Study Stopped
Low Accrual
Pembrolizumab With or Without Chemotherapy Before Surgery in Treating Patients With Stage I-IIIA Non-Small Cell Lung Cancer
A Phase 2 Study of Neoadjuvant Pembrolizumab-Based Combination Immunotherapy in the Treatment of Early Stage Non-Small Cell Lung Cancer
2 other identifiers
interventional
N/A
1 country
1
Brief Summary
This phase II trial studies how well pembrolizumab with or without chemotherapy works when given before surgery in treating patients with stage I-IIIA non-small cell lung cancer. Immunotherapy with pembrolizumab, may induce changes in body?s immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as cisplatin and pemetrexed, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab with or without chemotherapy may shrink the cancer prior to surgery and decrease the likelihood of the cancer returning following surgery.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started May 2020
Typical duration for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 16, 2019
CompletedFirst Posted
Study publicly available on registry
August 20, 2019
CompletedStudy Start
First participant enrolled
May 29, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2023
CompletedMarch 4, 2022
February 1, 2022
3.3 years
August 16, 2019
February 17, 2022
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of patients with a >= 2-fold increase in the number of tumor-infiltrating immune cells (TIICs) in post- versus (vs.) pre-pembrolizumab treatment tumor specimens
Will be summarized by descriptive statistics (median and range).
Up to 2 years
Secondary Outcomes (5)
Proportion of participants reporting treatment-related adverse events (AEs)
Up to 2 years
Overall Response Rate
Up to 2 years
Clinical Benefit Rate
Up to 2 years
Median Progression-Free Survival (PFS)
12 months
Median Progression-Free Survival (PFS)
24 months
Study Arms (2)
Cohort A (pembrolizumab)
EXPERIMENTALPatients receive 200mg pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 4 weeks following study treatment.
Cohort B (pembrolizumab, cisplatin pemetrexed)
EXPERIMENTALPatients receive 200mg pembrolizumab IV over 30 minutes and chemotherapy (cisplatin/pemetrexed) IV on day 1. Treatment repeats every 21 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery within 4 weeks following study treatment.
Interventions
Given IV
Given IV
Given IV
Given IV
Undergo surgery
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed NSCLC, performed on a biopsy that occurred within the last 60 days
- Computed tomography (CT) within the last 30 days showing radiographic stage I to IIIa lung cancer (mediastinal staging biopsy is allowed but not required) by the American Joint Committee on Cancer (AJCC) 8th edition
- Documentation that the patient is a candidate for surgical resection of their lung cancer by an American Board of Thoracic Surgery-certified surgeon
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by the investigator
- Adequate tissue specimens for correlative biomarker analysis. The patient should be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) prior to initiation of treatment on day 1. Patients for whom newly-obtained samples cannot be provided (e.g. inaccessible or patient safety concern) may submit an archived specimen only upon agreement from the principal investigator
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE version (v)5.0 grade 1
- Be willing and able to provide written informed consent for the trial
- Absolute neutrophil count (ANC) \>= 1500 cells/ microlitre(uL) (within 10 days prior to the start of trial treatment)
- Platelets \>= 100 000 cells/uL (within 10 days prior to the start of trial treatment)
- Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks) (within 10 days prior to the start of trial treatment)
- Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance, glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl) \>= 30 mL/min for patients with creatinine levels \> 1.5 x institutional ULN (within 10 days prior to the start of trial treatment)
- Total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 x ULN (within 10 days prior to the start of trial treatment)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2.5 x ULN (=\< 5 x ULN for patients with liver metastases) (within 10 days prior to the start of trial treatment)
- International normalized ratio (INR) OR prothrombin time (PT) =\< 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (within 10 days prior to the start of trial treatment)
- +6 more criteria
You may not qualify if:
- Is ineligible for an operation based on medical or oncologic contraindications to surgery
- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of trial treatment
- Note: Patients who have entered the follow-up phase of an investigational trial may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
- Has any component of small cell tumor in the specimen, e.g. mixed NSCLC/small cell
- Has received prior therapy with an anti-Programmed cell death protein 1 (PD-1), anti-Programmed death-ligand 1 (PD-L1) , or anti-Programmed death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
- Has severe hypersensitivity \>= grade 3) to pembrolizumab and/or any of its excipients
- Has a history of (non-infectious) pneumonitis / interstitial lung disease that required treatment with steroids or has current pneumonitis / interstitial lung disease that requires steroids
- Has a known history of human immunodeficiency virus (HIV) infection
- Note: No HIV testing is required unless mandated by local health authority
- Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection
- Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
- Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
- Has received prior radiotherapy within 2 weeks of start of trial treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease
- Has received a live vaccine within 30 days prior to the first dose of trial drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
- Has evidence of clinically significant interstitial lung disease
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of California, San Franciscolead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matthew A Gubens, MD
University of California, San Francisco
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
August 16, 2019
First Posted
August 20, 2019
Study Start
May 29, 2020
Primary Completion
August 31, 2023
Study Completion
August 31, 2023
Last Updated
March 4, 2022
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share