Clinical Trials /

A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

NCT04194944

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 17479
  • SECONDARY ID: J2G-MC-JZJC
  • SECONDARY ID: 2019-001979-36
  • NCT ID: NCT04194944

Conditions

  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
SelpercatinibLY3527723, LOXO-292Selpercatinib
CarboplatinPemetrexed with or without Pembrolizumab
CisplatinPemetrexed with or without Pembrolizumab
PemetrexedPemetrexed with or without Pembrolizumab
PembrolizumabPemetrexed with or without Pembrolizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
SelpercatinibExperimentalSelpercatinib administered orally.
  • Selpercatinib
Pemetrexed with or without PembrolizumabActive ComparatorPemetrexed administered intravenously (IV) plus the investigator's discretion of carboplatin IV or cisplatin IV with or without pembrolizumab IV.
  • Carboplatin
  • Cisplatin
  • Pemetrexed
  • Pembrolizumab
Pemetrexed with PembrolizumabActive ComparatorPemetrexed administered IV plus the investigator's discretion of carboplatin IV or cisplatin IV with pembrolizumab IV.
  • Carboplatin
  • Cisplatin
  • Pemetrexed
  • Pembrolizumab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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)
Safety Issue:
Description:PFS by BICR (with or without Pembrolizumab)

Secondary Outcome Measures

Measure:PFS by BICR (with Pembrolizumab)
Time Frame:Baseline to Progressive Disease or Death from Any Cause (Estimated at up to 24 Months)
Safety Issue:
Description:PFS by BICR (with Pembrolizumab)
Measure:PFS2 (with or without Pembrolizumab)
Time Frame:Baseline to Second Disease Progression or Death from Any Cause (Estimated at up to 36 Months)
Safety Issue:
Description:PFS2 (with or without Pembrolizumab)
Measure: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)
Safety Issue:
Description:ORR: Percentage of Participants with CR or PR by BICR (with Pembrolizumab)
Measure: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)
Safety Issue:
Description:ORR: Percentage of Participants with CR or PR by BICR (with or without Pembrolizumab)
Measure: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)
Safety Issue:
Description:DOR by BICR (with Pembrolizumab)
Measure:DOR by BICR (with or without Pembrolizumab)
Time Frame:Baseline through Disease Progression or Death (Estimated at up to 24 Months)
Safety Issue:
Description:DOR by BICR (with or without Pembrolizumab)
Measure:Overall Survival (OS) (with Pembrolizumab)
Time Frame:Baseline to Date of Death from Any Cause (Estimated at up to 48 Months)
Safety Issue:
Description:OS (with Pembrolizumab)
Measure:OS (with or without Pembrolizumab)
Time Frame:Baseline to Date of Death from Any Cause (Estimated at up to 48 Months)
Safety Issue:
Description:OS (with or without Pembrolizumab)
Measure: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)
Safety Issue:
Description:Intracranial ORR: Percentage of Participants with Intracranial CR or PR by BICR (with or without Pembrolizumab)
Measure:Intracranial DOR by BICR (with or without Pembrolizumab)
Time Frame:Baseline through Disease Progression or Death (Estimated at up to 24 Months)
Safety Issue:
Description:Intracranial DOR by BICR (with or without Pembrolizumab)
Measure:Time to Deterioration of Pulmonary Symptoms (with Pembrolizumab)
Time Frame:Baseline to Deterioration of Pulmonary Symptoms (Estimated at up to 24 Months)
Safety Issue:
Description:Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) (with Pembrolizumab)
Measure:Time to Deterioration of Pulmonary Symptoms (with or without Pembrolizumab)
Time Frame:Baseline to Deterioration of Pulmonary Symptoms (Estimated at up to 24 Months)
Safety Issue:
Description:Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-SAQ (with or without Pembrolizumab)
Measure: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
Safety Issue:
Description: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)

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eli Lilly and Company

Trial Keywords

  • targeted therapy

Last Updated

December 9, 2019