Non-small Cell Lung CancerPhase 1NCT01454102
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 Phase 1 study testing Nivolumab, Gemcitabine and Cisplatin in people with Non-small Cell Lung Cancer, run by Bristol-Myers Squibb at 12 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer
- What is being tested?
- Nivolumab, Gemcitabine and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 472 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 16 Dec 2011to 23 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 16Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States9 sites
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Ut Southwestern Medical Center At Dallas
Dallas, Texas, 75390-8852
Duke University Medical Center
Durham, North Carolina, 27710
Ucla
Los Angeles, California, 90095
Yale University
New Haven, Connecticut, 06520
Memorial Sloan Kettering Nassau
New York, New York, 10065
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
University of Washington - Seattle Cancer Care Alliance
Seattle, Washington, 98109
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Canada3 sites
Local Institution
Hamilton, Ontario, L8V 5C2
Local Institution
Ottawa, Ontario, K1H 8L6
Local Institution
Toronto, Ontario, M5G 2M9
About this study
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)
- 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.
- Conditions
- Non-small Cell Lung Cancer
- Being tested
- Nivolumab, Gemcitabine, Cisplatin, Pemetrexed, Paclitaxel
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabBiological
Also called BMS-936558
GemcitabineDrug
CisplatinDrug
PemetrexedDrug
PaclitaxelDrug
CarboplatinDrug
BevacizumabDrug
ErlotinibDrug
IpilimumabBiological
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Nivolumab; Drug: Gemcitabine; Drug: Cisplatin |
| Arm B: 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 Receives: Biological: Nivolumab; Drug: Cisplatin; Drug: 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 Receives: Biological: Nivolumab; Drug: Paclitaxel; Drug: 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 Receives: Biological: Nivolumab; Drug: 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 Receives: Biological: Nivolumab; Drug: Erlotinib |
| Arm F: Nivolumab | Experimental | Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes Receives: Biological: Nivolumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab |
| 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 Receives: Biological: Nivolumab |
| 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 Receives: Biological: Nivolumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
| 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 Receives: Biological: Nivolumab; Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Measured: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Number of Participants Who Experienced Selected Adverse Events
The number of participants who experienced an AE of interest due to any cause is presented. Endocrine, Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, and
Hypersensitivity/Infusion select AEs were identified that are potentially associated with the use of nivolumab, based on the following 4 guiding principles:
- AEs that may differ in type, frequency, or severity from AEs caused by non-immunotherapies
- AEs that may require immunosuppression (eg, corticosteroids) as part of their management
- AEs whose early recognition and management may mitigate severe toxicity
- AEs for which multiple event terms may be used to describe a single type of AE, thereby necessitating the pooling of terms for full characterization.
Measured: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests
The number of subjects with selected hepatic laboratory abnormalities is reported.
AST= aspartate aminotransferase; ALT= alanine aminotransferase; ULN= upper limit of normal.
Measured: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests
The number of subjects with selected thyroid laboratory abnormalities is reported. FT3 and FT4 test abnormalities were considered for a 2-week window after the abnormal TSH test date.
TSH= thyroid-stimulating hormone; FT3= Free T3; FT4= Free T4; LLN= lower limit of normal; ULN= upper limit of normal
Measured: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Secondary outcomes (2)
Objective Response Rate (ORR)
ORR was defined as the percentage of all treated participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria as per investigator assessment. This proportion was multiplied by 100 and expressed as a percentage. BOR was defined as the best response designation recorded between the date of randomization and the date of progression, or the date of subsequent anticancer therapy, whichever occurred first. CR or PR determinations included in the BOR assessment were confirmed by a second scan at least 4 weeks after the criteria for responses were first met. For participants without progression or subsequent therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial progression.
Measured: From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months)
Progression-Free Survival Rate (PFSR) at Week 24
Progression-Free Survival (PFS) was defined as the time from the date of first dose of study medication to the date of first disease progression or death, if death occurred within 100 days of the final dose of study drug. Among participants without previous RECIST-defined progression, participants who died beyond 100 days and those who remained alive were censored at the last tumor assessment date (before subsequent therapy).
PFSR at week 24 was defined as the proportion of subjects remaining progression free and surviving at 24 weeks. The proportion was calculated by the product-limit method (Kaplan-Meier estimate), which takes into account censored data, and expressed as a percentage.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2011 (estimated)
- Study start16 Dec 2011
- Primary completion20 Jul 2016
- Study completion23 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 472 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01454102
- Sponsor's protocol ID
- CA209-012
- Status last verified
- Sep 2021
- First submitted
- 16 Sep 2011
- Last updated
- 12 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 27354485Rizvi 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.
PubMed 27354481Hellmann 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.
PubMed 27932067
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01454102
- Acronym / sponsor ID
- CA209-012
- Conditions
- Non-small Cell Lung Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 472 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 16 Dec 2011 (actual)
- Primary completion
- 20 Jul 2016 (actual)
- Study completion
- 23 Jul 2021 (actual)
- First posted
- 18 Oct 2011 (estimated)
- Results
- Posted 5 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| Arm A: Nivolumab + Gemcitabine + Cisplatin | Experimental | Biological: Nivolumab, Drug: Gemcitabine, Drug: CisplatinNivolumab 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 |
| Arm B: Nivolumab + Pemetrexed + Cisplatin | Experimental | Biological: Nivolumab, Drug: Cisplatin, Drug: PemetrexedNivolumab 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 |
| Arm C: Nivolumab + Paclitaxel + Carboplatin | Experimental | Biological: Nivolumab, Drug: Paclitaxel, Drug: CarboplatinNivolumab 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 |
| Arm D: Nivolumab + Bevacizumab maintenance | Experimental | Biological: Nivolumab, Drug: BevacizumabNivolumab 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 |
| Arm E: Nivolumab + Erlotinib | Experimental | Biological: Nivolumab, Drug: ErlotinibNivolumab 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 |
| Arm F: Nivolumab | Experimental | Biological: NivolumabNivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes |
| Arm G: Nivolumab + Ipilimumab | Experimental | Biological: Nivolumab, Biological: IpilimumabIn 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 | Biological: Nivolumab, Biological: IpilimumabIn 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 | Biological: Nivolumab, Biological: IpilimumabIn 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 | Biological: Nivolumab, Biological: IpilimumabIn 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 | Biological: NivolumabIn 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 | Biological: NivolumabIn 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 | Biological: NivolumabNSCLC 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 | Biological: Nivolumab, Biological: IpilimumabIn 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 | Biological: Nivolumab, Biological: IpilimumabNivolumab 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 | Biological: Nivolumab, Biological: IpilimumabNivolumab 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 | Biological: Nivolumab, Biological: IpilimumabNivolumab 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 | Biological: Nivolumab, Biological: IpilimumabNivolumab 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 | Biological: Nivolumab, Biological: IpilimumabNivolumab at specified dose/schedule until PD or discontinuation due to toxicity Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: BMS-936558 | Biological | Arm A: Nivolumab + Gemcitabine + Cisplatin, Arm B: Nivolumab + Pemetrexed + Cisplatin, Arm C: Nivolumab + Paclitaxel + Carboplatin, Arm D: Nivolumab + Bevacizumab maintenance, Arm E: Nivolumab + Erlotinib, Arm F: Nivolumab, Arm G: Nivolumab + Ipilimumab, Arm H: Nivolumab + Ipilimumab, Arm I: Nivolumab + Ipilimumab, Arm J: Nivolumab + Ipilimumab, Arm K: Nivolumab, Arm L: Nivolumab, Arm M: Nivolumab, Arm N: Nivolumab + Ipilimumab, Arm O: Nivolumab + Ipilimumab, Arm P: Nivolumab + Ipilimumab, Arm Q: Nivolumab + Ipilimumab, Arm R: Nivolumab + Ipilimumab, Arm S: Nivolumab + Ipilimumab |
| Gemcitabine | Drug | Arm A: Nivolumab + Gemcitabine + Cisplatin |
| Cisplatin | Drug | Arm A: Nivolumab + Gemcitabine + Cisplatin, Arm B: Nivolumab + Pemetrexed + Cisplatin |
| Pemetrexed | Drug | Arm B: Nivolumab + Pemetrexed + Cisplatin |
| Paclitaxel | Drug | Arm C: Nivolumab + Paclitaxel + Carboplatin |
| Carboplatin | Drug | Arm C: Nivolumab + Paclitaxel + Carboplatin |
| Bevacizumab | Drug | Arm D: Nivolumab + Bevacizumab maintenance |
| Erlotinib | Drug | Arm E: Nivolumab + Erlotinib |
| Ipilimumab | Biological | Arm G: Nivolumab + Ipilimumab, Arm H: Nivolumab + Ipilimumab, Arm I: Nivolumab + Ipilimumab, Arm J: Nivolumab + Ipilimumab, Arm N: Nivolumab + Ipilimumab, Arm O: Nivolumab + Ipilimumab, Arm P: Nivolumab + Ipilimumab, Arm Q: Nivolumab + Ipilimumab, Arm R: Nivolumab + Ipilimumab, Arm S: Nivolumab + Ipilimumab |
Primary outcome
Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death
Time frame: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling.
Number of Participants Who Experienced Selected Adverse Events
Time frame: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
The number of participants who experienced an AE of interest due to any cause is presented. Endocrine, Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, and Hypersensitivity/Infusion select AEs were identified that are potentially associated with the use of nivolumab, based on the following 4 guiding principles: * AEs that may differ in type, frequency, or severity from AEs caused by non-immunotherapies * AEs that may require immunosuppression (eg, corticosteroids) as part of their management * AEs whose early recognition and management may mitigate severe toxicity * AEs for which multiple event terms may be used to describe a single type of AE, thereby necessitating the pooling of terms for full characterization.
Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests
Time frame: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
The number of subjects with selected hepatic laboratory abnormalities is reported. AST= aspartate aminotransferase; ALT= alanine aminotransferase; ULN= upper limit of normal.
Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests
Time frame: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
The number of subjects with selected thyroid laboratory abnormalities is reported. FT3 and FT4 test abnormalities were considered for a 2-week window after the abnormal TSH test date. TSH= thyroid-stimulating hormone; FT3= Free T3; FT4= Free T4; LLN= lower limit of normal; ULN= upper limit of normal
2 secondary outcomes
Objective Response Rate (ORR)
Time frame: From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months)
Progression-Free Survival Rate (PFSR) at Week 24
Time frame: 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27354485Gettinger 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.
- Background: PubMed 27354481Rizvi 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.
- Background: PubMed 27932067Hellmann 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.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
- FDA Safety Alerts and RecallsLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab, Gemcitabine and Cisplatin in people with Non-small Cell Lung Cancer, run by Bristol-Myers Squibb at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death (time frame: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01454102, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.