Melanoma Therapy Injected Directly Into Lesions

International Approvals > Medscape Medical News
EU Likes Melanoma Therapy Injected Directly Into Lesions

Zosia Chustecka
Disclosures | October 23, 2015


A new treatment for melanoma that is injected directly into the lesion has been recommended for approval in Europe.

The product, talimogene laherparepvec (Imlygic, Amgen), described as the first oncolytic immunotherapy, is destined for use in adults with unresectable melanoma that is regionally or distantly metastatic (stage IIIB, IIIC, and IVM1a) with no bone, brain, lung, or other visceral disease, according to the European Medicines Agency (EMA).

This product has also recently been recommended for approval in the United States, where it will be marketed as T-VEC. A US Food and Drug Administration decision is due by October 27.

Talimogene laherparepvec is a first-in-class advanced therapy medicinal product (ATMP), derived from a virus that has been genetically engineered to infect and kill cancer cells. The recommendation for approval was based on an assessment carried out by the Committee for Advanced Therapies (CAT), the European agency's expert committee for ATMPs.

The EMA explains that the product is derived from a herpes simplex virus-1 that has been genetically engineered to infect and replicate within cancer cells and to produce the protein granulocyte macrophage colony-stimulating factor (GM-CSF). It is thought to work in two ways. It enters the tumor cell and uses the cell's energy stores to replicate, eventually overwhelming the cell and causing it to die. By producing the protein GM-CSF, it also stimulates the patient's immune system to recognize and destroy tumor cells. Once an infected tumor cell dies, copies of the virus are released into the patient's bloodstream to infect more tumor cells. Although the product can also enter healthy cells, it is not able to replicate in these healthy cells and so it does not kill them, the agency points out.

The recommendation for approval is based on efficacy data that come from one randomized controlled trial (known as OPTiM) in adults with unresectable regionally or distantly metastatic melanoma. The study enrolled 436 patients, with 295 patients treated with talimogene laherparepvec compared with 141 patients treated with GM-CSF.

Analysis of the subset of patients in the study whose disease had not spread to the lung or other internal organs (249 patients with stage IIIB, IIIC, and IVM1a disease) showed a benefit in patients treated with talimogene laherparepvec, with a durable response rate of 25% vs 1% with GM-CSF alone, according to the EMA.

A durable response was defined as disappearance of the tumors or at least 50% reduction of tumors lasting at least 6 months, until patients' health declined or they required subsequent therapy, the agency noted.

An exploratory analysis in these patients suggested improvements in survival in patients treated with talimogene laherparepvec, the agency noted, but it points out that "this is not yet fully clear." It addition, there are no comparative data with other approved therapies for melanoma, which have already been shown to improve overall survival.

Overall, the expert committee considered that the product is relatively well-tolerated in patients with cancer and concluded that the medicine's benefits outweigh its risks, the agency stated.

The OPTiM study was published in May in the Journal of Clinical Oncology (2015;33:2780-2788), as reported at the time. The data in the publication are a little different to what the EMA cites in its press release, as in the publication, the durable response rate with the product was reported as 16.3% vs 2.1% with GM-CSF. In addition, it reports complete responses in 10.8% of patients on the product, compared with <1.0% on GM-CSF. "Durable responses to T-VEC were seen across all disease stages tested, including in patients within each subset of stage IV disease," said the authors, led by Howard L. Kaufman, MD, FACS, from the Rutgers Cancer Institute of New Jersey in New Brunswick. Noting that T-VEC could potentially delay or prevent relapses or preclude progression to later disease stages, they add that it "represents a novel potential new treatment option for patients with injectable metastatic melanoma and limited visceral disease." Dr. Kaufman told Medscape Medical News at the time: "Despite all the advances in the field of melanoma, many patients do not respond to treatment."

"Some patients are not able to tolerate some of the drugs for a variety of reasons, and so any agent that has some activity is important," he added.

"Interestingly, I think one of the more important things in the data is that nearly 11% of the patients had a complete response.... We don't often see that in melanoma studies. I think that's very significant," he commented.