A Multicenter, Double Blind, Randomized, Controlled Study of M7824 with Concurrent Chemoradiation Followed by M7824 versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants with Unresectable Stage III Non-small Cell Lung Cancer
- Conditions
- lung cancerNon-small cell lung cancer10038666
- Registration Number
- NL-OMON52935
- Lead Sponsor
- Merck
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
Participants are eligible to be included in the study only if all the following
criteria apply:
Age
1. Are * 18 years of age at the time of signing the informed consent. In Japan,
if a patient is < 20 years, the written informed consent from his/her parent or
guardian will be required in addition to the patient*s written consent., Type
of Participant and Disease Characteristics
2. Participants must have measurable or non-measurable but evaluable disease
assessed by the Investigator. Participants must have histologically documented
NSCLC who present with Stage III locally advanced, unresectable disease
(International Association for the Study of Lung Cancer Staging Manual in
Thoracic Oncology [IASLC Staging Manual in Thoracic Oncology], v8).
3. Availability of tumor material (< 6 months old) adequate for biomarker
analysis is
Mandatory for all participants and central laboratory confirmation is required.
For participants enrolled in the safety run-in, PD-L1 expression will be tested
retrospectively by a central laboratory. For participants enrolled in the
expansion part of the study, PD-L1 expression must be tested by the central
laboratory and results available before randomization. Only results from the
central laboratory testing will be used for randomization and if PD-L1 status
is non-evaluable, the participant is not eligible for this study. Tumor samples
obtained by endoscopic biopsies, core needle biopsies, excisional biopsies,
punch biopsies, and surgical specimen that are < 6 months old and adequate for
biomarker analysis are acceptable. Biopsies obtained by fine needle aspiration
are not acceptable., 4. Participants with tumor harboring an EGFR sensitizing
(activating) mutation, ALK
translocation, ROS-1 rearrangement are eligible. These tests are not required
for enrollment in the study.
5. Participants with ongoing post-obstructive pneumonia due to the tumor are
eligible.
6. If a pleural effusion is present, the following criteria must be met to
exclude malignant
involvement (incurable T4 disease):
a. When pleural fluid is visible on both the CT scan and on a chest x-ray, a
thoracentesis is required to confirm that the pleural fluid is cytologically
negative.
b. Participants with exudative pleural effusions are excluded, regardless of
cytology.
c. Participants with effusions that are minimal, i.e., are too small to safely
tap are eligible.
7. Participants must be at least 3 weeks from prior thoracotomy (if performed).
8. Participants must have adequate pulmonary function defined as a forced
expiratory volume in 1 second (FEV1) * 1.2 liters or * 50% of predicted normal
volume measured within 3 weeks prior to randomization. If participants do not
meet the above criteria, treatment with inhaled steroids and bronchodilators
can be initiated if clinically indicated and eligibility can be reassessed
after 1-2 weeks.
9. ECOG performance status of 0 to 1 at Screening and on the day of first dose.
10. Life expectancy *12 weeks.
11. Have adequate organ function as indicated by the following laboratory values
a. Adequate hematological function defined by absolute neutrophil count (ANC) *
1.5
× 109/L, platelet count * 100 × 109/L, and hemoglobin * 9 g/dL.
b. Adequate hepatic function defined by a total bilirubin level * 1.5 × upper
limit of nor
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1. Mixed small cell with non-small cell lung cancer histology.
2. Greater than minimal, exudative, or cytologically positive pleural effusions.
3. Recent major surgery within 4 weeks prior to entry into the study (excluding
the placement
of vascular access) that would prevent administration of study drug.
4. Active or prior documented inflammatory bowel disease (e.g., Crohn*s
disease, ulcerative colitis).
5. History of organ transplant that requires therapeutic immunosuppression.
6. Significant acute or chronic infections including, among others:
a. Known history of positive test for human immunodeficiency virus (HIV) or
known
acquired immunodeficiency syndrome (testing at Screening is not required). If an
Investigator has a strong suspicion of HIV infection without known history for a
participant in Screening, however participant refuses testing, discuss with
Medical
Monitor to assess eligibility. (Note: HIV testing is not mandated for study
inclusion;
however, if it is performed at any point in Screening or while on study, a site
must
consent the participant for HIV testing as per local standard guidance.)
b. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (HBV
surface
antigen positive and HBV core antibody positive with reflex to positive HBV
DNA, or
HBV core antibody positive alone with reflex to positive HBV DNA, or positive
HCV
antibody with reflex to positive HCV RNA) at Baseline. Discuss with the Medical
Monitor if history of HBV or HCV infection is known. If medically indicated,
participants infected with HBV must be treated and on a stable dose of
antivirals (e.g,
entecavir, tenofovir, or lamivudine; adefovir or interferon are not allowed) at
study entry
and with planned monitoring and management according to appropriate labeling
guidance. Participants on active HCV therapy at study entry must be on a stable
dose
without documented clinically significant impaired liver function test or
hematologic
abnormalities (must meet criteria above) and with planned monitoring and
management
according to appropriate labeling guidance. HBV and/or HCV viral titers must be
monitored according to SoA in these participants.
c. Participants with active tuberculosis (history of exposure or history of
positive
tuberculosis test; plus presence of clinical symptoms, physical, or
radiographic findings).
7. Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive
heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac
arrhythmia,
active peptic ulcer disease or gastritis, active bleeding diatheses, or
psychiatric illness/social situations that would limit compliance with study
requirements or
compromise the ability of the patient to give written informed consent.
Participants with history of bleeding diathesis or recent major bleeding events
considered by the Investigator as high risk for investigational drug treatment
are also excluded.
8. Chronic Obstructive Pulmonary Disease exacerbation or other respiratory
illness requiring hospitalization or precluding study therapy within 30 days
before randomization.
9. Known clinical history of tuberculosis, lung sarcoidosis and Inter
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS according to RECIST 1.1 assessed by IRC</p><br>
- Secondary Outcome Measures
Name Time Method <p>* Occurrence of TEAEs and treatment-related AEs<br /><br>* OS<br /><br>* Changes from Baseline in pulmonary function tests and images and association<br /><br>with study intervention:<br /><br>- DLCO<br /><br>- HRCT<br /><br>- FEV1 and FVC<br /><br>- 6-min WT<br /><br>* PD-L1 expression in tumors at Baseline assessed with IHC and association with<br /><br>efficacy<br /><br>* Objective response according to RECIST assessed by IRC<br /><br>* Duration of response assessed from CR or PR until PD, death, or last tumor<br /><br>assessment<br /><br>* PK profile of M7824 in terms of Ceoi and Ctrough during treatment and Safety<br /><br>followup visit.<br /><br>* Immunogenicity of M7824 as measured by ADA assays from Screening through last<br /><br>Safety Follow-up visit.</p><br>