Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT03157128 | A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001) | PHASE1 | ACTIVE NOT_RECRUITING | 857 | — | — | May 2, 2017 | Feb 1, 2027 | Apr 16, 2026 | 85 | United States, Australia +14 |
The MTD is defined as the highest dose level at which none of the first 3 treated patients, or not more than 1 of the first 6 treated patients, experiences a DLT. A DLT is any adverse events that starts on or after first administration of study drug, as defined by National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. * Any Grade(G) ≥3 nonhematologic toxicity, excluding * G3 AST, ALT, and/or total bilirubin elevation for \<7 days. * G3 neutropenia \<7 days * G3 thrombocytopenia without clinically significant bleeding * G3 or G4 lymphopenia. * First occurrence of G3 or G4 electrolyte abnormalities * G3 fatigue, weakness, nausea; other manageable constitutional symptom * G3 or G4 vomiting or diarrhea that lasts for \<48hours with antiemetic/antidiarrheal medication in case of G3 and \<24 hours in case of G4 * G4 manageable constitutional symptom.
Phase 1: RP2D
Objective Response Rate was defined as the percentage of participants with best overall response of confirmed response (CR), or Partial response (PR). Response was confirmed by a repeat assessment no less than 28 days. * CR is defined as disappearance of all target lesions. * PR is defined as at least a 30% decrease in the sum of diameter (LD for non-nodal lesions and short axis diameter \[SAD\] for nodal lesions) of target lesions, taking as reference the baseline sum LD. ORR was assessed by independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. 95% confidence interval was calculated using Clopper-Pearson method.
| Arm | Type | Description |
|---|---|---|
| Phase 1: 20 mg Selpercatinib QD | EXPERIMENTAL | Participants received Selpercatinib 20 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 20 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 20 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 40 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 40 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 60 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 60 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 160 mg Selpercatinib QD | EXPERIMENTAL | Participants received Selpercatinib 160 milligrams (mg) administered orally once daily (QD), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 80 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 80 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 120 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 120 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 160 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 200 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 200 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 1: 240 mg Selpercatinib BID | EXPERIMENTAL | Participants received Selpercatinib 240 milligrams (mg) administered orally twice daily (BID), in a 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 1: RET Fusion Solid Tumor | EXPERIMENTAL | Participants with Rearranged during transfection (RET) Fusion solid tumor progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 2: RET Fusion Solid Tumor Without Standard Therapy | EXPERIMENTAL | Participants with RET Fusion solid tumor without standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 3: RET Mutant MTC | EXPERIMENTAL | Participants with RET mutant medullary thyroid cancer (MTC) progressed on/intolerant to standard first line therapy received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 4: RET Mutant MTC Without Standard Therapy | EXPERIMENTAL | Participants with RET mutant MTC without prior standard first line therapy or other kinase inhibitor(s) with anti-RET activity received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 5: Advanced RET Altered Solid Tumor | EXPERIMENTAL | Participants with RET altered solid tumor (cohorts 1-4, disease not measurable; MTC not eligible for Cohort 3 or 4; MTC syndrome spectrum cancer; circulating free tumor DNA \[cfDNA+\] for RET alteration not known to be present in tumor) received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Phase 2, Cohort 6: RET Inhibitor-Discontinued Participants | EXPERIMENTAL | Participants otherwise eligible for Cohorts 1-5 who discontinued other RET inhibitors received Selpercatinib 160 milligrams (mg) administered orally twice daily (BID), in a continuous 28-day treatment cycle. Treatment was continued until disease progression, unacceptable toxicity, or treatment discontinuation for other reasons. |
| Name | Type | Description |
|---|---|---|
| LOXO-292 | DRUG | Oral LOXO-292 |
Key Inclusion Criteria: For Phase 1: * Participants with a locally advanced or metastatic solid tumor that: * Has progressed on or is intolerant to standard therapy, or * For which no standard therapy exists, or in the opinion of the Investigator, are not candidates for or would be unlikely to tol...