Carcinoma, Non-Small-Cell Lung
Conditions
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.
Interventions
DRUGSelpercatinib
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Loxo Oncology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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), next generation sequencing (NGS), or another molecular test per sponsor's approval. * 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| EFS | 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) | Randomization to death from any cause (estimated as up to 9 years)] | OS |
| Time to Distant Disease Recurrence in the Central Nervous System (CNS) | 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) | 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 | 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 | 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 | 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, India, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Puerto Rico, Romania, Russia, Singapore, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORCall 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
Outcome results
None listed