50MO - Adoptive cell therapy with tumor-infiltrating lymphocytes in combination with nivolumab in patients with advanced melanoma

Background

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is an effective treatment option for patients with advanced melanoma, but not all patients benefit. Combining PD-1 blockade to antagonize the immunosuppressive tumor microenvironment with TIL-ACT may synergize to enhance the anti-tumor potential.

Methods

We set up this single center investigator-initiated phase I trial (BaseTIL, CA209-7H9) at the University Hospital Basel, Switzerland, to investigate feasibility and safety of TIL-ACT followed by PD-1 blockade. We included adult patients with advanced cutaneous melanoma with disease progression after at least one PD-1 based systemic treatment line. Study procedures included the following steps: surgical tumor collection, ex vivo TIL expansion, preparative lymphodepletion (LD) with cyclophosphamide and fludarabine, TIL transfer and in vivo TIL stimulation with daily interleukin-2 (IL-2) at 125’000 IE/kg s.c. for 10 days, followed by 240 mg nivolumab i.v. every 2 weeks for the duration of 2 years. Nine patients were planned for inclusion.

Results

Between 2020 and 2022, we enrolled 11 patients and 9 underwent a TIL transfer (median transfused cell number: 64.9 x 10⁹). Two patients did not start LD, one with rapid disease progression, and one had bacterial contamination of the TIL product. Nine patients received at least 1 dose of IL-2 (median number of doses: 8; range: 1-10) and 7 started nivolumab (median number of cycles: 7; range 2-23). All nine patients had adverse events (AEs) related to TIL-ACT (LD, TIL transfer, IL-2). The most common non-hematological AEs of ≥ grade 2 were cytokine-release syndrome (4/9) (including 1 patient with a grade 4 event which led to trial discontinuation), hypertension (4/9) and fever/chills (4/9). No nivolumab-associated AEs of ≥ grade 2 occurred. Tumor regression occurred in most patients (7/9) at the first imaging scan performed approximately 1 month after TIL-ACT. Best radiographic response was partial response in 2 and stable disease in 3. Progressive disease occurred in 4 patients.

Conclusions

TIL-ACT with nivolumab seems feasible and safe. Larger populations are needed to further determine feasibility, efficacy, and safety of this combination therapy.

Clinical trial identification

NCT04165967.

Legal entity responsible for the study

University Hospital Basel.

Funding

BMS.

Disclosure

D. König: Financial Interests, Institutional, Advisory Board: AstraZeneca, Amgen, Sanofi, MSD, Merck; Financial Interests, Institutional, Other, Support for attending meetings and/or travel: Roche, Amgen, Sanofi; Financial Interests, Institutional, Invited Speaker: Mirati. L. Jeker: Financial Interests, Personal, Stocks or ownership: Cimeio Therapeutics AG. B. Kasenda: Financial Interests, Institutional, Speaker, Consultant, Advisor: Roche, Riemser, Incyte; Financial Interests, Institutional, Research Funding: AbbVie; Financial Interests, Institutional, Advisory Board: Astellas. H. Läubli: Financial Interests, Institutional, Funding: BMS, MSD, Alector; Financial Interests, Institutional, Research Funding: BMS, Novartis, GlycoEra, Palleon Pharmaceuticals. All other authors have declared no conflicts of interest.