Neoadjuvant talimogene laherparepvec (T-VEC) followed by surgery significantly improved survival, when compared with surgery alone, in patients with advanced, resectable melanoma, according to research published in Nature Medicine.

T-VEC is an HSV-1-based oncolytic immunotherapy approved to treat unresectable melanoma. In a phase 2 trial ( Identifier: NCT02211131), researchers tested T-VEC in patients with resectable stage IIIB-IVM1a melanoma.

The trial enrolled 150 patients from 48 sites in 9 countries. The patients were randomly assigned to receive T-VEC and then undergo surgical resection of melanoma lesions (76 patients) or undergo surgery alone (74 patients).

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The median age was 63.5 years (range, 34-85 years) in the T-VEC arm and 59.0 years (range, 21-85 years) in the surgery-alone arm. Most patients in each arm were men (64.5% and 63.5%, respectively), White (96.1% and 98.6%), and had a performance status of 0 (88.2% and 85.1%).

The study’s primary endpoint was 2-year recurrence-free survival (RFS). Secondary and exploratory endpoints included overall survival (OS), pathological complete response (pCR), and safety.

The median follow-up was 32.1 months for the T-VEC arm and 30.9 months for the surgery-alone arm. In the T-VEC arm, 13 patients (17.1%) achieved a pCR. In this group, 6 patients had stable disease and 2 had progressive disease before surgery.

The estimated 2-year RFS rate was 29.5% in the T-VEC arm and 16.5% in the surgery-alone arm (hazard ratio [HR], 0.75; 80% CI, 0.58-0.96), indicating a 25% reduction in disease recurrence with T-VEC.

The 2-year local RFS rate was 36.5% in the T-VEC arm and 27.5% in the surgery-alone arm (HR, 0.83; 80% CI, 0.64-1.08). The 2-year regional RFS rate was 39.2% and 25.4%, respectively (HR, 0.77; 80% CI, 0.59-1.01). The 2-year distant metastasis-free survival rate was 33.7% and 19.5%, respectively (HR, 0.74; 80% CI, 0.58-0.96).

The 2-year OS rate was 88.9% in the T-VEC arm and 77.4% in the surgery-alone arm (HR, 0.49; 80% CI, 0.30-0.79), indicating a 51% reduction in mortality with T-VEC.

The differences in RFS and OS between the 2 arms persisted at 3 years. The estimated 3-year RFS rate was 28.1% in the T-VEC arm and 16.9% in the surgery-alone arm (HR, 0.74; 80% CI, 0.57-0.95).

The 3-year event-free survival rate was 50.3% in the T-VEC arm and 32.7% in the surgery-alone arm (HR, 0.58, 80% CI=0.44-0.78). The 3-year OS rate was 83.2% and 71.6%, respectively (HR, 0.54; 80% CI, 0.36-0.83).

Treatment-emergent adverse events (TEAEs) during T-VEC administration were observed in 91.8% of patients, and 5.5% had grade 3 or higher TEAEs. The most common TEAEs of any grade were influenza-like illness (35.6%) and pyrexia (32.9%).

Overall, neoadjuvant T-VEC was considered well tolerated, and TEAEs were consistent with previous reports for T-VEC.

“As neoadjuvant immunotherapies move into the spotlight for the future treatment landscape for advanced melanoma, intralesional therapies such as oncolytic viruses will be an area of interest,” the researchers wrote. “Although the results of our trial are not sufficient to justify routine use of neoadjuvant T-VEC outside the protocol setting at this time, they support further investigation of T-VEC in the neoadjuvant setting for resectable high-risk melanoma.”

Disclosures: This research was supported by Amgen, Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Dummer R, Gyorki DE, Hyngstrom J, et al. Neoadjuvant talimogene laherparepvec plus surgery versus surgery alone for resectable stage IIIB-IVM1a melanoma: A randomized, open-label, phase 2 trial. Nat Med. Published online October 4, 2021. doi:10.1038/s41591-021-01510-7