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Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. 2019
Linh T Nguyen, and
Samuel D Saibil, and
Valentin Sotov, and
Michael X Le, and
Leila Khoja, and
Danny Ghazarian, and
Luisa Bonilla, and
Habeeb Majeed, and
David Hogg, and
Anthony M Joshua, and
Michael Crump, and
Norman Franke, and
Anna Spreafico, and
Aaron Hansen, and
Ayman Al-Habeeb, and
Wey Leong, and
Alexandra Easson, and
Michael Reedijk, and
David P Goldstein, and
David McCready, and
Kazuhiro Yasufuku, and
Thomas Waddell, and
Marcelo Cypel, and
Andrew Pierre, and
Bianzheng Zhang, and
Sarah Boross-Harmer, and
Jane Cipollone, and
Megan Nelles, and
Elizabeth Scheid, and
Michael Fyrsta, and
Charlotte S Lo, and
Jessica Nie, and
Jennifer Y Yam, and
Pei Hua Yen, and
Diana Gray, and
Vinicius Motta, and
Alisha R Elford, and
Stephanie DeLuca, and
Lisa Wang, and
Stephanie Effendi, and
Ragitha Ellenchery, and
Naoto Hirano, and
Pamela S Ohashi, and
Marcus O Butler
Tumor Immunotherapy Program, Princess Margaret Cancer Centre, Toronto, Canada.
Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Secondary endpoints were safety and assessment of immune correlates following TIL infusion. Twelve metastatic melanoma patients were treated with non-myeloablative lymphodepleting chemotherapy, TIL, and low-dose subcutaneous IL-2 (125,000 IU/kg/day, maximum 9-10 doses over 2 weeks). All but one patient had previously progressed after treatment with immune checkpoint inhibitors. No unexpected adverse events were observed, and patients received an average of 6.8 doses of IL-2. By RECIST v1.1, two patients experienced a partial response, one patient had an unconfirmed partial response, and six had stable disease. Biomarker assessment confirmed an increase in IL-15 levels following lymphodepleting chemotherapy as expected and a lack of peripheral regulatory T-cell expansion following protocol treatment. Interrogation of the TIL infusion product and monitoring of the peripheral blood following infusion suggested engraftment of TIL. In one responding patient, a population of T cells expressing a T-cell receptor Vβ chain that was dominant in the infusion product was present at a high percentage in peripheral blood more than 2 years after TIL infusion. This study shows that this protocol of low-dose IL-2 following adoptive cell transfer of TIL is feasible and clinically active. (ClinicalTrials.gov identifier NCT01883323.).
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Leila Khoja, and
Danny Ghazarian, and
Luisa Bonilla, and
Habeeb Majeed, and
David Hogg, and
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Ayman Al-Habeeb, and
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