This study has been transitioned to CTIS with ID 2023-506784-33-00 check the CTIS register for the current data. To compare EFS of participants in the primary analysis population with Stage II-IIIA RET fusion-positive NSCLC treated with…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
RET fusion-positive, Stage IB-IIIA NSCLC
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Parameter:
- To compare Event-free survival (EFS) of participants in the primary analysis
population with Stage II-IIIA RET fusion-positive NSCLC treated with
selpercatinib versus placebo.
Outcome:
- EFS by investigator assessment in the primary analysis population.
Secondary outcome
Parameter:
- To compare EFS of participants in the overall population with Stage IB-IIIA
RET fusion-positive NSCLC treated with selpercatinib versus placebo.
Outcome:
- EFS by investigator assessment in the overall population
- overall survival (OS)
- EFS by blinded independent central review (BICR)
- Time to distant disease recurrence in the central nervous system (CNS) by
investigator assessment and BICR
- Progression-free survival on the next line of treatment (PFS2) by
investigator assessment
Parameter:
- To evaluate the safety and tolerability of selpercatinib versus placebo in
the primary analysis and overall populations.
Outcome:
- Safety per CTCAE v5.0 (including, but not limited to): incidence and severity
of TEAEs, SAEs, deaths, and clinical laboratory abnormalities.
Parameter:
- To assess/evaluate performance of RET from investigator-identified
laboratories compared to a single Lilly-designated RET test.
Outcome:
- The positive predictive value of RET tests from investigator- identified
laboratories with respect to the Lilly-designated RET test
Parameter:
- To compare onset or worsening of NSCLC symptoms in participants treated with
selpercatinib versus placebo.
Outcome:
- Mean change from baseline over time in NSCLC symptoms as measured by NSCLC
Symptom Assessment Questionnaire (NSCLC-SAQ).
- Time to onset or worsening of NSCLC symptoms as measured by NSCLC-SAQ.
Parameter:
- To compare physical functioning in participants treated with selpercatinib
versus placebo.
Outcome:
- Mean change from baseline overtime in physical functioning as measured by
European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire (EORTC-IL19) or Physical Functioning Scale (items 1-5) of the
European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire Core 30 Version 3.0 (EORTC QLQ-C30).
- Time to deterioration of physical functioning as measured by EORTCIL19 or
Physical Functioning Scale (items 1-5) of the EORTC QLQ-C30.
Background summary
Lung cancer is the most common type of cancer and the most common cause of
cancer deaths worldwide, with 2 million new cases and 1.76 million deaths in
2018 (Ferlay et al. 2019). Approximately 30% of patients with non-small cell
lung cancer (NSCLC) present with early- Stage (IB-IIIA) disease (Morgensztern
et al. 2010). The standard of care options for these patients are definitive
locoregional therapies with or without adjuvant therapy, followed by
surveillance until disease progression or recurrence (NCCN 2020). Up to
two-thirds of these patients develop recurrence and eventually die of
metastatic disease (van den Berg et al. 2015; Grass et al. 2019; Schneider et
al. 2020). As a result, there is a need for therapies that can further delay
disease recurrence or progression following definitive treatment and adjuvant
therapy currently available. In addition, while many adjuvant trials focus on
participants following complete surgical resection, they do not address the
unmet medical need of early-stage patients who cannot or do not undergo
resection and who instead receive definitive radiotherapy with a curative
intent, including participants with lung cancer that has targetable mutations
such as REarranged during Transfection (RET) fusion.
Participants with RET fusion-positive NSCLC have an identifiable oncogenic
driver. However, in the adjuvant setting these participants still receive the
same standard-of-care treatments as participants with NSCLC who do not have a
driver alteration; that is, definitive therapy, with or without prior
platinum-based chemotherapy, followed by surveillance until disease recurrence
or progression.
Given the compelling activity of selpercatinib in metastatic RET
fusion-positive NSCLC patients, a manageable safety profile, and the growing
body of evidence that targeting the underlying driver of disease can improve
outcomes regardless of stage of disease (Wu et al. 2020), it is hypothesized
that treatment with selpercatinib during the surveillance period following
completion of therapies with a curative intent; e.g., definitive locoregional
therapy (such as surgery or radiotherapy) and applicable adjuvant chemotherapy,
as determined by the investigator, will improve outcomes for patients with
Stage IB-IIIA RET fusion-positive NSCLC.
Study objective
This study has been transitioned to CTIS with ID 2023-506784-33-00 check the CTIS register for the current data.
To compare EFS of participants in the primary analysis population with Stage
II-IIIA RET fusion-positive NSCLC treated with selpercatinib versus placebo.
Study design
Study comparing the efficacy and safety of selpercatinib twice daily (BID) to
placebo in participants with RET fusion-positive Stage IB-IIIA NSCLC following
completion of therapies with a curative intent; e.g. definitive locoregional
treatment (such as surgery or radiotherapy) and applicable adjuvant
chemotherapy, as determined by the investigator.
Up to approximately 170 participants will be randomized 1:1 to receive either
selpercatinib or placebo, using the following stratification factors:
- disease stage (Stages IB, Stage II, Stage IIIA)
- prior definitive therapy (surgery, radiotherapy).
