Neo-adjuvant T-VEC plus nivolumab combination therapy for resectable early-stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: The NIVEC trial.

TPS9607 Background: The prognosis of patients with melanoma is significantly correlated with disease stage and has greatly improved with the introduction of the currently approved therapies. Trials investigating neo-adjuvant treatment with immune checkpoint inhibitors (ICI) have shown high pathologic response rates up to 25-80%, however, still a large group of patients derive no (durable) clinical benefit. Treatment with talimogene laherparepvec (T-VEC), a modified herpes simplex virus type-1, is approved for patients with unresectable stage IIIB-IVM1a melanoma, with high and durable response rates and a mild toxicity profile. Earlier trials have suggested that T-VEC has the capacity to heighten the immune response and to elicit an abscopal effect in melanoma when given in combination with ICI. Combination ICI and intralesional T-VEC has already been investigated in patients with unresectable stage IIIB-IV disease, however, no data is available yet on the potential benefit of this combination therapy in neo-adjuvant setting. This is the first trial investigating the efficacy and safety of neo-adjuvant treatment of T-VEC in combination with nivolumab (anti-PD-1 antibody), followed by surgical resection in patients with resectable stage IIIB-IVM1a melanoma, with the potential of high pathologic response rates and acceptable toxicity. Methods: In this single center, single arm, phase II study, a total of 24 patients ≥18 years of age and a good clinical performance score with treatment naïve, stage IIIB-IVM1a melanoma (AJCC 8th edition) with injectable disease and resectable (sub)cutaneous satellite or in-transit metastases and/or tumor positive lymph nodes, will be included. Patients will receive four courses of T-VEC up to 4mL (first dose as seroconversion dose) and three doses of nivolumab (240mg flatdose) every two weeks, followed by surgical resection in week nine. The primary endpoint of this trial is pathologic response rate, with the aim to show a high major pathologic (near-complete or complete) response rate up to 45%. Secondary endpoints are safety according to CTCAE v5.0, the rate of delay of surgery and event free survival. Additionally, prognostic and predictive biomarker research and health-related quality of life evaluation will be performed. Enrollment started in June 2020 in the Netherlands Cancer Institute, with currently 13 of the 24 planned patients treated. Clinical trial information: NCT04330430.