Tumour-infiltrating lymphocyte therapy versus ipilimumab in advanced melanoma: randomised phase 3 trial of the Netherlands Cancer Institute (ClinicalTrials.gov NCT02278887)
Phase 3N = 168NCT02278887
- Population
- Patients with unresectable stage IIIC or IV melanoma; 86% had disease refractory to anti-PD-1 treatment.
- Design
- Multicentre, open-label, randomised phase 3 trial, 1:1. TIL arm: nonmyeloablative lymphodepleting chemotherapy (cyclophosphamide plus fludarabine), infusion of at least 5x10^9 TILs, then high-dose interleukin-2. Control arm: ipilimumab 3 mg per kilogram.
- Primary endpoint
- PFS
- Arms
- TIL therapy (experimental, n = 84): Lymphodepleting cyclophosphamide plus fludarabine, TIL infusion (at least 5x10^9 cells), high-dose interleukin-2
- Ipilimumab (control, n = 84): Ipilimumab 3 mg per kilogram
- People
- Rohaan MW, senior author Haanen JBAG, Netherlands Cancer Institute (trial sponsor per ClinicalTrials.gov); author affiliations in the Netherlands and Denmark
PFSHR 0.50 (95% CI 0.35–0.72)Δ median PFS+4.1 monthsΔ ORR+28 pointsΔ median OS+6.9 months
Show the numbers
| Endpoint | Analysis | TIL therapy | Ipilimumab | Effect |
|---|---|---|---|---|
| PFSProgression-free survival | primaryRohaan 2022 | median 7.2 months (4.2–13.1) | median 3.1 months (3.0–4.3) | HR 0.50 (95% CI 0.35–0.72)P<0.001Hazard ratio is for progression or death. |
| ORRRandomised patients (84 per arm); the abstract states ITT for the PFS sentence in which these percentages appearObjective response (proportion of patients with an objective response) | primaryRohaan 2022 | 49% (38–60%) | 21% (13–32%) | — |
| OSRandomised patients; the abstract states ITT for PFS and does not repeat it for OSOverall survival (median) | primaryRohaan 2022 | median 25.8 months | median 18.9 months (13.8–32.6) | The 95% CI of the TIL median is 18.2 months to not reached (not stored as a numeric interval). The abstract gives no hazard ratio or p value for overall survival. |
| Endpoint | Analysis | TIL therapy | Ipilimumab | Effect |
|---|---|---|---|---|
| PFSProgression-free survival | primaryRohaan 2022 | median 7.2 months (4.2–13.1) | median 3.1 months (3.0–4.3) | HR 0.50 (95% CI 0.35–0.72)P<0.001Hazard ratio is for progression or death. |
| ORRRandomised patients (84 per arm); the abstract states ITT for the PFS sentence in which these percentages appearObjective response (proportion of patients with an objective response) | primaryRohaan 2022 | 49% (38–60%) | 21% (13–32%) | — |
| OSRandomised patients; the abstract states ITT for PFS and does not repeat it for OSOverall survival (median) | primaryRohaan 2022 | median 25.8 months | median 18.9 months (13.8–32.6) | The 95% CI of the TIL median is 18.2 months to not reached (not stored as a numeric interval). The abstract gives no hazard ratio or p value for overall survival. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 0.5 | 0.35–0.72 |
- TIL therapy (experimental)
- Ipilimumab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | TIL therapy | Ipilimumab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 61.8% | 32.7% |
| 9 | 42.0% | 13.4% |
| 14 | 26.0% | 4.4% |
| 18 | 17.7% | 1.8% |
- TIL therapy (experimental)
- Ipilimumab (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | TIL therapy | Ipilimumab |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 16 | 65.1% | 55.6% |
| 32 | 42.3% | 30.9% |
| 48 | 27.5% | 17.2% |
| 65 | 17.4% | 9.2% |