48O - Safety and Efficacy of Combined Treatment with Tumor Infiltrating Lymphocytes (TILs) and Oncolytic Adenovirus TILT-123 for Patients with Metastatic Melanoma - Results from a Phase I Trial

Background

Tumor Infiltrating Lymphocyte (TIL) therapy has recently proved effective in patients with metastatic melanoma. Oncolytic adenovirus TILT-123 (igrelimogene litadenorepvec) is armed with tumor necrosis factor-alpha and interleukin-2 which were selected specifically for their ability to enhance TIL cytotoxicity without the need for preconditioning chemotherapy or postconditioning IL2.

Methods

In a phase I, open-label, 3+3 dose-escalating multicenter trial, patients with stage IV melanoma were treated with multiple intravenous and intratumoral injections of TILT-123 and a one- or two-time treatment with TILs. TILs were grown from resected tumor tissue and administered without pre- or post-conditioning treatment regimens. The primary endpoint of the study was safety of TILT-123. Secondary endpoints included safety and efficacy of TILT-123 in combination with TILs.

Results

Sixteen patients with CPI resistant progressive cutaneous (7), mucosal (5) and uveal (4) metastatic melanoma were treated. Median age was 65.5 years (25-75). The most frequently reported adverse events (AEs) related to TILT-123 were fever (63%) and pain at the injection site (44%) while most frequent AEs related to TIL therapy were fever (50%) and chills (24%). No dose-limiting toxicity was observed and the combination of TILT-123 and TIL therapy did not increase the severity of AEs. 31% of patients experienced treatment related serious adverse events. In d78 imaging, RECIST1.1 responses were observed in two patients while disease control rate was 38 % (6/16). Responders included one patient (cutaneous) with an ongoing partial response and one patient (mucosal) with a durable complete response. Further, two patients (uveal and cutaneous) had long lasting stable disease (> 10 months). PET evaluation on d78 revealed disease control in 6/13 evaluable patients, including 4 partial or minor responses. On d36, after 4 injections of TILT-123 and before TILs, 4 partial or minor responses were seen in PET.

Conclusions

The combination of TILT-123 and TIL therapy is safe and feasible in patients with metastatic melanoma. Clinical activity in hard-to-treat melanoma subtypes was observed.

Clinical trial identification

NCT04217473.

Legal entity responsible for the study

TILT Biotherapeutics.

Funding

TILT Biotherapeutics.

Disclosure

T.J. Monberg: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Co-investigator in clinical trial: Lytix Biopharma, TILT Biotherapeutics. V. Cervera-Carrascon: Financial Interests, Personal, Full or part-time Employment: TILT Biotherapeutics Ltd; Financial Interests, Personal, Stocks/Shares: TILT Biotherapeutics Ltd. E. Ellebæk: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Personal, Other, Travel and conference expenses: MSD, Pierre Fabre. 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). C. Kistler: Financial Interests, Personal, Full or part-time Employment: TILT Biotherapeutics; Financial Interests, Personal, Stocks/Shares, shareholder. J. Clubb: Financial Interests, Personal, Full or part-time Employment, Part-time project manager: TILT Biotherapeutics; Financial Interests, Personal, Stocks/Shares: TILT Biotherapeutics. L. Haybout: Financial Interests, Institutional, Full or part-time Employment: Tilt Biotherapeutics Ltd. D.C.A. Quixabeira: Financial Interests, Institutional, Full or part-time Employment: TILT Biotherapeutics. R. Havunen: Financial Interests, Personal, Full or part-time Employment: TILT Biotherapeutics; Financial Interests, Personal, Other, Options: TILT Biotherapeutics. S. Sorsa: Financial Interests, Personal, Full or part-time Employment: TILT Biotherapeutics Ltd; Financial Interests, Personal, Stocks/Shares: TILT Biotherapeutics Ltd. A. Hemminki: Financial Interests, Personal, Stocks/Shares: Targovax ASA, TILT Biotherapeutics; Financial Interests, Personal, Full or part-time Employment: TILT Biotherapeutics. 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.