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)

NCT ID: NCT01454102

Last Updated: 2021-10-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

472 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-12-16

Study Completion Date

2021-07-23

Brief Summary

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* 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

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Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Gemcitabine

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Arm B: 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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Cisplatin

Intervention Type DRUG

Pemetrexed

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Paclitaxel

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Bevacizumab

Intervention Type DRUG

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Erlotinib

Intervention Type DRUG

Arm F: Nivolumab

Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

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

Group Type EXPERIMENTAL

Nivolumab

Intervention Type BIOLOGICAL

Ipilimumab

Intervention Type BIOLOGICAL

Interventions

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Nivolumab

Intervention Type BIOLOGICAL

Gemcitabine

Intervention Type DRUG

Cisplatin

Intervention Type DRUG

Pemetrexed

Intervention Type DRUG

Paclitaxel

Intervention Type DRUG

Carboplatin

Intervention Type DRUG

Bevacizumab

Intervention Type DRUG

Erlotinib

Intervention Type DRUG

Ipilimumab

Intervention Type BIOLOGICAL

Other Intervention Names

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BMS-936558

Eligibility Criteria

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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

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Bristol-Myers Squibb

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

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Ucla

Los Angeles, California, United States

Site Status

Yale University

New Haven, Connecticut, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, United States

Site Status

Memorial Sloan Kettering Nassau

New York, New York, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Ut Southwestern Medical Center At Dallas

Dallas, Texas, United States

Site Status

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Local Institution

Hamilton, Ontario, Canada

Site Status

Local Institution

Ottawa, Ontario, Canada

Site Status

Local Institution

Toronto, Ontario, Canada

Site Status

Countries

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United States Canada

References

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Gettinger S, Rizvi NA, Chow LQ, Borghaei H, Brahmer J, Ready N, Gerber DE, Shepherd FA, Antonia S, Goldman JW, Juergens RA, Laurie SA, Nathan FE, Shen Y, Harbison CT, Hellmann MD. Nivolumab Monotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Sep 1;34(25):2980-7. doi: 10.1200/JCO.2016.66.9929. Epub 2016 Jun 27.

Reference Type BACKGROUND
PMID: 27354485 (View on PubMed)

Rizvi NA, Hellmann MD, Brahmer JR, Juergens RA, Borghaei H, Gettinger S, Chow LQ, Gerber DE, Laurie SA, Goldman JW, Shepherd FA, Chen AC, Shen Y, Nathan FE, Harbison CT, Antonia S. Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Sep 1;34(25):2969-79. doi: 10.1200/JCO.2016.66.9861. Epub 2016 Jun 27.

Reference Type BACKGROUND
PMID: 27354481 (View on PubMed)

Hellmann MD, Rizvi NA, Goldman JW, Gettinger SN, Borghaei H, Brahmer JR, Ready NE, Gerber DE, Chow LQ, Juergens RA, Shepherd FA, Laurie SA, Geese WJ, Agrawal S, Young TC, Li X, Antonia SJ. Nivolumab plus ipilimumab as first-line treatment for advanced non-small-cell lung cancer (CheckMate 012): results of an open-label, phase 1, multicohort study. Lancet Oncol. 2017 Jan;18(1):31-41. doi: 10.1016/S1470-2045(16)30624-6. Epub 2016 Dec 5.

Reference Type BACKGROUND
PMID: 27932067 (View on PubMed)

Related Links

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Other Identifiers

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CA209-012

Identifier Type: -

Identifier Source: org_study_id

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