A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) versus Docetaxel in Previously Treated Subjects with Non-Small Cell Lung Cancer
- Conditions
- lung cancer1002910710038666
- Registration Number
- NL-OMON47020
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
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 nonsmall 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 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 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.
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 < or <= 10 mg of prednisone or its equivalent.
6. Have baseline imaging scan done within 30 days of the first dose of MK-3475
7. Have adequately recovered from adverse events of previous anticancer therapy.
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 ECI-ies 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, 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-PDL2, 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.
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 interstitial lung disease or a history of pneumonitis.
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 had an allogeneic tissue/solid organ transplant.;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
4. have active and untreated brain metastasis.
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall Survival, (OS)<br /><br>Progression Free Survival, (FPS)</p><br>
- Secondary Outcome Measures
Name Time Method <p>Overall Response Rate (ORR)<br /><br>response duration per RECIST 1.1 based on blinded independent radiologists*<br /><br>review.</p><br>