RET inhibitor · small molecule

selpercatinib

13 active trials across 7 of our biomarkers, targeting RET. 8 active approvals for a biomarker on marked.bio.

Also known as LOXO-292, Retevmo, Retsevmo.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

Therapy	Biomarker	Tumour	United States	European Union
selpercatinib FDA, 2020 locally advanced or metastatic, RET fusion Accelerated approval 08/05/2020; regular approval 21/09/2022. Source EU (EMA), 2021 advanced RET fusion-positive, not previously treated with a RET inhibitor EU marketing authorisation 11/02/2021 (conditional, since switched to standard). First line added later (date not checked). Source Retevmo, Retsevmo	RET fusion or mutation	NSCLC	Approved 2020	Approved 2021
In the FDA approval summary LIBRETTO-001 single-arm, 69 untreated; 247 after platinum Response 84% (untreated); 61% (after platinum) (73-92; 55-67)Lasting 20.2 months (untreated); 28.6 months (after platinum) Trial details and side effects Patients RET fusion-positive NSCLC (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Later trial LIBRETTO-431 (NCT04194944; first line vs platinum-pemetrexed with or without pembrolizumab, 129 vs 83 patients): median PFS 24.8 vs 11.2 months, HR 0.47 (0.31-0.70). Published trial result (NEJM 2023), not in the FDA summary. Notes FDA approval summary (2022); side effects are those in 25% or more of patients. Source FDA approval summary In the EU summary (EPAR) LIBRETTO-001 single-arm, 69 untreated; 105 after platinum Response 84% (untreated); 64% (after platinum) Trial details and side effects Patients RET fusion-positive NSCLC (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Later trial LIBRETTO-431 (NCT04194944; first line vs platinum-pemetrexed with or without pembrolizumab, 129 vs 83 patients): median PFS 24.8 vs 11.2 months, HR 0.47 (0.31-0.70). Published trial result (NEJM 2023), not in the FDA summary. Notes EU figures from the EPAR summary; trial details and side effects from the US approval. Source EU summary (EPAR)
selpercatinib FDA, 2020 advanced or metastatic RET-mutant MTC, adults and children >=2 years Accelerated approval 2020 (age 12+); children 2+ added 29/05/2024; traditional approval 27/09/2024 (LIBRETTO-531). Source EU (EMA), 2021 advanced RET-mutant MTC, adults and children >=2 years EU marketing authorisation 11/02/2021. Source Retevmo, Retsevmo	RET fusion or mutation	medullary thyroid	Approved 2020	Approved 2021
In the FDA approval summary LIBRETTO-531 vs cabozantinib or vandetanib PFS not reached vs 16.8 months, HR 0.28 (0.17-0.48) Trial details and side effects Patients RET-mutant MTC, no prior kinase inhibitor (NCT04211337) Most common side effects hypertension, oedema, dry mouth, fatigue, diarrhoea Notes FDA approval summary (2024); side effects are those in 25% or more of patients. Earlier single-arm LIBRETTO-001 results: response 73% (untreated, 88 patients) and 69% (after cabozantinib/vandetanib, 55 patients). Source FDA approval summary In the EU summary (EPAR) LIBRETTO-001 (MTC cohorts) single-arm, 151 after cabozantinib/vandetanib; 142 not treated with them Response 74% (previously treated); 81% (not previously treated) Trial details and side effects Patients RET-mutant MTC (NCT03157128) Most common side effects hypertension, oedema, dry mouth, fatigue, diarrhoea Notes EU figures from the EPAR summary (single-arm). The randomised LIBRETTO-531 results are under the US approval. Side effects as listed for the drug's main approval (same label). Source EU summary (EPAR)
selpercatinib FDA, 2022 locally advanced or metastatic RET fusion-positive solid tumours after prior systemic therapy or with no satisfactory alternative, adults and children >=2 years Accelerated approval 21/09/2022 (adults); children 2+ 2024; traditional approval 14/07/2026. Source EU (EMA), 2024 advanced RET fusion-positive solid tumours when treatments not targeting RET give limited benefit or are exhausted, adults and children >=2 years Extension of the EU authorisation (year not checked against the EMA procedure history). Source Retevmo, Retsevmo	RET fusion or mutation	solid tumours (tumour-agnostic)	Approved 2022	Approved 2024
In the FDA approval summary LIBRETTO-001 (other tumours) and LIBRETTO-121 single-arm, 75 patients Response 47% (35-59)Lasting 24.5 months Trial details and side effects Patients RET fusion-positive tumours other than NSCLC and thyroid (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Notes FDA approval summary (2026). Side effects as listed for the drug's main approval (same label). Source FDA approval summary In the EU summary (EPAR) LIBRETTO-001 (other tumours) and LIBRETTO-121 single-arm, 52 (mostly pancreatic or colon) Response 44%Lasting 37 months on average Trial details and side effects Patients RET fusion-positive tumours other than NSCLC and thyroid (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Notes EU figures from the EPAR summary; trial details and side effects from the US approval. Side effects as listed for the drug's main approval (same label). Source EU summary (EPAR)
selpercatinib FDA, 2020 advanced or metastatic RET fusion-positive thyroid cancer, radioactive-iodine refractory, adults and children >=2 years Accelerated approval 08/05/2020 (age 12+); children 2+ added 29/05/2024. Source EU (EMA), 2021 advanced RET fusion-positive thyroid cancer, radioactive-iodine refractory, adults and children >=2 years EU marketing authorisation 11/02/2021. Source Retevmo, Retsevmo	RET fusion or mutation	thyroid	Approved 2020 accelerated	Approved 2021
In the FDA approval summary LIBRETTO-001 (thyroid cohorts) single-arm, 19 previously treated; 8 systemic-naive Response 79% (previously treated); 100% (systemic-naive) (54-94; 63-100)Lasting 87% and 75% of responses lasted 6 months or more Trial details and side effects Patients RET fusion-positive thyroid cancer, radioactive-iodine refractory (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Notes FDA approval summary (2020, first data cut). Side effects as listed for the drug's main approval (same label). Source FDA approval summary In the EU summary (EPAR) LIBRETTO-001 (thyroid cohorts) single-arm, 19 after sorafenib/lenvatinib; 24 after radioactive iodine only Response 79% (previously treated); 96% (radioactive iodine only) Trial details and side effects Patients RET fusion-positive thyroid cancer, radioactive-iodine refractory (NCT03157128) Most common side effects oedema, diarrhoea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, headache Notes EU figures from the EPAR summary; trial details and side effects from the US approval. Side effects as listed for the drug's main approval (same label). Source EU summary (EPAR)

