Although immune checkpoint inhibitors and targeted therapies have profoundly improved outcome of patients with (advanced) melanoma, approximately 50% of patients still die from their disease within 5 years following diagnosis of stage IV disease1. Thus, there is a great unmet need for novel treatment options in this patient population.
Adoptive cell therapy with TIL is a (elaborative and time-consuming) treatment modality with promising response rates of 36–70% in heavily pre-treated patients with advanced melanoma, observed in multiple phase 1/2 trials2,3. Dr John Haanen (Netherlands Cancer Institute, the Netherlands) and colleagues performed the first investigator-driven, open-label, randomised-controlled, phase 3 clinical trial (NCT02278887) comparing treatments with TIL and ipilimumab4.
In the trial, 168 patients with unresectable, stage III–IV cutaneous melanoma who had progression after 1 line of systemic treatment (no ipilimumab) were randomised to receive TIL treatment (single infusion of ≥5x109 TILs) or ipilimumab (3 mg/kg every 3 weeks, max. 4 doses). About 90% of the patients had received prior anti-PD1 therapy. Primary endpoint of study was PFS in the intention-to-treat (ITT) population; secondary endpoints were overall and complete response rate (RR), overall survival (OS), and safety.
The trial met its endpoint: with a median follow-up of 33 months, median PFS was 7.2 months for the patients randomised to TIL treatment versus 2.1 months for the patients treated with ipilimumab (HR 0.50; P<0.001). PFS rates at 6 months were 52.7% and 21.4%, respectively. TIL therapy was superior to ipilimumab in all pre-specified subgroups. ORR was 48.8% in the TIL-treated patients (20.2% complete response) versus 21.4% in the ipilimumab-treated patients (7.1% complete response).
Immature OS data showed a trend in favour of TIL treatment; median OS was 25.8 months in the TIL-treated patients versus 18.9 months in the ipilimumab-treated patients (HR 0.83; P=0.39). Safety of TIL treatment was manageable and scores for health-related quality-of-life were significantly higher in TIL-treated patients during the 60 months of follow-up (mean difference at 6 months: 7.7; P<0.01).
“This first randomised phase 3 trial demonstrates that second-line TIL significantly improves PFS compared with ipilimumab in patients with unresectable, advanced melanoma. Therefore, TIL could become a possible new treatment option for this population,” Dr Haanen concluded.