DETERMINE
Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial
Phase 2N = 571NCT01843374
- Population
- Adults (18 years or older) with unresectable pleural or peritoneal malignant mesothelioma that had progressed after one or two previous systemic treatments for advanced disease; ECOG performance status 0 or 1; measurable disease by modified RECIST version 1.0 (pleural) or RECIST version 1.1 (peritoneal).
- Design
- Multicentre, international, double-blind, placebo-controlled phase 2b trial at 105 centres in 19 countries. Randomised 2:1 in blocks of three, stratified by EORTC status (low versus high risk), line of therapy (second versus third) and anatomic site (pleural versus peritoneal), to intravenous tremelimumab 10 mg/kg or placebo every 4 weeks for 7 doses and every 12 weeks thereafter until a discontinuation criterion was met. Primary endpoint overall survival in the ITT population; data cutoff 24 January 2016. Recruitment 17 May 2013 to 4 December 2014.
- Primary endpoint
- OS
- Arms
- Tremelimumab (experimental, n = 382): Tremelimumab 10 mg/kg every 4 weeks for 7 doses, then every 12 weeks
- Placebo (control, n = 189): Placebo on the same schedule
- People
- Maio M
OSHR 0.92 (95% CI 0.76–1.12)Δ median OS+0.4 months
Show the numbers
| Endpoint | Analysis | Tremelimumab | Placebo | Effect |
|---|---|---|---|---|
| OS | primaryMaio 2017 | median 7.7 months (6.8–8.9) | median 7.3 months (5.9–8.7) | HR 0.92 (95% CI 0.76–1.12)P=0.41At the cutoff, 307 of 382 (80%) patients in the tremelimumab group and 154 of 189 (81%) in the placebo group had died. Treatment-emergent adverse events of grade 3 or worse occurred in 246 of 380 (65%) patients with tremelimumab and 91 of 189 (48%) with placebo (the most common were dyspnoea in 34 (9%) patients with tremelimumab versus 27 (14%) with placebo, diarrhoea in 58 (15%) versus one (<1%), and colitis in 26 (7%) versus none). Treatment-emergent events leading to death occurred in 36 (9%) of 380 patients with tremelimumab and 12 (6%) of 189 with placebo; treatment-related adverse events leading to death occurred in five (1%) patients in the tremelimumab group and none in the placebo group. |
| Endpoint | Analysis | Tremelimumab | Placebo | Effect |
|---|---|---|---|---|
| OS | primaryMaio 2017 | median 7.7 months (6.8–8.9) | median 7.3 months (5.9–8.7) | HR 0.92 (95% CI 0.76–1.12)P=0.41At the cutoff, 307 of 382 (80%) patients in the tremelimumab group and 154 of 189 (81%) in the placebo group had died. Treatment-emergent adverse events of grade 3 or worse occurred in 246 of 380 (65%) patients with tremelimumab and 91 of 189 (48%) with placebo (the most common were dyspnoea in 34 (9%) patients with tremelimumab versus 27 (14%) with placebo, diarrhoea in 58 (15%) versus one (<1%), and colitis in 26 (7%) versus none). Treatment-emergent events leading to death occurred in 36 (9%) of 380 patients with tremelimumab and 12 (6%) of 189 with placebo; treatment-related adverse events leading to death occurred in five (1%) patients in the tremelimumab group and none in the placebo group. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.92 | 0.76–1.12 |
- Tremelimumab (experimental)
- Placebo (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Tremelimumab | Placebo |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 5 | 63.8% | 62.2% |
| 10 | 40.6% | 38.7% |
| 14 | 28.4% | 26.5% |
| 19 | 18.1% | 16.5% |
Appears in
Sources
Maio M, Scherpereel A, Calabrò L, Aerts J, Perez SC, Bearz A, et al. Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial. Lancet Oncol. 2017;18(9):1261-1273.