Biomarkers

Biomarker	Active trials	All trials	Furthest active phase
RET fusion or mutation	13	14	Phase 4
BRAF V600E	2	3	Phase 4
ALK fusion	1	2	Phase 2
EGFR exon 19 deletion / L858R	1	2	Phase 2
MET exon 14 skipping	1	2	Phase 2
NTRK1/2/3 fusion	1	1	Phase 4
ROS1 fusion	1	2	Phase 2

Trials

13 of 14 trials shown

A Study of Selpercatinib (LY3527723) in Participants With Rearranged During Transfection (RET)-Altered Cancers in India

Not yet recruiting Phase 4 Eli Lilly Started 2026Primary completion 2029-10 NCT07822880

selpercatinib FDA EU

Participants with one of the following RET-altered cancers:

RET fusion or mutationThyroid Neoplasms, Carcinoma, Non-Small-Cell Lung
Genotype-Driven Neoadjuvant Therapy for Locally Advanced Thyroid Cancer: A Real-World Cohort Study

Not yet recruiting Phase 4 Fujian Medical University Started 2025Primary completion 2027-12 NCT07010393

dabrafenib FDA EUtrametinib FDA EUselpercatinibpralsetiniblenvatiniblarotrectinibanlotinibpembrolizumabsintilimabcabozantinibBemosuzumab

BRAF V600E mutation

BRAF V600ERET fusion or mutationNTRK1/2/3 fusionThyroid Neoplasms
A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)

Active, not recruiting Phase 3 Eli Lilly Started 2021Primary completion 2026-01 NCT04819100

selpercatinib FDA EU

Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR), next generation sequencing (NGS), or a…

RET fusion or mutationCarcinoma, Non-Small-Cell Lung
A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer

Active, not recruiting Phase 3 Eli Lilly Started 2020Primary completion 2023-05 NCT04211337

selpercatinib FDA EUcabozantinibvandetanib

A defined/acceptable RET gene alteration identified in a tumor, germline deoxyribonucleic acid (DNA) or blood sample.

RET fusion or mutationMedullary Thyroid Cancer
A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Active, not recruiting Phase 3 Eli Lilly Started 2020Primary completion 2023-05 NCT04194944

selpercatinib FDA EUcarboplatincisplatinpemetrexedpembrolizumab

A RET gene fusion in tumor and/or blood from a qualified laboratory.

RET fusion or mutationNon-Small Cell Lung Cancer
Selpercatinib Pre-RAI in Patients With RET Fusion Thyroid Cancer (RAISE)

Recruiting Phase 2 Children's Hospital of Philadelphia Started 2024Primary completion 2030-11 NCT06458036

selpercatinib FDA EU

Identification of an activating RET gene alteration (fusion or mutation).

RET fusion or mutationDifferentiated Thyroid Cancer, Pediatric Cancer, Cancer, Cancer, Thyroid
Restor. I-131 Upt. + Selpercatinib in RET F-P RAI-R TC

Recruiting Phase 2 Massachusetts General Hospital Started 2023Primary completion 2025-03 NCT05668962

selpercatinib FDA EUSodium Iodine I-131rhTSH

…astic thyroid cancer that is metastatic and/or unresectable AND harbors a known oncogenic RET gene fusion, performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent…

RET fusion or mutationThyroid Cancer, Thyroid Carcinoma, Metastatic Thyroid Cancer, Follicular Thyroid Cancer
Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial

Active, not recruiting Phase 2 National Cancer Institute (NCI) Started 2021Primary completion 2024-09 NCT04320888

selpercatinib FDA EU

…e Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial

RET fusion or mutationHematopoietic and Lymphatic System Neoplasm, Recurrent Ependymoma, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma
Selpercatinib Before Surgery for the Treatment of RET-Altered Thyroid Cancer

Active, not recruiting Phase 2 M.D. Anderson Cancer Center Started 2021Primary completion 2027-11 NCT04759911

selpercatinib FDA EU

Having an activating RET gene alteration (fusion or mutation).

RET fusion or mutationMalignant Thyroid Gland Neoplasm, Poorly Differentiated Thyroid Gland Carcinoma, Recurrent Thyroid Gland Carcinoma, Thyroid Gland Anaplastic Carcinoma
Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial)

Active, not recruiting Phase 2 SWOG Cancer Research Network Started 2020Primary completion 2026-12 NCT04268550

selpercatinib

This includes EGFR sensitizing mutations, EGFR T790M, ALK gene fusion, ROS1 gene fusion, KRAS activating mutation, BRAF V600E mut…

EGFR exon 19 deletion / L858RBRAF V600EMET exon 14 skippingALK fusionROS1 fusionRET fusion or mutationRecurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
A Study of Selpercatinib (LY3527723) in Participants With Advanced Solid Tumors Including RET Fusion-positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation

Active, not recruiting Phase 2 Eli Lilly Started 2020Primary completion 2021-03 NCT04280081

selpercatinib FDA EU

Evidence of a RET gene alteration in tumor and/or blood.

RET fusion or mutationSolid Tumor, Medullary Thyroid Cancer
A Study of Oral LOXO-292 (Selpercatinib) in Pediatric Participants With Advanced Solid or Primary Central Nervous System (CNS) Tumors

Active, not recruiting Phase 1/2 Eli Lilly Started 2019Primary completion 2024-11 NCT03899792

selpercatinib FDA EU

Evidence of an activating RET gene alteration in the tumor and/or blood

RET fusion or mutationMedullary Thyroid Cancer, Infantile Myofibromatosis, Infantile Fibrosarcoma, Papillary Thyroid Cancer
A Study of Selpercatinib (LOXO-292) in Participants With Advanced Solid Tumors, RET Fusion-Positive Solid Tumors, and Medullary Thyroid Cancer (LIBRETTO-001)

Active, not recruiting Phase 1/2 Eli Lilly Started 2017Primary completion 2025-02 NCT03157128

selpercatinib FDA EU

A RET gene alteration is not required initially.

RET fusion or mutationNon-Small Cell Lung Cancer, Medullary Thyroid Cancer, Colon Cancer, Any Solid Tumor
Testing the Use of Targeted Treatment for RET Positive Advanced Non-small Cell Lung Cancer

Withdrawn Phase 2 SWOG Cancer Research Network Started 2022 NCT05364645

carboplatinpemetrexedselpercatinib

This includes EGFR sensitizing mutations, EGFR T790M mutations, ALK gene fusions, ROS1 gene fusion, KRAS activating mutations, BR…

EGFR exon 19 deletion / L858RBRAF V600EMET exon 14 skippingALK fusionROS1 fusionRET fusion or mutationLung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8

Approvals and pivotal results

Biomarkers

Sponsors

Trials