1465 - Phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) with S-1 in patients with stage IV pancreatic cancer.

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.