NCT04330430: NIVEC

Neo-adjuvant T-VEC + Nivolumab Combination Therapy for Resectable Early Metastatic (stage IIIB/C/D-IV M1a) Melanoma with Injectable Disease

Completed Phase 2 Last updated 12 March 2025

What this trial tests

Phase 2 trial testing T-VEC in Melanoma Stage III in 24 participants. Completed in 29 January 2025.

Timeline

8 September 2020

Primary endpoint
9 April 2023

29 January 2025

Quick facts

Lead sponsor	The Netherlands Cancer Institute
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	8 September 2020
Primary completion	9 April 2023
Estimated completion	29 January 2025
Sites	1 location across Netherlands

Drugs / interventions tested

• T-VEC — full drug profile →

Conditions studied

• Melanoma Stage III — all drugs for Melanoma Stage III →
• Melanoma Stage IV — all drugs for Melanoma Stage IV →

Sponsor

The Netherlands Cancer Institute

Who can join

18 and older, any sex, with Melanoma Stage III or Melanoma Stage IV. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Currently, standard treatment options available for Stage III melanoma include locoregional management (i.e. surgery) or systemic treatment (adjuvant to surgery or primarily in the case of unresectable disease).

Adjuvant treatment options have shown major improvements in overall survival (OS) and relapse free survival (RFS) in resected stage III or IV melanoma.

In daily practice, T-VEC monotherapy is used for unresectable Stage IIIB-IVM1a (injectable) disease, whereas Nivolumab is used for stage IV melanoma (among other systemic therapies).

The next major developments are in neo-adjuvant treatment options for resectable stage III disease, where 3 small studies reported high response rates with systemic immunotherapy.

This study evaluates the combination treatment of T-VEC + Nivolumab in the neo-adjuvant setting. The concept is that T-VEC can turn an immune desolate "cold" tumor into an immunogenic "hot" tumor. The hypothesis is that this will upregulate the expression of PD-L1 and make it more susceptible for treatment with an anti-PD-1 agent. The investigators believe neo-adjuvant Nivolumab + T-VEC will thus change the tumor microenvironment in patients with stage IIIB/C/D/IVM1a (AJCC 8) melanoma with resectable cutaneous or subcutaneous satellite or in-transit metastases (ITM) and/or tumor positive lymph nodes. With this trial the investigators aim to determine safety and feasibility of combination neo-adjuvant Nivolumab + T-VEC in patients with stage III melanoma with resectable ITM and/or tumor positive lymph nodes. The treatment schedule is based on 4 courses of intralesional T-VEC and 3 courses of intravenous Nivolumab. T-VEC first, in order to achieve the best synergistic effect with influx of CD8+ T cells prior to the first Nivolumab dose. T-VEC monotherapy with the dose 108 PFU/mL is given every 2 weeks (± 3) days after 3 weeks of the first T-VEC dose (with the first dose of T-VEC 106 PFU/mL to allow for seroconversion) , and Nivolumab can be given either every 2 weeks or every 4 weeks. Therefore we suggest the same dosing schedule for T-VEC and Nivolumab every 2 weeks for the purpose of this trial.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Signal pathways of melanoma and targeted therapy.
   Guo W, Wang H, Li C. · · 2021 · cited 251× · PMID 34924562 · DOI 10.1038/s41392-021-00827-6
2. Melanoma Management: From Epidemiology to Treatment and Latest Advances.
   Lopes J, Rodrigues CMP, Gaspar MM, Reis CP. · · 2022 · cited 98× · PMID 36230575 · DOI 10.3390/cancers14194652
3. Oncolytic Herpes Simplex Virus-Based Therapies for Cancer.
   Aldrak N, Alsaab S, Algethami A, Bhere D, et al · · 2021 · cited 61× · PMID 34207386 · DOI 10.3390/cells10061541
4. Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma.
   Ceci C, Atzori MG, Lacal PM, Graziani G. · · 2020 · cited 58× · PMID 33212945 · DOI 10.3390/cancers12113401
5. Biomaterial-Based In Situ Cancer Vaccines.
   Bo Y, Wang H. · · 2024 · cited 55× · PMID 36649567 · DOI 10.1002/adma.202210452
6. The Current State of Treatment and Future Directions in Cutaneous Malignant Melanoma.
   Ernst M, Giubellino A. · · 2022 · cited 49× · PMID 35453572 · DOI 10.3390/biomedicines10040822
7. Current clinical landscape of oncolytic viruses as novel cancer immunotherapeutic and recent preclinical advancements.
   Yun CO, Hong J, Yoon AR. · · 2022 · cited 45× · PMID 36091031 · DOI 10.3389/fimmu.2022.953410
8. Trial watch: intratumoral immunotherapy.
   Humeau J, Le Naour J, Galluzzi L, Kroemer G, et al · · 2021 · cited 45× · PMID 34676147 · DOI 10.1080/2162402x.2021.1984677