Amsterdam and Herlev, July 11th 2022. The Netherlands Cancer Institute, Amsterdam, The Netherlands (NKI) and the National Center for Cancer Immune Therapy, Department of Oncology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark (CCIT-DK) today announced primary results from the phase 3 M14TIL trial evaluating infusion of autologous in vitro expanded tumor-infiltrating lymphocytes (TILs) versus ipilimumab in patients with unresectable or metastatic melanoma. The trial met its primary endpoint of progression-free survival (PFS). Follow up for secondary endpoints is ongoing. These are the first Phase 3 data to be reported from a trial evaluating cellular therapy based on TILs. “Treatment with TILs in various forms has been studied for over two decades, however no randomized phase 3 trial was conducted to date. M14TIL demonstrate that TIL therapy is active in melanoma, and superior to standard ipilimumab in anti-PD-1 refractory patients" said John Haanen and Inge Marie Svane, Principal Investigators of M14TIL, in a joint statement. “Immune checkpoint inhibitors based on anti-PD-1 have revolutionized the treatment of melanoma. However, there is a sizable proportion of patients who do not obtain a durable benefit. The results of this study suggest that infusion of autologous TILs can be included in the armamentarium of active treatments for melanoma to further improve clinical outcomes".
This therapy is based on infusion of in vitro expanded autologous TILs preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 (1). It is a personalized treatment strategy, that include resection of tumor from an individual patient, followed by in vitro isolation, activation and expansion of the TILs from the resected tumor. After 3-6 weeks of culture, TILs are re-infused back into the same patient intravenously(2). Multiple ongoing phase I and II studies are evaluating TIL treatment in diverse solid tumor types. M14TIL is the first phase 3 trial to demonstrate a benefit for patients.
NKI and CCIT-DK will present the primary results of the study at an upcoming medical meeting. M14TIL trial findings will be discussed with EU regulatory authorities in 2022. NKI and CCIT-DK will seek registration of TIL treatment in The Netherlands and Denmark.
NKI and CCIT thank the patients, families and healthcare personnel who were involved in the M14TIL trial. The study was supported financially by The Dutch Cancer Society, The Netherlands Organization for Health Research and Development, The Dutch Ministry of Health, Wealth and Sport, Stichting Avento, Copenhagen University Hospital, Herlev, The Danish Cancer Society, The Capital Region of Denmark, Aase and Ejnar Danielsens Foundation. No commercial entities were involved in this study.
About M14TIL
M14TIL (clinicaltrials.gov identifier NCT 02278887) is an investigator-sponsored, randomized, controlled phase 3 study evaluating TIL infusion preceded by non-myeloablative chemotherapy and followed by high dose bolus interleukin-2 compared to ipilimumab in 168 patients with unresectable or metastatic melanoma. The primary endpoint of the trial is progression-free survival (PFS) according to RECIST 1.1. Secondary endpoints are PFS at 6 months according to RECIST 1.1, PFS according to immune-related response criteria (irRC), overall response rate, complete response rate, overall survival, safety and health technology assessment. Follow up for the secondary endpoints is ongoing.
About TIL therapy
TILs are lymphocytes naturally occurring at the tumor site. Multiple phase 1 and phase 2 studies conducted in the previous decades demonstrated preliminary activity of TIL therapy to induce durable complete responses in melanoma and other cancers(2).
About Melanoma
Melanoma is an aggressive form cancer, where a certain type of pigment-producing cell that is primarily located in the skin grows uncontrolled. Melanoma is curable in most cases when treated at an early stage, when the disease is located only in the skin. However, when the disease spreads beyond the skin (metastatic melanoma), it is characterized by a high level of lethality despite best current care. Current medical treatments are effective only in a proportion of patients. The incidence of melanoma is rising steadily worldwide.
References
1. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science (80- ). 2015;348:62–8.
2. Granhøj JS, Witness Præst Jensen A, Presti M, Met Ö, Svane IM, Donia M. Tumor-infiltrating lymphocytes for adoptive cell therapy:
recent advances, challenges, and future directions.
Expert Opin Biol Ther [Internet]. Expert Opin Biol Ther; 2022 [cited 2022 Jun 25];22:627–41. Available from: https://pubmed.ncbi.nlm.nih.gov/35414331/