IMCgp100-202
Tebentafusp versus investigator's choice in HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma (IMCgp100-202)
Phase 3N = 378NCT03070392
- Population
- Previously untreated HLA-A*02:01-positive patients with metastatic uveal melanoma.
- Design
- Open-label, randomised phase 3 trial (as described in the NEJM abstracts); randomisation 2:1, stratified by lactate dehydrogenase level.
- Primary endpoint
- OS
- Arms
- Tebentafusp (experimental, n = 252): Tebentafusp
- Investigator's choice (control, n = 126): Single-agent pembrolizumab, ipilimumab or dacarbazine, as chosen by the investigator (assigned: pembrolizumab 103 [82%], ipilimumab 16 [13%], dacarbazine 7 [6%], per the 3-year report)
- People
- Nathan P, IMCgp100-202 Investigators
OSHR 0.51 (95% CI 0.37–0.71)Δ 12-month OS+14 pointsPFSHR 0.73 (95% CI 0.58–0.94)Δ 6-month PFS+12 pointsOSHR 0.68 (95% CI 0.54–0.87)Δ median OS+4.7 months
Show the numbers
| Endpoint | Analysis | Tebentafusp | Investigator's choice | Effect |
|---|---|---|---|---|
| OSOverall survival at 1 year (primary analysis) | primaryNathan 2021 | 73% at 12 mo | 59% at 12 mo | HR 0.51 (95% CI 0.37–0.71)P<0.001Hazard ratio is for death. Per the 3-year report, this primary analysis was the prespecified first interim analysis (data cutoff 13 October 2020, 150 deaths), which crossed the prespecified OS boundary. |
| PFSProgression-free survival at 6 months | primaryNathan 2021 | 31% at 6 mo | 19% at 6 mo | HR 0.73 (95% CI 0.58–0.94)P=0.01Hazard ratio is for disease progression or death. OS was the primary endpoint; the 3-year report (full text) describes PFS at the time of the primary analysis as the hierarchical secondary end point. |
| OSITT (the 3-year report's full text states the exploratory efficacy analyses were in the intention-to-treat population)Overall survival, median and at 3 years (minimum follow-up 36 months) | long term-updateHassel 2023 | median 21.6 months (19.0–24.3); 27% at 3 y | median 16.9 months (12.9–19.5); 18% at 3 y | HR 0.68 (95% CI 0.54–0.87)Minimum follow-up 36 months. Hazard ratio is for death (stratified). The 3-year report describes its efficacy analyses as exploratory; it gives no P value for this comparison. Medians' 95% CIs are from the full text. Estimated overall survival in the full text at 1, 2 and 3 years: 72%, 45%, 27% with tebentafusp and 60%, 30%, 18% with control. |
| Endpoint | Analysis | Tebentafusp | Investigator's choice | Effect |
|---|---|---|---|---|
| OSOverall survival at 1 year (primary analysis) | primaryNathan 2021 | 73% at 12 mo | 59% at 12 mo | HR 0.51 (95% CI 0.37–0.71)P<0.001Hazard ratio is for death. Per the 3-year report, this primary analysis was the prespecified first interim analysis (data cutoff 13 October 2020, 150 deaths), which crossed the prespecified OS boundary. |
| PFSProgression-free survival at 6 months | primaryNathan 2021 | 31% at 6 mo | 19% at 6 mo | HR 0.73 (95% CI 0.58–0.94)P=0.01Hazard ratio is for disease progression or death. OS was the primary endpoint; the 3-year report (full text) describes PFS at the time of the primary analysis as the hierarchical secondary end point. |
| OSITT (the 3-year report's full text states the exploratory efficacy analyses were in the intention-to-treat population)Overall survival, median and at 3 years (minimum follow-up 36 months) | long term-updateHassel 2023 | median 21.6 months (19.0–24.3); 27% at 3 y | median 16.9 months (12.9–19.5); 18% at 3 y | HR 0.68 (95% CI 0.54–0.87)Minimum follow-up 36 months. Hazard ratio is for death (stratified). The 3-year report describes its efficacy analyses as exploratory; it gives no P value for this comparison. Medians' 95% CIs are from the full text. Estimated overall survival in the full text at 1, 2 and 3 years: 72%, 45%, 27% with tebentafusp and 60%, 30%, 18% with control. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.51 | 0.37–0.71 |
| PFS | 0.73 | 0.58–0.94 |
| OS | 0.68 | 0.54–0.87 |
- Tebentafusp (experimental)
- Investigator's choice (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Tebentafusp | Investigator's choice |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 14 | 63.8% | 56.3% |
| 27 | 42.0% | 33.0% |
| 41 | 26.8% | 18.6% |
| 54 | 17.7% | 10.9% |
Appears in
Sources
Nathan P, Hassel JC, Rutkowski P, Baurain JF, Butler MO, Schlaak M, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021;385(13):1196-1206.
Hassel JC, Piperno-Neumann S, Rutkowski P, Baurain JF, Schlaak M, Butler MO, et al. Three-Year Overall Survival with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2023;389(24):2256-2266.