ESMO field directly tackles the therapeutic potential of TIL therapy in melanoma

The 2022 European Society of Medical Oncology (ESMO) Annual Meeting was held
in Paris on September 9~13, local time.
As the most prestigious and influential oncology conference in Europe, ESMO Annual Conference covers basic research, translational research and the latest clinical research progress, providing a broad and excellent academic platform
for clinical practice and multidisciplinary discussions.
Tumor-invasive lymphocyte (TIL) therapy is an experimental cell therapy being developed for the treatment of solid tumors and is considered one of the most promising forms of
tumor treatment.
At this year's ESMO Annual Meeting, the Phase 3 study data of TIL for melanoma was announced, demonstrating the therapeutic potential
of TIL in solid tumors.

Immune checkpoint inhibitors and targeted therapies have greatly improved the prognosis
of patients with advanced melanoma.
However, about half of patients still do not experience lasting benefit, so there is still a large unmet need
for treatment.
TIL is a reclusing cell therapy with a response rate (ORR) of 36-70%
in patients with advanced melanoma observed in multiple phase 1/2 trials.
To date, there are no Phase 3 trial data confirming the role of
TIL in melanoma.

This multicenter, open-label, phase 3 trial enrolled patients aged 18-75 years with unresectable stage IIIC-IV (version 7) melanoma and was randomized 1:1 to TIL or ipilimumab (3 mg/kgq3wks for up to 4 doses).

Stratify
patients according to BRAFV600 mutation status, number of treatment lines, and center.
Patients randomized to TIL underwent resection of melanoma lesions (2-3 cm) to achieve ex vivo growth and expansion of T cells
.
Nonmyeloablative lymphadencyte abolition chemotherapy with cyclophosphamide + fludarabine followed by high-dose interleukin-2
is preceded by 5x109TIL infusion.
The primary endpoint was progression-free survival (PFS)
assessed according to the RECIST 1.
1 criteria.
Secondary endpoints were overall and complete response rate, overall survival (OS), and safety
.

A total of 168 patients were included, most of whom (86%) did not respond to anti-PD-1 monoclonal antibody therapy and were randomly assigned to TIL (n=84) or ipilimumab (n=84).

The median follow-up was 33.
0 months, with a median PFS of 7.
2 months (95% CI, 4.
2-13.
1) in the TIL group and 3.
1 months (95% CI, 3.
0-4.
3) in the ipilimumab group (HR: 0.
50 [95% CI, 0.
35-0.
72]; P<0.
001).

The ORR was 48.
8% (95% CI, 38% to 60%) in the TIL group and 21.
4% (95% CI, 13% to 32%) in the ipilimumab group, with 20.
2% and 7.
1% of patients in complete response
, respectively.

Median OS was 25.
8 months (95% CI, 18.
2-not achieved) in the TIL group and 18.
9 months (95% CI, 13.
8-32.
6) in the ipilimumab group (HR: 0.
83 [95% CI, 0.
54-1.
27]; P=0.
39）
。

In terms of safety, all patients in the TIL group and 57.
3% of patients in the ipilimumab group experienced ≥ grade 3 treatment-related adverse events
.
In addition, patients in the TIL group had higher
health-related quality of life scores compared with the ipilimumab group.

This multicenter phase 3 study, the first randomized trial of TIL therapy in solid tumors, showed that TIL significantly improved PFS compared with ipilimumab, the vast majority of patients refractory to anti-PD-1 monoclonal antibody and TIL may be a new treatment option
for these patients.

References:

J.
B.
A.
G.
Haanen, et al.
Treatment with tumor-infiltrating lymphocytes (TIL) versus ipilimumab for advanced melanoma: results from a multicenter, randomized phase 3 trial.
2022 ESMO.
Abstract LBA3.