Pembrolizumab in Treating Patients With EGFR Mutant, Tyrosine Kinase Inhibitor Naive Advanced Non-Small Cell Lung Cancer

NCT02879994 | Completed Phase 2 Results DMC

• 3 other identifiers: 15-001818NCI-2016-00861Garon Pembrolizumab IST NSCLC
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer that have not received prior tyrosine kinase inhibitor therapy and has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may block growth in different ways by targeting certain cells.

Conditions

Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) Determined as the Percentage of Patients Achieving Complete Response or Partial Response as Respectively Defined in RECIST 1.1

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by accessed by radiographic imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 14 months

Secondary Outcomes (2)

• Number of Participants With Adverse Events According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 14 Months

• Efficacy (Progression Free Survival (PFS) and Overall Survival (OS)) Assessed by RECIST 1.1

  assessed for up to 14 months

Study Arms (1)

Treatment (pembrolizumab)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for up to 35 courses in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI)
• Have a life expectancy of at least 3 months
• Have a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) and have at least one measurable lesion as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; the target lesion(s) should also have bi-dimensional measurability for RECIST 1.1 evaluation on study
• Have an EGFR mutation (sensitizing or non-sensitizing)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Absolute neutrophil count (ANC) \>= 1,500 /microliters(mcL)
• Platelets \>= 100,000 / mcL
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum 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)) \>= 60 mL/min for subject with creatinine levels \> 1.5 x institutional ULN
• Serum total bilirubin =\< 1.5 x ULN OR direct bilirubin =\< ULN for subjects with total bilirubin levels \> 1.5 ULN
• Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase (SGOT)) and alanine transferase (ALT) (serum glutamate pyruvate transaminase (SGPT)) =\< 2.5 X ULN OR =\< 5 X ULN for subjects with liver metastases
• Albumin \>= 2.5 mg/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) =\< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
• Activated partial thromboplastin time (aPTT) =\< 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
• Have provided tissue for PD-L1 biomarker analysis from a newly obtained formalin fixed tumor tissue from a biopsy of a tumor lesion not previously irradiated; the tissue sample must be received and evaluated by the study site prior to start of treatment; fine needle aspirates are not acceptable; needle or excisional biopsies, or resected tissue is required

You may not qualify if:

• Has received prior therapy with an EGFR tyrosine kinase inhibitor (such as erlotinib, gefitinib, afatinib, rociletinib, or AZD9291) for NSCLC
• Is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of trial treatment; the 30 day window should be applied to the last dose of an antineoplastic investigational agent or last use of an investigational device with antineoplastic intent
• Is receiving systemic steroid therapy within three days prior to the first dose of trial treatment or receiving any other form of immunosuppressive medication (corticosteroid use on study for management of early combined immunosuppression (ECIs) is allowed)
• Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC or radiation therapy)
• Has received prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of trial treatment; received thoracic radiation therapy of \> 30 Gy within 6 months of the first dose of trial treatment
• Has received prior therapy with an anti-programmed cell death protein 1 (PD-1), anti-PD-L1, anti-programmed cell death 1 ligand 2 (PD-L2), anti-cluster of differentiation 137 (CD137), or anti-cytotoxic t-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways); has participated in another MK-3475 clinical trial
• Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 3 years since initiation of that therapy; Note: the time requirement for no evidence of disease for 3 years does not apply to the NSCLC tumor for which a subject is enrolled in this trial; the time requirement also does not apply to subjects who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by magnetic resonance imaging \[MRI\] for at least two weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are using no steroids for at least three days prior to study medication
• Has an active autoimmune disease, or a documented history of autoimmune disease that required systemic steroids or immunosuppressive agents; subjects with vitiligo or resolved childhood asthma/atopy would be exception to this rule; subjects that require inhaled steroid or local steroid injections will not be excluded from the study; subjects with hypothyroidism not from autoimmune disease and stable on hormone replacement will not be excluded from the study
• Has had an allogeneic tissue/solid organ transplant
• Has received or will receive a live vaccine within 30 days prior to the first administration of study medication; seasonal flu vaccines that do not contain live virus are permitted
• Has an active infection requiring intravenous systemic therapy
• Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
• Has known active hepatitis B or C; active hepatitis B is defined as a known positive hepatitis B surface antigen (HBsAg) result; active hepatitis C is defined by a known positive hepatitis (Hep) C antibody (Ab) result and known quantitative hepatitis C virus (HCV) ribonucleic acid (RNA) results greater than the lower limits of detection of the assay
• 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

• Jonsson Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Lisberg A, Cummings A, Goldman JW, Bornazyan K, Reese N, Wang T, Coluzzi P, Ledezma B, Mendenhall M, Hunt J, Wolf B, Jones B, Madrigal J, Horton J, Spiegel M, Carroll J, Gukasyan J, Williams T, Sauer L, Wells C, Hardy A, Linares P, Lim C, Ma L, Adame C, Garon EB. A Phase II Study of Pembrolizumab in EGFR-Mutant, PD-L1+, Tyrosine Kinase Inhibitor Naive Patients With Advanced NSCLC. J Thorac Oncol. 2018 Aug;13(8):1138-1145. doi: 10.1016/j.jtho.2018.03.035. Epub 2018 Jun 1.

  PMID: 29874546 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Edward Garon
• Organization: Jonsson Comprehensieve Cancer Center

egaron@mednet.ucla.edu

(310)586-2098

Study Officials

• Edward Garon

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: September 15, 2016
• Primary Completion: November 30, 2017
• Study Completion: January 3, 2019
• Last Updated: July 14, 2021
• Results First Posted: July 14, 2021

Record last verified: 2019-09

Locations

US (1)