Nivolumab Plus Cisplatin/Pemetrexed or Cisplatin/Gemcitab... | NCT03366766

ID	Type	Description	Link
JT 11371	Other Identifier	JeffTrial Number

Name	Class
Bristol-Myers Squibb	INDUSTRY

Label	Type	Description	Intervention Names
Cohort I (nivolumab, cisplatin, pemetrexed disodium)	Experimental	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity	Biological: Nivolumab Drug: Cisplatin Drug: Pemetrexed Disodium
Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride)	Experimental	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity.	Biological: Nivolumab Drug: Gemcitabine Hydrochloride

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab	Biological	Given IV	Cohort I (nivolumab, cisplatin, gemcitabine hydrochloride) Cohort I (nivolumab, cisplatin, pemetrexed disodium)

Measure	Description	Time Frame
Major Pathologic Response (mpCR) Defined as < 10% Viable Tumor	For the primary endpoint, the major pathologic response rate was calculated as a percentage of patients who achieved a major pathologic response (i.e., <10% viable tumor) or pathologic complete response. Then, the major pathologic response rate was tested with the exact binomial test under the null hypothesis that the true major pathologic response rate is ≤ 0.19. The corresponding 95% Clopper-Pearson confidence limits were reported too.	Up to 63 days

Measure	Description	Time Frame
Number of Adverse Events	Number of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Safety data will be summarized descriptively.	Up to 6 months
Progression Free Survival

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pathologically confirmed non small cell lung cancer (NSCLC), not previously treated, with a plan to undergo surgery
Stage I-IIIA (stage I tumors must be >= 4 cm) per AJCC 8th edition
Tumor sample must be available for PD-L1 testing; archival tissue within 3 months of study enrollment will be used; if archival tissue is unavailable, a fresh biopsy will be taken
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
While blood cells 2000/ul or more
Absolute neutrophil count 1500/ul or more
Platelets 100,000/ul or more
Hemoglobin 9 g/dl or more; (transfusion permitted)
Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin < 3 mg/dl)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 x the upper limit of normal
Glomerular filtration rate (GFR) greater than or equal to 40 ml/min using the Cockcroft-Gault formula or serum creatinine less than or equal to 1.5 x (ULN) upper limit of normal
Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 21 days of the study enrollment
Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 23 weeks after the last dose of study drugs; "women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level more than 40 mIU/mL
Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year; men who are receiving the study medications will be instructed to adhere to contraception for 31 weeks after the last dose of study drugs; men who are azoospermic do not require contraception
All subjects must be able to comprehend and sign a written informed consent document

Exclusion Criteria:

Patients who have participated in a study with an investigational agent or device within 2 weeks of enrollment
Any prior radiotherapy to the lung
Any prior treatment for NSCLC
Epidermal growth factor receptor (EGFR) or alkaline phosphatase (ALK) activating alteration
Any prior therapy with anti-PD-1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Any history of a sever hypersensitivity reaction to any monoclonal antibody
Any history of allergy to the study drug components
Any concurrent malignancies- exceptions include- basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy; patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 3 years post-diagnosis
Participants with an active autoimmune disease or any other condition requiring systemic treatment with either corticosteroids within 14 days (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 30 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.• Patients with evidence of interstitial lung disease or active, non-infectious pneumonitis. Patients with a history of interstitial lung disease or non-infectious pneumonitis requiring treatment with steroids are also excluded.
Patients with a known human immunodeficiency virus infection (HIV 1/2 antibodies) or acquired immunodeficiency syndrome (HIV/AIDS), active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
Patients who have received a live vaccine within 30 days prior initiation of the systemic regimen
Patients must not be receiving any other investigational agents
Patients with uncontrolled intercurrent illnesses including, but not limited to an active infection requiring systemic therapy or a known psychiatric or substance abuse disorder(s) that would interfere with cooperation with the requirements of the trial
Women must not be pregnant (as above) or breastfeeding

Name	Affiliation	Role
Rita Axelrod, MD	Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Abington Hospital - Jefferson Health		Abington	Pennsylvania	19001	United States
Sidney Kimmel Cancer Center at Thomas Jefferson University

Label	URL
Sidney Kimmel Cancer Center at Thomas Jefferson University	View source
Thomas Jefferson University Hospital	View source

ID	Title	Description
FG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 27, 2019

ID	Title	Description
BG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
BG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG00110 BG00214

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Major Pathologic Response (mpCR) Defined as < 10% Viable Tumor

For the primary endpoint, the major pathologic response rate was calculated as a percentage of patients who achieved a major pathologic response (i.e., <10% viable tumor) or pathologic complete response. Then, the major pathologic response rate was tested with the exact binomial test under the null hypothesis that the true major pathologic response rate is ≤ 0.19. The corresponding 95% Clopper-Pearson confidence limits were reported too.

The primary endpoint was pre-scpecified in the protocol to be analyzed collectively. This outcome was intended to be evaluated across all participants together, not by individual regimen, so the arms were combined for this analysis.

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to 63 days

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Combined Cohort (All Patient Receiving Nivolumab IV	Cohort I: Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV Cohort II: Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV

Units	Counts
Participants	OG0004 OG00110 OG00214

Title

Denominators

Categories

Title	Measurements
	OG00075(19.4 to 99.4) OG00180.0(44.4 to 97.5) OG00278.6(49.2 to 95.3)

Secondary

Number of Adverse Events

Number of adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Safety data will be summarized descriptively.

