MK-3475 versus SOC in 1L Subjects with PD-L1 Strong Metastatic NSCLC

Phase 1

Conditions: MedDRA version: 17.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
on-Small Cell Lung Carcinoma
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-000323-25-IT

Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 300

Inclusion Criteria

1. Have a histologically or cytologically confirmed diagnosis of stage IV, EGFR wt and EML4/ALK fusion negative NCSLC and have received no prior systemic chemotherapy treatment for their metastatic NSCLC. Completion of treatment with chemotherapy as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic disease.
2. Subject must have at least one radiographically measurable lesion per RECIST 1.1 as determined by blinded independent central radiology review; eligibility will be determined by central review of the screening CT images.
3. Be =18 years of age on day of signing informed consent.
4. Have a life expectancy of at least 3 months
5. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status
6. Have adequate organ function
7. Subject has no 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, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.
8. Have provided newly obtained formalin fixed tumor tissue from a biopsy of a tumor lesion AFTER the diagnosis of metastatic disease has been made AND from a site not previously irradiated. Biopsies obtained PRIOR to the administration of any systemic therapy administered for the treatment of a subject’s tumor (such as neoadjuvant/adjuvant therapy) will not permitted for analysis. The tissue sample must be received by the central vendor prior to randomization. Fine needle aspirates are not acceptable. Needle or excisional biopsies, or resected tissue is required.
- Investigators must be able to produce the source documentation of the EGFR, ALK or KRAS mutation status in all subjects with non-squamous histologies AND for subjects in whom testing is clinically recommended. If any of the three (KRAS, EGFR or ALK) are documented as mutated or rearranged, additional information regarding the mutation status of the other molecules is not required as these mutations/rearrangements are mutually exclusive. If unable to test for these molecular changes, formalin fixed paraffin embedded tumor tissue of any age should be submitted to a central laboratory designated by the Sponsor for such testing. Subjects with non-squamous histologies will not be randomized until EGFR mutation, ALK translocation status and/or KRAS mutation status is available in source documentation at the site.
9. Have a PD-L1 strong tumor as determined by IHC at a central laboratory; only PD-L1 strong subjects will be randomized.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

Exclusion Criteria

1. Has an EGFR sensitizing mutation and/or an EML4/ALK translocation.
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. Tumor specimen is not evaluable for PD-L1 expression by the central laboratory. If an additional tumor specimen is submitted AND evaluable for PD-L1 expression, the subject will be eligible to participate if PD-L1 expression is assessed as strong” by the central laboratory.
4. Is receiving systemic steroid therapy > 3 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 is allowed or as a pre-medication for the control chemotherapies is allowed). Subjects who are receiving daily steroid replacement therapy serve as an exception to this rule. Daily prednisone at doses of 5-7.5 mg is an example of replacement therapy. Equivalent hydrocortisone doses are also permitted if administered as a replacement therapy.
5. Is expected to require any other form of systemic or localized antineoplastic therapy while on trial (including maintenance therapy with another agent for NSCLC, radiation therapy, and/or surgical resection).
6. Has received prior systemic cytotoxic chemotherapy, biological therapy, 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 palliative radiotherapy of 30Gy or less within 7 days of the first dose of trial treatment.
7. 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).
8. Has known symptomatic 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. Subjects with brain metastases for whom complete surgical resection would be clinically appropriate are excluded from the study.
9. Has an active autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects that require inhaled corticosteroids would not be excluded from the study. Subjects with a history of autoimmune disease who have not required systemic steroids or immunosuppressive agents for 2 years prior to signing informed consent would not be excluded from this study, however subjects with any history of autoimmune induced thyroid dysfunction WILL be excluded from this study. Subjects with vitiligo or resolved childhood asthma/atopy would not be excluded from the study. Subjects that require local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement would not be excluded from the study.
10. Has had an allogeneic tissue/solid organ transplant.
11. Has had a history of pneumonitis that has required oral or IV steroids. Subjects whose pneumonitis was solely a result of ra