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)

February 29, 2024 updated by: Loxo Oncology, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

77

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Beijing
      • Beijing, Beijing, China, 100142
        • Beijing Cancer Hospital
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Southern Medical University Nanfang Hospital
      • Guangzhou, Guangdong, China, 510120
        • The First Affiated Hospital Of Guangzhou Medical University
    • Hunan
      • Changsha, Hunan, China, 410013
        • Hunan Cancer Hospital
    • Jilin
      • Changchun, Jilin, China, 130000
        • Jilin Cancer Hospital
    • Shandong
      • Jinan, Shandong, China, 250013
        • Jinan Central Hospital
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center
      • Shanghai, Shanghai, China, 200120
        • Shanghai East Hospital
    • Shanghai/China
      • Shanghai, Shanghai/China, China, 200030
        • Shanghai Chest Hospital
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Tianjin Medical University Cancer Institute & Hospital
    • Zhejiang
      • HangZhou, Zhejiang, China, 310022
        • Zhejiang Cancer Hospital
      • Hangzhou, Zhejiang, China, 310014
        • Zhejiang Provincial People's Hospital
      • Hangzhou, Zhejiang, China, 310003
        • The First Affiliated Hospital, Zhejiang University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Selpercatinib
Selpercatinib 160 milligrams (mg) administered orally twice daily (BID).
Administered orally
Other Names:
  • LOXO-292
  • LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Analysis Set: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by Independent Review Committee (IRC)
Time Frame: Date of First Dose to Disease Progression or Death (up to 12 Months)
ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.
Date of First Dose to Disease Progression or Death (up to 12 Months)
Enrolled Population: Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) as Assessed by IRC
Time Frame: Date of First Dose to Disease Progression or Death (Up to 12 months)
ORR is the summary measure of best overall response (BOR) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR is defined as the best response designation for each participant that is recorded between the date of the first dose of selpercatinib and the date of documented disease progression per RECIST 1.1 or the date of subsequent therapy, whichever occurs first, and subsequently confirmed. BOR will be categorized as complete response (CR), partial response (PR). CR is defined as Disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR At least 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD.
Date of First Dose to Disease Progression or Death (Up to 12 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Enrolled Population: Duration of Response (DoR) as Assessed by IRC
Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first), and subsequently confirmed, to the date of disease progression or death, whichever occurs earlier.
Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
Enrolled Population: Time to Response (TTR) as Assessed by IRC
Time Frame: Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)
TTR is defined as the number of months elapsed between the date of the first dose of selpercatinib and the first documentation of objective response (CR or PR, whichever occurs earlier) that is subsequently confirmed.
Date of First Dose to First Occurrence of Confirmed Tumor Response (Up to 6 months)
Enrolled Population: Time to Best Response (TTBR) as Assessed by IRC
Time Frame: Date of First Dose to First Occurrence of PR (If Subject's Best Overall Response [BOR] is PR) or CR (If Subject's BOR is CR) (Up to 8 months)
TTR is defined as the number of months elapsed between the date of the first dose of selpercatinib and the first documentation of objective response (CR or PR, whichever occurs earlier) that is subsequently confirmed.
Date of First Dose to First Occurrence of PR (If Subject's Best Overall Response [BOR] is PR) or CR (If Subject's BOR is CR) (Up to 8 months)
Enrolled Population: 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 as Assessed by IRC
Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)
CBR based on the percentage of participants with best overall response of CR, PR, or stable disease (SD) lasting 16 or more weeks following initiation of selpercatinib as assessed by IRC. CR is defined as disappearance of all target lesions. Any pathologic nodes (whether target or non-target lesions) must have a reduction in short axis diameter (SAD) to less than 10 mm. PR is defined as at least a 30% decrease in the sum of the diameters (SOD) (LD for non-nodal lesions) and SAD for nodal lesions) of target lesions, taking as reference the baseline sum LD. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Baseline through Disease Progression or Death Due to Any Cause (Up to 12 Months)
Enrolled Population: Progression Free Survival (PFS) as Assessed by IRC
Time Frame: Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)
PFS is defined as the number of months elapsed between the date of the first dose and the earliest date of documented disease progression or death (whatever the cause). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest sum on study) for target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5.0 mm. Progressive disease for non-target lesion is defined as the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Baseline to Progressive Disease or Death from Any Cause (Up to 12 Months)
Enrolled Population: Overall Survival (OS)
Time Frame: Baseline to Date of Death from Any Cause (Up to 12 Months)
OS is defined as the number of months elapsed between the date of the first dose and the date of death (whatever the cause). Participants who are alive or lost to follow-up as of the data cutoff date will be right-censored.
Baseline to Date of Death from Any Cause (Up to 12 Months)
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Selpercatinib
Time Frame: PK: Cycle 1 Day 1: Predose, 1 h, 2, h, 4 h, 8 h, 12 h postdose PK: Cycle 1 Day 8: Predose, 1 h, 2, h, 4 h, 8 h postdose
Serial blood samples for intensive PK monitoring will be collected for 12 participants.
PK: Cycle 1 Day 1: Predose, 1 h, 2, h, 4 h, 8 h, 12 h postdose PK: Cycle 1 Day 8: Predose, 1 h, 2, h, 4 h, 8 h postdose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 16, 2020

Primary Completion (Actual)

March 25, 2021

Study Completion (Estimated)

November 20, 2025

Study Registration Dates

First Submitted

February 20, 2020

First Submitted That Met QC Criteria

February 20, 2020

First Posted (Actual)

February 21, 2020

Study Record Updates

Last Update Posted (Estimated)

March 1, 2024

Last Update Submitted That Met QC Criteria

February 29, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing 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.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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