A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
Summary
The reason for this study is to see if the study drug selpercatinib compared to a standard treatment is effective and safe in participants with rearranged during transfection (RET) fusion-positive non-squamous non-small cell lung cancer (NSCLC) that has spread to other parts of the body. Participants who are assigned to the standard treatment and discontinue due to progressive disease have the option to potentially crossover to selpercatinib.
Timeline
- Start
- 2020-02-17
- Primary completion
- 2023-05-01
- Completion
- 2030-06
Outcome
Met primary endpoint
registry p = 0.0002; Hazard Ratio (HR) 0.465 (95% CI 0.309 to 0.699) NCT04194944 ↗
registry p = 0.0001; Hazard Ratio (HR) 0.482 (95% CI 0.331 to 0.700) NCT04194944 ↗
paper Treatment with selpercatinib led to significantly longer progression-free survival than platinum-based chemotherapy with or without pembrolizumab among patients with advanced RET fusion-positive NSCLC. PMID 37870973 ↗
release “In the Phase 3 LIBRETTO-431 study, Retevmo more than doubled progression-free survival (PFS)” lilly.com ↗
Publications
- Duke ES, Bradford D, Sinha AK, Li X, Mishra-Kalyani PS, de Claro RA, Larkins E, Drezner N. Selpercatinib and the Crossover Conundrum: Potential Impact of Postprogression Therapies on Overall Survival. J Clin Oncol. 2026 May 20;44(15):1457-1464. doi: 10.1200/JCO-25-02375. Epub 2026 Apr 17.
- Perol M, Solomon BJ, Goto K, Park K, Nadal E, Bria E, Martin C, Bar J, Williams JN, Puri T, Li J, Uh MK, Lin BK, Zhou C. CNS Protective Effect of Selpercatinib in First-Line RET Fusion-Positive Advanced Non-Small Cell Lung Cancer. J Clin Oncol. 2024 Jul 20;42(21):2500-2505. doi: 10.1200/JCO.24.00724. Epub 2024 Jun 3.
- Zhou C, Solomon B, Loong HH, Park K, Perol M, Arriola E, Novello S, Han B, Zhou J, Ardizzoni A, Mak MP, Santini FC, Elamin YY, Drilon A, Wolf J, Payakachat N, Uh MK, Rajakumar D, Han H, Puri T, Soldatenkova V, Lin AB, Lin BK, Goto K; LIBRETTO-431 Trial Investigators. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC. N Engl J Med. 2023 Nov 16;389(20):1839-1850. doi: 10.1056/NEJMoa2309457. Epub 2023 Oct 21.
- Claerhout S, Lehnert S, Vander Borght S, Spans L, Dooms C, Wauters E, Vansteenkiste J, Weynand B, Deraedt K, Bourgain C, Vanden Bempt I. Targeted RNA sequencing for upfront analysis of actionable driver alterations in non-small cell lung cancer. Lung Cancer. 2022 Apr;166:242-249. doi: 10.1016/j.lungcan.2022.02.013. Epub 2022 Mar 1.
- Solomon BJ, Zhou CC, Drilon A, Park K, Wolf J, Elamin Y, Davis HM, Soldatenkova V, Sashegyi A, Lin AB, Lin BK, F Loong HH, Novello S, Arriola E, Perol M, Goto K, Santini FC. Phase III study of selpercatinib versus chemotherapy +/- pembrolizumab in untreated RET positive non-small-cell lung cancer. Future Oncol. 2021 Mar;17(7):763-773. doi: 10.2217/fon-2020-0935. Epub 2020 Nov 5.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Comparator | Carboplatin | Small molecule | 5 unknown | Intravenous |
| Comparator | Cisplatin | Other / unclassified | 75 mg/m2 | Intravenous |
| Comparator | Pembrolizumab | Monoclonal antibody | 200 mg | Intravenous |
| Comparator | Pemetrexed | Small molecule | 500 mg/m2 | Intravenous |
| Subject | Selpercatinib | Small molecule | 160 mg | Oral |