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)

Non-small Cell Lung Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT01454102
• Other study ID #: CA209-012
• Status: Completed
• Phase: Phase 1
• Start date: December 16, 2011
• Est. completion date: July 23, 2021

Study information

• Verified date: September 2021
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. - 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 472
• Est. completion date: July 23, 2021
• Est. primary completion date: July 20, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• Nivolumab

Drug:
• Gemcitabine

• Cisplatin

• Pemetrexed

• Paclitaxel

• Carboplatin

• Bevacizumab

• Erlotinib

Biological:
• Ipilimumab

Locations

Country	Name	City	State
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	Ottawa	Ontario
Canada	Local Institution	Toronto	Ontario
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Ut Southwestern Medical Center At Dallas	Dallas	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Ucla	Los Angeles	California
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Nassau	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Primary	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.	From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)
Primary	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.	From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Primary	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	From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)
Secondary	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.	From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months)
Secondary	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.	24 weeks

External Links

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