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

Phase 1

• Conditions: MedDRA version: 18.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-01-30
• Last Update Posted: 16 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. 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 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. 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 of this eligibility criterion.
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)
b. Subjects with an ALK translocation must also be able to demonstrate progression of disease on crizotinib
6) Have a performance status of 0 or 1 on the ECOG Performance Scale.
7) Have adequate organ function
8) Have provided tissue for PD-L1 biomarker analysis from a formalin fixed paraffin embedded tumor tissue sample or a newly obtained formalin fixed tumor tissue from a recent biopsy of a tumor lesion not previously irradiated; no systemic antineoplastic therapy may be administered between the PD-L1 biopsy and initiating study medication. Although patients using tyrosine kinase inhibitors prior to treatment on this protocol may continue using these until it is time to begin the appropriate wash out period for these medications. For patients in whom obtaining a new tumor biopsy will be medically inappropriate, the investigator may appeal to the Sponsor’s study clinical director, and if there is agreement, the investigator may submit an archival formalin-fixed, paraffinembedded tumor specimen for PD-L1 analysis. The tissue sample must be received and evaluated by the central vendor prior to randomization.
a. Investigators must be able to produce the source documentation of the EGFR mutation status or ALK translocation status.
b. If a patient is known to have one molecular alteration (either sensitizing EGFR mutation or ALK translocation), then testing for the other alteration is not required.
c. If a patient is known to have a mutation in KRAS, then testing for an EGFR mutation or for an ALK translocation will not be required given that all of these molecular alterations are mutually exclusive in patients with non-squamous NSCLC.
d. For patients enrolled who are known to have a tumor of predominantly squamous histology, molecular testing for EGFR mutation and ALK translocation will not be required as this is not standard of care and is not part of current diagnostic guidelines.
9) Have a PD-L1 positive (either strongly or weakly) tumor as determined by IHC at a central laboratory.
10) Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major

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 ntineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC or radiation therapy).
4)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 of 30Gy or less within 7 days of the first dose of trial treatment.
5)Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, nti-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). Has participated in another MK-3475 clinical trial.
6)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 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.
7)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 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.
8)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.
9) Has had an allogeneic tissue/solid organ transplant.
10) 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.
11)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.
12)Has an active infection requiring intravenous systemic therapy.
13)Has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
14)Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result.

Study & Design

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