Phase I/II canon study: Oncolytic immunotherapy for the treatment of non-muscle invasive bladder (NMIBC) cancer using intravesical coxsackievirus A21.

Pandha, Hardev; Annels, Nicola; Simpson, Guy R.; Mostafid, Hugh; Harrington, Kevin; Melcher, Alan; Grose, Mark; Davies, B.; Au, Gough G.; Karpathy, Roberta; Shafren, Darren R.

doi:10.1200/jco.2016.34.15_suppl.e16016

Cited by 6 publications

(3 citation statements)

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“…The phase I/II CANON study evaluated tolerability of intravesical administration of CAVATAK in patients with nonmuscle invasive bladder cancer. Interim analysis showed clinical activity of CAVATAK, evidenced by complete tumor response, viral replication within tumor, and viral‐induced apoptosis . In a phase II, multicenter, open‐label study entitled CAVATAK in Late‐stage Melanoma (CALM), intratumoral injection of CAVATAK was administered in 57 patients with unresectable stage IIIC–IVM1c melanoma .…”

Section: Intratumoral Immunotherapiesmentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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Intratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor‐derived antigens and subsequent activation of tumor‐specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV‐10 and toll‐like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa‐Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T‐VEC), a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T‐VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting ≥6 months) over subcutaneous GM‐CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T‐VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T‐VEC in the treatment of advanced melanoma as a model for future solid tumor indications. Implications for Practice This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T‐VEC is the only U.S. Food and Drug Administration (FDA)‐approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T‐VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T‐VEC, the only U.S. FDA‐approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T‐VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.

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Section: Intratumoral Immunotherapiesmentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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“…It binds to CVA21 receptors, also known as intercellular adhesion molecule-1 (ICAM-1), that are upregulated on NMIBC cells, and it exerts its antitumor effects via the lytic viral cycle. [19,20] Interestingly, ICAM-1 expression is further enhanced in NMIBC when CVA21 is combined with Mitomycin C.[20] Hence, a recently completed phase I trial combined CVA21 with mitomycin C in pre-TURBT patients, which was tolerated well. [20]…”

Section: Bcg-naïvementioning

confidence: 99%

Current clinical trials in non–muscle invasive bladder cancer

Siddiqui

Grant

Sanford

et al. 2017

Urologic Oncology: Seminars and Original Investigations

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Background The treatment options for non-muscle invasive bladder cancer (NMIBC) remain limited. BCG was the last major breakthrough in bladder cancer therapy almost 4 decades ago. There have been improvements in the understanding of immune therapies and cancer biology, leading to the development of novel agents. This has led to many clinical trials that are currently underway to find the next generation of therapies for NMIBC. Method We reviewed clinicaltrials.org and pubmed.gov to find the recently completed and ongoing clinical trials in NIMBC. Included in this review are clinical trials that are currently active and trials that were completed in and after 2014. Result Many trials with BCG naïve and BCG unresponsive/recurrent/refractory/failure NMIBC patients are either currently underway or have been recently completed. A wide variety of novel therapeutic agents are being investigated that range from cytotoxic agents to immunomodulatory agents to targeted molecular therapies. Other approaches include cancer vaccines, gene therapies, and chemoradiation potentiation agents. Novel drug delivery methods are also being tested. Conclusion This comprehensive update of current trials provides researchers an overview of the current clinical trial landscape for patients with NMIBC.

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“…In a phase 2 study of CVA21 in patients with stage IIIC/IV melanoma ( N = 57), the immune-related 1-year progression-free survival rate was 28% and the 1-year survival rate was 75% [ 70 ]. Initial studies for tolerance of CVA21 are underway in patients with non–muscle-invasive bladder cancer; preliminary results indicate clinical activity and notable signs of viral-induced tumor inflammation [ 71 ]. Reolysin ® , a naturally occurring, unmodified strain of reovirus known for exploiting activated RAS signaling, has recently undergone phase 1 and 2 studies in patients with solid tumors [ 49 , 72 ], and was granted Orphan Drug Designation by the United States Food and Drug Administration in 2015 for the treatment of ovarian cancer [ 73 ].…”

Section: Current Oncolytic Viruses and Trialsmentioning

confidence: 99%

Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer

Hamid

Hoffner

Gasal

et al. 2017

Cancer Immunol Immunother

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Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g., adenovirus, reovirus) with a diverse range of genetic modifications are currently being investigated for the treatment of a variety of cancers. The oncolytic virus that has advanced the furthest in clinical development is talimogene laherparepvec, a recombinant HSV-1 virus expressing granulocyte-macrophage colony-stimulating factor (GM-CSF). In a phase 3 study in patients with unresectable metastatic melanoma, intralesional talimogene laherparepvec treatment resulted in a higher durable response rate compared with subcutaneous GM-CSF treatment (16.3 versus 2.1%; P < 0.001). Notably, responses were observed at uninjected lesions including visceral lesions, indicating a systemic antitumor response had occurred. Studies evaluating combination treatments involving oncolytic viruses and immunologic agents are ongoing. This review focuses on the mechanisms of action for oncolytic viruses and highlights select agents and combinations currently in development.

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Phase I/II canon study: Oncolytic immunotherapy for the treatment of non-muscle invasive bladder (NMIBC) cancer using intravesical coxsackievirus A21.

Cited by 6 publications

References 0 publications

Intratumoral Immunotherapy—Update 2019

Intratumoral Immunotherapy—Update 2019

Current clinical trials in non–muscle invasive bladder cancer

Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer

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