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)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01454102
First received: September 16, 2011
Last updated: July 9, 2014
Last verified: May 2014

September 16, 2011
July 9, 2014
December 2011
November 2016   (final data collection date for primary outcome measure)
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of drug related adverse events [ Time Frame: Up to 100 days after the last dose of study drug (approximately 36 weeks) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of serious adverse events [ Time Frame: Up to 100 days after the last dose of study drug (approximately 36 weeks) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: At screening (up to 28 days prior to first treatment) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 8 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 2 Day 1 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 3 Day 1 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Cycle 4 Day 1 ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: Day 1 of every cycle from Cycle 4 until progression (approximately 24 weeks) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of Nivolumab in combination with chemotherapy measured by frequency of clinical laboratory test by worst toxicity grade [ Time Frame: End of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by frequency of adverse events [ Time Frame: Up to 30 days after last dose of study drug (or longer) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by serious adverse events [ Time Frame: Up to 90 days after last dose of study drug (or longer) ] [ Designated as safety issue: Yes ]
  • Safety and tolerability of BMS-936558 in combination with chemotherapy measured by laboratory abnormalities and death [ Time Frame: Up to 90 days after last dose of study drug (expect to be 24 month) ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01454102 on ClinicalTrials.gov Archive Site
  • ORR based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of subjects treated in arms A, B, C and D [ Time Frame: At screening (up to 28 days prior to first treatment), C4D1 (Week 10), every 6 weeks until C8D1, and then every 3 months thereafter until progression (approximately 24 weeks) or end of treatment for subjects who continue treatment beyond progression ] [ Designated as safety issue: No ]

    C4D1=Cycle 4 Day 1

    C8D1=Cycle 8 Day 1

    Objective Response Rate (ORR) is defined as the proportion of all treated subjects whose best overall response is either a complete response (CR) or partial response (PR)

  • PFSR based on RECIST 1.1 of subjects treated in arms A, B, C and D [ Time Frame: At screening (up to 28 days prior to first treatment), C4D1 (Week 10), every 6 weeks until C8D1, and then every 3 months thereafter until progression (approximately 24 weeks) or end of treatment for subjects who continue treatment beyond progression ] [ Designated as safety issue: No ]
    Progression Free Survival Rate (PFSR) is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
  • ORR based on RECIST 1.1 of subjects treated in arms E, F, K, L, M, O, P, Q, R, S [ Time Frame: At screening (up to 28 days prior to first treatment), C6D1 (Week 11), C9D1 (Week 17), C12D1 (Week 23) and then every 3 months thereafter until progression (approximately 24 weeks) ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of all treated subjects whose best overall response is either a CR or PR
  • PFSR based on RECIST 1.1 of subjects treated in arms E, F, K, L, M, O, P, Q, R, S [ Time Frame: At screening (up to 28 days prior to first treatment), C6D1 (Week 11), C9D1 (Week 17), C12D1 (Week 23) and then every 3 months thereafter until progression (approximately 24 weeks) ] [ Designated as safety issue: No ]
    PFSR is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
  • ORR based on RECIST 1.1 of subjects treated in arms G, H, I, J and N [ Time Frame: C4D1 (Week 10), C7D1 (Week 17), C10D1 (Week 23) and then every 3 months thereafter until disease progression (approximately 24 weeks) ] [ Designated as safety issue: No ]
    ORR is defined as the proportion of all treated subjects whose best overall response is either a CR or PR
  • PFSR based on RECIST 1.1 of subjects treated in arms G, H, I, J and N [ Time Frame: C4D1 (Week 10), C7D1 (Week 17), C10D1 (Week 23) and then every 3 months thereafter until disease progression (approximately 24 weeks) ] [ Designated as safety issue: No ]
    PFSR is defined as the probability a subject remaining progression-free and/or surviving to 24 weeks. The probability will be calculated by the product limit method (Kaplan-Meier method) which takes into account censored data
  • Objective response rate (ORR) defined as the proportion of all treated subjects whose best response is either a complete response (CR) or partial response (PR) [ Time Frame: From the date of first dose of study drug until the date of first documented progression, or date of death, whichever come first (expect to be 24 month) ] [ Designated as safety issue: No ]
  • Disease control rate (DCR) defined as the proportion of all treated subjects whose best response is either a CR or PR or stable disease (SD) lasting for 24 weeks or greater [ Time Frame: From the date of first dose of study drug until date of first documented progression, or date of death, whichever come first (expect to be 24 month) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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)
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)

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.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-small Cell Lung Cancer
  • Biological: Nivolumab
    Other Name: BMS-936558
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Pemetrexed
  • Drug: Paclitaxel
  • Drug: Carboplatin
  • Drug: Bevacizumab
  • Drug: Erlotinib
  • Biological: Ipilimumab
  • Experimental: Arm A: Nivolumab + Gemcitabine + Cisplatin

    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

    Interventions:
    • Biological: Nivolumab
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Experimental: Nivolumab + Pemetrexed + Cisplatin

    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

    Interventions:
    • Biological: Nivolumab
    • Drug: Cisplatin
    • Drug: Pemetrexed
  • Experimental: Arm C: Nivolumab + Paclitaxel + Carboplatin

    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

    Interventions:
    • Biological: Nivolumab
    • Drug: Paclitaxel
    • Drug: Carboplatin
  • Experimental: Arm D: Nivolumab + Bevacizumab maintenance

    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

    Interventions:
    • Biological: Nivolumab
    • Drug: Bevacizumab
  • Experimental: Arm E: Nivolumab + Erlotinib

    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

    Interventions:
    • Biological: Nivolumab
    • Drug: Erlotinib
  • Experimental: Arm F: Nivolumab
    Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes
    Intervention: Biological: Nivolumab
  • Experimental: Arm G: Nivolumab + Ipilimumab

    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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm H: Nivolumab + Ipilimumab

    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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm I: Nivolumab + Ipilimumab

    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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm J: Nivolumab + Ipilimumab

    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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm K: Nivolumab

    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

    Intervention: Biological: Nivolumab
  • Experimental: Arm L: Nivolumab

    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

    Intervention: Biological: Nivolumab
  • Experimental: Arm M: Nivolumab

    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

    Intervention: Biological: Nivolumab
  • Experimental: Arm N: Nivolumab + Ipilimumab

    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

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm O: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm P: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm Q: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm R: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
  • Experimental: Arm S: Nivolumab + Ipilimumab

    Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

    Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity

    Interventions:
    • Biological: Nivolumab
    • Biological: Ipilimumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
412
November 2017
November 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.
United States,   Canada
 
NCT01454102
CA209-012
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP