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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04280081
Recruitment Status : Recruiting
First Posted : February 21, 2020
Last Update Posted : September 17, 2020
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The reason for this study is to see if the study drug selpercatinib is safe and effective in participants in China with rearranged during transfection (RET) fusion-positive solid tumors, medullary thyroid cancer (MTC) and other tumors with RET activation.

Condition or disease Intervention/treatment Phase
Solid Tumor Medullary Thyroid Cancer Drug: Selpercatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Oral Selpercatinib (LOXO-292) in Patients With Advanced Solid Tumors, Including Rearranged in Transfection (RET) Fusion-Positive Solid Tumors, Medullary Thyroid Cancer and Other Tumors With RET Activation
Actual Study Start Date : March 16, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : April 30, 2023

Arm Intervention/treatment
Experimental: Selpercatinib
Selpercatinib given orally.
Drug: Selpercatinib
Administered orally
Other Names:
  • LY3527723
  • LOXO-292

Primary Outcome Measures :
  1. Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by Independent Review Committee [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 30 Months) ]
    ORR: Percentage of Participants with CR or PR by IRC

Secondary Outcome Measures :
  1. Duration of Response (DoR) by IRC [ Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months) ]
    DoR by IRC

  2. Time to Response (TTR) by IRC [ Time Frame: Baseline to Date of CR or PR (Estimated at up to 30 Months) ]
    TTR by IRC

  3. Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve CR, PR or Stable Disease (SD) With a Duration of At Least 16 or More Weeks [ Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Estimated at up to 30 Months) ]
    CBR: Percentage of Participants Who Achieve CR, PR or SD With a Duration of At Least 16 or More Weeks

  4. Progression Free Survival (PFS) by IRC [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 30 Months) ]
    PFS by IRC

  5. Overall Survival (OS) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 60 Months) ]

  6. Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib [ Time Frame: Baseline through End of Study (Estimated at up to 60 Months) ]
    PK: AUC of Selpercatinib

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Participants with a locally advanced or metastatic solid tumor.
  • Evidence of a RET gene alteration in tumor and/or blood.
  • Measurable or non-measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, with no sudden deterioration 2 weeks prior to the first dose of study treatment.
  • Archived tumor tissue sample available for cohort 1 and 2.
  • Cohorts 1 and 2: failed or intolerant to standard of care.
  • Cohorts 1-2: enrollment will be restricted to participants with evidence of a RET gene alteration in tumor (i.e., not just blood). However, a positive germline DNA test for a RET gene mutation as defined in the protocol is acceptable in the absence of tumor tissue testing for participants with MTC.
  • Cohorts 1-2: at least one measurable lesion as defined by RECIST v1.1 and not previously irradiated (unless progressive disease for the irradiated lesion[s] has been radiographically documented).

Exclusion Criteria:

  • Cohorts 1-2, an additional validated oncogenic driver that could cause resistance to selpercatinib treatment if known.
  • Prior treatment with a selective RET inhibitor(s) (including investigational selective RET inhibitor(s), such as BLU-667, RXDX-105, etc).
  • Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
  • Any unresolved toxicities from prior therapy greater than common terminology criteria for adverse events (CTCAE) Grade 1 except where otherwise noted in this eligibility criteria at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum therapy-related neuropathy.
  • Symptomatic primary central nervous system (CNS) tumor, symptomatic CNS metastasis, leptomeningeal carcinomatosis, or untreated spinal cord compression.
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) > 470 milliseconds.
  • History of Human Immunodeficiency Virus (known HIV 1/2 antibodies positive); participants with unknown HIV status do not need to be tested.
  • History of active hepatitis B (known positive hepatitis B surface antigen [HbsAg] and quantitative hepatitis B DNA greater than the upper limit of detection of the assay) or C (known positive hepatitis C antibody and quantitative hepatitis C RNA greater than the upper limit of detection of the assay); participants with unknown hepatitis B/hepatitis C status do not need to be tested.
  • Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. Screening for chronic conditions is not required.
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
  • Uncontrolled symptomatic hyperthyroidism or hypothyroidism
  • Uncontrolled symptomatic hypercalcemia or hypocalcemia.
  • Concurrent use of drugs known to prolong QTc.
  • Pregnancy or lactation. Breast-feeding should be interrupted when selpercatinib is started; breast-feeding can be resumed 3 months after discontinuation of selpercatinib.
  • Active second malignancy other than minor treatment of indolent cancers with prior sponsor approval.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04280081

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Contact: There will be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

Show Show 19 study locations
Sponsors and Collaborators
Eli Lilly and Company
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eli Lilly and Company
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Responsible Party: Eli Lilly and Company Identifier: NCT04280081    
Other Study ID Numbers: 17492
J2G-GH-JZJK ( Other Identifier: Eli Lilly and Company )
First Posted: February 21, 2020    Key Record Dates
Last Update Posted: September 17, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Eli Lilly and Company:
Non-Small Cell Lung Cancer
Targeted Therapy
Medullary Thyroid Carcinoma
Thyroid Cancer
RET Alteration
Additional relevant MeSH terms:
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Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Thyroid Neoplasms
Brain Stem Neoplasms
Thyroid Diseases
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Infratentorial Neoplasms
Brain Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases