canerpaturev (TBI-1401) / Takara - LARVOL DELTA

Oncolytic virotherapy and tumor microenvironment modulation. (PubMed, Clin Exp Med) - "Among the most significant advancements, T-VEC, an FDA-approved herpesvirus, has been modified to express GM-CSF, enhancing immune activation in metastatic melanoma. Similarly, JX-594, a vaccinia virus, has been engineered for selective replication in tumor cells, demonstrating the potential of OVs to combine direct oncolysis with immune modulation. Other HSV-based OVs, such as HF10 and HSV1716, further highlight the ability of OVs to enhance immune cell infiltration and increase antigen presentation within the TME...Advances in viral engineering and immunomodulation hold the potential to revolutionize cancer treatment, offering more precise and effective therapeutic options. This review provides a comprehensive analysis of current progress in oncolytic virotherapy, emphasizing its potential to remodel the TME and improve clinical outcomes."

Biomarker • IO biomarker • Journal • Review • Immune Modulation • Immunology • Infectious Disease • Measles • Melanoma • Novel Coronavirus Disease • Oncology • Respiratory Diseases • Solid Tumor

Talimogene Laherparepvec (T-VEC): Expanding Horizons in Oncolytic Viral Therapy Across Multiple Cancer Types. (PubMed, Anticancer Agents Med Chem) - "By exploring recent trials, such as T-VEC with neoadjuvant chemotherapy in triple-negative breast cancer and pembrolizumab in HNSCC, highlighting its versatility. Comparative analysis with other oncolytic viruses like HF-10, oncorine (H101), and measles virus variants positions T-VEC within the virotherapy landscape. Key challenges-systemic delivery, immune clearance, and biomarker development for patient selection-are addressed alongside strategies to enhance immune modulation through novel combinations. This review underscores T-VEC's expanding role in cancer treatment, offering clinicians' and researchers' insights to optimize its therapeutic horizons across diverse malignancies."

IO biomarker • Journal • Breast Cancer • Head and Neck Cancer • Herpes Simplex • Immune Modulation • Immunology • Infectious Disease • Measles • Melanoma • Non-melanoma Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • CSF2

Clinical outcomes of immunotherapy in metastatic pancreatic carcinoma: A systematic review and meta-analysis. (ASCO-GI 2025) - "Immunotherapies included were GVAX, tremelimumab, Mesothelin-specific Chimeric Antigen Receptor T cells, durvalumab, pembrolizumab, canerpaturev, Sotigalimab, nivolumab, CO-1.01, allogeneic natural killer cell immunotherapy, Anti-EGFR chimeric antigen receptor-modified T cells, bispecific antibody armed T cells, and clivatuzumab tetraxetan... This meta-analysis demonstrates that novel immunotherapies have promising results on metastatic pancreatic cancer. Future new clinical trials with a follow-up on current early-phase results are needed."

Clinical data • Metastases • Retrospective data • Review • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • MSLN

Synergistic anti-tumor effects of oncolytic virus and anti-programmed cell death protein 1 antibody combination therapy: For suppression of lymph node and distant metastasis in a murine melanoma model. (PubMed, Biochem Biophys Res Commun) - "Therefore, we investigated whether canerpaturev (C-REV) and aPD-1 antibody combination therapy suppresses tumor progression in a murine melanoma model...These findings suggest that direct anti-tumor effects by infecting and destroying cancer cells from within and indirect anti-tumor effects enhanced by the combination therapy worked simultaneously to suppress tumor progression. Our results may provide evidence to support the usefulness of OV and aPD-1 antibody combination therapy as a neoadjuvant therapy in the surgical treatment of melanoma."

Combination therapy • Journal • Oncolytic virus • Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor

New Treatment Horizons in Uveal and Cutaneous Melanoma. (PubMed, Life (Basel)) - "Talimogene laherparepvec (T-VEC) is an FDA-approved oncolytic virus for CM treatment, and other oncolytic viruses, such as coxsackieviruses and HF-10, are being investigated. Furthermore, combining oncolytic viruses with immunotherapies, such as CAR-T cell therapy, holds great potential. Understanding the intrinsic molecular features of melanoma and their role in shaping novel therapeutic approaches provides insights into targeted interventions and paves the way for more effective treatments for CM and UM."

IO biomarker • Journal • Review • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • EIF1AX • GNA11 • GNAQ • SF3B1

Subgroup analysis of a phase II multicenter trial of HF10, oncolytic virus immunotherapy, and ipilimumab combination treatment in unresectable or metastatic melanoma patients (ESMO Asia 2017) - P2; "The combination HF10 and ipi treatment demonstrated a favorable benefit/risk profile and encouraging antitumor activity in unresectable or metastatic melanoma pts."

