MK-3475 vs. Docetaxel in Second-Line Non-Small Cell Lung Cancer

• Conditions: lung cancer non-small cell (Non-Small Cell Lung Cancer, NSCLC); MedDRA version: 17.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004391-19-IT
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-19
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 920

Inclusion Criteria

1) Be willing and able to provide written informed consent/assent for the trial.
2) Be =18 years of age on day of signing informed consent.
3) Have a life expectancy of at least 3 months.
4) Have a histologically or cytologically confirmed diagnosis of NSCLC and have at least one measurable lesion as defined by RECIST 1.1. The target lesion(s) should also have bi-dimensional measurability for irRC evaluation on study.
5) Have experienced investigator determined radiographic progression per RECIST 1.1 of NSCLC after treatment with at least two cycles of a platinum-containing doublet for stage IIIB/IV or recurrent disease. The site’s study team must have reviewed pretrial images that are of diagnostic quality from at least 2 dates to determine that radiographic progression has occurred per RECIST 1.1 following initiation of the first-line platinum-containing doublet. A platinum-containing doublet is defined as a platinum-based cytotoxic systemic agent administered in the same cycle as another cytotoxic systemic chemotherapeutic agent. The central imaging vendor must have received these scans and have confirmed that they are of acceptable diagnostic quality prior to randomization in this trial for a possible retrospective analysis. The central vendor will not be confirming eligibility prior to randomization. Completion of treatment with a platinum-containing doublet as adjuvant therapy within 1 year of signing ICF will satisfy the prior treatment requirement.
a. Subjects with an EGFR sensitizing mutation must also be able to demonstrate progression of disease on the EGFR tyrosine kinase inhibitor (either erlotinib, gefitinib, or afatinib) in a similar manner to that above for the platinumcontaining doublet. Radiographic images that demonstrate progression after
initiation of the EGFR tyrosine kinase inhibitor therapy and after initiation of the platinum-containing doublet must also be submitted similarly for subjects with an EGFR sensitizing mutation prior to randomization. Subjects with an EGFR sensitizing mutation may have been treated previously with the
tyrosine kinase inhibitor separately from the platinum-containing doublet; the order of treatment does not matter, but progression of disease as determined by RECIST 1.1 must be demonstrable for both regimens. An exception to this rule is the patient whose NSCLC tumor has an EGFR sensitizing mutation who receives four cycles of a platinum doublet, does not experience progression of disease, and begins therapy with an EGFR tyrosine kinase inhibitor as a maintenance therapy within 28 days of the last administration of the platinum doublet chemotherapy. For this patient, only one set of images demonstrating progression on the EGFR tyrosine kinase inhibitor is required for submission to the independent imaging vendor.
b. Subjects with an ALK translocation must also be able to demonstrate progression of disease on crizotinib in a similar manner to that above for the platinum-containing doublet. Radiographic images that demonstrate progression after initiation of crizotinib and after initiation of the platinum containing
doublet must also be submitted similarly for subjects with an ALK translocation prior to randomization. Subjects with an ALK translocation may have been treated previously with the tyrosine kinase inhibitor separately from the platinum-containing doublet; the order of treatment does not matter, but progression of disease as determined by RECIST 1.1 must be demonstrable for b

Exclusion Criteria

1) Has received prior therapy with docetaxel for NSCLC.
2) 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.
3) 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 ECIs or as a pre-medication for docetaxel is allowed).
4) 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).
5) 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; received prior tyrosine kinase inhibitor therapy or completed palliative radiotherapy within 7 days of the first dose of trial treatment.
6) Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-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.
7) Has a known history of prior malignancy except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
- Note: The time requirement for no evidence of disease for 5 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.
8) 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 MRI for at least four 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.
9) Has an active autoimmune disease, or a documented history of autoimmune disease, or a syndrome that requires 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.
10) Has had an allogeneic tissue/solid organ transplant.
11) Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.
12) Has received or will receive a live vaccine within 30 days prior to the first administration of study medication. Sea

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified