1222 - Results from phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer

Background

Canerpaturev (C-REV, formerly 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 in combination with gemcitabine + nab-paclitaxel (G-nP) in patients with stage III or IV unresectable pancreatic cancer. We report the safety and antitumor activity data of this study.

Methods

The patients (pts) received C-REV at 1x10⁶ or 1x10⁷ TCID₅₀/mL (up to 2mL, depending on tumor size) intratumorally by EUS-guidance at a 2-week interval in addition to 1000 mg/m² gemcitabine and 125 mg/m² nab-paclitaxel by intravenous infusion on days 1, 8, and 15 of a 4-week cycle. 3 + 3 pts enrolled to determine the recommended dose (RD), followed by 10 pts enrolled at RD. The study treatment could continue up to 1 year if eligible for injection. The primary endpoint was dose limiting toxicity (DLT); the secondary endpoints were Adverse events (AEs) assessed per NCI-CTCAE v4.0, best overall response rate (BORR) at 16-week by RECIST v1.1 and progression-free survival (PFS).

Results

Sixteen pts were enrolled and treated: 44% (7/16) men, age range from 51 to 72 years old, disease UICC stage 75% III, 25% IV. No DLTs were observed. As of 16 Apr 2019, 25% (4/16) pts had C-REV-related ≥G3 AE. 81% (13/16) pts had G-nP-related ≥G3 AEs, and the majority of ≥G3 AEs were similar as the AEs previously reported in G-nP therapy. BORR was 44% (7 PRs). Disease control rate was 94% (7 PRs and 8 SDs). Median PFS was 9.7 months in Stage III and 8.5 months in Stage IV. No deaths were observed at the median follow-up time of 8.1 months. Three pts continued the treatment up to 1 year, and the treatment of 5 pts is ongoing. We will present the updated data.

Conclusions

Intratumoral C-REV serial injections are safe and well-tolerated in combination with G-nP. The combination of C-REV and G-nP suggested a favorable benefit/risk profile and encouraging antitumor activity as the 1^st line treatment of unresectable pancreatic cancer.

Clinical trial identification

TBI1401-03.

Editorial acknowledgement

Legal entity responsible for the study

Takara Bio Inc.

Funding

Takara Bio Inc.

Disclosure

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. S. Hijioka: Honoraria (self): Novartis; Honoraria (self): Teijin Pharma; Honoraria (self): Norvel Pharma; Honoraria (self): Pfizer; Honoraria (self): Fujifilm medical; Honoraria (self): Olympus; Honoraria (self): Zeon medical; Shareholder / Stockholder / Stock options: Chugai. T. Ioka: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Speaker Bureau / Expert testimony: Otsuka; Advisory / Consultancy: Shire; Advisory / Consultancy, Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Chugai Pharmaceutical; Speaker Bureau / Expert testimony: Yakult Honsha; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Baxalta/Shire; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Incyte. 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. 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. J. Furuse: Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono; 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): Sanofy; Honoraria (self), Advisory / Consultancy: Fujifilm Toyama Chemical; Honoraria (self): Nobel pharma; Honoraria (self): Pfizer; Honoraria (self): Sawai; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: AbbVie; Advisory / Consultancy: Shire Japan; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Takara bio; 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. 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; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): ASLAN Pharmaceuticals. All other authors have declared no conflicts of interest.