This study is being conducted to evaluate the efficacy and safety of durvalumab adjuvant therapy compared to placebo in patients with completely resected stage II-III NSCLC who have undergone curative intent therapy (complete resection ± neoadjuvant…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of durvalumab compared to placebo as measured by DFS in
the PD-L1 TC>=1% analysis set
Secondary outcome
To assess the efficacy of durvalumab compared to placebo as measured by DFS in
all randomized patients
To assess the efficacy of durvalumab compared to placebo as measured by DFS in
the PD-L1 TC>=1% analysis set and in all randomized patients
To assess the efficacy of durvalumab compared to placebo on post-recurrence
outcomes
To assess the efficacy of durvalumab compared to placebo as measured by OS in
the PD-L1 TC>=1% analysis set and in all randomized patients
To assess patient-reported symptoms, functioning, and HRQoL in patients treated
with durvalumab compared to placebo
To investigate the relationship between a patient*s baseline PD-L1 TC
expression and efficacy of study treatments
Background summary
Up to 30% of patients with NSCLC present with surgically resectable disease.
For patients with stage II-IIIA and select IIIB disease, surgery and adjuvant
SoC chemotherapy results in 5-year disease-free survival (DFS) rates of only
~40%. Long-term survival is improved through administration of chemotherapy in
the immediate post-operative setting, yet chemotherapy in the first-line
metastatic setting results in no long-term survival benefit and
progression-free survival (PFS) benefits of only a small number of months.
There is evidence that identification of MRD through detection of ctDNA
post-surgery can accurately predict disease recurrence. Detection of MRD at a
time when there is no radiologic evidence of disease provides an opportunity
for earlier therapeutic intervention. Patients with MRD (MRD-positive [MRD+])
experience inferior recurrence-free survival compared to patients without
detectable MRD (MRD-negative [MRD-]). Therefore, MRD+ patients could benefit
from earlier intervention and escalation of treatment; furthermore, MRD-
patients (the majority of whom are cured by surgery alone) could be spared from
more intensive therapy and the resulting unnecessary toxicity.
Clinical data suggest that earlier intervention with immunotherapy as adjuvant
therapy following curative intent treatment could improve outcomes in
early-stage NSCLC, prevent progression, and circumvent the need to expose
patients to potentially more toxic chemotherapy regimens in the metastatic
setting.
Study objective
This study is being conducted to evaluate the efficacy and safety of durvalumab
adjuvant therapy compared to placebo in patients with completely resected stage
II-III NSCLC who have undergone curative intent therapy (complete resection ±
neoadjuvant and/or adjuvant therapy), and who become MRD+ during a 96-week
surveillance period.
Study design
Phase Ill, double blinded, placebo-controlled, randomized study.
Randomisation 1:1 to:
- Durvalumab (IV) 26 cycles
- Placebo (IV) 26 cycles
284 patients will receive treatment once they turn MRD+ and have no evidence of
recurrence according to RECIST 1.1.
Intervention
Patients will receive (unless there is unacceptable toxicity, withdrawal of
consent, or another discontinuation criterion is
met):
* treatment group 1: patients receive (via IV infusion) 1500 mg durvalumab for
26 cycles
* treatment group 2: patients receive (via IV infusion) placebo for 26 cycles
Study burden and risks
Patiënts are subject to the following assessments throughout the study:
- Anamnesis (at screening, including medical history)
- Physical examination
- ECOG performance status
- Vital functions (blood pressure, heartrate, body temperature and respiratory
rhythm)
- Body weight measurement
- brain MRI/CT scan with IV contrast (only at screening)
- ECG
- blood-, stools- and urine examination
- questionnaires (EORTC QLQ-C30, EORTC QLQ-LC13, EQ-5D-5L, PGIS, PRO-CTCAE)
- pregnancy test when applicable
- AE/SAE assessment
- IP administration
- CT+PET scan at screening for staging purposes
Durvalumab activates the immune system of the body and this can cause adverse
effects. Adverse effects can arise during or within
several hours/days after the administration of the IV line. The adverse effects
that are known, are obtained from previous studies. It
is possible that the patient might suffer from 1 or all of the following
adverse effects: fever, fatigue, rash or hives, change in blood
pressure, decrease in the amount of thrombocytes, inflammation of the lungs,
inflammation of the nervous system, inflammation of
the pancreas, inflammation of the liver, inflammation of the intestines,
changes in nodes that regulate hormone production.
In this study certain conditions are incorporated for early signaling of these
severe adverse effects. Moreover, the study procedures might also cause the
following ailments:
- pain or bruises through collection of blood
- rash through ECG stickers
- health risks through radiation of CT-scan/MRI
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Prinses Beatrixlaan 582
Den Haag 2595BM
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed NSCLC with resectable stage II-III disease who have
undergone curative intent
therapy (complete resection of the primary tumor ± neoadjuvant and/or adjuvant
therapy) per SoC
• A contrast-enhanced CT/MRI scan of the chest and abdomen (including liver and
adrenal glands) along with brain MRI must have been done for surgical planning
prior to surgery
• Complete resection of the primary NSCLC is mandatory
• Patients should have completed curative intent therapy
• Confirmation of suitable resected tumor tissue and whole blood sample
• Post-adjuvant therapy or post-operative CT scan of the chest and abdomen and
brain MRI
• Consents to be accessible for q6w plasma sample collection for MRD evaluation
and for q12w CT scans during the 96-week surveillance period
Inclusion criteria for second screening period:
• CT scan of the chest and abdomen and brain MRI performed within the 28 days
prior to randomization to confirm no evidence of RECIST 1.1-defined disease
recurrence and/or metastasis
• Complete post-operative wound healing
• Must have recovered from all acute, reversible toxic effects from chemotherapy
• Adequate organ and marrow function
• Must have a life expectancy of at least 12 weeks
Exclusion criteria
Unequivocal evidence of disease recurrence or tissue biopsy-proven disease
recurrence
• EGFR-mutant and/or ALK-translocation
• Mixed small cell and NSCLC histology
• Require re-resection or are deemed to have unresectable NSCLC by a
multidisciplinary evaluation that must
include a thoracic surgeon who performs lung cancer surgery as a significant
part of their practice.
• Active or prior documented autoimmune or inflammatory disorders
• Uncontrolled intercurrent illness (see protocol page 67)
• History of another primary malignancy (check for exceptions)
• History of active primary immunodeficiency
• Active infection including tuberculosis, hepatitis B, hepatitis C virus or HIV
• Received any IO therapy in the adjuvant setting or any prior exposure to
durvalumab
• Received any radiotherapy in the neoadjuvant setting
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer
treatment (with exceptions)
• Current or prior use of immunosuppressive medication within 14 days before
the first dose of IP (with exceptions)
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 |
|---|---|
| EudraCT | EUCTR74839.056.20-NL |
| ClinicalTrials.gov | NCT04642469 |
| CCMO | NL74839.056.20 |