A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC) (LIBRETTO-432)

• ClinicalTrials.gov Identifier: NCT04819100
• Recruitment Status: Recruiting
• First Posted: March 26, 2021
• Last Update Posted: March 8, 2023
• Sponsor: Loxo Oncology, Inc.
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company ( Loxo Oncology, Inc. )

Tracking Information

• First Submitted Date: March 25, 2021
• First Posted Date: March 26, 2021
• Last Update Posted Date: March 8, 2023
• Actual Study Start Date: December 20, 2021
• Estimated Primary Completion Date: August 31, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2021)

Event-Free Survival (EFS) [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years) ]

EFS by Investigator Assessment in the Primary Analysis Population

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 19, 2022)

• EFS [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years) ]
  EFS by investigator assessment in the overall population
• Overall Survival (OS) [ Time Frame: Randomization to death from any cause (estimated as up to 9 years)] ]
  OS
• EFS [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)] ]
  EFS by blinded independent central review (BICR)
• Time to Distant Disease Recurrence in the Central Nervous System (CNS) [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years) ]
  Time to distant disease recurrence in the CNS by investigator assessment and BICR
• Progression Free Survival on the Next Line of Treatment (PFS2) [ Time Frame: Randomization to disease progression on the next line of treatment or death from any cause (estimated as up to 9 years) ]
  PFS2 by investigator assessment
• Positive Predictive Value (PPV) of Rearranged during Transfection (RET) Tests from Investigator-Identified Laboratories with Respect to the Lilly-Designated RET Test [ Time Frame: Baseline ]
  PPV of RET Tests from Investigator-Identified Laboratories with Respect to the Lilly-Designated RET Test
• Mean Change from Baseline over Time in NSCLC Symptoms [ Time Frame: Baseline to treatment discontinuation (estimated as up to 3 years) ]
  NSCLC symptoms will be measured using the 7-item NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ). The NSCLC-SAQ measures the severity/frequency of the following core symptoms: Cough, pain, dyspnea, fatigue, and appetite. Raw scores range from 0 to 4 and the total score ranges from 0-20. Higher scores represent worse symptoms.
• Mean Change from Baseline over Time in Physical Function [ Time Frame: Baseline to treatment discontinuation (estimated as up to 3 years) ]
  Physical function will be measured by the 5 physical function items in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) (also known as the EORTC IL 19 questionnaire). Raw scores range from 0-20. Higher scores indicate worst function.

Original Secondary Outcome Measures (submitted: March 25, 2021)

• EFS [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years) ]
  EFS by investigator assessment in the overall population
• Overall Survival (OS) [ Time Frame: Randomization to death from any cause (estimated as up to 9 years)] ]
  OS
• EFS [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years)] ]
  EFS by blinded independent central review (BICR)
• Time to Distant Disease Recurrence in the Central Nervous System (CNS) [ Time Frame: Randomization to disease recurrence/progression or death from any cause (estimated as up to 7 years) ]
  Time to distant disease recurrence in the CNS by investigator assessment and BICR
• Progression Free Survival on the Next Line of Treatment (PFS2) [ Time Frame: Randomization to disease progression on the next line of treatment or death from any cause (estimated as up to 9 years) ]
  PFS2 by investigator assessment
• Positive Predictive Value (PPV) of Local Lab Tests Compared to Central Lab Test to Detect Rearranged during Transfection (RET) Gene Fusion [ Time Frame: Baseline ]
  PPV of local lab tests compared to central lab test to detect RET gene fusion
• Mean Change from Baseline over Time in NSCLC Symptoms [ Time Frame: Baseline to treatment discontinuation (estimated as up to 3 years) ]
  NSCLC symptoms will be measured using the 7-item NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ). The NSCLC-SAQ measures the severity/frequency of the following core symptoms: Cough, pain, dyspnea, fatigue, and appetite. Raw scores range from 0 to 4 and the total score ranges from 0-20. Higher scores represent worse symptoms.
• Mean Change from Baseline over Time in Physical Function [ Time Frame: Baseline to treatment discontinuation (estimated as up to 3 years) ]
  Physical function will be measured by the 5 physical function items in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) (also known as the EORTC IL 19 questionnaire). Raw scores range from 0-20. Higher scores indicate worst function.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Selpercatinib After Surgery or Radiation in Participants With Non-Small Cell Lung Cancer (NSCLC)
• Official Title: LIBRETTO-432: A Placebo-controlled Double-Blinded Randomized Phase 3 Study of Adjuvant Selpercatinib Following Definitive Locoregional Treatment in Participants With Stage IB-IIIA RET Fusion-Positive NSCLC
• Brief Summary: The reason for this study is to see if the study drug, selpercatinib, compared to placebo is effective and safe in delaying cancer return in participants with early-stage non-small cell lung cancer (NSCLC), who have already had surgery or radiation. Participants who are assigned to placebo and stop the study drug because their disease comes back or gets worse have the option to potentially crossover to selpercatinib. Participation could last up to three years.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Selpercatinib
  Administered orally.
  Other Names:

