Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication RETEVMO ® is a kinase inhibitor indicated for the treatment of: Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test ( 1.1 ) Adult and pediatric patients 2 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved… FDA label
Also known as [14C]-Selpercatinib, LY3527723, LOXO-292
Selpercatinib · 6 trials · 10 indications
EFS by Investigator Assessment in the Primary Analysis Population
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.
PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, or death from any cause in the absence of BICR-documented progressive disease. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.
ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.
A DLT was any of the adverse events that starts on or after the first administration of study drug listed below, as defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. * Any Grade(G) ≥3 nonhematologic toxicity except G3 fatigue, nausea, tendon reflex decrease, weight gain attributable to normal growth and development. * G3 vomiting/diarrhea was DLT only if it persists \>48 h despite standard of care treatment. * G4 vomiting/diarrhea was DLT regardless of duration. * Any toxicity, regardless of the NCI CTCAE v5.0 grade, resulting in discontinuation or dose reduction of treatment (except symptoms related to progressive disease (PD)). * G4/G3 thrombocytopenia with G1 or higher bleeding. * G4 anemia lasting \>8 days, despite supportive therapy. * G4 neutropenia, lasting \>8 days, despite supportive therapy
ORR: Percentage of participants who achieve best overall response Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST). * CR is defined as disappearance of all target lesions. * PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
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 |
|---|---|---|
| Selpercatinib | EXPERIMENTAL | Selpercatinib administered orally. |
| Placebo | PLACEBO_COMPARATOR | Placebo administered orally. |
| Selpercatinib - Treatment A (TRT A) | EXPERIMENTAL | 160 milligram (mg) Selpercatinib administered orally twice daily (BID) continuously in 21-day cycles. |
| Pemetrexed and Platinum with or without Pembrolizumab - (TRT B) | ACTIVE_COMPARATOR | Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose of 750 mg\] IV), or cisplatin (75 mg/m2 cisplatin IV) on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles. |
| Cabozantinib or Vandetanib - Treatment B (TRT B) | ACTIVE_COMPARATOR | 140 mg Cabozantinib administered orally daily (QD) or 300 mg Vandetanib administered orally QD per physician choice. Cabozantinib Adolescent Dose: 40 mg/m2. Vandetanib Adolescent Dose: * 0.7 - \<0.9 - 100 mg every other day (QOD) * 0.9 - \<1.2 - 100 mg QD * 1.2 - \<1.6 - 7-day schedule 100 mg - 200 mg - 100 mg - 200 mg - 100 mg - 200 mg - 100 mg * ≥1.6 - 200 QD |
| Cohort 1: Medullary Thyroid Cancer (MTC) Group | EXPERIMENTAL | Participants in this cohort had MTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| Cohort 2: Papillary Thyroid Cancer (PTC) Group | EXPERIMENTAL | Participants in this cohort had PTC and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| Cohort 3: Other Cancer Group | EXPERIMENTAL | Participants in this cohort had other (REarranged during Transfection (RET)-altered non-thyroid) cancer and received 160 mg of selpercatinib BID orally on Days 1 through 28 of a 28-day cycle. The treatment was continued until participants experienced a progressive disease, unacceptable toxicity, or other protocol-defined reason for discontinuation. |
| 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 |
|---|---|---|
| Selpercatinib | DRUG | Administered orally. |
| Placebo | DRUG | Administered orally. |
| Carboplatin | DRUG | Administered IV |
| Cisplatin | DRUG | Administered IV |
| Pemetrexed | DRUG | Administered IV |
| Pembrolizumab | DRUG | Administered IV |
| Cabozantinib | DRUG | Administered orally |
| Vandetanib | DRUG | Administered orally |
| LOXO-292 | DRUG | Oral LOXO-292 |
Inclusion Criteria: * Must have histologically confirmed Stage IB, II, or IIIA NSCLC. * Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR), next generation sequencing (NGS), or another molecular test per sponsor's approval. * Must have received definitive loco...
Selpercatinib is an investigational small molecule being studied in oncology for RET-driven cancers, including non-small cell lung cancer, medullary thyroid cancer, and advanced solid tumors with RET activation. It is being evaluated in biomarker-selected patient populations, meaning participants are chosen based on RET alterations such as RET fusions or RET mutations.
Selpercatinib targets RET, a receptor tyrosine kinase, and is classified as an inhibitor. It also engages RET fusion partners CCDC6 and KIF5B, which drive RET activation in some tumors. By inhibiting RET signaling, the drug is designed to act on cancers that depend on RET pathway activation, including RET fusion-positive and RET-mutant tumors.
Selpercatinib is being developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. The compound is also referenced in research settings as LY3527723. Lilly is running the clinical program across multiple countries in North America, Europe, Asia, Latin America, and Australia.
Selpercatinib is in Phase 3 clinical development. It is investigational and is not described as approved. The program includes Phase 3 studies in non-small cell lung cancer and RET-mutant medullary thyroid cancer, plus a Phase 2 study in advanced solid tumors including RET fusion-positive solid tumors and medullary thyroid cancer.
Selpercatinib is being studied in four registered trials. NCT04819100 is a Phase 3 study after surgery or radiation in non-small cell lung cancer. NCT04194944 is a Phase 3 study in advanced or metastatic RET fusion-positive non-small cell lung cancer. NCT04211337 is a Phase 3 study in RET-mutant medullary thyroid cancer, and NCT04280081 is a Phase 2 study in advanced solid tumors.
Yes, [14C]-Selpercatinib is an alternative name for selpercatinib. The bracketed carbon-14 label denotes a radiolabeled form of the same molecule used in research, so readers searching either name are looking at the same drug asset. Selpercatinib is also known by the code LY3527723 in Lilly's study titles.