A randomized, phase 3 trial with anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) versus placebo for patients with early stage NSCLC after resection and completion of standard adjuvant therapy (PEARLS)
- Conditions
- non-small cell lung cancer / lung cancer1003866610029107
- Registration Number
- NL-OMON53053
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 50
Patient enrollment will follow a three- steps procedure as illustrated in
Section 4 (step 1 registration, step 2 central confirmation of PD-L1 status,
step 3 randomization). Patients must meet all of the criteria described in
Sections 3.1, 3.2 and 3.3 to be eligible for randomization in step 3.
1) Registration - step 1 (ORTA step 1)
Before patient registration, written informed consent for tumor testing must be
given according to ICH/GCP and national/local regulations. For patients that
accept to participate in the translational research, we recommend the informed
consent for translational research be signed before registration step 1;
Pathological diagnosis of NSCLC confirmed at surgery, any histology is eligible;
Confirmed UICC v7 stage IB with T >= 4 cm, II-IIIA NSCLC after complete surgical
resection (lobectomy, sleeve lobectomy, bi-lobectomy or pneumonectomy) as
documented in the pathology report;
(Note: TNM stage according to the 7th edition of the TNM classification for
lung cancer)
Resection margins proved microscopically free (R0); Resection margins should
must be considered to beare evaluated at the bronchial, venous and arterial
stumps, peribronchial soft tissue, any peripheral margin near the tumor or of
additionally resected tissue;
A systematic complete mediastinal lymph node dissection or a lobe-specific
mediastinal lymph node dissection (Appendix K) is recommended. At a minimum,
the pathology and/or operative report must include the examination of at least
two different mediastinal lymph node (N2) levels, one of which is the
subcarinal (level 7) and the second of which is lobe-specific;
A systematic nodal dissection is recommended or at least a lobe-specific
systematic nodal dissection. However, the intraoperative lymph node evaluation
can be accepted if no lymph nodes are found in those area and there is clear
documentation in the operative report by the surgeon of exploration of the
required lymph node areas. At minimum, the pathology and/or operative report
should include the examination of at least two different mediastinal nodal (N2)
station with one being subcarinal (level 7);
In the uncommon clinical situation where the surgeon thoroughly examines a
particular mediastinal lymph node level and does not find any lymph nodes, that
mediasintal lymph node level may be counted among the minimum two required
levels. However, the surgeon must clearly document in the operative report or
in a separate written statement that the lymph node level was explored and no
lymph nodes were present. Normal appearing lymph nodes, if present, must be
biopsied or/removed;
No extracapsular nodal extension of the tumor in resected mediastinal (N2)
lymph nodes. Extracapsular tumor extension is permitted in resected N1 lymph
nodes;
The highest mediastinal node removed can be positive for malignancy;.
Carcinoma in situ can be present at bronchial margin;.
Patients with two synchronous primary non-small cell lung cancers are excluded
from the study;
Availability of tumor sample obtained at surgical resection for PD-L1
Immunohistochemistry (IHC) expression assessment. Patients must submit the
tumor sample during screening for PD-L1 IHC expression testing at a central
pathology laboratory. Patients will be eligible to participate regardless of
the level of PD
Please refer to D4a. All eligibility criteria are listed in this section.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary/ dual -primary endpoints<br /><br>* DFS in the PD-L1 strong positive sub-group;<br /><br>* DFS in the overall population .<br /><br><br /><br>Timepoint(s) of evaluation of this end point:<br /><br><br /><br>1. Every 12 weeks (± 2 weeks) during the 1st year after randomization,every 6<br /><br>months (± 4 weeks) for the 2nd and 3rd year, yearly (± 4<br /><br>weeks) for year 4 and 5. Thereafter at least yearly up to year 10.<br /><br>2. Every 12 weeks (± 2 weeks) during the 1st year after randomization,every 6<br /><br>months (± 4 weeks) for the 2nd and 3rd year, yearly (± 4<br /><br>weeks) for year 4 and 5. Thereafter at least yearly up to year 10.</p><br>
- Secondary Outcome Measures
Name Time Method