This article is more than 5 years old. Information may no longer be current.
Ipilimumab plus T-VEC shows promise for metastatic melanoma
Click Here to Manage Email Alerts
Talimogene laherparepvec plus ipilimumab demonstrated safety and efficacy among patients with untreated, unresectable advanced melanoma, according to study results published in Journal of Clinical Oncology.
“Tumor immunotherapy has become an established treatment of metastatic melanoma and is being increasingly applied to other cancer types,” Igor Puzanov, MD, MSCI, associate professor of medicine at Vanderbilt University School of Medicine, and colleagues wrote. “A hallmark of tumors likely to respond to immunotherapy is a lymphocyte-predominant tumor microenvironment. To date, immunotherapy designed to promote lymphocyte accumulation within established tumors, activate lymphocyte function and cytotoxicity, and prevent T-cell suppression has shown the most promise.”
Igor Puzanov
Puzanov and colleagues sought to determine the safety and efficacy of ipilimumab (Yervoy, Bristol-Myers Squibb) — a cytotoxic T-lymphocyte antigen-4 inhibitor — in combination with the talimogene laherparepvec (Imlygic; BioVex, Amgen) in patients with previously untreated and unresectable stage IIIB or stage IV metastatic melanoma. Talimogene laherparepvec — commonly referred to as T-VEC — is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1
The study included data from 19 patients (median age, 61 years; range, 29-84; 58% women) treated at one of five U.S. cancer centers. The researchers assigned patients to intratumorally administered T-VEC (106 plaque-forming units/mL on week 1, then 108 plaque-forming units/mL on week 4 and every 2 weeks thereafter), in combination with four infusions of IV ipilimumab (3 mg/kg every 3 weeks, beginning week 6).
The incidence of dose-limiting toxicities served as the primary endpoint. Objective response rate and safety served as secondary endpoints.
The median survival follow-up was 20 months (range, 1-25.4).
Patients treated with T-VEC had a median duration of treatment of 13.3 weeks (range, 2-95.4).
The safety analysis included all patients. The researchers did not observe any dose-limiting toxicities or new safety signals. Both T-VEC and ipilimumab were given at their full therapeutic doses.
All patients experienced at least one adverse event; however, no patients discontinued treatment due to adverse events. Commonly observed adverse events included chills (n = 11), pyrexia (n = 11) and fatigue (n = 9), as well as diarrhea, pruritus and rash (n = 8 each).
Five patients (26.3%) experienced grade 3 or higher adverse events. Three patients (15.8%) had adverse events attributable to T-VEC and four (21.1%) had adverse events attributable to ipilimumab.
Nausea was as the only serious adverse event reported by more than one patient (n = 2). Other serious adverse events (n = 1 for each) included pyrexia, fatigue, diarrhea, influenza-like illness, dehydration and vomiting.
The study cohort had an ORR of 50% (95% CI, 26-74). Four patients (22%) achieved a confirmed complete response, all of whom remained in remission at 1 year. Five patients (28%) achieved a partial response and four patients (22%) had stable disease.
All but one patient with a confirmed response achieved a response lasting 6 months or greater. The durable response rate was 44%.
Responses occurred in injected and uninjected lesions. Of injectable lesions, 74% (n = 26 of 34) had a regression of 50% or greater, and 31% (n = 11) regressed completely.
Uninjected lesions regressed by 50% or more in 52% (n = 12 of 23) of patients, with 39% (n = 9) regressing completely.
Median PFS and OS have not been reached. The researchers calculated 12- and 18-month PFS probabilities of 50% for each. The OS probabilities were 72% at 12 months and 67% at 18 months.
“An ongoing, randomized phase 2 trial on the basis of this study comparing [T-VEC] plus ipilimumab with ipilimumab alone in patients with advanced melanoma is underway,” Puzanov and colleagues wrote. “The combination of [T-VEC] with immune checkpoint inhibitors may represent potential new treatment options for patients with regionally or distantly metastatic melanoma with or without visceral disease that is injectable and cannot adequately be addressed by surgery.” – by Cameron Kelsall
Disclosure: Puzanov reports travel expenses from and consultant roles with Amgen, Genentech and Merck. Please see the full study for a list of all other researchers’ relevant financial disclosures.
Click Here to Manage Email Alerts