Phase I/II study protocol to assess safety and efficacy of adoptive cell therapy with anti-PD-1 plus low-dose pegylated-interferon-alpha in patients with metastatic melanoma refractory to standard of care treatments: the ACTME trial
Gerrit-Jan Liefers,
Sjoerd H van der Burg,
Monique K van der Kooij,
Marten Visser,
Linda de Bruin,
Ellen Kapiteijn,
Els M E Verdegaal,
Caroline E van der Minne,
Pauline M Meij,
Inge C F M Roozen,
Mare A Jonker,
Shelley van den Bosch,
Frank M Speetjens
Affiliations
Gerrit-Jan Liefers
Surgery, Leids Universitair Medisch Centrum, Leiden, The Netherlands
Sjoerd H van der Burg
Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
Monique K van der Kooij
Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Marten Visser
Oncode Institute, Utrecht, The Netherlands
Linda de Bruin
Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
Ellen Kapiteijn
Department of Medical Oncology, Leiden University Medical Center, Leiden, Zuid-Holland, Netherlands
Els M E Verdegaal
3 Department of Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, The Netherlands
Caroline E van der Minne
Medical Oncology, Oncode Institute, Leiden University Medical Center, Leiden, Netherlands
Pauline M Meij
Clinical Pharmacy & Toxicology, Leiden University Medical Center, Leiden, The Netherlands
Inge C F M Roozen
Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Mare A Jonker
Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Shelley van den Bosch
Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
Frank M Speetjens
1 Department of Medical Oncology, Leiden Universitair Medisch Centrum, Leiden, Zuid-Holland, The Netherlands
Introduction Treatment with anti-PD-1 immunotherapy does not lead to long-lasting clinical responses in approximately 60% of patients with metastatic melanoma. These refractory patients, however, can still respond to treatment with tumour infiltrating lymphocytes (TIL) and interferon-alpha (IFNa). A combination of TIL, pegylated-interferon-alpha (PEG-IFNa) and anti-PD-1 is expected to provide a safe, feasible and effective therapy for patients with metastatic melanoma, who are refractory to standard of care treatment options.Methods and analysis Patients are treated in two phases. In phase I, the safety of the combination TIL and anti-PD-1 is assessed (cohort 1) according to CTCAE 4.03 criteria. Subsequently, the safety of cotreatment with PEG-IFNa is tested in cohort 2. The efficacy will be evaluated in the second phase of the trial. Efficacy is evaluated according to RECIST 1.1 and immune-related response criteria. Clinical and immunological parameters will be evaluated for their relation with clinical responsiveness.Ethics and dissemination Ethical approval of the trial was obtained from the Central Committee on Research Involving Human Subjects in the Netherlands. The trial results will be shared with the scientific community at (inter)national conferences and by publication in a peer-reviewed journal.Trial registration number NCT03638375; Pre-results.
