57P - Anatomical location of metastasis and composition of the final infusion product in metastatic melanoma (MM) patients treated with tumor-infiltrating lymphocytes (TIL)

Background

Adoptive cellular therapy (ACT) with TIL recently showed promising results in a multicenter phase 3 trial evaluating TIL in MM patients (NCT02278887). In this, 39 (49 %) of TIL-treated patients obtained a complete or partial response according to RECIST 1.1. The potential impact of the location of the resected metastasis for TIL production on the phenotype of the final TIL infusion product is essential knowledge for future development of TIL therapy.

Methods

Cryopreserved samples of TIL infusion product from all patients with unresectable stage IIIC-IV MM treated in the phase 3 trial were analyzed using multiparametric flow cytometry. Here, we investigated if the anatomical location of the metastasis used for TIL production impacted the composition of the final TIL infusion product. The Kruskal-Wallis test was used to test for statistical significance.

Results

In total, 80 patients were treated with TIL. Respectively, 37 (46.3 %), 29 (36.3 %), and 14 (17.5 %) underwent resection of a lymph node, (sub)cutaneous or a visceral metastasis for TIL production. Visceral metastases included lung (n=8), liver (n=2), spleen (n=1), small intestine (n=1), adrenal gland (n=1), and peritoneum (n=1). The location of the metastasis used for TIL production did not impact clinical response (p=0.84) or the composition of the final TIL infusion product, with no difference in the total number of TIL produced in major subsets including CD45+ CD3+ (p=0.42), CD8+ TCRab+ (p=0.37), CD4+ TCRab+ (p=0.09) or CD3+ TCRgd+ (p=0.36). For both CD4+ and CD8+ TIL, differentiation into naïve (CCR7+ CD45RO-), effector memory (CCR7- CD45RO+), central memory (CCR7+ CD45RO+), and terminally differentiated effector memory cells (CCR7- CD45RO-) was also not affected by the site of metastasectomy.

Conclusions

The anatomical location of the metastasis used for TIL production did not impact clinical response, the absolute number of TIL produced, or the overall phenotypic composition of the final TIL infusion product. Thus, easily accessible MM lesions can be preferred without the risk of impacting TIL phenotype or clinical outcome.

Clinical trial identification

NCT02278887, EudraCT 2013-005406-54.

Legal entity responsible for the study

National Center for Cancer Immune Therapy (CCIT-DK), Herlev Hospital (Denmark) and the Netherlands Cancer Institute (NKI), Amsterdam (the Netherlands).

Funding

This study was supported by the Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, AVLFoundation, Copenhagen University Hospital, Herlev, the Danish Cancer Society and Capital Region of Denmark Research Foundation.

Disclosure

T.H. Borch: Other, Personal, Other, Speaker's honoraria: Bristol Myers Squibb. W. Van Houdt: Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Advisory Board: Belpharma, Sanofi, MSD; Financial Interests, Personal, Other, travel grant: Novartis; Financial Interests, Institutional, Local PI: BMS. M. Donia: Financial Interests, Personal, Other, Advisor: Achilles Therapeutics; Non-Financial Interests, Personal, Other, Sub-investigator of clinical trial with connected translational research: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary data access: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary Data Access: Genentech; Other, Personal, Other, Chairman of the Melanoma and Non-melanoma Skin Cancer Scientific Committee: Danish Medicines Council (Medicinrådet). J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Iovance Biotherapeutics, AstraZeneca; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Advisory Board: Third Rock Venture, CureVac, Imcyse; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio, Sastra Cell Therapy; Non-Financial Interests, Personal, Member: ASCO, AACR, SITC; Other, Personal, Other, Editor-in-Chief IOTECH: ESMO; Other, Personal, Other, Editorial Board ESMO Open: ESMO; Other, Personal, Other, Editorial Board: Kidney Cancer. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS; Financial Interests, Institutional, Research Grant: Enara Bio, Adaptimmune, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Personal, Principal Investigator: BMS, Novartis, Roche, TILT Biotherapeutics, Lytix Biopharma. All other authors have declared no conflicts of interest.