Benefit-risk assessment • Checkpoint inhibition • Clinical • Oncolytic virus • P2 data • Melanoma

Topline Results from Phase II of Combination Treatment with Canerpaturev (HF10), an Oncolytic Viral Immunotherapy, and Ipilimumab in Patients with Unresectable or Metastatic Melanoma after Anti-PD-1 Therapy (ESMO 2018) - P2; "The combination of C-REV with ipi did not show the exacerbate ipi toxicity, and had a favorable benefit/risk profile. The encouraging antitumor activity was observed in Japanese pts who had received prior therapies such as PD-1. It is recently well-known that the response to ipi after anti-PD-1 therapy was unsatisfactory and associated with a high frequency of severe irAEs, in particular Asian populations."

Clinical • IO biomarker • Oncolytic virus • P2 data • PD(L)-1 Biomarker • Melanoma

Results from phase I study of the oncolytic viral immunotherapy agent canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer. (ASCO-GI 2019) - P1; "The recommended dose was determined as 1x107 TCID50/mL. The combination of C-REV and the standard chemotherapy demonstrated a favorable benefit/risk profile and encouraging antitumor activity in Japanese patients with unresectable pancreatic cancer."

Combination therapy • IO biomarker • Oncolytic virus • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer

Metformin enhances the antitumor activity of oncolytic herpes simplex virus HF10 (canerpaturev) in a pancreatic cell cancer subcutaneous model. (PubMed, Sci Rep) - "Our findings suggest that combination of C-REV and metformin enhances systemic antitumor immunity. This study may provide insights into the mechanism of action of OV therapy plus metformin combination against various tumor models."

Journal • Herpes Simplex • Immune Modulation • Inflammation • Oncology • Pancreatic Cancer • CD8 • ITGAE • PD-1

Final results from phase II of combination with canerpaturev (formerly HF10), an oncolytic viral immunotherapy, and ipilimumab in unresectable or metastatic melanoma in second-or later line treatment (ESMO 2019) - P2; "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 1 st 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 ≥ 2 nd -line setting."

Clinical • IO biomarker • Oncolytic virus • P2 data • PD(L)-1 Biomarker • Melanoma • Oncology • Solid Tumor

[VIRTUAL] Neoadjuvant Canerpaturev (C-REV) Oncolytic Immunotherapy in Combination with Nivolumab (Nivo) in Resectable Advanced Melanoma (SMR 2021) - No abstract available

Clinical • Combination therapy • Oncolytic virus • Melanoma • Oncology • Solid Tumor

Final results of phase I trial of HF10, oncolytic virus immunotherapy, in Japanese patients with refractory superficial cancers (ESMO Asia 2017) - No abstract available.

Clinical • Oncolytic virus • P1 data • Oncology

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 (ESMO 2019) - "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."

Clinical • Combination therapy • IO biomarker • Oncolytic virus • P1 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

The efficacy and safety of oncolytic viruses in the treatment of intermediate to advanced solid tumors: a systematic review and meta-analysis. (PubMed, Transl Cancer Res) - "A total of 22 studies involving 3,996 patients were included in this analysis, including 13 H101 studies, 5 T-VEC studies, 2 Pexa-Vec studies, 1 HF10 study and 1 Reolysin study...The adverse events (AEs) associated with the other OVs mainly included fever, nausea and vomiting, leukopenia, and hypotension. OVs are effective and well tolerated for the treatment of intermediate to advanced solid cancer and represent a promising therapeutic approach for solid cancers."

Journal • Oncolytic virus • Retrospective data • Review • Gastrointestinal Cancer • Gene Therapies • Head and Neck Cancer • Hematological Disorders • Hepatocellular Cancer • Hypotension • Leukopenia • Lung Cancer • Melanoma • Oncology • Solid Tumor

S-1 facilitates canerpaturev (C-REV)-induced antitumor efficacy in a triple-negative breast cancer model. (PubMed, Nagoya J Med Sci) - "S-1, an oral formulation containing the 5-fluorouracil (5-FU) prodrug tegafur and the two enzyme modulators gimeracil and oteracil, is used as a key chemotherapeutic agent for metastatic recurrent breast cancer...Our study suggests that MDSCs may be an important cellular target for breast cancer treatment. The combination of C-REV and S-1 is a new approach that might be directly translated into future clinical trials against TNBC."

Clinical • IO biomarker • Journal • Preclinical • Breast Cancer • Herpes Simplex • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD8 • IFNG

Immunological impact of canerpaturev (C-REV, formerly HF10), an oncolytic viral immunotherapy, with or without ipilimumab (Ipi) for advanced solid tumor patients (pts). (ASCO 2019) - P2; "Our results suggest C-REV injection in the tumor local site have potential to enhance systemic immune response of Ipi. Clinical trial information: NCT03153085"

Clinical • IO biomarker • Oncolytic virus • PD(L)-1 Biomarker • Melanoma • Oncology • Solid Tumor

Efficacy and genetic analysis for a phase II multicenter trial of HF10, a replication-competent HSV-1 oncolytic immunotherapy, and ipilimumab combination treatment in patients with stage IIIb-IV unresectable or metastatic melanoma. (ASCO 2018) - P2; "The combination HF10 and ipilimumab treatment demonstrated a favorable benefit/risk profile and encouraging antitumor activity in advanced melanoma pts by inducing immune-cell infiltration in the tumor microenvironment."

