SECOMBIT
Sequential Combo Immuno and Target Therapy (SECOMBIT) Study
Phase 2N = 209NCT02631447
- Population
- Untreated metastatic BRAF V600-mutant melanoma; 209 patients randomised
- Design
- Randomised, three-arm, noncomparative phase 2 trial in 37 sites in nine countries: arm A encorafenib plus binimetinib until progression, then ipilimumab plus nivolumab; arm B ipilimumab plus nivolumab until progression, then encorafenib plus binimetinib; arm C encorafenib plus binimetinib for 8 weeks, then ipilimumab plus nivolumab until progression, then encorafenib plus binimetinib. Primary end point overall survival at 2 years, tested against a null hypothesis of median overall survival of 15 months or less. The registry record lists 251 enrolled; the paper randomised 209 (69, 71, 69). All three arms are typed 'experimental' because the trial is noncomparative and the abstracts name no control arm.
- Primary endpoint
- OS
- Arms
- Targeted therapy first (arm A) (experimental, n = 69): Encorafenib 450 mg once daily plus binimetinib 45 mg twice daily until progression, then ipilimumab 3 mg per kilogram plus nivolumab 1 mg per kilogram every 3 weeks for four cycles, then nivolumab 3 mg per kilogram every 2 weeks
- Immunotherapy first (arm B) (experimental, n = 71): Ipilimumab plus nivolumab until progression, then encorafenib plus binimetinib
- Targeted induction then immunotherapy (arm C) (experimental, n = 69): Encorafenib plus binimetinib for 8 weeks, then ipilimumab plus nivolumab until progression, then encorafenib plus binimetinib
- People
- Ascierto PA, senior author Chiarion Sileni V
Show the numbers
| Endpoint | Analysis | Targeted therapy first (arm A) / Immunotherapy first (arm B) / Targeted induction then immunotherapy (arm C) | Control | Effect |
|---|---|---|---|---|
| OSIntention-to-treat population (209 randomised) | primarymedian follow-up 32.2 monthsAscierto 2023 | 65% at 2 y (54–76%); 54% at 3 y (41–67%) | — | Noncomparative design: no between-arm test. Median overall survival was not reached in any arm; the primary end point was met in all arms against a null hypothesis of a median of 15 months or less. The abstract prints '58 to 72' as the 95% CI of the arm C 3-year rate (60%); an interval that sits 2 points below and 12 points above the estimate looks inconsistent with n=69, so it is not recorded pending the full text. |
| Endpoint | Analysis | Targeted therapy first (arm A) / Immunotherapy first (arm B) / Targeted induction then immunotherapy (arm C) | Control | Effect |
|---|---|---|---|---|
| OSIntention-to-treat population (209 randomised) | primarymedian follow-up 32.2 monthsAscierto 2023 | 65% at 2 y (54–76%); 54% at 3 y (41–67%) | — | Noncomparative design: no between-arm test. Median overall survival was not reached in any arm; the primary end point was met in all arms against a null hypothesis of a median of 15 months or less. The abstract prints '58 to 72' as the 95% CI of the arm C 3-year rate (60%); an interval that sits 2 points below and 12 points above the estimate looks inconsistent with n=69, so it is not recorded pending the full text. |
- Targeted therapy first (arm A) (experimental)
- Immunotherapy first (arm B) (experimental)
- Targeted induction then immunotherapy (arm C) (experimental)
Data table (modelled values)
| Months | Targeted therapy first (arm A) | Immunotherapy first (arm B) | Targeted induction then immunotherapy (arm C) |
|---|---|---|---|
| 0 | 100.0% | 100.0% | 100.0% |
| 10 | 84.8% | 88.5% | 86.4% |
| 19 | 71.4% | 78.3% | 74.6% |
| 29 | 60.0% | 68.2% | 64.8% |
| 39 | 54.0% | 62.0% | 60.0% |
Appears in
Sources
Ascierto PA, Mandalà M, Ferrucci PF, Guidoboni M, Rutkowski P, Ferraresi V, et al. Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial. J Clin Oncol. 2023;41(2):212-221.