Nippon Kayaku; Honoraria (self), Speaker Bureau / Expert testimony: Kyowa Hakko Kirin; Honoraria (self): Daiichi Sankyo; Honoraria (self): Bayer Yakuhin; Honoraria (self): Teijin Pharma; Honoraria (self), Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Yakult Honsha; Research grant / Funding (institution): Takara Bio; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): BeiGene; Research grant / Funding (institution): Takeda. J. Furuse: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; Honoraria (self): Novartis; Honoraria (self), Research grant / Funding (institution): Yakult; Honoraria (self): Teijin pharma; Honoraria (self): Shionogi; Honoraria (self): EA pharma; Honoraria (self), Advisory / Consultancy: Eli Lilly Japan; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self): Mochida; Honoraria (self): Servier Japan; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self): Fujifilm Toyama Chemical; Honoraria (self): Nobel pharma; Honoraria (self): Pfizer; Honoraria (self): Sawai; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Fujifilm; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Shire Japan; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Takarabio; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Sumitomo Dainippon. M. Ikeda: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Yakuhin; Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self): Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Yakult; Advisory / Consultancy: Otsuka Pharmaceutical; Advisory / Consultancy: Daiichi-Sankyo; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self), Advisory / Consultancy: Teijin Pharma; Honoraria (self): EA Pharma; Honoraria (self): Kaken Pharmaceutical; Advisory / Consultancy: Shire; Honoraria (self): MSD; Advisory / Consultancy, Research grant / Funding (institution): ASLAN Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharmaceutical; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Nano Carrier; Honoraria (self): Gilead; Advisory / Consultancy: Astellas Pharma; Research grant / Funding (institution): Takeda Pharmaceutical; Research grant / Funding (institution): J-Pharma; Advisory / Consultancy: Micron. H. Kasuya: Research grant / Funding (institution): Takara Bio. M. Tanaka: Full / Part-time employment: Takara Bio. Y. Hashimoto: Advisory / Consultancy, Speaker Bureau / Expert testimony: Medicos Hirata; Research grant / Funding (institution): Takara Bio; Speaker Bureau / Expert testimony: Taiho Pharmaceuticals; Speaker Bureau / Expert testimony: Boston Scientific. All other authors have declared no conflicts of interest.
Resources from the same session
1109 - First Canadian Interim Analysis from the Phase IIIb CompLEEment-1 Ribociclib + Letrozole HR+ HER2- Advanced Breast Cancer Trial
Presenter: Cristiano Ferrario
Session: Poster Display session 2
Resources:
Abstract
4401 - Real-world effectiveness of first-line palbociclib + letrozole for metastatic breast cancer 4 years post approval in the US
Presenter: Jonathan Kish
Session: Poster Display session 2
Resources:
Abstract
5876 - Palbociclib-Fulvestrant (PALBO-FUL) and Everolimus -Exemestane (EVE-EXE) for Second line Hormonal Treatment (HT) of Metastatic Breast Cancer (MBC) with Lobular Histology: a Propensity Score Matched Analysis of a Multicenter ‘Real-World’ Patients (pts) Series.
Presenter: Armando Orlandi
Session: Poster Display session 2
Resources:
Abstract
3587 - Dose-escalation study of G1T48, an oral selective estrogen receptor degrader (SERD), in postmenopausal women with ER+/HER2- locally advanced or metastatic breast cancer (ABC)
Presenter: E Dees
Session: Poster Display session 2
Resources:
Abstract
5696 - Final results of the STEM trial: SFX-01 in the Treatment and Evaluation of ER+ Her2- Metastatic breast cancer (mBC)
Presenter: Sacha Howell
Session: Poster Display session 2
Resources:
Abstract
1475 - Alpelisib (ALP) + Fulvestrant (FUL) in Hormone-Receptor Positive (HR+), Human Epidermal Growth Factor Receptor-2–Negative (HER2–) Advanced Breast Cancer (ABC): Subgroup Analysis by Presence of Visceral Metastasis (VM) in the SOLAR-1 Trial
Presenter: Mario Campone
Session: Poster Display session 2
Resources:
Abstract
2549 - Phase 1 Dose Escalation Study of a Selective Androgen Receptor Modulator RAD140 in Estrogen Receptor Positive (ER+), HER2 Negative (HER2-) Breast Cancer (BC)
Presenter: Erika Hamilton
Session: Poster Display session 2
Resources:
Abstract
3787 - A Phase I study of XZP-3287, a novel oral CDK4/6 Inhibitor, administered on a continuous dosing schedule, in patients with advanced solid tumours
Presenter: Binghe Xu
Session: Poster Display session 2
Resources:
Abstract
4835 - Phase-I dose-escalation and expansion study of the PARP inhibitor, fluzoparib (SHR3162), in patients with advanced solid tumors
Presenter: Huiping Li
Session: Poster Display session 2
Resources:
Abstract
5083 - Phase 2 study of DHP107 (Liporaxel®, oral paclitaxel) in first-line, HER2 negative recurrent/metastatic breast cancer (OPTIMAL study, NCT03315364)
Presenter: Jin-Hee Ahn
Session: Poster Display session 2
Resources:
Abstract