Clinical Trial: NCT01454102 - My Cancer Genome

NCT01454102

Description:

- 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.

Related Conditions:

Non-Small Cell Lung Carcinoma

Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT01454102

Trial Eligibility

Document

Title

Brief Title: 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)
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)

Clinical Trial IDs

ORG STUDY ID: CA209-012
NCT ID: NCT01454102

Conditions

Non-small Cell Lung Cancer

Interventions

Drug	Synonyms	Arms
Nivolumab	BMS-936558	Arm A: Nivolumab + Gemcitabine + Cisplatin
Gemcitabine		Arm A: Nivolumab + Gemcitabine + Cisplatin
Cisplatin		Arm A: Nivolumab + Gemcitabine + Cisplatin
Pemetrexed		Arm B: Nivolumab + Pemetrexed + Cisplatin
Paclitaxel		Arm C: Nivolumab + Paclitaxel + Carboplatin
Carboplatin		Arm C: Nivolumab + Paclitaxel + Carboplatin
Bevacizumab		Arm D: Nivolumab + Bevacizumab maintenance
Erlotinib		Arm E: Nivolumab + Erlotinib
Ipilimumab		Arm G: Nivolumab + Ipilimumab

Purpose

Trial Arms

Name	Type	Description	Interventions
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	Nivolumab Gemcitabine 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	Nivolumab Cisplatin 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	Nivolumab Paclitaxel 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	Nivolumab 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	Nivolumab Erlotinib
Arm F: Nivolumab	Experimental	Nivolumab solution intravenously every 2 weeks until PD or discontinuation due to toxicity. Administered over 60 minutes	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	Nivolumab 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	Nivolumab 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	Nivolumab 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	Nivolumab 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	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	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	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	Nivolumab 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	Nivolumab 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	Nivolumab 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	Nivolumab 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	Nivolumab 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	Nivolumab Ipilimumab

Eligibility 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

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

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)
Safety Issue:
Description:	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.

Secondary Outcome Measures

Measure:	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)
Safety Issue:
Description:	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.

Measure:	Progression-Free Survival Rate (PFSR) at Week 24
Time Frame:	24 weeks
Safety Issue:
Description:	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.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	Bristol-Myers Squibb

Last Updated

March 5, 2020

Clinical Trials /

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)