Evidenzprofil_LIBRETTO-001_Selpercatinib
Lungenkarzinom · Version 5.1
| 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) (NCT03157128) | |||||
| Short Name | Design | Population | Intervention | Comparator | Outcomes |
|---|---|---|---|---|---|
| LIBRETTO-001 17477, J2G-OX-JZJA, LOXO-RET-17001, 2017-000800-59 |
N/a (not applicable), Single Group Assignment, Phase 1,Phase 2 Open Label study | Patients with Stage 3-4 and ECOG 0-2 Non-Small Cell Lung Cancer | 1. LOXO-292 (N=0)1 2. Selpercatinib RET fusion+ NSCLC (N=253)2 3. Selpercatinib RET fusion+ NSCLC and intracranial metastases (N=80)3 4. Selpercatinib RET fusion+ NSCLC and intracranial metastases and measurable CNS disease (N=22)4 5. Selpercatinib RET fusion+ NSCLC and intracranial metastases and non-measurable CNS disease (N=58)5 |
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| Levels of Evidence | |||||
| GRADE | ⊕⊖⊖⊖a,b,c | We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. | |||
| 1: Phase 1 - Multiple doses of LOXO-292 (selpercatinib) Phase 2 - The maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D); 2: Phase 2 - 160 milligrams (mg) Selpercatinib twice a day (BID) for patients with RET fusion+ and NSCLC; 3: Phase 2 - 160 milligrams (mg) Selpercatinib twice a day (BID) for patients with RET fusion+ and NSCLC and intracranial metastases; 4: Phase 2 - 160 milligrams (mg) Selpercatinib twice a day (BID) for patients with RET fusion+ and NSCLC and intracranial metastases and measurable CNS disease; 5: Phase 2 - 160 milligrams (mg) Selpercatinib twice a day (BID) for patients with RET fusion+ and NSCLC and intracranial metastases and non-measurable CNS disease | |||||
| a: Open Label Study;b: Non-randomized Study;c: Studydesign - Phase II | |||||
| Outcome | Selpercatinib RET fusion+ NSCLC and intracranial metastases N=80 |
GRADE | |
|---|---|---|---|
| Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Patients with RET fusion-positive NSCLC with intracranial metastses: Subbiah, V 2021. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial.. ; 27 (15); 4160-4167* | |||
| Dichotomous Outcomes | |||
| PFS - Time To Event | N=80 | 13.7 [10.9; ] | ⊕⊖⊖⊖a |
| IC-DOR - None | N=80 | [9.3; ] | ⊕⊖⊖⊖ |
| IC-ORR - TuDD | N=80 | 38 (47.5%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3)1 | N=80 | 9 (11.25%) | ⊕⊖⊖⊖ |
| AE (Any)2 | N=80 | 38 (47.5%) | ⊕⊖⊖⊖ |
| AE (Any)3 | N=80 | 38 (47.5%) | ⊕⊖⊖⊖ |
| AE (Any)4 | N=80 | 31 (38.75%) | ⊕⊖⊖⊖ |
| AE (Any)5 | N=80 | 31 (38.75%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3)5 | N=80 | 9 (11.25%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3)4 | N=80 | 14 (17.5%) | ⊕⊖⊖⊖ |
| AE (CTCAE ≥3)6 | N=80 | 17 (21.25%) | ⊕⊖⊖⊖ |
| TAE (CTCAE ≥3)6 | N=80 | 13 (16.25%) | ⊕⊖⊖⊖ |
| TAE (Any)3 | N=80 | 35 (43.75%) | ⊕⊖⊖⊖ |
| TAE (Any)4 | N=80 | 25 (31.25%) | ⊕⊖⊖⊖ |
| TAE (CTCAE ≥3)4 | N=80 | 11 (13.75%) | ⊕⊖⊖⊖ |
| TAE (Any)5 | N=80 | 23 (28.75%) | ⊕⊖⊖⊖ |
| TAE (CTCAE ≥3)5 | N=80 | 7 (8.75%) | ⊕⊖⊖⊖ |
| TAE-D (Any) | N=80 | 0 (0%) | ⊕⊖⊖⊖ |
| TAE-Disc (Any) | N=80 | 2 (2.5%) | ⊕⊖⊖⊖ |
| Outcome | Selpercatinib RET fusion+ NSCLC and intracranial metastases and measurable CNS disease N=22 |
GRADE | |
| Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Patients with RET fusion-positive NSCLC with intracranial metastses and measurable CNS disease: Subbiah, V 2021. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial.. ; 27 (15); 4160-4167** | |||
| Dichotomous Outcomes | |||
| IC-ORR - TuDD | N=22 | 18 (81.82%) | ⊕⊖⊖⊖ |
| Outcome | Selpercatinib RET fusion+ NSCLC and intracranial metastases and non-measurable CNS disease N=58 |
GRADE | |
| Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Patients with RET fusion-positive NSCLC with intracranial metastses and non-measurable CNS disease: Subbiah, V 2021. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial.. ; 27 (15); 4160-4167*** | |||
| Dichotomous Outcomes | |||
| IC-ORR - TuDD | N=58 | 20 (34.48%) | ⊕⊖⊖⊖ |
| Outcome | Selpercatinib RET fusion+ NSCLC N=253 |
GRADE | |
| Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial. Patients with RET fusion-positive NSCLC: Subbiah, V 2021. Intracranial Efficacy of Selpercatinib in RET Fusion-Positive Non-Small Cell Lung Cancers on the LIBRETTO-001 Trial.. ; 27 (15); 4160-4167**** | |||
| Dichotomous Outcomes | |||
| AE (Any)2 | N=253 | 111 (43.87%) | ⊕⊖⊖⊖ |
| AE (Any)3 | N=253 | 102 (40.32%) | ⊕⊖⊖⊖ |
| AE (Any)5 | N=253 | 85 (33.6%) | ⊕⊖⊖⊖ |
| TAE (Any)5 | N=253 | 69 (27.27%) | ⊕⊖⊖⊖ |
| TAE (Any)3 | N=253 | 91 (35.97%) | ⊕⊖⊖⊖ |
| TAE (Any)2 | N=253 | 66 (26.09%) | ⊕⊖⊖⊖ |
| *Database cutoff: 15.12.2019 **Database cutoff: 15.12.2019 ***Database cutoff: 15.12.2019 ****Database cutoff: 15.12.2019 |
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| 1: Hyponatraemia; 2: Diarrhoea; 3: Dry mouth; 4: Alanine aminotransferase increased; 5: Aspartate aminotransferase increased; 6: Hypertension | |||
| a: Missing individual analysis of combined endpoint componenets (progression) | |||
| AE: Adverse Events; Any: Any Grade; CTCAE ≥3: Common Terminology Criteria for Adverse Events, Grade ≥3; IC-DOR: Intracranial Duration Of Response; IC-ORR: Intracranial Objective Response Rate; PFS: Progression-Free Survival; TAE: Treatment-related Adverse Events; TAE-D: Treatment-related Adverse Events Leading to Death; TAE-Disc: Treatment-related Adverse Events Leading to Treatment Discontinuation; TuDD: Time to Definitive Deterioration | |||