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T-VEC plus ipilimumab appears safe, effective for unresected melanoma
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NEW YORK — Talimogene laherparepvec combined with ipilimumab demonstrated tolerability at the planned doses without dose-limiting toxicities in patients with unresected, stage IIIB to IV melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting in New York.
The combination also demonstrated higher overall and complete response rates than typical for either agent alone, results showed.
Talimogene laherparepvec (T-VEC, Amgen) — a systemically active oncolytic immunotherapy derived from herpes simplex virus type 1 — yielded a higher durable response (≥ 6 months) than granulocyte-macrophage colony-stimulating factor (GM-CSF) in a phase 3 melanoma trial, according to study background.
Igor Puzanov, MD, MSCI, FACP, of the division of hematology-oncology at Vanderbilt University Medical Center, and colleagues sought to evaluate the safety and efficacy of T-VEC in combination with ipilimumab (Yervoy, Bristol-Myers Squibb).
There were 19 patients enrolled with unresected stage IIIB to IV melanoma (58% stage IV M1b/c). Over half of those enrolled (58%) were women, 42% were aged 65 years or older and 18 of the patients received T-VEC and ipilimumab.
The patients received T-VEC intralesionally at weeks 1 and 4 and every other week thereafter. Patients also received 3 mg/kg ipilimumab every 3 weeks starting at week 6 for a maximum of four infusions.
Treatment continued until the occurrence of dose-limiting toxicity — defined as any grade 4 or worse adverse event or any grade 3 or worse immune-related adverse event within 6 weeks of treatment with ipilimumab — tumor disappearance or progressive disease.
Overall, no dose-limiting toxicities occurred during the evaluation period. Grade 3 or grade 4 adverse events occurred in 32% of patients. Two patients experienced grade 3 or grade 4 immune-related adverse events, which included one patient who experienced grade 3 hypophysitis, grade 3 adrenal insufficiency and grade 3 diarrhea, and one patient who experienced grade 4 elevated amylase and lipase.
One patient experienced grade 5 progressive disease with central nervous system metastases.
The objective response rate was 56%, which included a 33% complete response rate. The median time to response was 5.3 months.
Researchers noted that the presence of activated CD8 T cells increased after T-VEC, and then further increased after treatment with T-VEC plus ipilimumab.
“T-VEC plus ipilimumab is tolerable at the planned doses with no dose-limiting toxicities,” Puzanov and colleagues concluded. These data suggest higher [overall response] and [complete response] rates than with either agent alone, and that T-VEC can complement ipilimumab.”
A phase 2 trial comparing the addition of T-VEC to ipilimumab vs. ipilimumab alone is ongoing, according to the researchers. – by Cameron Kelsall
Reference:
Puzanov I, et al. Results from a phase 1b multicenter trial evaluating safety and efficacy of talimogene laherparepvec (T-VEC) plus ipilimumab in patients with previously untreated, unresected Stage IIIB-IV melanoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.
Disclosure: Puzanov reports travel expenses from Amgen and Roche. One other researcher reports travel expenses from Alkermes, Amgen, EMD Serono, Merck, Prometheus and Sanofi.