Clinical trial NCT01454102
Conditions: Non-small Cell Lung Cancer
Sponsor: Bristol-Myers Squibb
Start date: 2011-12-16; Completion date: 2021-07-23
Enrollment: 472 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.
* 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:

Arms: arm 1: 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 arm 2: 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 arm 3: 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 arm 4: 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 arm 5: 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 arm 6: Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes arm 7: In Squamous histology subjects (NSCLC)

Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

Followed by Nivolumab administered until PD or discontinuation due to toxicity arm 8: In non-squamous histology subjects (NSCLC)

Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity arm 9: In squamous histology subjects (NSCLC)

Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity arm 10: In non-squamous histology subjects (NSCLC)

Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity arm 11: In squamous histology subjects (NSCLC)

Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered as switch maintenance therapy. A cycle is 2 weeks arm 12: In non-squamous histology subjects (NSCLC)

Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes as switch maintenance therapy. A cycle is 2 weeks arm 13: NSCLC subjects with untreated, asymptomatic brain metastases and have no evidence of cerebral edema

Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered for up to an hour as monotherapy. A cycle is 2 weeks arm 14: In subjects with any histology (NSCLC)

Nivolumab solution administered intravenously prior to Ipilimumab on Day 1 of each cycle. Combination regimen will be provided for 4 cycles

Ipilimumab solution administered intravenously on Day 1 of each cycle, for 4 cycles

Followed by Nivolumab administered every 2 weeks until PD or discontinuation due to toxicity arm 15: Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity arm 16: Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity arm 17: Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity arm 18: Nivolumab at specified dose/schedule until PD or discontinuation due to toxicity

Ipilimumab at specified dose/schedule until PD or discontinuation due to toxicity arm 19: 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: intervention 1: Nivolumab intervention 2: Gemcitabine intervention 3: Cisplatin intervention 4: Pemetrexed intervention 5: Paclitaxel intervention 6: Carboplatin intervention 7: Bevacizumab intervention 8: Erlotinib intervention 9: Ipilimumab
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None

Protocol documents: