Abstract 1625
Background
Canerpaturev (C–REV) is an oncolytic, spontaneous mutant of HSV-1, and is one of immunotherapies that can not only kill tumor cells but also modulate immune responses. We report the efficacy of Phase II multicenter trial of combination therapy using C-REV and ipilimumab (ipi) in melanoma patients (pts) who were refractory or intolerant to prior therapies.
Methods
Key entry criteria: age ≥ 20 yrs, ECOG PS 0-2, AJCC 7th Stage IIIB-IV unresectable melanoma, who received prior therapies and had measurable non-visceral lesion(s) suitable for C-REV injections. C-REV was injected into each tumor (1 x 107 TCID50/mL/dose, up to 5 mL); 4 injections q1wk; then up to 15 injections q3wks. Ipi (3 mg/kg) was administered 4 times, q3wks. Primary endpoint was Best Overall Response Rate (BORR) by immune-related response criteria (irRC).
Results
28 pts were enrolled. Disease stage: 7.1% IIIB, 28.6% IIIC and 64.3% IV, and disease type: 39.3% acral lentiginous and 21.4% mucosal melanoma. Anti-PD-1 antibody was previously used in 89.3%. Severe adverse events (AEs, ≥G3) related to the study treatment was 35.7 %. Of 27 efficacy evaluable pts, BORR and disease control rate by irRC 11.1% and 55.6%, respectively. Pts with irPR and durable irSD longer than 24 wks were confirmed in 22.2 % (6 pts) and had no deaths (follow-up period: 298 - 446 days). The median OS was 318.0 days (95% C.I. 211.00 – not reached).
Conclusions
In melanoma, various immunotherapies and molecular targeted drugs have been approved for treatment options, but there are still unmet medical needs in particular in pts who failed in the 1st line therapy. In this trial, C-REV did not show the exacerbation in ipi toxicity and patients with irPR and durable irSD contributed to prolonging OS. Thus, C-REV plus ipi has potential to become a new treatment option for melanoma in ≥ 2nd-line setting.
Clinical trial identification
NCT03153085.
Editorial acknowledgement
Legal entity responsible for the study
Takara Bio Inc.
Funding
Takara Bio Inc.
Disclosure
K. Yokota: Research grant / Funding (institution): Takara Bio Inc. T. Isei: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono Pharmaceutical Co., Ltd.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis Pharma K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD K.K.; Honoraria (self): Mochida Pharmaceutical Co., Ltd.; Honoraria (self): Pfizer Japan Inc.; Honoraria (self), Travel / Accommodation / Expenses: Kaken Pharmaceutical Co.,Ltd.; Honoraria (self): Daiichi Sankyo Company, Limited.; Honoraria (self), Travel / Accommodation / Expenses: Maruho Co.,Ltd. ; Honoraria (self), Travel / Accommodation / Expenses: Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): POLA-Pharma; Advisory / Consultancy: Merck Biopharma Co., Ltd; Research grant / Funding (institution): Takara Bio Inc.; Research grant / Funding (institution): Array BioPharma, Inc.; Research grant / Funding (institution): Amgen Inc. H. Uhara: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ono Pharmaceutical Co., LTD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD K.K.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis Pharma K.K.; Honoraria (self), Research grant / Funding (institution): Maruho Co.,Ltd. ; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb K.K.; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution): POLA-Pharma; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Kyowa Hakko Kirin Co., Ltd.; Speaker Bureau / Expert testimony: Janssen Pharmaceutical K.K.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Mitsubishi Tanabe Pharma Corporation; Research grant / Funding (institution): Taiho Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Eisai Co., Ltd. ; Research grant / Funding (institution): AbbVie GK.; Research grant / Funding (institution): Maruho Co.,Ltd. ; Research grant / Funding (institution): Daiichi Sankyo Company, Limited. ; Research grant / Funding (institution): Tsumura & Co.; Research grant / Funding (institution): Mochida Pharmaceutical Co., Ltd.; Research grant / Funding (institution): Nippon Kayaku Co.,Ltd.; Research grant / Funding (institution): Torii Pharmaceutical Co.,Ltd; Research grant / Funding (institution): Kaken Pharmaceutical Co.,Ltd. Y. Fujisawa: Advisory / Consultancy: Eli Lilly Japan K.K. ; Advisory / Consultancy: Novartis Pharma K.K.; Research grant / Funding (institution): Ono Pharmaceutical Co., LTD; Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Research grant / Funding (institution): Eisai Co., Ltd. ; Research grant / Funding (institution): Takara Bio Inc. T. Takenouchi: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: MSD K.K.; Speaker Bureau / Expert testimony: Novartis Pharma K.K.; Speaker Bureau / Expert testimony: Chugai Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Bristol-Myers Squibb K.K.; Research grant / Funding (institution): Takara Bio Inc. Y. Kiyohara: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Ono Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): MSD K.K.