Study intervention (selpercatinib or placebo) will be administered twice a day
in continuous 28-day cycles. Treatment will continue until disease recurrence
or progression, unacceptable toxicity, or another protocol-defined reason for
study discontinuation, for a maximum treatment duration of 3 years. A
placebo-controlled trial is considered appropriate for this population since
the standard of care following definitive therapy and appropriate adjuvant
therapy for each participant is surveillance. As a result, participants will
not forego any proven active treatment by participating in this study.
Participants randomly assigned to Arm B who discontinue treatment for disease
recurrence or progression (per RECIST v1.1 and/or histopathological
confirmation) may be eligible for crossover to selpercatinib. Crossover
treatment will be optional at the discretion of the investigator.
Intervention
Study intervention (selpercatinib or placebo) will be administered twice a day
in continuous 28-day cycles. Treatment will continue until disease recurrence
or progression, unacceptable toxicity, or another protocol-defined reason for
study discontinuation, for a maximum treatment duration of 3 years. A
placebo-controlled trial is considered appropriate for this population since
the standard of care following definitive therapy and appropriate adjuvant
therapy for each participant is surveillance. As a result, participants will
not forego any proven active treatment by participating in this study.
Participants randomly assigned to Arm B who discontinue treatment for disease
recurrence or progression (per RECIST v1.1 and/or histopathological
confirmation) may be eligible for crossover to selpercatinib. Crossover
treatment will be optional at the discretion of the investigator.
Study burden and risks
Selpercatinib was well tolerated across all tumour types studied in
LIBRETTO-001 (n=702 participants), with a safety profile characterized by
recognizable toxicities, which can be monitored, reversed with dose
interruption, or addressed through dose reduction or concomitant medication.
Any grade treatment-emergent adverse event (TEAE)s were reported in 20% or more
of participants; most events were reported as low grade. The Grade 3 or 4 TEAEs
that were reported in at least 5% of participants. A total of 5% of
participants discontinued due to an adverse reaction.
Although the study procedures in Study JZJX are generally consistent with
standard of care, increased monitoring of vital signs (including blood
pressure), haematology, hepatic panels, and electrocardiograms (ECGs) occur in
the initial cycles to monitor for potential toxicities of interest.
Additionally, a data monitoring committee (DMC) will assess unblinded safety
data during the trial on a regular basis. The DMC will evaluate all
safety-related data provided for each meeting to determine whether a change in
the conduct of the trial is warranted for the safety of patients.
Given the high unmet need for additional therapies to treat RET fusion-positive
NSCLC, the clinical safety profile of selpercatinib, and the clinical efficacy
observed in patients with RET altered solid tumours (including NSCLC) in
LIBRETTO-001, the risk/benefit assessment supports
evaluation of selpercatinib in the proposed patient population.
Island House, Eastgate Business Park, Little Island na
Cork Co.
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Island House, Eastgate Business Park, Little Island na
Cork Co.
NL
Listed location countries
Age
Inclusion criteria
-Must have histologically confirmed Stage IB, II, or IIIA NSCLC. Staging will
be according to the Tumour, Node, Metastasis staging system for lung cancer
-Must have an activating RET gene fusion in tumour 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
-a. Participants must have undergone the available anti-cancer therapy
(including chemotherapy or durvalumab) or not be suitable for it, based on the
investigator's discretion.
-Patients must have completely recovered from definitive therapy (surgery or
radiotherapy) as well as adjuvant therapy at the time of randomization
-Must have Eastern Cooperative Oncology Group (ECOG) performance status score
of 0 or 1
-Adequate hematologic, hepatic and renal function
-Willingness of men and women of reproductive potential to observe
conventional and effective birth control for the duration of treatment and for
2 weeks after. Men must refrain from donating sperm and must agree to using
condom. Women of child-bearing potential must not be breastfeeding during
treatment and for at least 2 weeks after the last dose of study drug
-Written informed consent.
Exclusion criteria
-Additional oncogenic driver mutations of NSCLC, e.g., ALK fusion, or activating mutations of EGFR -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 (non-infectious) pneumonitis that required steroids -Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of study treatment or prolongation of the QT interval corrected for heart rate using Fridericia*s formula (QTcF) >470 msec on more than 1 ECG obtained during the baseline period -Uncontrolled human immunodeficiency virus (HIV)-1/2 infection -Has 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 (e.g., hypertension, diabetes, clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal carcinomatosis, pericardial effusion, or pleural effusion). Screening for chronic conditions is not required -Major surgery, excluding placement of vascular access, within 4 weeks of study drug -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 >=2 years previously and not currently active -Have a known hypersensitivity to any of the excipients of selpercatinib -Prior treatment with selpercatinib or pralsetinib -Taking a concomitant medication that is known to cause QTc prolongation -Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study. -have participated, within the last 30 days; (3 months in the UK), in a clinical study involving an investigational product. If the previous investigational product has a long half-life, 5 half-lives or 30 days (3 months in the UK) whichever is longer should have passed.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2023-506784-33-00 |
| EudraCT | EUCTR2020-005191-35-NL |
| CCMO | NL76609.091.21 |