Imlygic (talimogene laherparepvec)

Here, we describe a case of a woman with stage IIIC melanoma undergoing intralesional talimogene laherparepvec (T-VEC) therapy who developed a spreading erythematous rash on her left leg, accompanied by fatigue and leg swelling. Skin biopsy revealed recurrent melanoma, with SOX10 and Melan-A positivity, and imaging showed features concerning for multifocal disease recurrence in the left popliteal fossa. This case highlights an unusual presentation of melanoma recurrence and underscores the importance of biopsy in -evaluating new skin findings in patients with a history of melanoma.

Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting...Finally, we explored the feasibility of the intravenous application of oncolytic viruses and their future development directions. We believe that the diversified treatment design of oncolytic viruses will bring more surprises to the immunotherapy of refractory tumors.

Intratumoral T-VEC was administered with the following partners: gemcitabine/carboplatin (n = 8), nab-paclitaxel (n = 7), paclitaxel (n = 2), or ET (n = 2). In conclusion, the addition of intratumoral T-VEC to CT or ET was safe in patients with ABC and injectable locoregional disease, supporting the continued investigation of direct intratumoral immunomodulatory strategies that can enhance local and systemic immune responses. NCT03554044.

P2, N=43, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Nov 2025 --> Nov 2026

P=N/A, N=187, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=300 --> 187 | Trial completion date: Jan 2038 --> Jan 2026 | Trial primary completion date: Jan 2038 --> Jan 2026

P1, N=10, Not yet recruiting, Johns Hopkins University | Initiation date: Nov 2025 --> Feb 2026

These clinical and translational findings support the further development of oncolytic virotherapy/ILP combinations to activate both systemic and local antitumor immunity, including in tumor types such as sarcoma, which are largely refractory to current treatment with immunotherapy.

Clinically, T-VEC combined with pembrolizumab achieves a 48.6% ORR with grade ≥3 AEs occurring in <20% of patients-superior to either monotherapy or conventional chemoradiotherapy. Integration of artificial intelligence with biomarkers-such as neutralizing antibody titers, ISG expression, and STING methylation-may further enable personalized OV-based therapies. This review discusses OV therapy's mechanisms, clinical impact, and future prospects in melanoma treatment.

Talimogene laherparepvec (T-VEC), a genetically modified oncolytic herpes simplex virus type 1 (HSV-1) engineered to secrete granulocyte-macrophage colony stimulating factor (GM-CSF), has received United States Food and Drug Administration (FDA) approval for melanoma treatment...Notably, the oHSV-IL12 monotherapy showed comparable therapeutic outcomes to the combination of oHSV-GMCSF and oHSV-IL12 in both rechallenge and survival experiments. These findings position oHSV-IL12 as a promising novel candidate for HCC immunotherapy.

P1, N=28, Completed, SOLTI Breast Cancer Research Group | Active, not recruiting --> Completed

P2, N=68, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2027 | Trial primary completion date: Sep 2025 --> Sep 2027

P1, N=10, Not yet recruiting, Johns Hopkins University