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Active, Not Recruiting

NCT Number: NCT04194944

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Oncología e Investigación de Buenos Aires, Berazategui, Buenos Aires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Selpercatinib

Drug

Administered orally

Other names: LY3527723, LOXO-292

carboplatin

Drug

Administered IV

Cisplatin

Drug

Administered IV

Pemetrexed

Drug

Administered IV

Pembrolizumab

Drug

Administered IV

Primary outcomes

  1. Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)

    Time frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

    PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.

  2. PFS by BICR (With or Without Pembrolizumab)

    Time frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

    PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.

Secondary outcomes

  1. Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)

    Time frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

    DCR by BICR (with Pembrolizumab) is defined as the number of participants who achieve a BOR of complete response (CR), partial response (PR), or stable disease (SD) lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.

  2. Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)

    Time frame: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

    DCR by BICR (with or without Pembrolizumab) is defined as the number of participants who achieve a BOR of CR, PR, or SD lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.

  3. PFS2 (With Pembrolizumab)

    Time frame: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months

    PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.

  4. PFS2 (With or Without Pembrolizumab)

    Time frame: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months

    PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.

  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 Up to 31 Months

    ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.

  6. ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)

    Time frame: Baseline through Disease Progression or Death Up to 31 Months

    ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.

  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 Up to 31 Months

    DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.

  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 Up to 31 Months

    DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.

  9. Overall Survival (OS) (With Pembrolizumab)

    Time frame: Baseline to Date of Death from Any Cause Up to 38 Months

    Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data was censored on the last date the participant is known to be alive.

  10. OS (With or Without Pembrolizumab)

    Time frame: Baseline to Date of Death from Any Cause Up to 38 Months

    Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.

  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 up to 31 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 Up to 31 Months

    Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)

  13. Median 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 Up to 31 Months

    Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab)

  14. Median 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 Up to 31 Months

    Median 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 Up to 31 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 Up to 31 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. Median Time to CNS Progression Per RECIST 1.1 by BICR (With Pembrolizumab)

    Time frame: Baseline through CNS Progression or Death Up to 31 Months

    Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab)

  19. Median Time to CNS Progression Per RECIST 1.1 by BICR (With or Without Pembrolizumab)

    Time frame: Baseline through CNS Progression or Death Up to 31 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 Up to 31 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 Up to 31 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 Up to 31 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 Up to 31 Months

    Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab)

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Collaborators

  • Loxo Oncology, Inc.

Registry information

Official study 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

Acronym: LIBRETTO-431

Important dates

Study start
2020
Primary completion
2023
Study completion
2030
First posted
Dec 11, 2019
Registry last updated
Oct 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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