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

Phase 1

• Conditions: MedDRA version: 20.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-04-10
• Last Update Posted: 30 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• 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 non-small cell lung cancer (NSCLC) and have at least one measurable lesion as defined by RECIST 1.1.
5)Have experienced investigator determined radiographic progression per RECIST 1.1 of NSCLC after treatment with a platinum-containing doublet for stage IIIB/IV or recurrent disease. The site’s study team must have reviewed pre-trial 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 prior to randomization in this trial for a possible retrospective analysis of this eligibility criterion. The central vendor will not be confirming eligibility prior to randomization. Completion of treatment with a platinum-containing doublet as adjuvant therapy within one year of signing informed consent 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 or gefitinib) in a similar manner to that above for the platinum-containing 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 for the patient to be eligible.
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. Radiogaphic 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 both regimens.
6)Have a performance status of 0 or 1 on the ECOG Perf

Exclusion Criteria

1)Has received prior therapy with docetaxel for NSCLC.
2)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 ECI-ies or as a pre-medication for docetaxel is allowed).
3)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).
4)Has received maintenance chemotherapy (chemotherapy for subjects with a stable or better response to the prior line of treatment) with an additional agent other than that used in the first-line regimen (switch maintenance). The exception to this rule is the patient who has an EGFR sensitizing mutation in the tumor who is treated with four cycles of a platinum doublet chemotherapy followed by an EGFR tyrosine kinase inhibitor.
5)Has received prior systemic cytotoxic chemotherapy, biological therapy (e.g., cetuximab), major surgery within 3 weeks of the first dose of trial treatment; received radiation therapy of > 30 Gy within 6 months of the first dose of trial treatment; received prior tyrosine kinase inhibitor therapy or palliative radiotherapy of 30Gy or less 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-Cytotxic 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).
7)Has a known history of prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, and 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 tumor for which a subject is enrolled in the 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 intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement will not be excluded from the study.
10) Has interstitial lung disease or a history of pneumonitis.
11)Has an active infection requiring intravenous systemic therapy.
12)Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies

Study & Design

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