ES_cFAQ_SEL200_CLINICAL_DEVELOPMENT

Descripción general de los ensayos clínicos de selpercatinib

Las alteraciones genómicas en la quinasa RET (reordenamiento durante la transfección) provocan una señalización de RET sobreactiva y un crecimiento celular incontrolado. Estas alteraciones incluyen fusiones y mutaciones puntuales activadas.1

En un ensayo de fase 1/2 en curso, primero en seres humanos, en pacientes con tumores con alteraciones del gen RET, el tratamiento con selpercatinib ha demostrado actividad antitumoral en pacientes con:

CMT con mutación del gen RET; y
tumores con fusión de RET positiva (cáncer pulmonar no microcítico (CPNM) y cáncer de tiroides).2-14

El desarrollo clínico con selpercatinib continúa en tumores con alteraciones del gen RET.15-22 Los ensayos clínicos en curso de selpercatinib en pacientes con tumores con alteraciones del gen RET se presentan en la Ensayos clínicos de selpercatinib en tumores con alteraciones del gen RET.

**Ensayos clínicos de selpercatinib en tumores con alteraciones del gen RET15-23**
Ensayo	Promotor	Fase	Tipo de tumor	Régimen	Criterios principales de valoración	Número/estado de NCT
LIBRETTO-43117,24	Eli Lilly and Company	3 abierta	Pacientes a partir de 18 años sin tratamiento previo con CPNM no escamoso en estadio IIIB-IIIC o IV no apto para cirugía radical o radioterapia	Selpercatinib frente a quimioterapia basada en platino y pemetrexed con o sin pembrolizumab	SLP según RCIC	NCT04194944 En reclutamiento25
LIBRETTO-53114,18	Eli Lilly and Company	3 abierta	Pacientes a partir de 12 años (según las restricciones de edad de las autoridades reguladoras locales) con CMT con mutación RET progresivo y avanzado, no tratados con un inhibidor de quinasa.	Selpercatinib frente a la elección del médico de cabozantinib o vandetanib	SLFB según RCIC	NCT04211337 En reclutamiento26
LIBRETTO-0012-7,10-13,16	Loxo Oncology, Inc.	1/2 abierta	Pacientes a partir de 12 años con CPNM, CMT, cáncer de colon y tumores sólidos avanzados	Fase 1 Múltiples dosis de selpercatinib para determinar la DMT Fase 2 DMT/RP2D	Fase 1 DMT RP2D Fase 2 ORR conforme a RECIST 1.1 o RANO según la determinación de un IRC	NCT03157128 En reclutamiento
LIBRETTO-32119	Eli Lilly and Company	2 abierta	Pacientes a partir de 18 años de China con tumores con alteraciones del gen RET.	Selpercatinib	ORR según IRC	NCT04280081 Activo, pero sin reclutamiento
LIBRETTO-12123,27	Loxo Oncology, Inc.	1/2 abierta	Pacientes pediátricos con CMT, MI, fibrosarcoma infantil, CPT y STB	Fase 1 Múltiples dosis de selpercatinib para determinar la DMT Fase 2 DMT/RP2D	Fase 1 TLD de selpercatinib oral en pacientes con tumores sólidos avanzados y en pacientes con tumores del SNC Fase 2 ORR conforme a RECIST 1.1 o RANO según la determinación de un IRC	NCT03899792 En reclutamiento
LOXO-292 EAP15	Loxo Oncology, Inc.	Pacientes individuales, tratamiento con PEI/según protocolo	Pacientes con CPNM, CMT, CPT, cáncer de colon, de mama y de páncreas, así como otros tumores sólidos	Acceso ampliado abierto a selpercatinib	Acceso ampliado	NCT03906331 Temporalmente no disponible
NCI-COG MATCH pediátrico20	National Cancer Institute	2 abierta	Pacientes pediátricos (de 12 meses a 21 años) con tumores sólidos (incluso del SNC) con linfomas con metástasis (avanzados) o trastornos histiocíticos que tienen alteraciones del gen RET activadoras.	Selpercatinib	ORR	NCT04320888 En reclutamiento
NCI-COG MATCH pediátrico Protocolo de selección21	National Cancer Institute	2 abierta	Pacientes pediátricos (de 12 meses a 21 años) con tumores sólidos, linfomas no Hodgkin o trastornos histiocíticos que han progresado después de recibir al menos una línea de tratamiento sistémico estándar o para los que no existe un tratamiento estándar que haya demostrado prolongar la supervivencia.	Selpercatinib es una de las 12 intervenciones.	ORR	NCT03155620 En reclutamiento
Ensayo de tratamiento LUNG-MAP22	Southwest Oncology Group	2 abierta	Pacientes con CPNM recurrente en estadio IV con fusión del gen RET positiva.	Selpercatinib	ORR según RCIC	NCT04268550 En reclutamiento

Abreviaturas: RCIC = revisión centralizada independiente y ciega; SNC = sistema nervioso central; COG = Grupo de Oncología Infantil; TLD = toxicidad limitante de la dosis; EAP = programa de acceso ampliado; MI = miofibromatosis infantil; PEI = producto en fase de investigación clínica; IRC = comité de revisión independiente; MATCH = análisis molecular para la elección de terapia; CMT = cáncer medular de tiroides; DMT = dosis máxima tolerada; NCI = National Cancer Institute; CPNM = cáncer de pulmón no microcítico; ORR = tasa de respuesta objetiva; SLP = supervivencia libre de progresión; CPT = carcinoma papilar de tiroides; RANO = evaluación de respuesta en neurooncología; RECIST = criterios de evaluación de respuesta en tumores sólidos; RET = reordenamiento durante la transfección; RP2D = dosis recomendada de la fase 2; STB = sarcoma de tejidos blandos; SLFB = supervivencia libre de fracaso bioquímico.

Referencias

1Drilon A, Hu ZI, Lai GGY, Tan DSW. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167. https://doi.org/10.1038/nrclinonc.2017.175

2Oxnard GR, Subbiah V, Park K, et al. Clinical activity of LOXO-292, a highly selective RET inhibitor, in patients with RET fusion+ non-small cell lung cancer an update from ASCO 2018. Poster presented at: 19th Annual World Conference on Lung Cancer (WCLC); September 23-26, 2018; Toronto, Canada. https://www.loxooncology.com/docs/presentations/WCLC_2018-LOXO292.PDF

3Wirth LJ, Cabanillas ME, Sherman EJ, et al. Clinical activity of LOXO-292, a highly selective RET inhibitor, in patients with RET-altered thyroid cancers: an update from ASCO 2018. Talk presented at: 88th Annual Meeting of the American Thyroid Association; October 3-7, 2018; Washington, DC. https://www.loxooncology.com/docs/presentations/ATA_2018_LOXO-292_Final.pdf

4Shah MH, Sherman EJ, Robinson B, et al. Selpercatinib (LOXO-292) in patients with RET-altered thyroid cancer. J Clin Oncol. 2020;38(15 suppl):3594. American Society of Clinical Oncology abstract 3594. https://doi.org/10.1200/JCO.2020.38.15_suppl.3594

5Subbiah V, Gainor JF, Oxnard GR, et al. Intracranial activity of selpercatinib (LOXO-292) in RET fusion-positive non-small cell lung cancer (NSCLC) patients on the LIBRETTO-001 trial. Poster presented at: 56th Annual Meeting of the American Society of Clinical Oncology (ASCO Virtual); May 29-31, 2020. J Clin Oncol. 2020;38(15 suppl):9516. https://meetinglibrary.asco.org/record/186081/abstract

6Goto K, Oxnard GR, Tan DSW, et al. Selpercatinib (LOXO-292) in patients with RET-fusion+ non-small cell lung cancer. J Clin Oncol. 2020;38(15 suppl):3584. American Society of Clinical Oncology abstract 3584. https://doi.org/10.1200/JCO.2020.38.15_suppl.3584

