Although cell therapies such as CAR-T have been approved and used successfully to treat haematological cancers, there are currently no cell therapies approved for the treatment of solid tumours. However, positive data recently presented by Iovance Biotherapeutics from its lead candidate, tumour-infiltrating lymphocyte (TIL) therapy lifileucel, in heavily pre-treated melanoma patients suggests an approval could be expected as early as next year. A total of 298 industry-sponsored trials are currently ongoing investigating cell therapies in non-haematological cancers, says GlobalData.
Jessica McCormack, Oncology and Hematology Analyst at GlobalData, comments, “Iovance’s data in melanoma and other solid tumours, particularly in patients who have failed multiple lines of prior therapy, suggests that cellular therapies may yet present viable options for patients with solid tumours. There is currently no standard of care for melanoma patients who progress on immune checkpoint inhibitors, and if BRAF-positive, BRAF/MEK inhibitors. Should results remain positive, this type of TIL therapy could be transformative for this patient group, who would otherwise have very limited therapeutic options.”
Most ongoing cell therapy trials in non-haematological cancers are in the early stages; just five per cent are in Phases III or II/III, while 74 per cent of trials are in Phase I or I/II. These are also being sponsored by a large range of companies. Iovance looks set to be the leading figure in this space, with five ongoing Phase II trials, of which three are potentially registrational – more than any other company.
McCormack continues, “While CAR-T has revolutionized the way in which haematological malignancies, such as acute lymphoblastic leukaemia and B-cell lymphomas are treated, solid tumours present different problems to liquid tumours. Solid tumours can be inaccessible to cell therapies, which must first exit the bloodstream to gain access to the tumour site and then potentially overcome the dense extracellular matrix. The tumour microenvironment may also be immunosuppressive. Finally, the identification of targetable antigens for solid tumours has also been a problem.”
Iovance has been able to circumvent the issue of identifying effective tumour targets by utilizing TILs that are derived specifically from each patients’ tumour. These target a large range of tumour-specific antibodies and also means no additional genetic modifications are necessary, unlike with CAR-T.
McCormack concludes, “Melanoma is a relatively immunogenic cancer, which means that there is the potential for the isolation of multiple TILs with different specificities from the tumour sample. Iovance has also shown positive data in cervical cancer and head and neck cancer, and have ongoing trials of its LN-145 product in non-small cell lung cancer. This suggests that Iovance could bring its TIL therapies into a range of solid tumours in the future.”