MK-3475 and Gemcitabine in Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This is a study for patients with previously-treated advanced non-small cell lung cancer (NSCLC). The study will evaluate the safety of adding an investigational drug, MK-3475 to standard treatment with gemcitabine. The study will also try to identify the best dose of MK-3475 to give in combination with gemcitabine.

Detailed Description
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This study is an open-label, non-randomized phase I study, followed by open-label non-randomized phase II study. The first cohort of patients will receive 200 milligrams (mg) of MK-3475 by intravenous infusion over a 21-day period called a cycle along with Gemcitabine 1250 mg/m2 given on Days 1 and 8 of each 21-day cycle for up to 6 cycles. Patients will be seen in the study clinic 12 times over 126 days for an evaluation of signs and symptoms that may represent drug toxicity. Patients may continue to receive MK-3475 (without gemcitabine) for up to 2 years.

Official Title
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A Phase I/II Study of MK-3475 With Gemcitabine in Patients With Previously-Treated Advanced Non-small Cell Lung Cancer (NSCLC)

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: MK-3475
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men with advanced, histologically proven NSCLC. Patients must have received at least one but no more than three prior systemic therapies for advanced disease. Any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with anti-PD1 therapy or gemcitabine should be resolved to less than Grade 1. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Women of childbearing potential must have a negative pregnancy test Ability to give informed consent and comply with the protocol. Anticipated survival minimum 3 months. Prior therapy with investigational agents must have been completed at least 3 weeks prior to study enrollment. Patients must have normal organ and marrow function as seen on protocol-defined blood test results Archived tumor tissue (minimum of 8 slides for paraffin-embedded tumor tissue) available Measurable disease by RECIST 1.1 criteria. Treated brain metastases will be allowed, provided they are asymptomatic. Radiation for symptomatic lesions outside the Central nervous system (CNS) must have been completed at least 2 weeks prior to study enrollment. Exclusion Criteria: Prior therapy with any anti-PD-1, anti-PD-L1, or anti-CTLA4 antibody. Prior therapy with gemcitabine. Prior complications from radiation, such as history of radiation pneumonitis or pulmonary edema that, in the opinion of the investigator, may have risk of increasing toxicity with anti-PD1 therapy. Active autoimmune disease except vitiligo or stable hypothyroidism. Active and ongoing steroid use, except for non-systemically absorbed treatments (such as inhaled or topical steroid therapy for asthma, cardiopulmonary disease (COPD), allergic rhinitis). Active other malignancy, except for controlled basal cell skin carcinoma. HIV positive and/or Hepatitis B or C positive. Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in this protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-3475 + Gemcitabine<br>200mg MK-3475 200 given by IV infusion every 3 weeks, for 2 years, or until disease progression and Gemcitabine 1250 mg/m2 iv Days 1, 8 every 3 weeks, for maximum 6 cycles. | Drug: MK-3475<br>* Investigational drug.<br>* Other names: Anti-PD-1, Pembrolizumab;Drug: Gemcitabine<br>* Standard care drug.<br>* Other names: Gemzar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Toxicities (determine any changes in signs or symptoms that may represent drug toxicity) | Patients are seen in clinic 12 times over 126 days to determine any changes in signs or symptoms that may represent drug toxicity. | 126 Days (six 21-day cycles) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Patients will have CT scans after every two cycles for up to 2 years to assess changes in tumor sizes. | 2 years | 
| Overall Survival | Patients will be contacted every 12 weeks following end of treatment to determine survival status until death, withdrawal of consent, or the end of the study, whichever occurs first. | Every 12 weeks (up to 2 years) | 
| Disease Response | Patients will have CT scans to assess changes in tumor sizes. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, lung cancer, Gemzar, Pembrolizumab, Anti-PD-1, Immunotherapy