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Trial record 1 of 1 for:    LIBRETTO-431
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A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer (LIBRETTO-431)

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.
 
ClinicalTrials.gov Identifier: NCT04194944
Recruitment Status : Recruiting
First Posted : December 11, 2019
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE December 9, 2019
First Posted Date  ICMJE December 11, 2019
Last Update Posted Date July 7, 2020
Actual Study Start Date  ICMJE March 16, 2020
Estimated Primary Completion Date December 13, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 9, 2019)
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (with or without Pembrolizumab) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 24 Months) ]
PFS by BICR (with or without Pembrolizumab)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2019)
  • PFS by BICR (with Pembrolizumab) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 24 Months) ]
    PFS by BICR (with Pembrolizumab)
  • PFS2 (with or without Pembrolizumab) [ Time Frame: Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 36 Months) ]
    PFS2 (with or without Pembrolizumab)
  • Overall Response Rate (ORR): Percentage of Participants with Complete Response (CR) or Partial Response (PR) by BICR (with Pembrolizumab) [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 24 Months) ]
    ORR: Percentage of Participants with CR or PR by BICR (with Pembrolizumab)
  • ORR: Percentage of Participants with CR or PR by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 24 Months) ]
    ORR: Percentage of Participants with CR or PR by BICR (with or without Pembrolizumab)
  • Duration of Response (DoR) by BICR (with Pembrolizumab) [ Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Estimated at up to 24 Months) ]
    DOR by BICR (with Pembrolizumab)
  • DOR by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 24 Months) ]
    DOR by BICR (with or without Pembrolizumab)
  • Overall Survival (OS) (with Pembrolizumab) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 48 Months) ]
    OS (with Pembrolizumab)
  • OS (with or without Pembrolizumab) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 48 Months) ]
    OS (with or without Pembrolizumab)
  • Intracranial ORR: Percentage of Participants with Intracranial CR or PR by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 24 Months) ]
    Intracranial ORR: Percentage of Participants with Intracranial CR or PR by BICR (with or without Pembrolizumab)
  • Intracranial DOR by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through Disease Progression or Death (Estimated at up to 24 Months) ]
    Intracranial DOR by BICR (with or without Pembrolizumab)
  • Time to Deterioration of Pulmonary Symptoms (with Pembrolizumab) [ Time Frame: Baseline to Deterioration of Pulmonary Symptoms (Estimated at up to 24 Months) ]
    Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) (with Pembrolizumab)
  • Time to Deterioration of Pulmonary Symptoms (with or without Pembrolizumab) [ Time Frame: Baseline to Deterioration of Pulmonary Symptoms (Estimated at up to 24 Months) ]
    Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-SAQ (with or without Pembrolizumab)
  • The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement) [ Time Frame: Baseline ]
    The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
Official Title  ICMJE LIBRETTO-431: A Multicenter, Randomized, Open-Label, Phase 3 Trial Comparing LOXO-292 to Platinum-Based and Pemetrexed Therapy With or Without Pembrolizumab as Initial Treatment of Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Selpercatinib
    Administered orally
    Other Names:
    • LY3527723
    • LOXO-292
  • Drug: Carboplatin
    Administered IV
  • Drug: Cisplatin
    Administered IV
  • Drug: Pemetrexed
    Administered IV
  • Drug: Pembrolizumab
    Administered IV
Study Arms  ICMJE
  • Experimental: Selpercatinib
    Selpercatinib administered orally.
    Intervention: Drug: Selpercatinib
  • Active Comparator: Pemetrexed with or without Pembrolizumab
    Pemetrexed administered intravenously (IV) plus the investigator's discretion of carboplatin IV or cisplatin IV with or without pembrolizumab IV.
    Interventions:
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Pemetrexed
    • Drug: Pembrolizumab
  • Active Comparator: Pemetrexed with Pembrolizumab
    Pemetrexed administered IV plus the investigator's discretion of carboplatin IV or cisplatin IV with pembrolizumab IV.
    Interventions:
    • Drug: Carboplatin
    • Drug: Cisplatin
    • Drug: Pemetrexed
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 9, 2019)
400
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 13, 2026
Estimated Primary Completion Date December 13, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed, Stage IIIB-IIIC or Stage IV non-squamous NSCLC that is not suitable for radical surgery or radiation therapy.
  • A RET gene fusion in tumor and/or blood from a qualified laboratory.
  • Tumor tissue in sufficient quantity to allow for retrospective central analysis of RET fusion status.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Adequate hematologic, hepatic and renal function.
  • Willingness of men and women of reproductive potential to observe conventional and highly effective birth control for the duration of treatment and for 6 months after.
  • Ability to swallow capsules.

Exclusion Criteria:

  • Additional validated oncogenic drivers in NSCLC if known.
  • Prior systemic therapy for metastatic disease. Chemotherapy in the adjuvant/neoadjuvant setting is permitted if it was completed at least 12 months prior to randomization.
  • Major surgery within 3 weeks prior to planned start of selpercatinib.
  • Radiotherapy for palliation within 1 week of the first dose of study treatment or within 6 months prior to the first dose of study treatment if more than 30 Gy to the lung.
  • Symptomatic central nervous system (CNS) metastases, 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.
  • Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment.
  • Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
  • Pregnancy or lactation.
  • Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or malignancy diagnosed ≥2 years previously and not currently active.
  • Symptomatic ascites or pleural effusion.
  • Requiring chronic treatment with steroids.

Exclusion Criteria for Participants Receiving Pembrolizumab:

  • History of interstitial lung disease or interstitial pneumonitis.
  • Active autoimmune disease or any illness or treatment that could compromise the immune system.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: There will be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 ClinicalTrials.gov@lilly.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   China,   Czechia,   France,   Germany,   Greece,   Hong Kong,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Poland,   Romania,   Russian Federation,   Singapore,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04194944
Other Study ID Numbers  ICMJE 17479
J2G-MC-JZJC ( Other Identifier: Eli Lilly and Company )
2019-001979-36 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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.
URL: http://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Loxo Oncology, Inc. a wholly owned subsidiary of Eli Lilly and Company
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP