Clinical Trials /

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)

NCT01454102

Description:

There is no formal research hypothesis to be statistically tested in this protocol. - 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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Study of Nivolumab (<span class="go-doc-concept go-doc-intervention">BMS-936558</span>) in Combination With <span class="go-doc-concept go-doc-intervention">Gemcitabine</span>/<span class="go-doc-concept go-doc-intervention">Cisplatin</span>, <span class="go-doc-concept go-doc-intervention">Pemetrexed</span>/<span class="go-doc-concept go-doc-intervention">Cisplatin</span>, <span class="go-doc-concept go-doc-intervention">Carboplatin/Paclitaxel</span>, <span class="go-doc-concept go-doc-intervention">Bevacizumab</span> Maintenance, <span class="go-doc-concept go-doc-intervention">Erlotinib</span>, <span class="go-doc-concept go-doc-intervention">Ipilimumab</span> or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell <span class="go-doc-concept go-doc-disease">Lung Cancer</span> (NSCLC) (CheckMate 012)

Title

  • Brief Title: 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)
  • Official Title: A Multi-arm Phase I Safety Study of Nivolumab 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)
  • Clinical Trial IDs

    NCT ID: NCT01454102

    ORG ID: CA209-012

    Trial Conditions

    Non-small Cell Lung Cancer

    Trial Interventions

    Drug Synonyms Arms
    Gemcitabine Arm A: Nivolumab + Gemcitabine + Cisplatin
    Cisplatin Arm A: Nivolumab + Gemcitabine + Cisplatin, Nivolumab + Pemetrexed + Cisplatin
    Pemetrexed Nivolumab + Pemetrexed + Cisplatin
    Paclitaxel Arm C: Nivolumab + Paclitaxel + Carboplatin
    Carboplatin Arm C: Nivolumab + Paclitaxel + Carboplatin
    Bevacizumab Arm D: Nivolumab + Bevacizumab maintenance
    Erlotinib Arm E: Nivolumab + Erlotinib

    Trial Purpose

    There is no formal research hypothesis to be statistically tested in this protocol.

    - 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.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm A: Nivolumab + Gemcitabine + Cisplatin Experimental Nivolumab solution intravenously every 3 weeks until progressive disease (PD) or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle Gemcitabine solution intravenously on Day 1 and Day 8 of every cycle for 4 cycles Cisplatin solution intravenously on Day 1 of each cycle for 4 cycles Gemcitabine, Cisplatin
    Nivolumab + Pemetrexed + Cisplatin Experimental Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle Pemetrexed solution intravenously on Day 1 of every cycle for 4 cycles Cisplatin solution intravenously on Day 1 of each cycle for 4 cycles Cisplatin, Pemetrexed
    Arm C: Nivolumab + Paclitaxel + Carboplatin Experimental Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle Paclitaxel solution intravenously on Day 1 of every cycle for 4 cycles Carboplatin area under curve (AUC) 6 solution intravenously on Day 1 of every cycle for 4 cycles Paclitaxel, Carboplatin
    Arm D: Nivolumab + Bevacizumab maintenance Experimental Nivolumab solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle Bevacizumab administered prior to intravenous infusion on Cycle 1 Day 1 followed by intravenous infusion every 3 weeks on Cycle 2 onwards and until PD or discontinuation due to toxicity Bevacizumab
    Arm E: Nivolumab + Erlotinib Experimental Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered prior to chemotherapy on Day 1 of each cycle Erlotinib tablet by mouth daily until PD or discontinuation due to toxicity Erlotinib
    Arm F: Nivolumab Experimental Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes
    Arm G: Nivolumab + Ipilimumab Experimental In Squamous histology subjects (NSCLC) Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles Followed by Nivolumab administered until PD or discontinuation due to toxicity
    Arm H: Nivolumab + Ipilimumab Experimental In non-squamous histology subjects (NSCLC) Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity
    Arm I: Nivolumab + Ipilimumab Experimental In squamous histology subjects (NSCLC) Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity
    Arm J: Nivolumab + Ipilimumab Experimental In non-squamous histology subjects (NSCLC) Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity
    Arm K: Nivolumab Experimental In squamous histology subjects (NSCLC) Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered as switch maintenance therapy. A cycle is 2 weeks
    Arm L: Nivolumab Experimental In non-squamous histology subjects (NSCLC) Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as switch maintenance therapy. A cycle is 2 weeks
    Arm M: Nivolumab Experimental NSCLC subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered for up to an hour as monotherapy. A cycle is 2 weeks
    Arm N: Nivolumab + Ipilimumab Experimental In subjects with any histology (NSCLC) Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity
    Arm O: Nivolumab + Ipilimumab Experimental Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity
    Arm P: Nivolumab + Ipilimumab Experimental Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity
    Arm Q: Nivolumab + Ipilimumab Experimental Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity
    Arm R: Nivolumab + Ipilimumab Experimental Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity
    Arm S: Nivolumab + Ipilimumab Experimental Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of drug related adverse events

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of serious adverse events

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade

    Secondary Outcome Measures

    ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of subjects treated in arms A, B, C and D

    PFSR based on RECIST 1.1 of subjects treated in arms A, B, C and D

    ORR based on RECIST 1.1 of subjects treated in arms E, F, K, L, M, O, P, Q, R, S

    PFSR based on RECIST 1.1 of subjects treated in arms E, F, K, L, M, O, P, Q, R, S

    ORR based on RECIST 1.1 of subjects treated in arms G, H, I, J and N

    PFSR based on RECIST 1.1 of subjects treated in arms G, H, I, J and N

    Trial Keywords