MedTrace Logo

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

NCT04330430 · Status: COMPLETED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 24

Last updated 2025-03-12

No results posted yet for this study

Summary

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.

Conditions

  • Melanoma Stage III
  • Melanoma Stage IV

Interventions

DRUG

T-VEC

The treatment schedule is based on 4 courses of intralesional T-VEC and 3 courses of intraveneous 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 10\^8 PFU/mL is given every 2 weeks after 3 weeks of the first T-VEC dose (with the first dose of T-VEC 10\^6 PFU/mL to allow for seroconversion), and Nivolumab will be given every 2 weeks.

Sponsors & Collaborators

  • Amgen

    collaborator INDUSTRY

  • The Netherlands Cancer Institute

    lead OTHER

Principal Investigators

  • John Haanen, Prof. · Medical oncologist/researcher

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2020-09-08
Primary Completion
2023-04-09
Completion
2025-01-29

Countries

  • Netherlands

Study Locations

More Related Trials

Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04330430 on ClinicalTrials.gov