36MO - Location and size of metastasectomy in melanoma patients treated with tumor-infiltrating lymphocytes (TIL) in relation to clinical outcome

Background

Development of novel treatment options is essential for patients with metastatic melanoma (MM), as about half derive no durable benefit upon first-line treatment. Adoptive cell therapy with TIL has shown encouraging results in a recently completed multicenter phase 3 trial evaluating TIL in MM patients (NCT02278887); 39 (49%) patients showed a response (complete or partial) and 2 (3%) patients were not evaluable for response. Resection of a melanoma lesion (≥2-3cm) was required for the ex vivo outgrowth and expansion of TIL. However, the impact of location and size of metastasectomy used for TIL production on response is yet unknown.

Methods

Location and size of metastasectomy used for TIL production in relation to clinical response were evaluated in patients with unresectable stage IIIC-IV MM treated with TIL in a recently completed phase 3 trial. Regression analyses and corresponding Likelihood Ratio- and F-tests were performed to test statistical significance.

Results

Manufacturing of TIL was successful in 82/83 (98.8%) patients for whom production was started. In total, 80 patients were treated with a median number of 40.9x10⁹ TIL (range 4.9 – 110.4), of which 36 (45%), 34 (42.5%) and 10 (12.5%) underwent resection of a lymph node, (sub)cutaneous or visceral metastasis for TIL manufacturing, respectively. Visceral metastases included lung (n=6), liver (n=1), adrenal gland (n=1), small intestine (n=1) and spleen (n=1). Median time from randomization to metastasectomy was 10.3 days (range -14.5 – 22.5). In 10 (12.5%) patients, a second metastasectomy was performed due to initial insufficient TIL outgrowth. Location of metastasectomy had no influence on clinical response (p=0.949) or on the number of cells produced (p=0.540). In 50 (62.5%) patients 1 lesion of ≥ 2-3cm and in 30 (37.5%) patients >1 lesion was resected to obtain the required ≥ 2-3cm, with no differences in resulting cell numbers (p=0.115).

Conclusions

A high success rate of TIL manufacturing was observed for MM patients treated with TIL in a recently completed multicenter phase 3 trial. Location and size of metastasectomy had no impact on clinical response or cell numbers, making TIL a robust treatment option.

Clinical trial identification

NCT02278887.

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

The Dutch Cancer Society, the Netherlands Organization for Health Research and Development, the Dutch Ministry of Health, Stichting Avento, AVL Foundation, Copenhagen University Hospital, Herlev, the Danish Cancer Society and Capital Region of Denmark Research Foundation.

Disclosure

T. Holz Borch: Financial Interests, Personal, Invited Speaker: BMS. J.H. van den Berg: Financial Interests, Institutional, Research Grant: NEON therapeutics, BMS, MedImmune. W. Van Houdt: Financial Interests, Institutional, Invited Speaker: Amgen, BMS; Financial Interests, Institutional, Advisory Board: Belpharma; Financial Interests, Institutional, Expert Testimony: Sanofi, MSD; Financial Interests, Personal, Other, travel grant: Novartis. A.C.J. van Akkooi: Financial Interests, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, Novartis, MSD - Merck, Merck-Pfizer, Pierre Fabre, Sanofi, Sirius Medical, 4SC, Provectus; Financial Interests, Institutional, Research Grant, NIVEC study: Amgen; Financial Interests, Institutional, Research Grant: Merck-Pfizer. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS, MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Personal, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; 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, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; 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. All other authors have declared no conflicts of interest.