Clinical • IO biomarker • Oncolytic virus • P2 data • Melanoma

Results from phase I study of the oncolytic viral immunotherapy agent canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer. (ASCO-GI 2019) - P1; "The recommended dose was determined as 1x107 TCID50/mL. The combination of C-REV and the standard chemotherapy demonstrated a favorable benefit/risk profile and encouraging antitumor activity in Japanese patients with unresectable pancreatic cancer."

Combination therapy • IO Biomarker • Oncolytic Virus • P1 data

Current status of intralesional agents in treatment of malignant melanoma. (PubMed, Ann Transl Med) - "This review focuses on the current status of IT agents currently under clinical trials in melanoma. Reviewed therapies include T-VEC, T-VEC with immune checkpoint inhibitors including ipilimumab and pembrolizumab or other agents, RP1, OrienX010, Canerpaturev (C-REV, HF10), CAVATAK (coxsackievirus A21, CVA21) alone or in combination with checkpoint inhibitors, oncolytic polio/rhinovirus recombinant (PVSRIPO), MAGE-A3-expressing MG1 Maraba virus, VSV-IFNbetaTYRP1, suicide gene therapy, ONCOS-102, OBP-301 (Telomelysin), Stimulation of Interferon Genes Pathway (STING agonists) including DMXAA, MIW815 (ADU-S100) and MK-1454, PV-10, toll-like receptors (TLRs) agonists including TLR-9 agonists (SD-101, CMP-001, IMO-2125 or tilsotolimod, AST-008 or cavrotolimod, MGN1703 or lefitolimod), CV8102, NKTR-262 plus NKTR-214, LHC165, G100, intralesional interleukin-2, Daromun (L19IL2 plus L19TNF), Hiltonol (poly-ICLC), electroporation including calcium electroporation and plasmid..."

Journal • Review • Gene Therapies • Immune Modulation • Inflammation • Melanoma • Oncology • Solid Tumor • CD40 • IL12A • MAGEA3 • TYRP1

Oncolytic herpes simplex virus HF10 (canerpaturev, C-REV) promotes accumulation of CD8 PD-1 tumor-infiltrating T cells in PD-L1- enriched tumor microenvironment. (PubMed, Int J Cancer) - "In addition, changes in expression of TIM-3 and TIGIT were not observed on CD8 TILs after C-REV treatment. Taken together, our findings may reveal mechanisms that allow oncolytic viruses to trigger an antitumor immune response, irrespective of a PD-L1-enriched tumor microenvironment, by recruitment of CD8 PD-1 TILs."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Herpes Simplex • Immune Modulation • Inflammation • Oncology • CD8 • HAVCR2 • PD-1 • PD-L1 • TIGIT

Oncolytic activity of naturally attenuated herpes-simplex virus HF10 against an immunocompetent model of oral carcinoma. (PubMed, Mol Ther Oncolytics) - "Immunohistochemical staining showed that HF10 induced infiltration of CD8-positive T cells around HSV-infected cells in the tumor mass, implying increased anti-tumor immunity. We successfully established an oral cancer cell line and showed that HF10 is a promising therapeutic agent for oral cancer."

Journal • Head and Neck Cancer • Herpes Simplex • Oncology • Oral Cancer • Solid Tumor • Tongue Carcinoma • CD8

Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (clinicaltrials.gov) - P2; N=7; Terminated; Sponsor: University of Utah; Active, not recruiting ➔ Terminated; DSMC Recommendation

Clinical • Combination therapy • Oncolytic Virus • Trial termination • Melanoma • Oncology • Solid Tumor

A phase 2 multicenter trial to evaluate efficacy and safety of HF10 oncolytic virus immunotherapy and ipilimumab in patients with unresectable stage IIIB-IV melanoma (SMR 2016) - Ambassador: Robert H. I. Andtbacka; P2, N=46; "HF10+ipi treatment does not appear to exacerbate ipi toxicity, is safe, well tolerated and has both local and systemic antitumor activity, with promising response rates when combined with ipi in patients with prior therapy."

P2 data • Melanoma KOL Tracker

Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (clinicaltrials.gov) - P2; N=20; Not yet recruiting; Sponsor: University of Utah; Initiation date: Oct 2017 ➔ Jan 2018

Trial initiation date • Biosimilar • Melanoma • Oncology • Solid Tumor

S-1 Facilitates C-REV Induced Anti-Tumor Efficacy in Triple Negative Breast Cancer Mode (ASGCT 2020) - "Canerpaturev (C-REV) is a highly attenuated, replication-competent mutant strain of oncolytic herpes simplex virus type 1...Considering that MDSC is known as the cells to suppress both innate and adaptive immune responses, the combination could induce a systemic antitumor immune response. From our result, S-1 is expected to be a promising agent in combination with C-REV in TNBC."

Clinical