Tumour-infiltrating lymphocyte treatment for advanced melanoma

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Published: 10 Sep 2022
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Dr John Haanen - Netherlands Cancer Institute, Amsterdam, Netherlands

Dr John Haanen speaks to ecancer on his open-label phase 3 trial which studied treatment with tumour-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma. 

Immune checkpoint inhibitors and targeted therapies have greatly improved the outcome of patients (pts) with advanced melanoma. However, as approximately half will not derive durable benefits, a large unmet need for additional treatment options remains. 

In this multicenter, open-label phase 3 trial, pts with unresectable stage IIIC-IV melanoma, ≥18 ≤ 75 years, were randomised 1:1 to TIL or ipilimumab. The primary endpoint was progression-free survival (PFS) per RECIST 1.1. Secondary endpoints were (overall and complete) RR, overall survival and safety.

The results demonstrated TIL therapy significantly improved PFS compared to ipilimumab in patients with advanced melanoma, the vast majority being anti-PD-1 refractory, making it a possible new treatment option in this patient population.

The background was that we still need additional treatments, innovative and effective treatments, for patients with melanoma. Of course, we’ve come quite a long… from far, where there was nothing ten years ago and now we have a number of very good treatment options. But still half of the patients succumb from their disease within five years of diagnosis of metastatic disease. So we still need to further improve that. The TIL trial gave us the opportunity to investigate a completely novel treatment option. 

What was the methodology behind the study?

The methodology was that it was a randomised controlled phase III trial where patients were randomised between receiving TIL therapy versus standard of care, ipilimumab. Most of these patients had failed anti-PD-1 treatment and the primary endpoint was progression free survival in the intention to treat population by investigator review.

What were the key findings?

The key results were that patients that received TIL had about a 50% reduction in progression or death compared to ipilimumab. That’s a very important signal that TIL therapy is highly effective. Also in terms of overall response rate we did see that there was a much higher response rate in TIL treated patients – 49% versus 21% in the ipilimumab group. Also the complete remission rate was high – 20% versus 7% – and especially patients with a complete remission have a very durable response to this treatment.

How can these results improve future treatment?

With these data, TIL therapy could become a novel treatment option for these patients. Now, that’s easier said than done because it’s not a simple treatment to establish. So currently we are working on and thinking about how to put this in the market to make sure that more patients than only the patients in the Netherlands can get access to this treatment. But for that we need EMA or FDA approval and that is something that takes time.