  • LY3527723
  • LOXO-292
• Drug: Placebo
  Administered orally.

Study Arms

• Experimental: Selpercatinib
  Selpercatinib administered orally.
  Intervention: Drug: Selpercatinib
• Placebo Comparator: Placebo
  Placebo administered orally.
  Intervention: Drug: Placebo

• Publications *: Tsuboi M, Goldman JW, Wu YL, Johnson ML, Paz-Ares L, Yang JC, Besse B, Su W, Chao BH, Drilon A. LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer. Future Oncol. 2022 Sep;18(28):3133-3141. doi: 10.2217/fon-2022-0656. Epub 2022 Aug 11.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 25, 2021): 170
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 30, 2032
• Estimated Primary Completion Date: August 31, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Must have histologically confirmed Stage IB, II, or IIIA NSCLC.
• Must have an activating RET gene fusion in tumor based on polymerase chain reaction (PCR) or next generation sequencing (NGS).

• Must have received definitive locoregional therapy with curative intent (surgery or radiotherapy) for Stage IB, II, or IIIA NSCLC.

  -- Must have undergone the available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, based on the investigator's discretion.

• Maximum time allowed between definitive therapy completion and randomization must be:

  • 10 weeks if no chemotherapy was administered
  • 26 weeks if adjuvant chemotherapy was administered
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 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 the study and for at least 2 weeks after last dose of study drug.

Exclusion Criteria:

• Additional oncogenic drivers in NSCLC, if known.
• Evidence of small cell lung cancer.
• Clinical or radiologic evidence of disease recurrence or progression following definitive therapy.
• Known or suspected interstitial fibrosis or interstitial lung disease or history of (noninfectious) pneumonitis that required steroids.
• Clinically significant active cardiovascular disease or history of myocardial infarction within six months prior to planned start of selpercatinib or prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) greater than 470 milliseconds.
• Have known uncontrolled human immunodeficiency virus (HIV)-1/2 infection.
• Have known active hepatitis B or C.
• Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment.
• Major surgery within 4 weeks prior to planned start of selpercatinib.
• Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
• Other malignancy unless nonmelanoma skin cancer, carcinoma in situ of the cervix or other in situ cancers or a malignancy diagnosed greater than or equal to two years previously and not currently active.
• Pregnancy or lactation.
• Prior treatment with a selective RET inhibitor (e.g. selpercatinib or pralsetinib).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: There may 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: Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, India, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Puerto Rico, Romania, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04819100
• Other Study ID Numbers: 18126; J2G-MC-JZJX ( Other Identifier: Eli Lilly and Company ); 2020-005191-35 ( 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

• 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: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company ( Loxo Oncology, Inc. )
• Original Responsible Party: Eli Lilly and Company
• Current Study Sponsor: Loxo Oncology, Inc.
• Original Study Sponsor: Eli Lilly and Company
• Collaborators: Eli Lilly and Company

Investigators

• 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: March 2023