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E-Poster Display

1927TiP - LIBRETTO-531: Selpercatinib in patients with treatment (Tx)-naïve RET-mutant medullary thyroid cancer (MTC)

Date

17 Sep 2020

Session

E-Poster Display

Presenters

Jorge Hernando

Citation

Annals of Oncology (2020) 31 (suppl_4): S1026-S1033. 10.1016/annonc/annonc293

Authors

J. Hernando1, V. Tarasova2, M.I. Hu3, E.J. Sherman4, M.S. Brose5, B. Robinson6, M. Tahara7, L.J. Wirth8, A. Sashegyi9, V. Soldatenkova9, B.K. Lin9, J. Wright9, A.O. Hoff10, S. Leboulleux11, R. Elisei12, J. Capdevila13

Author affiliations

  • 1 Medical Oncology Department, Vall d'Hebron University Hospital, 8035 - Barcelona/ES
  • 2 Endocrinology, H. Lee Moffitt Cancer Center & Research Institute, 33612 - Tampa/US
  • 3 Endocrine Neoplasia And Hormonal, University of Texas M. D. Anderson Cancer Center, 77030 - Houston/US
  • 4 Medical Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 5 Otorhinolaryngology: Head And Neck Surgery, University of Pennsylvania- Clinical Research Building, 19104 - Philadelphia/US
  • 6 Cancer Genetics Unit, The University of Sydney, Sydney/AU
  • 7 Head And Neck Medical Oncology Dept., National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 8 Center For Head And Neck Cancers, Massachusetts General Hospital, Harvard Medical School, 2114 - Boston/US
  • 9 Oncology, Eli Lilly and Company, 46285 - INDIANAPOLIS/US
  • 10 Endocrinology, Instituto do Cancer do Estado de São Paulo, Sao Paulo/BR
  • 11 Medecine Nuclear And Endocrine Oncology, Gustave Roussy, 94805 - Villejuif/FR
  • 12 Endocrinology, University of Pisa, Pisa/IT
  • 13 Medical Oncology Department, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
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Resources

Abstract 1927TiP

Background

Activating RET gene alterations are common in MTC, yet current RET mutant (mut) MTC Tx options are not ideal for many patients (pts). Despite improvements in progression free survival (PFS) and response rate with multikinase inhibitors (MKI), notable toxicity and tumor resistance may limit their long-term efficacy in RETmut MTC. Selpercatinib (LOXO-292), a selective and potent inhibitor of RET alterations including M918T, MKI resistance-associated V804M, and others, showed evidence of robust antitumor activity [objective response rate (ORR) 73% in phase I/II] and a well-tolerated profile in pts with MKI-naïve, advanced RETmut MTC. This global, open-label, randomized, controlled, phase III trial will compare selpercatinib to physician choice of cabozantinib or vandetanib in pts with MKI-naïve progressive advanced or metastatic RETmut MTC.

Trial design

Pts (n=400) will be randomized 2:1 to Arm A: selpercatinib (160 mg BID) or Arm B: physician choice of cabozantinib (140 mg QD) or vandetanib (300 mg QD). Stratification factors are mutation: M918T vs other and intended Tx if randomized to Arm B: cabozantinib vs vandetanib. For Arm B pts, crossover to selpercatinib is allowed at progression. Tx will continue until progressive disease (PD), unacceptable toxicity, withdrawal of consent or death. Major eligibility criteria are age ≥12 years; unresectable locally advanced or metastatic disease; RETmut identification by PCR or NGS on germline DNA, tumor or blood; sufficient tissue for central analysis of RET mutation; MKI-Tx naive; measurable disease and PD within 14 months by RECIST 1.1; ECOG performance status 0-2; adequate organ function. Exclusion criteria are presence of other oncogenic drivers or symptomatic CNS metastases. Tumor evaluations will be performed every 8 weeks for 24 weeks and then every 12 weeks. Treatment failure free survival, including radiographic PD, unacceptable toxicity (predefined by protocol) or death, is the primary endpoint. The key type I error controlled secondary endpoint is PFS by independent review. Other secondary endpoints are physician assessed PFS, ORR/duration of response, overall survival, PFS2, ORR by RET mutation status, safety profile and pharmacokinetics.

Clinical trial identification

NCT04211337.

Editorial acknowledgement

Hannah Davis, PhD, an Eli Lilly and Company employee, provided medical writing support.

Legal entity responsible for the study

Eli Lilly and Company.

Funding

Eli Lilly and Company.

Disclosure

J. Hernando: Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ipsen; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AAA; Speaker Bureau/Expert testimony: Angelini. V. Tarasova: Research grant/Funding (self), Travel/Accommodation/Expenses: Eli Lilly and Company; Research grant/Funding (self), Travel/Accommodation/Expenses: Exelixis. M.I. Hu: Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Blueprint Medicines. E.J. Sherman: Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: COTA Consulting; Advisory/Consultancy: Novartis; Advisory/Consultancy: Goldilocks; Advisory/Consultancy: Eisai; Advisory/Consultancy: Bristol-Myers Squibb. M.S. Brose: Advisory/Consultancy: Loxo Oncology; Advisory/Consultancy: Eli Lilly and Company; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Blueprint Medicines. B. Robinson: Advisory/Consultancy: Eisai; Advisory/Consultancy: Loxo Oncology. M. Tahara: Honoraria (self), Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bristol-Myers Squibb; Honoraria (self): Eisai; Honoraria (self): Merck Serono; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Ono Pharmaceutical; Advisory/Consultancy: Amgen; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): Rakuten Medical; Research grant/Funding (institution): Loxo; Research grant/Funding (institution): Novartis. L.J. Wirth: Advisory/Consultancy: Eisai; Speaker Bureau/Expert testimony: Bayer; Advisory/Consultancy: Genentech; Advisory/Consultancy: Loxo; Advisory/Consultancy: Merck. A. Sashegyi, V. Soldatenkova B.K. Lin, J. Wright: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly & Company. A.O. Hoff: Research grant/Funding (self): Bayer; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): Exelixis; Speaker Bureau/Expert testimony, (Latin American Thyroid Society Meeting - Buenos Aires 2019): Bayer; Advisory/Consultancy: Eli Lilly. S. Leboulleux: Research grant/Funding (self): Novartis; Research grant/Funding (self): Sanofi Genzyme. R. Elisei: Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony: Sanofi-Genzyme; Advisory/Consultancy, Speaker Bureau/Expert testimony: Loxo Oncology; Advisory/Consultancy, Speaker Bureau/Expert testimony: Ipsen. All other authors have declared no conflicts of interest.

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