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self): Novartis Pharma K.K.; Honoraria (self): Chugai Pharmaceutical Co., Ltd.; Honoraria (self): Toray Industries, Inc.; Honoraria (self), Research grant / Funding (institution): Merck Biopharma Co., Ltd; Honoraria (self): Boehringer Ingelheim Japan, Inc.; Research grant / Funding (institution): Takara Bio Inc.; Honoraria (self), Research grant / Funding (institution): Amgen Inc. H. Uchi: Research grant / Funding (institution): Takara Bio Inc. H. Saruta: Speaker Bureau / Expert testimony: Ono Pharmaceutical Co., Ltd.; Speaker Bureau / Expert testimony: Kyowa Hakko Kirin Co., Ltd.; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Minophagen Pharmaceutical Co., LTD.; Research grant / Funding (institution): MSD K.K.; Research grant / Funding (institution): Takara Bio Inc. H. Ihn: Research grant / Funding (institution): Takara Bio Inc. T. Inozume: Research grant / Funding (institution): Takara Bio Inc. D. Watanabe: Advisory / Consultancy: Japan vaccine; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Maruho Co.,Ltd. ; Research grant / Funding (institution): Sanofi K.K.; Research grant / Funding (institution): Nippon Zoki Pharmaceutical Co., Ltd. ; Research grant / Funding (institution): Daiichi Sankyo Company, Limited.; Research grant / Funding (institution): Takara Bio Inc. A. Takahashi: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self), Research grant / Funding (institution): Novartis Pharma K.K.; Research grant / Funding (institution): Takara Bio Inc. S. Fukushima: Research grant / Funding (institution): Takara Bio Inc. M. Tanaka: Full / Part-time employment: Takara Bio Inc. N. Yamazaki: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Ono Pharmaceutical Co., Ltd; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSD K.K.; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma K.K.; Research grant / Funding (institution): Takara Bio Inc.
Resources from the same session
4021 - Prospective pathological experience with research biopsies in the context of clinical trials at Vall d’Hebron Institute of Oncology
Presenter: Paolo Nuciforo
Session: Poster Display session 3
Resources:
Abstract
5603 - Development of a comprehensive next-generation targeted sequencing assay for detection of gene-fusions in solid tumors
Presenter: Vinay Mittal
Session: Poster Display session 3
Resources:
Abstract
4952 - Next-generation sequencing for better treatment strategy of cancer of unknown primary (CUP)
Presenter: Kang Kook Lee
Session: Poster Display session 3
Resources:
Abstract
4590 - Circulating-free DNA analysis from long-term surviving metastatic colorectal cancer patients undergoing surgery for resectable disease.
Presenter: Michele Ghidini
Session: Poster Display session 3
Resources:
Abstract
3696 - Ultra-sensitive detection of circulating tumor DNA identifies patients in high risk of recurrence in early stages melanoma
Presenter: Filip Janku
Session: Poster Display session 3
Resources:
Abstract
4295 - Identification of the founder BRCA1 mutation c.4117G>T (p.Glu1373*) recurring in Abruzzo and Lazio regions of Central Italy and predisposing to breast/ovarian and BRCA1-related cancers
Presenter: Daniela Di Giacomo
Session: Poster Display session 3
Resources:
Abstract
2214 - Enzalutamide (ENZA) and Apalutamide (APA) In vitro chemical reactivity studies and Activity in a Mouse Drug Allergy Model (MDAM)
Presenter: Mausumee Guha
Session: Poster Display session 3
Resources:
Abstract
5044 - Influence of genetic variation in COMT on cisplatin-induced nephrotoxicity in cancer patients.
Presenter: Bram Agema
Session: Poster Display session 3
Resources:
Abstract
3293 - Cardioprotective and anti-inflammatory effects of Empagliflozin during treatment with Doxorubicin: a cellular and preclinical study
Presenter: Vincenzo Quagliariello
Session: Poster Display session 3
Resources:
Abstract
3324 - Breast Cancer Organoids Model Treatment Response of HER2 Targeted Therapy in HER2-mutant Breast Cancer
Presenter: Xuelu Li
Session: Poster Display session 3
Resources:
Abstract