Larotrectinib in TRK fusion-positive solid tumours: pooled adult phase 1, paediatric phase 1/2 (SCOUT) and adolescent/adult phase 2 (NAVIGATE) protocols
Phase 1/2NCT02122913NCT02637687NCT02576431
- Population
- TRK fusion-positive solid tumours in adults and children (17 unique tumour types in the first 55 patients); thyroid carcinoma subset analysed separately
- Design
- Three protocols analysed together: an adult phase 1 study, a paediatric phase 1-2 study and an adolescent/adult phase 2 study of larotrectinib in patients with consecutively and prospectively identified TRK fusion-positive cancers. Primary endpoint of the combined analysis: overall response rate by independent review (NEJM 2018). Later pooled analyses and a thyroid-specific analysis used investigator-assessed response.
- Primary endpoint
- ORR
- Arms
- Larotrectinib (experimental): Larotrectinib orally; adults mostly 100 mg twice daily, paediatric patients mostly 100 mg/m2 (maximum 100 mg) twice daily (Hong 2020 abstract)
- People
- Drilon A, senior author Hyman DM
Show the numbers
| Endpoint | Analysis | Larotrectinib | Control | Effect |
|---|---|---|---|---|
| ORRFirst 55 patients with TRK fusion-positive cancers of 17 tumour types (independent review) | primaryDrilon 2018 | 75% (61–85%) | — | 55 patients, ages 4 months to 76 years. Investigator-assessed response rate 80% (95% CI 67 to 90). |
| PFSFirst 55 patients with TRK fusion-positive cancers | primaryDrilon 2018 | 55% at 12 mo | — | 55% of patients remained progression-free at 1 year; 71% of responses were ongoing at 1 year. Median duration of response and median PFS had not been reached. |
| ORR159 patients enrolled; 153 evaluable (investigator assessment) | long term-updateHong 2020 | 79% (72–85%) | — | 121 of 153 evaluable patients responded, including 24 (16%) complete responses. Between May 2014 and February 2019, 159 patients were enrolled and treated. |
| ORRTRK fusion-positive thyroid carcinoma, evaluable patients (28 of 29 treated); investigator assessment, data cut-off July 2020 | exploratoryWaguespack 2022 | 71% (51–87%) | — | 29 patients treated: 20 papillary, 2 follicular, 7 anaplastic. Complete response in 2 and partial response in 18 of 28 evaluable patients. Pooled from NCT02576431, NCT02122913 and NCT02637687. |
| ORRTRK fusion-positive papillary or follicular thyroid carcinoma, evaluable patients | exploratoryWaguespack 2022 | 86% (64–97%) | — | Subset of the thyroid analysis. |
| ORRTRK fusion-positive anaplastic thyroid carcinoma, evaluable patients | exploratoryWaguespack 2022 | 29% (4–71%) | — | Subset of the thyroid analysis; 7 patients with anaplastic carcinoma were treated, so the interval is wide. |
| PFSTRK fusion-positive thyroid carcinoma (29 patients treated) | exploratoryWaguespack 2022 | 69% at 2 y | — | 24-month rates were 81% for duration of response, 69% for PFS and 76% for overall survival. |
| OSTRK fusion-positive thyroid carcinoma (29 patients treated) | exploratoryWaguespack 2022 | 76% at 2 y | — | 24-month overall survival rate. |
| Endpoint | Analysis | Larotrectinib | Control | Effect |
|---|---|---|---|---|
| ORRFirst 55 patients with TRK fusion-positive cancers of 17 tumour types (independent review) | primaryDrilon 2018 | 75% (61–85%) | — | 55 patients, ages 4 months to 76 years. Investigator-assessed response rate 80% (95% CI 67 to 90). |
| PFSFirst 55 patients with TRK fusion-positive cancers | primaryDrilon 2018 | 55% at 12 mo | — | 55% of patients remained progression-free at 1 year; 71% of responses were ongoing at 1 year. Median duration of response and median PFS had not been reached. |
| ORR159 patients enrolled; 153 evaluable (investigator assessment) | long term-updateHong 2020 | 79% (72–85%) | — | 121 of 153 evaluable patients responded, including 24 (16%) complete responses. Between May 2014 and February 2019, 159 patients were enrolled and treated. |
| ORRTRK fusion-positive thyroid carcinoma, evaluable patients (28 of 29 treated); investigator assessment, data cut-off July 2020 | exploratoryWaguespack 2022 | 71% (51–87%) | — | 29 patients treated: 20 papillary, 2 follicular, 7 anaplastic. Complete response in 2 and partial response in 18 of 28 evaluable patients. Pooled from NCT02576431, NCT02122913 and NCT02637687. |
| ORRTRK fusion-positive papillary or follicular thyroid carcinoma, evaluable patients | exploratoryWaguespack 2022 | 86% (64–97%) | — | Subset of the thyroid analysis. |
| ORRTRK fusion-positive anaplastic thyroid carcinoma, evaluable patients | exploratoryWaguespack 2022 | 29% (4–71%) | — | Subset of the thyroid analysis; 7 patients with anaplastic carcinoma were treated, so the interval is wide. |
| PFSTRK fusion-positive thyroid carcinoma (29 patients treated) | exploratoryWaguespack 2022 | 69% at 2 y | — | 24-month rates were 81% for duration of response, 69% for PFS and 76% for overall survival. |
| OSTRK fusion-positive thyroid carcinoma (29 patients treated) | exploratoryWaguespack 2022 | 76% at 2 y | — | 24-month overall survival rate. |
Appears in
Sources
Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, et al. Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med. 2018;378(8):731-739.
Hong DS, DuBois SG, Kummar S, Farago AF, Albert CM, Rohrberg KS, et al. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. 2020;21(4):531-540.
Waguespack SG, Drilon A, Lin JJ, Brose MS, McDermott R, Almubarak M, et al. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. Eur J Endocrinol. 2022;186(6):631-643.