Retsevmo ® (selperkatinib)

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Klinisk utveckling av Retsevmo® ▼ (selperkatinib)

Selperkatinib är en oral, potent och selektiv hämmare i klinisk utveckling för behandling av patienter med cancer som innehåller abnormiteter i RET-kinaset.

Selpercatinib Clinical Trials Overview

Genomic alterations in the RET kinase lead to overactive RET signaling and uncontrolled cell growth. These alterations include fusions and activating point mutations.1

In an ongoing, first in human, phase 1/2 trial, in patients with RET-altered cancers, selpercatinib treatment demonstrated antitumor activity in patients with 

  • RET-mutant MTC, and

  • RET fusion-positive tumors (including NSCLC and thyroid cancer).2-14

Clinical development with selpercatinib continues in tumors with RET alterations.15-22 Ongoing selpercatinib clinical trials in patients with RET-altered tumors are presented in Table 1.

Table 1. Selpercatinib Clinical Trials in RET-Altered Cancers15-23

Trial

Sponsor

Phase

Tumor Type

Regimen

Primary Outcomes 

NCT Number/ Status

LIBRETTO-43117,24

Eli Lilly and Company

3 open-label

Treatment-naive patients 18 years and older with stage IIIB-IIIC or stage IV nonsquamous NSCLC that is not suitable for radical surgery or radiation therapy

Selpercatinib vs platinum-based chemotherapy and pemetrexed ± pembrolizumab

PFS by BICR

NCT04194944
Recruiting25

LIBRETTO-53114,18

Eli Lilly and Company

3 open-label 

Patients 12 years and older (as determined by local regulatory authorities age restrictions) with progressive, advanced, kinase Inhibitor naïve, RET-mutant MTC 

Selpercatinib vs physician's choice of cabozantinib or vandetanib

TFFS by BICR

NCT04211337
Recruiting26

LIBRETTO-0012-7,10-13,16


Loxo Oncology, Inc.

1/2 open-label

Patients 12 years and older with NSCLC, MTC, colon cancer, and advanced solid tumors

Phase 1
Multiple doses of selpercatinib to determine MTD
Phase 2

MTD/RP2D

Phase 1
MTD
RP2D
Phase 2

ORR based on RECIST 1.1 or RANO as determined by an IRC

NCT03157128
Recruiting

LIBRETTO-32119

Eli Lilly and Company

2 open-label

Patients 18 years and older in China with RET-altered tumors.

Selpercatinib

ORR by IRC

NCT04280081
Active, not recruiting

LIBRETTO-12123,27

Loxo Oncology, Inc.

1/2 open-label

Pediatric patients with MTC, IM, infantile fibrosarcoma, PTC, and STS

Phase 1
Multiple doses of selpercatinib to determine MTD
Phase 2

MTD/RP2D

Phase 1
DLTs of oral selpercatinib in patients with advanced solid tumors and in patients with CNS tumors
Phase 2

ORR based on RECIST 1.1 or RANO as determined by an IRC

NCT03899792
Recruiting

LOXO-292 EAP15

Loxo Oncology, Inc.

Individual patients, treatment IND/protocol

Patients with NSCLC, MTC, PTC, colon, breast, pancreatic cancers, and other solid tumors

Selpercatinib open-label expanded access

Expanded access

NCT03906331
Temporarily unavailable

NCI-COG Pediatric MATCH20

National Cancer Institute

2 open-label

Pediatric patients (12 months -21 years) with solid tumors (including CNS) that have metastasized (advanced), lymphomas, or histiocytic disorders that have activating RET gene alterations.

Selpercatinib

ORR

NCT04320888
Recruiting

NCI-COG Pediatric MATCH  Screening Protocol21

National Cancer Institute

2 open-label

Pediatric patients (12 months -21 years) with solid tumors, non-Hodgkin lymphomas, or histiocytic disorders that have progressed following at least one line of standard systemic therapy and/or for which no standard treatment exists that has been shown to prolong survival.

Selpercatinib is one of 12 interventions.

ORR

NCT03155620
Recruiting

A LUNG-MAP Treatment Trial22

Southwest Oncology Group

2 open-label

Patients with recurrent RET fusion-positive NSCLC that is stage IV.

Selpercatinib

ORR by BIRC

NCT04268550
Recruiting

Abbreviations: BICR = blinded independent central review; CNS = central nervous system; COG = Children’s Oncology Group; DLT = dose limiting toxicity; EAP = Expanded Access Program; IM = infantile myofibromatosis; IND = investigational new drug; IRC = independent review committee; MATCH = Molecular Analysis for Therapy Choice; MTC = medullary thyroid cancer; MTD = maximum tolerated dose; NCI = National Cancer Institute; NSCLC = non-small cell lung cancer; ORR = objective response rate; PFS = progression-free survival; PTC = papillary thyroid carcinoma; RANO = Response Assessment in Neuro-Oncology; RECIST = Response Evaluation Criteria in Solid Tumors; RET = rearranged during transfection; RP2D = recommended phase 2 dose; STS = soft tissue sarcoma; TFFS = treatment failure-free survival.

References

1. Drilon A, Hu ZI, Lai GG, et al. 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

2. Oxnard 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

3. Wirth 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

4. Shah MH, Sherman EJ, Robinson B, et al. Selpercatinib (LOXO-292) in patients with RET-altered thyroid cancer. Poster presented at: 56th Annual Meeting of the American Society of Clinical Oncology (ASCO Virtual); May 29-31, 2020. Accessed May 22, 2020. https://meetinglibrary.asco.org/record/187939/abstract

5. Subbiah 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. https://meetinglibrary.asco.org/record/186081/abstract

6. Goto K, Oxnard GR, Tan DSW, et al. Selpercatinib (LOXO-292) in patients with RET fusion-positive non-small cell lung cancer (NSCLC). Poster presented at: 56th Annual Meeting of the American Society of Clinical Oncology (ASCO Virtual); May 29-31, 2020. Accessed May 22, 2020. https://meetinglibrary.asco.org/record/188463/abstract

7. Takeda 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

8. Wirth 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

9. Drilon 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

10. Minchom 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

11. Wirth 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

12. McCoach C, Daniel S. W. Tan DSW, Besse B, et al. Hypersensitivity reactions to selpercatinib 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/hypersensitivity-reactions-hr-to-selpercatinib-in-ret-fusion-non-small-cell-lung-cancer-nsclc-patients-pts-following-immune-checkpoint-inhib

13. Gautschi 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

14. Hernando 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: 45th 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

15. Expanded 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

16. Phase 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

17. A 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

18. A study of selpercatinib (LY3527723) in participants with RET-mutant medullary thyroid cancer (LIBRETTO-531). ClinicalTrials.gov identifer: NCT04211337. Updated June 17, 2020. Accessed June 25, 2020. https://clinicaltrials.gov/ct2/show/NCT04211337?term=libretto-531&draw=2&rank=1

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

20. Selpercatinib 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 January 22, 2021. Accessed January 25, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04320888

21. Targeted 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 January 22, 2021. Accessed January 25, 2021. https://www.clinicaltrials.gov/ct2/show/NCT03155620

22. Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial). ClinicalTrials.gov identifier: NCT04268550. Updated November 9, 2020. Accessed January 25, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04268550

23. A 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

24. Loong 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

25. Lilly 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

26. Lilly 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

27. Guo 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(3):1-6. https://doi.org/10.1200/po.19.00021

Glossary

MTC = medullary thyroid cancer

NSCLC = non-small cell lung cancer

RET = rearranged during transfection

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Datum fӧr senaste ӧversyn January 25, 2021


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