OPTIC
Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial
Phase 2N = 283NCT02467270
- Population
- Adults with CP-CML resistant to or intolerant of at least 2 prior BCR-ABL1 TKIs, or with a BCR-ABL1 T315I mutation
- Design
- Randomized (1:1:1), open-label phase 2 trial of ponatinib starting doses of 45, 30 or 15 mg once daily; in the 45 mg and 30 mg cohorts the dose was reduced to 15 mg upon response (BCR-ABL1 IS transcript levels of 1% or less). The primary end point was response at 12 months.
- Primary endpoint
- BCR-ABL1 ≤1% (IS)
- Arms
- Ponatinib 45 mg starting dose (experimental, n = 94): Ponatinib 45 mg once daily, reduced to 15 mg on response
- Ponatinib 30 mg starting dose (experimental, n = 95): Ponatinib 30 mg once daily, reduced to 15 mg on response
- Ponatinib 15 mg (experimental, n = 94): Ponatinib 15 mg once daily
- People
- Cortes J, senior author Deininger M
Show the numbers
| Endpoint | Analysis | Ponatinib 45 mg starting dose / Ponatinib 30 mg starting dose / Ponatinib 15 mg | Control | Effect |
|---|---|---|---|---|
| BCR-ABL1 ≤1% (IS)Intention-to-treat as defined in the primary report: randomly assigned patients for whom BCR-ABL1 IS could be measured (denominators not stated in the abstract; 283 randomized, 282 treated, 94 treated per dose group)Response at 12 months (primary end point): BCR-ABL1 IS transcript levels of 1% or less | primaryCortes 2021 | 44.1% | — | The published intervals are 98.3% confidence intervals, not 95%: 31.7 to 57.0 (45 mg), 18.4 to 41.6 (30 mg) and 13.4 to 35.3 (15 mg). The trial's own conclusion was that optimal benefit and risk occurred with the 45 mg starting dose reduced to 15 mg on response; no between-arm test is reported in the abstract. |
| BCR-ABL1 ≤1% (IS)Intention-to-treat as defined in the 5-year report: randomized patients with e13a2/e14a2 transcripts at baseline (BCR-ABL1 IS measurable); cumulative rates by 5 yearsProportion achieving BCR-ABL1 IS of 1% or less by 5 years | long term-updateKantarjian 2026 | 60% at 5 y | — | Median follow-up 75 to 78 months. |
| PFSAll randomized patients (283), per the 5-year report (survival outcomes were analysed in all randomized patients)Five-year progression-free survival rate | long term-updateKantarjian 2026 | 63% at 5 y | — | Overall survival rates exceeded 80% (per-cohort values not given in the abstract). |
| Endpoint | Analysis | Ponatinib 45 mg starting dose / Ponatinib 30 mg starting dose / Ponatinib 15 mg | Control | Effect |
|---|---|---|---|---|
| BCR-ABL1 ≤1% (IS)Intention-to-treat as defined in the primary report: randomly assigned patients for whom BCR-ABL1 IS could be measured (denominators not stated in the abstract; 283 randomized, 282 treated, 94 treated per dose group)Response at 12 months (primary end point): BCR-ABL1 IS transcript levels of 1% or less | primaryCortes 2021 | 44.1% | — | The published intervals are 98.3% confidence intervals, not 95%: 31.7 to 57.0 (45 mg), 18.4 to 41.6 (30 mg) and 13.4 to 35.3 (15 mg). The trial's own conclusion was that optimal benefit and risk occurred with the 45 mg starting dose reduced to 15 mg on response; no between-arm test is reported in the abstract. |
| BCR-ABL1 ≤1% (IS)Intention-to-treat as defined in the 5-year report: randomized patients with e13a2/e14a2 transcripts at baseline (BCR-ABL1 IS measurable); cumulative rates by 5 yearsProportion achieving BCR-ABL1 IS of 1% or less by 5 years | long term-updateKantarjian 2026 | 60% at 5 y | — | Median follow-up 75 to 78 months. |
| PFSAll randomized patients (283), per the 5-year report (survival outcomes were analysed in all randomized patients)Five-year progression-free survival rate | long term-updateKantarjian 2026 | 63% at 5 y | — | Overall survival rates exceeded 80% (per-cohort values not given in the abstract). |
Appears in
Sources
Cortes J, Apperley J, Lomaia E, Moiraghi B, Undurraga Sutton M, Pavlovsky C, et al. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial. Blood. 2021;138(21):2042-2050.
Kantarjian H, Deininger M, Apperley JF, Arthur CK, Chuah C, Hochhaus A, et al. Five-year follow-up of OPTIC: long-term efficacy, safety, and mutation analyses of ponatinib in chronic-phase chronic myeloid leukemia from a randomized phase 2 trial. Leukemia. 2026;40(9):1882-1892.