Table 1.
Efficacy and safety of T-VEC monotherapies and combination therapies in the treatment of skin cancers.
| Reference | Study Drugs/Mechanisms of Action | Phase (n) |
Disease | Treatment | Overall Response Rate | Progression-Free Survival (Month) | Overall Survival (Month) |
|
|---|---|---|---|---|---|---|---|---|
| I | T-VEC monotherapy for melanoma | |||||||
| 1 | A Phase I Study of OncoVEXGM-CSF, a Second-Generation Oncolytic Herpes Simplex Virus Expressing Granulocyte Macrophage Colony-Stimulating Factor [6] | talimogene laherparepvec (TVEC)/oncolytic virus therapy (OVT) | Phase I (n = 30) |
Refractory cutaneous and subcutaneous metastases from breast cancer, gastrointestinal adenocarcinoma, Malignant Melanoma, and Epithelial cancer of head and neck |
TVEC | N/A | N/A | N/A |
| 2 | Phase II clinical trial of a granulocyte-macrophage colony-stimulating factor-encoding, second-generation oncolytic herpesvirus in patients with unresectable metastatic melanoma [7] | TVEC/OVT | Phase II (n = 50) |
Stage IIIc unresectable metastatic melanoma | TVEC | 26% | N/A | 16 |
| 3 | Final analyses of OPTiM: a randomized phase III trial of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in unresectable stage III–IV melanoma (NCT00769704) [8,9] |
TVEC/OVT GM-CSF/bone marrow stimulation |
Phase III (n = 436) |
Stage IIIB to IV melanoma | A: TVEC B: GM-CSF |
31.50% 6.40% |
N/A | 23.3 18.9 A: 73.7% at 1 year, 49.8% at 2 year, and 38.9% at 3 year B: 69.1% at 1 year, 40.3% at 2 year, and 30.4% at 3 year |
| II | T-VEC combinational therapy for melanoma | |||||||
| 1 | Randomized, open-label phase II study evaluating the efficacy and safety of talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone in patients with advanced, unresectable melanoma (NCT01740297) [10] |
TVEC/OVT Ipilimumab/CTLA-4 inhibitor |
Phase II (n = 198) |
Melanoma | A: TVEC + ipilimumab B: ipilimumab |
39% 18% |
8.2 6.4 |
86.9% at 1 year, 76.6% at 2 year 81.4% at 1 year, 67.7% at 2 year |
| 2 | A phase 1/3 multicenter trial of talimogene laherparepvec in combination with pembrolizumab for unresected, stage IIIB-IV melanoma. MASTERKEY-265 (NCT02263508) [11] |
TVEC/OVT Pembrolizumab/PD-1 inhibitor |
Phase 1b (n = 21) |
unresectable, stage IIIB-IVM1c melanoma | A: TVEC + Pembrolizumab B: Placebo + Pembrolizumab |
N/A | 25.6 25.5 |
N/A |
| 3 | 1037O MASTERKEY-265: A phase III, randomized, placebo (Pbo)-controlled study of talimogene laherparepvec (T) plus pembrolizumab (P) for unresectable stage IIIB–IVM1c melanoma (MEL). KENNOTE-034 (NCT02263508) [12] |
TVEC/OVT Pembrolizumab/PD-1 inhibitor |
Phase III (n = 692) |
unresectable stage III-IVM1c melanoma | A: TVEC + Pembrolizumab B: Placebo + Pembrolizumab |
48.60% 41.30% |
14.3 8.5 |
66% at 2 year 49.2 |
| 4 | PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma (NCT02288897) [13] |
PV-10 (10% rose Bengal disodium)/oncolytic immunotherapy | Phase III (n = 20) |
Cutaneous Melanoma | A: PV-10 (10% rose Bengal disodium) B: Dacarbazine, temozolomide or TVEC |
N/A Only has complete response rate (CRR) |
6.1 (1.5 to 28.9) 8.6 (1.8 to 14.4) |
N/A N/A |
| III | T-VEC treatment in other cutaneous cancer types | |||||||
| 1 | Talimogene laherparepvec induces durable response of regionally advanced Merkel cell carcinoma in 4 consecutive patients [14] | TVEC/OVT | (n = 4) | Regionally advanced Merkel cell carcinoma | TVEC | 100% | 16 + | 18.5 + |
| 2 | Pretreated anti-PD-1 refractory Merkel cell carcinoma successfully treated with the combination of PD-1/PD-L1 axis inhibitors and TVEC: a report of two cases [15] | TVEC/OVT | (n = 2) | Anti-PD-1 refractory Merkel cell Carcinoma | T-VEC and a PD-1/PD-L1 inhibitor | 100% | N/A | N/A |
| 3 | Immunotherapy for Nonmelanoma skin cancer: Facts and Hopes (NCT02819843) [16] |
TVEC/OVT | Phase II (n = 19) |
Cutaneous Melanoma Merkel Cell Carcinoma Other Solid Tumors |
TVEC + Radiotherapy | Study completion June 2023 |
Study completion June 2023 |
Study completion June 2023 |