LIBRETTO-001
A Phase 1/2 Study of Oral Selpercatinib (LOXO-292) in Patients With Advanced Solid Tumors, Including RET Fusion-Positive Solid Tumors, Medullary Thyroid Cancer, and Other Tumors With RET Activation (LIBRETTO-001)
Phase 1/2NCT03157128
- Population
- Advanced RET-mutant medullary thyroid cancer (with or without previous vandetanib or cabozantinib) and previously treated RET fusion-positive thyroid cancer; the 2024 update adds treatment-naive RET fusion-positive thyroid cancer
- Design
- Phase 1-2, single-arm, open-label trial of selpercatinib; this record covers the thyroid cancer cohorts. Phase 2 patients received the recommended dose of 160 mg twice daily. Primary endpoint objective response (complete or partial) determined by an independent review committee; secondary endpoints included duration of response, progression-free survival and safety. Cohort sizes are recorded on each result.
- Primary endpoint
- ORR
- Arms
- Selpercatinib (experimental): Selpercatinib 160 mg orally twice daily (recommended phase 2 dose, per the full text of the 2020 report)
- People
- Wirth LJ, senior author Cabanillas ME
Show the numbers
| Endpoint | Analysis | Selpercatinib | Control | Effect |
|---|---|---|---|---|
| ORRRET-mutant medullary thyroid cancer previously treated with vandetanib, cabozantinib or both: first 55 consecutively enrolled patients | primaryWirth 2020 | 69% (55–81%) | — | 55 patients. Response determined by independent review committee. Full text: complete response in 5 patients (9%) and partial response in 33 (60%); the data cut was 16 December 2019 (full text, Statistical Considerations). |
| PFSRET-mutant medullary thyroid cancer previously treated with vandetanib, cabozantinib or both (55 patients) | primaryWirth 2020 | 82% at 12 mo (69–90%) | — | Progression-free survival at 1 year. |
| ORRRET-mutant medullary thyroid cancer not previously treated with vandetanib or cabozantinib (88 patients) | primaryWirth 2020 | 73% (62–82%) | — | 88 patients. Efficacy in this cohort was prespecified as exploratory (full text, Statistical Considerations). |
| PFSRET-mutant medullary thyroid cancer not previously treated with vandetanib or cabozantinib (88 patients) | primaryWirth 2020 | 92% at 12 mo (82–97%) | — | Progression-free survival at 1 year. |
| ORRPreviously treated RET fusion-positive thyroid cancer (19 patients) | primaryWirth 2020 | 79% (54–94%) | — | 19 patients; histologies included papillary, poorly differentiated, anaplastic and Hurthle cell carcinomas (full text). Efficacy in this cohort was prespecified as exploratory. |
| PFSPreviously treated RET fusion-positive thyroid cancer (19 patients) | primaryWirth 2020 | 64% at 12 mo (37–82%) | — | Progression-free survival at 1 year. |
| ORRRET-mutant medullary thyroid cancer, cabozantinib/vandetanib-naive (143 patients) | long term-updateWirth 2024 | 82.5% (75.3–88.4%) | — | 143 patients; independent review committee. Complete response in 34 patients (23.8%). |
| PFSRET-mutant medullary thyroid cancer, cabozantinib/vandetanib-naive (143 patients) | long term-updatemedian follow-up 42.4 monthsWirth 2024 | 75.2% at 3 y (66.8–81.8%) | — | 143 patients. Median PFS not reached (95% CI lower bound 53.1 months, upper bound not estimable). |
| ORRRET-mutant medullary thyroid cancer previously treated with a multikinase inhibitor (152 patients) | long term-updateWirth 2024 | 77.6% (70.2–84.0%) | — | 152 patients. Complete response in 19 patients (12.5%). |
| PFSRET-mutant medullary thyroid cancer previously treated with a multikinase inhibitor (152 patients) | long term-updatemedian follow-up 44 monthsWirth 2024 | median 41.4 months; 54.6% at 3 y (45.6–62.8%) | — | 152 patients. The upper limit of the 95% CI for the median (30.2 to not estimable) cannot be recorded as a number. |
| ORRRET fusion-positive thyroid cancer, treatment-naive (24 patients; therapies other than radioactive iodine counted) | long term-updateWirth 2024 | 95.8% (78.9–99.9%) | — | 24 patients; histologically mixed thyroid cancers. |
| PFSRET fusion-positive thyroid cancer, treatment-naive (24 patients) | long term-updatemedian follow-up 24.9 monthsWirth 2024 | 87.3% at 3 y (56.4–96.8%) | — | 24 patients. Median PFS not reached (95% CI lower bound 44.2 months). |
| ORRRET fusion-positive thyroid cancer, previously treated (41 patients) | long term-updateWirth 2024 | 85.4% (70.8–94.4%) | — | 41 patients. |
| PFSRET fusion-positive thyroid cancer, previously treated (41 patients) | long term-updatemedian follow-up 30.4 monthsWirth 2024 | median 27.4 months; 49.5% at 3 y (31.1–65.4%) | — | 41 patients. The 95% CI for the median (14.5 to not estimable) cannot be recorded as a number. |
| Endpoint | Analysis | Selpercatinib | Control | Effect |
|---|---|---|---|---|
| ORRRET-mutant medullary thyroid cancer previously treated with vandetanib, cabozantinib or both: first 55 consecutively enrolled patients | primaryWirth 2020 | 69% (55–81%) | — | 55 patients. Response determined by independent review committee. Full text: complete response in 5 patients (9%) and partial response in 33 (60%); the data cut was 16 December 2019 (full text, Statistical Considerations). |
| PFSRET-mutant medullary thyroid cancer previously treated with vandetanib, cabozantinib or both (55 patients) | primaryWirth 2020 | 82% at 12 mo (69–90%) | — | Progression-free survival at 1 year. |
| ORRRET-mutant medullary thyroid cancer not previously treated with vandetanib or cabozantinib (88 patients) | primaryWirth 2020 | 73% (62–82%) | — | 88 patients. Efficacy in this cohort was prespecified as exploratory (full text, Statistical Considerations). |
| PFSRET-mutant medullary thyroid cancer not previously treated with vandetanib or cabozantinib (88 patients) | primaryWirth 2020 | 92% at 12 mo (82–97%) | — | Progression-free survival at 1 year. |
| ORRPreviously treated RET fusion-positive thyroid cancer (19 patients) | primaryWirth 2020 | 79% (54–94%) | — | 19 patients; histologies included papillary, poorly differentiated, anaplastic and Hurthle cell carcinomas (full text). Efficacy in this cohort was prespecified as exploratory. |
| PFSPreviously treated RET fusion-positive thyroid cancer (19 patients) | primaryWirth 2020 | 64% at 12 mo (37–82%) | — | Progression-free survival at 1 year. |
| ORRRET-mutant medullary thyroid cancer, cabozantinib/vandetanib-naive (143 patients) | long term-updateWirth 2024 | 82.5% (75.3–88.4%) | — | 143 patients; independent review committee. Complete response in 34 patients (23.8%). |
| PFSRET-mutant medullary thyroid cancer, cabozantinib/vandetanib-naive (143 patients) | long term-updatemedian follow-up 42.4 monthsWirth 2024 | 75.2% at 3 y (66.8–81.8%) | — | 143 patients. Median PFS not reached (95% CI lower bound 53.1 months, upper bound not estimable). |
| ORRRET-mutant medullary thyroid cancer previously treated with a multikinase inhibitor (152 patients) | long term-updateWirth 2024 | 77.6% (70.2–84.0%) | — | 152 patients. Complete response in 19 patients (12.5%). |
| PFSRET-mutant medullary thyroid cancer previously treated with a multikinase inhibitor (152 patients) | long term-updatemedian follow-up 44 monthsWirth 2024 | median 41.4 months; 54.6% at 3 y (45.6–62.8%) | — | 152 patients. The upper limit of the 95% CI for the median (30.2 to not estimable) cannot be recorded as a number. |
| ORRRET fusion-positive thyroid cancer, treatment-naive (24 patients; therapies other than radioactive iodine counted) | long term-updateWirth 2024 | 95.8% (78.9–99.9%) | — | 24 patients; histologically mixed thyroid cancers. |
| PFSRET fusion-positive thyroid cancer, treatment-naive (24 patients) | long term-updatemedian follow-up 24.9 monthsWirth 2024 | 87.3% at 3 y (56.4–96.8%) | — | 24 patients. Median PFS not reached (95% CI lower bound 44.2 months). |
| ORRRET fusion-positive thyroid cancer, previously treated (41 patients) | long term-updateWirth 2024 | 85.4% (70.8–94.4%) | — | 41 patients. |
| PFSRET fusion-positive thyroid cancer, previously treated (41 patients) | long term-updatemedian follow-up 30.4 monthsWirth 2024 | median 27.4 months; 49.5% at 3 y (31.1–65.4%) | — | 41 patients. The 95% CI for the median (14.5 to not estimable) cannot be recorded as a number. |
- Selpercatinib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Selpercatinib |
|---|---|
| 0 | 100.0% |
| 26 | 64.7% |
| 52 | 41.9% |
| 78 | 27.1% |
| 104 | 17.5% |
- Selpercatinib (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Selpercatinib |
|---|---|
| 0 | 100.0% |
| 17 | 65.0% |
| 34 | 42.3% |
| 51 | 27.5% |
| 69 | 17.5% |
Appears in
Sources
Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, et al. Efficacy of Selpercatinib in RET-Altered Thyroid Cancers. N Engl J Med. 2020;383(9):825-835.
Wirth LJ, Brose MS, Subbiah V, Worden F, Solomon B, Robinson B, et al. Durability of Response With Selpercatinib in Patients With RET-Activated Thyroid Cancer: Long-Term Safety and Efficacy From LIBRETTO-001. J Clin Oncol. 2024;42(27):3187-3195.