OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

Andtbacka, Robert Hans Ingemar; Collichio, Frances A.; Amatruda, Thomas T.; Senzer, Neil; Chesney, Jason; Delman, Keith A.; S̄pitler, Lynn E.; Puzanov, Igor; Doleman, Susan; Ye, Yining; Vanderwalde, Ari M.; Coffin, Robert S.; Kaufman, Howard L.

doi:10.1200/jco.2013.31.15_suppl.lba9008

Cited by 57 publications

(55 citation statements)

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“…5 The most successful oncolytic virus to date, talimogene laherparepvec (T-Vec), an oncolytic granulocyte-macrophage colony-stimulating factor (GM-CSF) producing herpes virus, was recently shown in a randomized phase 3 clinical trial to have a better durable response rate and a trend toward better overall survival compared to GM-CSF for unresectable melanoma. 6 There have also been encouraging results with the use of replicating vaccinia virus (VV) (New York City Board of Health Strain) expressing GM-CSF in patients with hepatocellular carcinoma where intralesional Pexa-Vec therapy (Sillajen) resulted in a 15% response rate (mRECIST) and prolongation of survival when high dose was compared to low-dose treatment. [7][8][9] VV has many potential advantages over other oncolytic viral backbones.…”

Section: Introductionmentioning

confidence: 99%

First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity

et al. 2015

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Oncolytic viral therapy utilizes a tumor-selective replicating virus which preferentially infects and destroys cancer cells and triggers antitumor immunity. The Western Reserve strain of vaccinia virus (VV) is the most virulent strain of VV in animal models and has been engineered for tumor selectivity through two targeted gene deletions (vvDD). We performed the first-in-human phase 1, intratumoral dose escalation clinical trial of vvDD in 16 patients with advanced solid tumors. In addition to safety, we evaluated signs of vvDD replication and spread to distant tumors, pharmacokinetics and pharmacodynamics, clinical and immune responses to vvDD. Dose escalation proceeded without dose-limiting toxicities to a maximum feasible dose of 3 × 10(9) pfu. vvDD replication in tumors was reproducible. vvDD genomes and/or infectious particles were recovered from injected (n = 5 patients) and noninjected (n = 2 patients) tumors. At the two highest doses, vvDD genomes were detected acutely in blood in all patients while delayed re-emergence of vvDD genomes in blood was detected in two patients. Fifteen of 16 patients exhibited late symptoms, consistent with ongoing vvDD replication. In summary, intratumoral injection of the oncolytic vaccinia vvDD was well-tolerated in patients and resulted in selective infection of injected and noninjected tumors and antitumor activity.

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Section: Introductionmentioning

confidence: 99%

First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity

et al. 2015

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“…In a recent phase III clinical trial, an oncolytic herpes simplex virus armed with granulocyte-macrophage colony-stimulating factor (T-VEC) showed superior durable response rates in advanced melanoma patients compared with subcutaneous administration of the recombinant granulocyte-macrophage colony-stimulating factor protein. 4 An oncolytic vaccinia virus expressing the same transgene (Pexa-Vec) has shown promising results in phase II clinical trials for hepatocellular carcinoma. 5 In this case, intratumoral administration of the virus led to an increase in serum concentrations of granulocyte-macrophage colony-stimulating factor and elevation of neutrophil counts in peripheral blood.…”

Section: Introductionmentioning

confidence: 99%

Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model

et al. 2015

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Gene transfer of potent immunostimulatory cytokines such as interleukin-12 (IL-12) is a potential treatment for advanced cancer. Different vectors and IL-12 modifications have been developed to avoid side effects associated with high serum levels of the cytokine, while preserving its antitumor properties. Here we have evaluated two alternative strategies using the Syrian hamster as a model for pancreatic cancer metastatic to the liver. Local administration of an oncolytic adenovirus (OAV) expressing a single-chain version of IL-12 caused transient, very intense elevations of IL-12 in serum, resulting in severe toxicity at sub-therapeutic doses. Anchoring IL-12 to the membrane of infected cells by fusion with the transmembrane domain of CD4 reduced systemic exposure to IL-12 and increased the tolerance to the OAV. However, only a modest increase in the therapeutic range was achieved because antitumor potency was also reduced. In contrast, systemic administration of a helper-dependent adenoviral vector (HDAd) equipped with a Mifepristone-inducible expression system allowed sustained and controlled IL-12 production from the liver. This treatment was well tolerated and inhibited the progression of hepatic metastases. We conclude that HDAds are safer than OAVs for the delivery of IL-12, and are promising vectors for immunogene therapy approaches against pancreatic cancer.

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“…was made. 13 Further logical arguments for IT delivery included the lack of a viral dilution that would occur as a result of i.v. delivery; clinical experience revealed that IT delivery was not technically difficult and was readily achievable.…”

Section: Debatementioning

confidence: 99%

Infectious Optimism following the 10th International Oncolytic Virus Meeting

Atherton

Evgin

Keller

et al. 2017

Molecular Therapy - Oncolytics

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OPTiM: A randomized phase III trial of talimogene laherparepvec (T-VEC) versus subcutaneous (SC) granulocyte-macrophage colony-stimulating factor (GM-CSF) for the treatment (tx) of unresected stage IIIB/C and IV melanoma.

Cited by 57 publications

References 0 publications

First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity

First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity

Safety and antitumor effect of oncolytic and helper-dependent adenoviruses expressing interleukin-12 variants in a hamster pancreatic cancer model

Infectious Optimism following the 10th International Oncolytic Virus Meeting

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