Trial Title:
Pembrolizumab and Chemotherapy Neoadjuvant/Adjuvant of NSCLC
NCT ID:
NCT05894889
Condition:
Stage IIIB(N2) Non-small Cell Lung Cancer
Stage IIA Non-small Cell Lung Cancer
Stage IIB Non-small Cell Lung Cancer
Stage IIIA Non-small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Carboplatin
Pembrolizumab
Pemetrexed
Conditions: Keywords:
Early stage NSCLC, neoadjuvant, adjuvant, pembrolizumab
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
None(Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Pembrolizumab 200 mg IV infusion
Description:
Biological: Pembrolizumab 200 mg IV infusion
Drug: nab-paclitaxel IV infusion
Drug: Carboplatin IV infusion
Drug: Pemetrexed IV infusion
Arm group label:
Pembrolizumab + Chemotherapy
Other name:
Drug: nab-paclitaxel IV infusion
Other name:
Drug: Carboplatin IV infusion
Other name:
Drug: Pemetrexed IV infusion
Summary:
This study is to evaluate the efficacy and safety of neoadjuvant pembrolizumab plus
chemotherapy following by pembrolizumab adjuvant in stage IIA-IIIB (N2) NSCLC
participants without sensitizing EGFR/ALK mutation. The study will also investigate the
role of CXCL13+PD1+ CD8 T cells in association with pathological response / resistance to
neoadjuvant immunotherapy by comparing the proportion of CXCL13+PD1+ CD8 T cells in all
CD8 T cells in post-treatment (surgical sample) between MPR group and non-MPR group.
Detailed description:
Lung cancer is still the world's leading cancer in terms of mortality. Although the early
screening of lung cancer has made great achievements, for example, many lung cancer
patients were already in the middle and late stage of lung cancer when they were
diagnosed. The majority of patients with resected Stage II and IIIA NSCLC are destined to
suffer tumor recurrence despite the administration of standard adjuvant or neoadjuvant
therapy. In recent years, neoadjuvant immunotherapy based on PD-1 receptor has provided
new opportunities for surgery of locally advanced NSCLC, including the positive results
from KEYNOTE-671 and KEYNOTE-091 study. However the mechanism of immunotherapy response
and resistance are still less understood.
CXCL13+ PD1+ CD8 T cells demonstrate an exhausted phenotype and have been proposed as a
surrogate of tumor antigen-specific T cell, a key subset of tumor-infiltrating immune
cells that have successfully recognized and killed tumor cells but kept from continued
functioning by immune checkpoints including PD-L1. Research on T cell exhaustion in
chronic viral infection has also suggested that T cell exhaustion is a result of chronic
antigen stimulation, corroborating with the notion that exhausted T cells inside the
tumor microenvironment represents successful tumor immune recognition
Therefore, in this study, we hypothesize that patients with resectable stage IIA-ⅢB(N2)
non-small cell lung cancer (NSCLC) without sensitizing EGFR/ALK mutation could benefit
from pembrolizumab combined with chemotherapy. Based on the single cell analysis of the
pre-treatment and post-treatment samples, we hypothesize that lack of CXCL13+PD1+ T cells
is one of the major resistance mechanisms of PD1/PD-L1 blockade.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Male/female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed diagnosis of [Stage II, IIIA or
IIIB(N2) NSCLC (AJCC Version 8)] will be enrolled in this study.
Note: mixed cellularity tumors are allowed. tumor should be considered resectable in
terms of surgeon's determinations before study entry by investigators. Lymph nodes
disease are recommended to have pathological confirmation. A PET-CT may be utilized
as a surrogate for pathologic staging by site's feasibility.
2. Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of
this protocol during the treatment period and for at least 1 year after the last
dose of study treatment and refrain from donating sperm during this period.
3. Female participants:
A female participant is eligible to participate if she is not pregnant (see Appendix
3), not breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during
the treatment period and for at least [180 days after the last dose of
carboplatin and for at least 120 days after the last dose of pembrolizumab,
whichever occurs latest].
4. The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial and may also provide consent for future
biomedical research.
5. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in
such lesions. Participants suspected with secondary lung cancer (eg. ground glass
nodules) were also eligible for this study (For solid nodules, biopsy, if available,
should be performed in case of any intrapulmonary metastasis).
6. Archival tumor tissue sample or newly obtained [core, incisional or excisional]
biopsy of a tumor lesion not previously irradiated has been provided.
Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
Newly obtained biopsies are preferred to archived tissue.
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the first dose of study
intervention.
8. Have adequate organ function as defined in the following table. Specimens must be
collected within 10 days prior to the start of study intervention.
Exclusion Criteria:
1. Have confirmed sensitizing EGFR mutation or ALK alterations. Note: EGFR and ALK
testing will be performed in local hospital, and do not need to be sent to the
central laboratory.
2. A WOCBP who has a positive urine pregnancy test within 72 hours prior to treatment
(see Appendix 3). If the urine test is positive or cannot be confirmed as negative,
a serum pregnancy test will be required.
Note: in the event that 72 hours have elapsed between the screening pregnancy test
and the first dose of study treatment, another pregnancy test (urine or serum) must
be performed and must be negative in order for subject to start receiving study
medication.
3. Has one of the following tumor locations/types:
- NSCLC involving the superior sulcus
- Large cell neuro-endocrine cancer
- Sarcomatoid tumor
4. Has had an allogenic tissue/solid organ transplant.
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or
with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg,
CTLA-4, OX 40, CD137).
6. Has received prior systemic anti-cancer therapy including investigational agents for
the current malignancy prior to [allocation].
7. Has received prior radiotherapy within 2 weeks of start of study intervention or
radiation-related toxicities requiring corticosteroids.
8. Has received a live vaccine or live-attenuated vaccine within 30 days before the
first dose of study intervention. Administration of killed vaccines is allowed.
Note: please refer to Section 5.5.2 for information on COVID-19 vaccines
9. Has received an investigational agent or has used an investigational device within 4
weeks prior to study intervention administration.
10. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
11. Known additional malignancy that is progressing or has required active treatment
within the past 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in
situ of the bladder, that have undergone potentially curative therapy are not
excluded.
12. Has a known severe hypersensitivity (≥Grade 3) to any of the study chemotherapy
agents and/or to any of their excipients.
13. Has active autoimmune disease that has required systemic treatment in the past 2
years except replacement therapy (eg., thyroxine, insulin, or physiologic
corticosteroid)
14. Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
15. Has an active infection requiring systemic therapy.
16. Has a known history of Human Immunodeficiency Virus (HIV) infection. Note: No HIV
testing is required unless mandated by local health authority.
17. Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA)
and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA)
infection.
Note: Hepatitis B and C screening tests are not required unless:
- Known history of HBV and HCV infection
- As mandated by local health authority
18. Has a history or current evidence of any condition, therapy, or laboratory
abnormality or other circumstance that might confound the results of the study,
interfere with the participant's participation for the full duration of the study,
such that it is not in the best interest of the participant to participate, in the
opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
20. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of trial treatment.
21. Participants who have had major surgery within 14 days of first treatment.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking University
Address:
City:
Beijing
Country:
China
Status:
Recruiting
Contact:
Last name:
Zemin Zhang, PhD
Phone:
+86 18201293339
Email:
zemin@pku.edu.cn
Facility:
Name:
Shanghai Pulmonary Hospital
Address:
City:
Shanghai
Country:
China
Status:
Recruiting
Contact:
Last name:
Chang Chen, PhD
Phone:
021-65115006
Email:
chenthoracic@163.com
Start date:
January 30, 2024
Completion date:
August 1, 2027
Lead sponsor:
Agency:
Peking University
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Shanghai Pulmonary Hospital, Shanghai, China
Agency class:
Other
Collaborator:
Agency:
Guangdong Provincial People's Hospital
Agency class:
Other
Collaborator:
Agency:
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class:
Other
Source:
Peking University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05894889
