Talimogene laherparepvec (T-VEC)

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment.

The median patient age was 63 years (range, 22–94), 70% of patients had a baseline ECOG PS score of 0, 30% had stage III disease, and 70% had stage IV disease (27% M1a; 21% M1b; and 22% M1c). Previous therapy for melanoma had been received by 53% of the patients.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment.

The first dose only was administered at 106 plaque-forming units (pfu)/mL to a maximum of 4 mL for all lesions combined. Subsequent doses were administered at 8 pfu/mL up to 4.0 mL for all injected lesions combined with the injected volume based on the size of the lesion. Injection into visceral lesions was not allowed.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment.

In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment. › In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

In patients with stage IIIB and IIIC disease, the DRR was 33% in the T-VEC group and 0% in the GM-CSF group.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment. › In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

In patients with stage IV M1a disease, the DRR was 16% in the T-VEC group and 2% in the GM-CSF group.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment. › In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

In patients with stage IV M1b disease, the DRR was 3% in the T-VEC group and 4% in the GM-CSF group.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment. › In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

In patients with stage IV M1c disease, the DRR was 7% in the T-VEC group and 3% in the GM-CSF group.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment. › In patients treated with T-VEC, 16% (95% CI, 12.0%–20.5%) had a DRR versus 2% (95% CI, 0%–4.5%) in patients who received GM-CSF. Subgroup analysis suggested that the differences in DRRs between T-VEC versus GM-CSF may be greater in earlier-stage disease and treatment-naïve disease, as follows:

Patients treated with T-VEC or GM-CSF as first-line therapy had a DRR of 24% versus 0%, respectively. However, patients who received treatment as second-line therapy or greater had a DRR of 10% versus 4%, respectively.

In a multinational open-label trial (NCT00769704), 436 patients were randomly assigned (2:1) to receive either intralesional T-VEC or subcutaneous GM-CSF for at least 6 months or until there were no more injectable lesions.[38][Level of evidence B3] Eligible patients had stage IIIB, IIIC, or IV melanoma with unresectable, bidimensionally measurable lesions. The primary end point was durable response rate (DRR) (complete response or partial response lasting for >6 months) as assessed by independent review. The study was stratified by site of first recurrence, presence of liver metastases, disease stage, and previous nonadjuvant systemic treatment.

The median duration of exposure to T-VEC was 23 weeks (5.3 months), with 26 patients exposed for more than 1 year. The most common adverse events in the T-VEC group were fatigue (50%), chills (49%), pyrexia (43%), nausea (36%), influenza-like illness (30%), and injection site pain. The rate of discontinuation resulting from toxicity to T-VEC was 4%, versus 2% in the GM-CSF group. Of the ten deaths in patients treated with T-VEC, eight deaths were considered the result of PD-1, salmonella infection, and one myocardial infarction; none were considered related to therapy, based on findings of the investigator.