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Trial record 1 of 1 for:    NCT04194944
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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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04194944
Recruitment Status : Active, not recruiting
First Posted : December 11, 2019
Last Update Posted : May 23, 2023
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company ( Loxo Oncology, Inc. )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Selpercatinib Drug: Carboplatin Drug: Cisplatin Drug: Pemetrexed Drug: Pembrolizumab Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: LIBRETTO-431: A Multicenter, Randomized, Open-Label, Phase 3 Trial Comparing Selpercatinib 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
Actual Study Start Date : February 17, 2020
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : July 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Selpercatinib
Selpercatinib administered orally.
 Drug: Selpercatinib
Administered orally
Other Names:
  • LY3527723
  • LOXO-292
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.
 Drug: Carboplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: Pemetrexed
Administered IV

Drug: Pembrolizumab
Administered IV
Active Comparator: Pemetrexed with Pembrolizumab
Pemetrexed administered IV plus the investigator's discretion of carboplatin IV or cisplatin IV with pembrolizumab IV.
 Drug: Carboplatin
Administered IV

Drug: Cisplatin
Administered IV

Drug: Pemetrexed
Administered IV

Drug: Pembrolizumab
Administered IV


Outcome Measures
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Primary Outcome Measures :
  1. Progression Free Survival (PFS) by Blinded Independent Central Review (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)

  2. PFS by 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)


Secondary Outcome Measures :
  1. Disease Control Rate (DCR) by BICR (with Pembrolizumab) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 24 Months) ]
    DCR by BICR (with Pembrolizumab)

  2. DCR by BICR (with or without Pembrolizumab) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 24 Months) ]
    DCR by BICR (with or without Pembrolizumab)

  3. PFS2 (with Pembrolizumab) [ Time Frame: Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 36 Months) ]
    PFS2 (with Pembrolizumab)

  4. 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)

  5. 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)

  6. 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)

  7. 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)

  8. DOR by BICR (with or without 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 or without Pembrolizumab)

  9. Overall Survival (OS) (with Pembrolizumab) [ Time Frame: Baseline to Date of Death from Any Cause (Estimated at up to 48 Months) ]
    OS (with Pembrolizumab)

  10. 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)

  11. Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 by BICR (with Pembrolizumab) [ Time Frame: Baseline through Central Nervous System (CNS) Progression or Death (Estimated at up to 24 Months) ]
    Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with Pembrolizumab)

  12. Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through CNS Progression or Death (Estimated at up to 24 Months) ]
    Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)

  13. Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab) [ Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause (Estimated at up to 24 Months) ]
    Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab)

  14. Intracranial DOR per RECIST 1.1 by BICR (with or without Pembrolizumab) [ Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause (Estimated at up to 24 Months) ]
    Intracranial DOR per RECIST 1.1 by BICR (with or without Pembrolizumab)

  15. 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)

  16. 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)

  17. 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)

  18. Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab) [ Time Frame: Baseline through CNS Progression or Death (Estimated at up to 24 Months) ]
    Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab)

  19. Time to CNS Progression per RECIST 1.1 by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through CNS Progression or Death (Estimated at up to 24 Months) ]
    Time to CNS Progression per RECIST 1.1 by BICR (with or without Pembrolizumab)

  20. Intracranial ORR: Percentage of Participants with Intracranial CR or PR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) by BICR (with Pembrolizumab) [ Time Frame: Baseline through CNS Progression or Death (Estimated at up to 24 Months) ]
    Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with Pembrolizumab)

  21. Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with or without Pembrolizumab) [ Time Frame: Baseline through CNS Progression or Death (Estimated at up to 24 Months) ]
    Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with or without Pembrolizumab)

  22. Intracranial DOR per RANO-BM by BICR (with Pembrolizumab) [ Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause (Estimated at up to 24 Months) ]
    Intracranial DOR per RANO-BM by BICR (with Pembrolizumab)

  23. Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab) [ Time Frame: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause (Estimated at up to 24 Months) ]
    Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab)


Eligibility Criteria
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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.


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

Inclusion Criteria:

  • Histologically or cytologically 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.
  • 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. Treatment (chemotherapy, immunotherapy, or biological therapy) in the adjuvant/neoadjuvant setting is permitted if it was completed at least 6 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 any radiotherapy 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, carcinomatous meningitis, 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 other in situ cancers or a malignancy diagnosed ≥2 years previously and not currently active.
  • Uncontrolled, disease related pericardial effusion 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.
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT04194944


Locations
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Sponsors and Collaborators
Loxo Oncology, Inc.
Eli Lilly and Company
Investigators
Layout table for investigator information
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
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Loxo Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04194944    
Other Study ID Numbers: 17479
J2G-MC-JZJC ( Other Identifier: Eli Lilly and Company )
2019-001979-36 ( EudraCT Number )
First Posted: December 11, 2019    Key Record Dates
Last Update Posted: May 23, 2023
Last Verified: May 2023
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.
URL: http://vivli.org/

Layout table for additional information
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 ( Loxo Oncology, Inc. ):
targeted therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
 Carboplatin
Pembrolizumab
Pemetrexed
Antineoplastic Agents
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors