Pembrolizumab With and Without Radiotherapy for Non-Small Cell Lung Cancer

NCT03217071 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 166520NCI-2017-01727
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized single-institution, phase II, open-label clinical trial of neoadjuvant pembrolizumab with or without low-dose stereotactic radiation therapy (SRT) in stage I-IIIA non-small lung cancer (NSCLC) patients who are planned to undergo surgical resection of their lung cancer.

Conditions

Non Small Cell Lung Cancer

Keywords

non small cell lung cancer, resectable

Outcome Measures

Primary Outcomes (2)

• Change in the Mean Number of Infiltrating Absolute Cluster of Differentiation 3 (CD3+) T Cells/ μm2

  The primary endpoint for this study is the change in the mean number of infiltrating CD3+ T cells/ μm2 in the lung cancer tissue from before and after pembrolizumab +/- SRT by group, based on quantification using immunohistochemistry (IHC) and image analysis by group.

  Up to 1 year

• Percentage of Participants Achieving a Two-fold Increase CD3+ T Cells/μm2

  The percentage of participants achieving a two-fold increase from baseline in CD3+ T cells/μm2 will be reported. The goal of achieving a two-fold increase in 40 percent (%) of the evaluable population is a reasonable one, as estimated from a previous study showing greater-than-three-fold increase in 57% of patients when CD3+ T cells/μm2 were measured in prostate cancer tissue treated with a cell- based cancer immunotherapy.

  Up to 1 year

Secondary Outcomes (6)

• Percentage of Participants With Treatment-Related Adverse Events (AEs)

  Up to 1 year

• Percentage of Participants With Grade 3 or Higher Immune-related AEs

  Up to 1 year

• Median Overall Survival in Months

  Up to 1 year

• Median Relapse Free Survival

  Up to 1 year

• Percentage of Participants With Distant Metastases

  Up to 1 year

Study Arms (2)

Pembrolizumab + Surgery

EXPERIMENTAL

Patients will receive 200mg pembrolizumab on Day 1 of each 3 week cycle, for 2 cycles, prior to surgery. Pembrolizumab will be administered via IV infusion for 30 minutes. Surgery will occur no later than 6 weeks following the last dose of pembrolizumab.

Drug: Pembrolizumab; Procedure: Surgery (Non-interventional, standard of care)

Pembrolizumab + Radiation + Surgery

EXPERIMENTAL

Patients will receive 200mg pembrolizumab on Day 1 of each 3 week cycle, for 2 cycles. Pembrolizumab will be administered via IV infusion for 30 minutes.Within the week (7 days +/- 3 days) following administration of the second cycle, a single 12 Gy dose of stereotactic radiation therapy (SRT) will be delivered to 50% of the primary tumor only. Definitive surgical resection will occur no later than 6 weeks following the last dose of pembrolizumab.

Drug: Pembrolizumab; Radiation: stereotactic radiation therapy (SRT); Procedure: Surgery (Non-interventional, standard of care)

Interventions

Pembrolizumab DRUG

All study participants will receive pembrolizumab every 3 weeks, for 2 cycles.

Also known as: Keytruda

Pembrolizumab + Radiation + Surgery; Pembrolizumab + Surgery

stereotactic radiation therapy (SRT) RADIATION

Patients in Cohort 2 of the Safety run-in and patients in the expansion cohort who are randomized to the 'pembrolizumab +radiation arm' will receive one dose of SRT within 1 week (+/- 3 days) following the second administration of pembrolizumab.

Pembrolizumab + Radiation + Surgery

Surgery (Non-interventional, standard of care) PROCEDURE

Standard of care surgery to remove cancer

Pembrolizumab + Radiation + Surgery; Pembrolizumab + Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be at least 18 years of age on day of signing informed consent.
• Demonstrate adequate organ function as defined below. All screening labs should be performed within 10 days of treatment initiation.
• System Laboratory Value Hematological Absolute neutrophil count (ANC) greater than or equal to 1,500 /microliter (mcL) Platelets greater than or equal to 100,000 / mcL Hemoglobin greater than or equal to 9 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) less than or equal to 1.5 X upper limit of normal (ULN) OR
• Greater than or equal to 60 mL/min for subject with creatinine levels greater than 1.5 X institutional ULN Hepatic Serum total bilirubin Less than or equal to 1.5 X ULN aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) Less than or equal to 2.5 X ULN
• Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT)
• Activated Partial Thromboplastin Time (aPTT) Less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Less than or equal to 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Creatinine clearance should be calculated per institutional standard.
• Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Is ineligible for an operation based on medical or oncologic contraindications to surgery.
• Has history of non-infectious pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease.
• Has evidence of interstitial lung disease.
• Has an active second malignancy, i.e. patient known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment. Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial if curative therapy has been completed, such as basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., Less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with less than or equal to Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Sue Yom: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; Radiosurgery; Surgical Procedures, Operative; Standard of Care

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Investigative Techniques; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Dr. Sue Yom, MD, PhD
• Organization: University of California, San Francisco

Sue.Yom@ucsf.edu

(415) 353-9893

Study Officials

• Sue Yom, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 13, 2017
• Study Start: October 4, 2017
• Primary Completion: March 31, 2022
• Study Completion: March 31, 2022
• Last Updated: October 23, 2024
• Results First Posted: October 23, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)