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.
Verified April 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: April 1, 2014
Last verified: April 2014
  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.

Condition Intervention Phase
Non-small Cell Lung Cancer
Biological: Nivolumab
Drug: Gemcitabine
Drug: Cisplatin
Drug: Pemetrexed
Drug: Paclitaxel
Drug: Carboplatin
Drug: Bevacizumab
Drug: Erlotinib
Biological: Ipilimumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ]

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 [ 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 or end of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ 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 or end of treatment (approximately 24 weeks) for subjects discontinued due to other reasons ] [ 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 and M [ 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 and M [ 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 and J [ 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 and J [ 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


Estimated Enrollment: 250
Study Start Date: December 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Nivolumab + Gemcitabine + Cisplatin

Nivolumab 10 mg/kg solution intravenously every 3 weeks until progressive disease (PD) or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks.

Gemcitabine 1250 mg/M² solution intravenously on Day 1 and Day 8 of every 3 weeks cycle for 4 cycles

Cisplatin 75 mg/M² solution intravenously on Day 1 of each 3 weeks cycle for 4 cycles

Biological: Nivolumab
Other Name: BMS-936558
Drug: Gemcitabine Drug: Cisplatin
Experimental: Arm B: Nivolumab + Pemetrexed + Cisplatin

Nivolumab 5 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks.

Pemetrexed 500 mg/M² solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles

Cisplatin 75 mg/M² solution intravenously on Day 1 of each 3 weeks cycle for 4 cycles

Biological: Nivolumab
Other Name: BMS-936558
Drug: Cisplatin Drug: Pemetrexed
Experimental: Arm C: Nivolumab + Paclitaxel + Carboplatin

Nivolumab 0.3 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks.

Paclitaxel 200 mg/M² solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles

Carboplatin area under curve (AUC) 6 solution intravenously on Day 1 of every 3 weeks cycle for 4 cycles

Biological: Nivolumab
Other Name: BMS-936558
Drug: Paclitaxel Drug: Carboplatin
Experimental: Arm D: Nivolumab + Bevacizumab maintenance

Nivolumab 5 mg/kg solution intravenously every 3 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 3 weeks.

Bevacizumab 15 mg/kg administered over 90 minute intravenous infusion on Cycle 1 Day 1 followed by a 60 minute intravenous infusion every 3 weeks on Cycle 2 onwards and until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Drug: Bevacizumab
Experimental: Arm E: Nivolumab + Erlotinib

Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes prior to chemotherapy on Day 1 of each cycle. A cycle is 2 weeks.

Erlotinib 150 mg tablet by mouth daily until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Drug: Erlotinib
Experimental: Arm F: Nivolumab
Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes. A cycle is 2 weeks.
Biological: Nivolumab
Other Name: BMS-936558
Experimental: Arm G: Nivolumab + Ipilimumab

In Squamous histology subjects (NSCLC)

Nivolumab 1 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles.

Ipilimumab 3 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles.

Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Experimental: Arm H: Nivolumab + Ipilimumab

In non-squamous histology subjects (NSCLC)

Nivolumab 1 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles.

Ipilimumab 3 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles.

Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Experimental: Arm I: Nivolumab + Ipilimumab

In squamous histology subjects (NSCLC)

Nivolumab 3 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles.

Ipilimumab 1 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles.

Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Experimental: Arm J: Nivolumab + Ipilimumab

In non-squamous histology subjects (NSCLC)

Nivolumab 3 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles.

Ipilimumab 1 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles.

Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab
Experimental: Arm K: Nivolumab

In squamous histology subjects (NSCLC)

Nivolumab 3 mg/kg 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.

Biological: Nivolumab
Other Name: BMS-936558
Experimental: Arm L: Nivolumab

In non-squamous histology subjects (NSCLC)

Nivolumab 3 mg/kg 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.

Biological: Nivolumab
Other Name: BMS-936558
Experimental: Arm M: Nivolumab

NSCLC subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema

Nivolumab 3 mg/kg solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as monotherapy. A cycle is 2 weeks

Biological: Nivolumab
Other Name: BMS-936558
Experimental: Arm N: Nivolumab + Ipilimumab

In subjects with any histology (NSCLC)

Nivolumab 1 mg/kg solution administered over 60 minutes intravenously prior to Ipilimumab on Day 1 of each cycle. A cycle is 3 weeks for combination regimen. Combination regimen will be provided for 4 cycles.

Ipilimumab 1 mg/kg solution administered over 90 minutes intravenously on Day 1 of each cycle, every 3 weeks for 4 cycles.

Followed by Nivolumab (3 mg/kg) administered every 2 weeks until PD or discontinuation due to toxicity.

Biological: Nivolumab
Other Name: BMS-936558
Biological: Ipilimumab

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01454102

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, California
Ucla Recruiting
Santa Monica, California, United States, 90404
Contact: Jonathan Goldman, Site 005    310-633-8400      
United States, Connecticut
Yale University Recruiting
New Haven, Connecticut, United States, 06520
Contact: Scott Gettinger, Site 014    203-737-4156      
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Scott Antonia, Site 013    813-745-3905      
United States, Maryland
The Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Julie Brahmer, Site 001    443-287-4114      
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Naiyer Rizvi, Site 010    646-888-4548      
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Neal Ready, Site 004    919-681-4768      
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Hossein Borghaei, Site 016    215-214-1472      
United States, Texas
Ut Southwestern Medical Center At Dallas Recruiting
Dallas, Texas, United States, 75390
Contact: David E Gerber, Site 006    214-648-6551      
United States, Washington
Seattle Cancer Care Alliance Recruiting
Seattle, Washington, United States, 98109
Contact: Laura Chow, Site 007    206-288-7445      
Canada, Ontario
Local Institution Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Site 008         
Local Institution Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Site 003         
Canada, Quebec
Local Institution Recruiting
Ottawa, Quebec, Canada, K1H 8L6
Contact: Site 002         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01454102     History of Changes
Other Study ID Numbers: CA209-012
Study First Received: September 16, 2011
Last Updated: April 1, 2014
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee
United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Gemcitabine
Pemetrexed
Bevacizumab
Cisplatin
Carboplatin
Paclitaxel
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on April 20, 2014