7Takeda M, Watanabe S, Rothenberg SM, et al. Complete response to selpercatinib (LOXO-292), a highly selective RET inhibitor, in a patient with RET fusion-positive breast cancer. Poster presented at: 111th Annual Meeting of the American Association for Cancer Research (AACR Virtual); June 22-24, 2020. https://www.abstractsonline.com/pp8/#!/9045/presentation/2693

8Wirth LJ, Sherman E, Robinson B, et al. Efficacy of selpercatinib in RET-altered thyroid cancers. N Engl J Med. 2020;383(9):825-835. https://dx.doi.org/10.1056/NEJMoa2005651

9Drilon A, Oxnard GR, Tan DSW, et al. Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. N Engl J Med. 2020;383(9):813-824. https://dx.doi.org/10.1056/NEJMoa2005653

10Minchom A, Tan D, Massarelli E, et al. Exploratory patient-reported outcomes (PROs) among patients with RET-fusion non-small cell lung cancer (NSCLC) in LIBRETTO-001: a phase 1/2 trial of selpercatinib poster presented at: 45th Annual Meeting of the European Society for Medical Oncology (ESMO Virtual); September 19-21, 2020. Accessed September 17, 2020. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/exploratory-patient-reported-outcomes-pros-among-patients-with-ret-fusion-non-small-cell-lung-cancer-nsclc-in-libretto-001-a-phase-i-ii-trial

11Wirth L, Robinson B, Boni V, et al. Exploratory patient-reported outcomes (PROs) among patients with RET-mutant medullary thyroid cancer in LIBRETTO-001: a phase 1/2 trial of selpercatinib (LOXO-292) poster presented at: 45th Annual Meeting of the European Society for Medical Oncology (ESMO Virtual); September 19-21, 2020. Accessed September 17, 2020. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/exploratory-patient-reported-outcomes-among-patients-with-ret-mutant-medullary-thyroid-cancer-in-libretto-001-a-phase-i-ii-trial-of-selpercatinib

12McCoach C, Tan DSW, Besse B, et al. Hypersensitivity reactions (HR) to selpercatinib in RET fusion+ non-small-cell lung cancer (NSCLC) patients (pts) following immune checkpoint inhibition (CPI). Poster presented at: Annual Meeting of the European Society for Medical Oncology (ESMO Virtual); September 19-21, 2020. Accessed September 17, 2020. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/hypersensitivity-reactions-hr-to-selpercatinib-in-ret-fusion-non-small-cell-lung-cancer-nsclc-patients-pts-following-immune-checkpoint-inhib

13Gautschi O, Drilon A, Tan DSW, et al. Efficacy and safety with selpercatinib (LOXO-292) by last prior systemic therapy received in patients with RET fusion-positive non-small-cell lung cancer (NSCLC). Poster presented at: Annual Meeting of the European Society for Medical Oncology (ESMO Virtual); September 19-21, 2020. Accessed September 17, 2020. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/efficacy-and-safety-with-selpercatinib-by-last-prior-systemic-therapy-received-in-patients-pts-with-ret-fusion-non-small-cell-lung-cancer-nsclc

14Hernando J, Tarasova V, Hu MI, et al. LIBRETTO-531: selpercatinib in patients with treatment (Tx)-naïve RET-mutant medullary thyroid cancer (MTC). Poster presented at: 45^th Congress of the European Society for Medical Oncology 45th Congress (ESMO Virtual); September 19-21, 2020. Accessed September 17, 2020. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/libretto-531-selpercatinib-in-patients-with-treatment-tx-naive-ret-mutant-medullary-thyroid-cancer-mtc

15Expanded access for the treatment of cancers with rearranged during transfection (RET) activation. ClinicalTrials.gov identifier: NCT03906331. Updated May 21, 2020. Accessed June 25, 2020. https://www.clinicaltrials.gov/ct2/show/NCT03906331

16Phase 1/2 study of LOXO-292 in patients with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). ClinicalTrials.gov identifier: NCT03157128. Updated May 28, 2020. Accessed June 12, 2020. https://www.clinicaltrials.gov/ct2/show/NCT03157128

17A study of selpercatinib (LY3527723) in participants with advanced or metastatic RET fusion-positive non-small cell lung cancer (LIBRETTO-431). ClinicalTrials.gov identifer: NCT04194944. Updated June 17, 2020. Accessed June 25, 2020. https://www.clinicaltrials.gov/ct2/show/NCT04194944

18A study of selpercatinib (LY3527723) in participants with RET-mutant medullary thyroid cancer (LIBRETTO-531). ClinicalTrials.gov identifier: NCT04211337. Updated September 9, 2022. Accessed September 19, 2022. https://clinicaltrials.gov/ct2/show/NCT04211337?term=libretto-531&draw=2&rank=1

19A 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 (LIBRETTO-321). ClinicalTrials.gov identifier: NCT04280081. Updated June 17, 2020. Accessed June 25, 2020. https://clinicaltrials.gov/ct2/show/record/NCT04280081

20Selpercatinib for the treatment of advanced solid tumors, lymphomas, or histiocytic disorders with activating RET gene alterations, a pediatric MATCH treatment trial. ClinicalTrials.gov identifier: NCT04320888. Updated July 18, 2022. Accessed August 3, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04320888

21Targeted therapy directed by genetic testing in treating pediatric patients with relapsed or refractory advanced solid tumors, non-Hodgkin lymphomas, or histiocytic disorders (the pediatric MATCH screening trial). ClinicalTrials.gov identifier: NCT03155620. Updated July 21, 2022. Accessed August 3, 2022. https://www.clinicaltrials.gov/ct2/show/NCT03155620

22Targeted treatment for RET fusion-positive advanced non-small cell lung cancer (A LUNG-MAP treatment trial). ClinicalTrials.gov identifier: NCT04268550. Updated July 7, 2022. Accessed August 3, 2022. https://www.clinicaltrials.gov/ct2/show/NCT04268550

23A study of oral LOXO-292 in pediatric patients with advanced solid or primary central nervous system tumors (LIBRETTO-121). ClinicalTrials.gov identifier: NCT03899792. Updated October 4, 2019. Accessed January 6, 2020. https://clinicaltrials.gov/ct2/show/NCT03899792

24Loong HHF, Goto K, Elamin Y, et al. LIBRETTO-431: selpercatinib in treatment (TX)-naïve patients with RET fusion-positive (RET+) non-small cell lung cancer (NSCLC). Poster presented at: 45th Annual Meeting of the European Society for Medical Oncology (ESMO Virtual); September 19-21, 2020. Accessed September 19, 2020. https://www.esmo.org/oncology-news/selpercatinib-shows-durable-efficacy-in-ret-fusion-positive-nsclc

25Lilly opens first ever randomized phase 3 clinical trial in treatment-naïve RET fusion positive non-small cell lung cancer [press release]. Indianapolis, IN: Eli Lilly and Company; December 11, 2019. Accessed January 6, 2020. https://www.prnewswire.com/news-releases/lilly-opens-first-ever-randomized-phase-3-clinical-trial-in-treatment-naive-ret-fusion-positive-non-small-cell-lung-cancer-300972812.html

26Lilly opens phase 3 clinical trial in RET-mutant medullary thyroid cancer [press release]. Indianapolis, IN: Eli Lilly and Company; December 30, 2019. Accessed January 6, 2020. https://www.prnewswire.com/news-releases/lilly-opens-phase-3-clinical-trial-in-ret-mutant-medullary-thyroid-cancer-300979626.html

27Guo R, Schreyer M, Chang JC, et al. Response to selective RET inhibition with LOXO-292 in a patient with RET fusion-positive lung cancer with leptomeningeal metastases. JCO Precis Oncol. 2019;3:1-6. https://doi.org/10.1200/po.19.00021

Está accediendo a contenido restringido.

¿Qué ensayos clínicos están en curso para Retsevmo® (selpercatinib)?