Study of Nivolumab (BMS-936558) in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) (CheckMate 012)
Condition: Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Nivolumab; Gemcitabine; Cisplatin; Pemetrexed; Paclitaxel; Carboplatin; Bevacizumab; Erlotinib; Ipilimumab
Intervention MeSH terms: Paclitaxel; Bevacizumab; Carboplatin; Gemcitabine; Nivolumab; Pemetrexed; Erlotinib Hydrochloride; Ipilimumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 472.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      -  The study is evaluating the safety and tolerability of Nivolumab (BMS-936558) when
           combined with three platinum-based doublet chemotherapy regimens (Cisplatin/Gemcitabine;
           Cisplatin/Pemetrexed; and Carboplatin/Paclitaxel) in subjects with NSCLC.

        -  The study is evaluating the safety and tolerability of Nivolumab as maintenance therapy
           in combination with Bevacizumab/Avastin that will be given after at least 4 cycles of
           platinum doublet chemotherapy.

        -  The study is evaluating the safety and tolerability of Nivolumab in combination with
           Erlotinib among epidermal growth factor receptor (EGFR) mutation positive non-squamous
           NSCLC subjects and as monotherapy in subjects with NSCLC.

        -  The study is evaluating the safety and tolerability of Nivolumab in combination with
           Ipilimumab in subjects with squamous and non-squamous NSCLC.

        -  The study is evaluating the safety and tolerability of Nivolumab as switch maintenance
           therapy in subjects with squamous and non-squamous NSCLC.

        -  The study is evaluating the safety and tolerability of Nivolumab as monotherapy among
           subjects with untreated, asymptomatic brain metastases and no evidence of cerebral
           edema.
    

Eligibility criteria:

        For more information regarding BMS clinical trial participation, please visit
        www.BMSStudyConnect.com

        Inclusion Criteria:

          -  Newly diagnosed and confirmed Stage IIIB/IV NSCLC

          -  Previously treated NSCLC with asymptomatic brain metastases (eligible for Arm M) See
             additional details below

          -  Men and women aged ≥18 years

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

          -  Subject must be chemotherapy naive (except Arm D, K, L and M). Prior use of epidermal
             growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is acceptable. For Arms
             D, K, and L, subjects must be non-progressors within 42 days after completion of
             first-line treatment with ≥4 cycles of Platinum Doublet chemotherapy with or without
             Bevacizumab. See below for Arm M

          -  Either a formalin fixed tissue block or a minimum of 10 slides of tumor sample
             (archived or fresh) must be available for biomarker evaluation (a local pathologist
             must review for adequacy of sampling)

          -  Life expectancy of at least 3 months

          -  Prior radiotherapy must have been completed at least 2 weeks prior to study entry

        For Arm M:

          -  No more than 4 brain metastases

          -  Each brain metastases ≤3 cm in size

          -  No evidence of cerebral edema

          -  Subjects must be free of neurologic symptoms related to metastatic brain lesions and
             must not have required or received systemic corticosteroids for ≥10 days prior to
             initiation of study treatment

          -  At least 1 measurable target brain lesion >0.5 cm and no larger than 3 cm in diameter
             and/or 2 measurable brain target lesions >0.3 cm

          -  No prior radiation therapy, surgery, or other local therapy for target brain lesions

          -  Must have received at least one prior systemic anticancer therapy for NSCLC

        Exclusion Criteria:

          -  Subjects with symptomatic brain metastases, spinal cord compression, or intractable
             back pain due to a compressive or destructive mass

          -  Subjects who require emergent use of systemic steroids, emergent surgery and/or
             radiotherapy

          -  Any active or history of a known autoimmune disease

          -  Subjects with previous malignancies (except non-melanoma skin cancers, in situ bladder
             cancer, gastric, or colon cancers or cervical cancers/dysplasia, or breast carcinoma
             in situ) are excluded unless a complete remission was achieved at least 2 years prior
             to study entry and no additional therapy is required or anticipated to be required
             during the study period

          -  History of Grade ≥2 neuropathy

          -  Subjects with interstitial lung disease that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity