Klinisk utveckling av Retsevmo® ▼ (selperkatinib)

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 Cancers^15-23

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: 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

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.