MedDRA version: 20.0 Level: LLT Classification code 10066490 Term: Progression of non-small cell lung cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: MK-3475
Product Code: MK-3475
Pharmaceutical Form: Powder for injection
INN or Proposed INN: pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive name:
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Merck)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Be willing and able to provide written informed consent/assent for the trial. 2)Be > or = 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 bidimensional 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. a. Subjects with an EGFR mutation must also be able to demonstrate progression of disease on the EGFR tyrosine kinase inhibitor (either erlotinib or gefitinib or afatinib) 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 6)Have a performance status of 0 or 1 on the ECOG Performance Scale. 7)Have provided tissue for PD-L1 biomarker analysis from a newly obtained formalinfixed 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. 8)Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention. 9)Have a PD-L1 positive (either strongly or weakly) tumor as determined by IHC at a central laboratory (either in the neoplastic cells themselves or in mononuclear inflammatory cells infiltrating the tumor). Inclusion Criteria for Optional Crossover from docetaxel to MK-3475 2mg/kg arm In order to be eligible for participation in the crossover phase, the subject must: 1. Be willing and able to provide written informed consent/assent for the trial. 2. Have been randomized into the docetaxel arm of MK-3475 PN010 study and taken at least one dose of study medication 3. Have experienced disease progression (either clinical or radiographic, as assessed by the investigator) from docetaxel or other subsequent anti-cancer therapies. 4. Have a performance status of 0 or 1 on the ECOG Performance Scale. 5. Subjects with known and treated brain metastasis are eligible provided they are clinically stable, and brain metastases have been treated. Steroid use for symptom control is allowed but the total daily dose should be =65 years) yes F.1.3.1 Number of subjects for this age range 368
Exclusion criteria
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. 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, 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. 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. 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. Exclusion Criteria for Optional Crossover from docetaxel to MK-3475 2mg/kg arm The subject must be excluded from participating in the trial if the subject: 1. Has withdrawn consent from study (MK-3475 PN010). 2. Have active pneumonitis of Grade 2 or greater or history of pneumonitis requiring systemic steroid therapy. 3. Has received thoracic radiation therapy of > 30 Gy within 6 months have active and untreated brain metastasis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1) Compare overall survival (OS) of previously-treated subjects with NSCLC in strongly positive PD-L1 stratum treated with MK-3475 compared to docetaxel. 2) Compare progression-free survival (PFS) per RECIST 1.1 by independent radiologists’ review of previously-treated subjects with NSCLC in strongly positive PD-L1 stratum treated with MK-3475 compared to docetaxel. 3) Evaluate OS of previously-treated subjects with NSCLC whose tumors express PD-L1 and are treated with MK-3475 compared to docetaxel. 4) Evaluate ORR per RECIST 1.1 by independent radiologists’ review in previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum treated with MK-3475 compared to docetaxel. 5) Evaluate safety and tolerability profile of MK-3475 in previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum.;Secondary Objective: 1) Evaluate overall response rate (ORR) per RECIST 1.1 by independent radiologists’ review of previously-treated subjects with NSCLC in the strongly positive PD-L1 stratum and in overall study population whose tumors express PD-L1 treated with MK-3475 compared to docetaxel. 2) Evaluate response duration per RECIST 1.1 by independent radiologists’ review in previously treated subjects with NSCLC in the strongly positive PD-L1 stratum and in overall study population treated with MK-3475 compared to docetaxel.;Primary end point(s): There are two primary endpoints of this study: overall survival (OS) and progression-free survival (PFS) per RECIST 1.1. -Overall survival (OS) is defined as the time from randomization to death due to any cause. Subjects without documented death at the time of the final analysis will be censored at the date of the last follow-up. - Progression-free survival is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent radiologists’ review or death due to any cause, whichever occurs first. Overall Survival is the gold st | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Importantly, PFS will also be assessed by irRC as determined by the investigators. ORR will be calculated by both methodologies, in addition to the duration of response. All main analyses will be performed in the strongly positive PD-L1 stratum. An analysis of ORR in those subjects whose tumors weakly express PD-L1 will be conducted at interim analysis 1 to determine if these subjects are likely to have some potential clinical benefit from the drug. An analysis that includes all patients will be conducted for primary and secondary endpoints if the study is positive for that endpoint in the strongly positive PD-L1 stratum. ;Timepoint(s) of evaluation of this end point: Biomarker testing will be occur during the course of the study. Evaluation of PFS and duration of response will be ongoing throughout the study. | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Lithuania, Netherlands, Portugal, Russian Federation, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactGregory Lubiniecki, M.D.
Merck Sharp & Dohme Corp., a subsidiary of Merck& Co.,
Outcome results
None listed