NEW YORK — Secondary endpoint results from a multicenter, randomized phase 3 trial showed talimogene laherparepvec conferred greater benefit than granulocyte-macrophage colony-stimulating factor for patients with unresected stage IIIB/IIIC or stage IV melanoma, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting in New York.
Talimogene laherparepvec (T-VEC, Amgen) is an oncolytic immunotherapy derived from herpes simplex virus type-1. Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.
The OPTiM trial included 436 patients with unresected melanoma with regional or distant metastases. Researchers assigned 295 patients to T-VEC intralesionally every 2 weeks. The other 141 received GM-CSF subcutaneously for the first 14 days of each 28-day cycle.
Median treatment duration was 23 weeks (range, 0.1-78.9) with T-VEC and 10 weeks (range, 0.6-72) with GM-CSF.
Durable response rate, defined as objective response lasting for at least 6 months, served as the primary endpoint. Secondary endpoints included OS, time to response onset, duration of response, best response and disease burden, and response interval.
Results presented at the 2013 ASCO Annual Meeting showed T-VEC was associated with a statistically significant improvement in durable response rate (26.4% vs. 5.7%) as calculated by a blinded endpoint assessment committee. An interim analysis also showed a trend toward improved OS with T-VEC (HR=0.79; 95% CI, 0.61-1.02).
An analysis of secondary endpoints revealed median time to onset of response was 4.1 months (range, 1.2 to 16.7) for patients assigned to T-VEC and 3.7 months (range, 1.9 to 9.1) for patients assigned to GM-CSF.
Median duration of response was not reached in the T-VEC arm, and the majority of responders were still in response as of the most recent tumor assessment. Patients who responded to T-VEC were more likely than those who responded to GM-CSF to maintain their response for at least 3 months (86.7% vs. 46.9%), at least 6 months (80.6% vs. 46.9%) and at least 12 months (65% vs. 46.9%).
T-VEC demonstrated a tolerable safety profile, according to researchers.
Researchers reported higher rates of fatigue (50.3% vs. 36.2%), chills (48.6% vs. 8.7%), pyrexia (42.8% vs. 8.7%), nausea (35.6% vs. 19.7%), flu-like illness (30.5% vs. 15%), pain at injection site (27.7% vs. 6.3%) and vomiting (21.2% vs. 9.4%) among patients assigned to T-VEC. Incidence of grade 3 or grade 4 cellulitis (2.1% vs. <1%) and fatigue (1.7% vs. <1%) were higher in the T-VEC arm, as was incidence of grade 3 or grade 4 vomiting, dehydration, deep vein thrombosis and tumor pain (1.7% vs. 0% for all).
For more information:
Kaufman H. Secondary endpoints from OPTiM: A multicenter, randomized phase 3 trial of talimogene laherparepvec vs. GM-CSF for the treatment of unresected stage IIIB/C and IV melanoma.
Disclosure: The researchers report research funding/honoraria from, consultant/advisory roles with, employment or leadership positions with, or stock ownership in Amgen, BioVex, Bristol-Myers Squibb, GlaxoSmithKline, Morphotek and Roche/Genentech.