Posted

Number

adverse events

Up to 6 months

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV

Units	Counts
Participants

Secondary

Progression Free Survival

The distribution of progression-free survival will be estimated using the Kaplan-Meier method.

Posted

Number

95% Confidence Interval

Probability of Survival

At 1 year

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Combined Cohort (All Patients Receiving Nivolumab IV)	Cohort I: Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV Cohort II: Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV

Secondary

Overall Survival

The distribution of overall survival will be estimated using the Kaplan-Meier method.

Posted

Number

95% Confidence Interval

Probability of Survival

Up to 1 year

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort I (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Combined Cohort (All Patient Receiving Nivolumab IV)	Cohort I: Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV Cohort II: Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV

Secondary

Overall Clinical Response

Will be summarized by presence of baseline measurable disease. Overall clinical response measured by Chest CT at 3 timepoints

Posted

Count of Participants

Participants

At Week 10

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Overall (Cohort I and Cohort II)	Overall includes both Cohorts combined. Cohort I: Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV Cohort II: Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV

Secondary

Overall Clinical Response

Will be summarized by presence of baseline measurable disease. Overall clinical response measured by Chest CT at 3 timepoints

Data for one participant in Cohort I and three participants in Cohort II was unavailable for this outcome measure. As a result, these cases could not be included in the analysis.

Posted

Count of Participants

Participants

At Month 3

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Overall (Cohort I and Cohort II)

Secondary

Overall Clinical Response

Will be summarized by presence of baseline measurable disease. Overall clinical response measured by Chest CT at 3 timepoints

Data for one participant in Cohort II was unavailable for this outcome measure. As a result, these cases could not be included in the analysis.

Posted

Count of Participants

Participants

At Month 6

ID	Title	Description
OG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV
OG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV
OG002	Overall (Cohort I and Cohort II)

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acidosis - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
acne - Grade 2	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Activity change - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Agitation	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Alanine Aminotransferase (ALT) increased - Grade 1	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Alanine Aminotransferase (ALT) increased - Grade 2	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Alkaline Phosphatase increased - Grade 2	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Allergic Rhinitis - Grade 1	Immune system disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected10 at risk
Alopecia - Grade 1	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Anemia - Grade 2	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Anemia - Grade1	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Anemia - Grade 3	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Anorexia - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0016 events6 affected10 at risk
Anxiety - Grade 1	Psychiatric disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Arthralgia - Grade 1	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Arthritis - Grade 1	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Aspartate Aminotransferase (AST) increased - Grade 1	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Alkaline Phosphatase increased - Grade 1	Hepatobiliary disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Decreased Hemoglobin - Grade 3	Blood and lymphatic system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Hypercalcemia - Grade 1	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected10 at risk
Hyperlipidemia - Grade 1	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected10 at risk
Bradycardia - Grade 1	Cardiac disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Orthostatic - Grade 1	Cardiac disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
tachycardia - Grade 1	Cardiac disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Ear discharge - Grade 1	Ear and labyrinth disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
hearing impairment - Grade 1	Ear and labyrinth disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Floaters - Grade 1	Eye disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Itchy eyes - Grade 1	Eye disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Puffy eyes - Grade 1	Endocrine disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected10 at risk
Vision changes - Grade 1	Eye disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Watering eyes - Grade 1	Eye disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0011 events1 affected10 at risk
Constipation - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Decreased Appetite - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Dental problem - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Diarrhea - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0016 events6 affected10 at risk
Diarrhea -Grade 2	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Flatulence - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Dysgeusia - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Gastroesophageal reflux disease - Grade 1	Vascular disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0012 events2 affected10 at risk
Indigestion - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Loose Tooth - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Mucus discharge - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Nausea - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG00110 events10 affected10 at risk
Nausea -Grade 2	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Poor dentition - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Shakiness - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Vomiting - Grade 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0017 events7 affected10 at risk
Activity change 1	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Chills - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Drooling - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Dry mouth - - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Dry mouth Grade 3	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Dry mouth - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Fall	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Fatigue - Grade1	General disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0016 events6 affected10 at risk
Fatigue - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events4 affected10 at risk
Fatigue - Grade 3	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Gait Disturbance - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Generalized Muscle Weakness - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Generalized muscle weakness - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Headaches - Grade 1	General disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0012 events2 affected10 at risk
Headaches - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Hoarseness	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Mediastinal lymphadenopathy - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Myalgia	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Neck Stiffness - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0015 events5 affected10 at risk
Pain - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Abdominal - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain-Back - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Pain-Back - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain-Bone - Grade1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Chest (non cardiac) - Grade	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Pain - Chest Wall - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain Extremity - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events4 affected10 at risk
Pain - Hip	General disorders	Systematic Assessment	EG0001 events1 affected4 at risk EG0010 events0 affected10 at risk
Pain - Incision site - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Pain - Joints - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Neck - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Rib - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Rib - Grade 2	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Scalp - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Pain - Stomach - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Palpable cord in right arm - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Palpable sclerosed veins - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Polydipsia - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Nasal congestion - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Sore throat - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events4 affected10 at risk
Congestion - Grade 1	General disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Hypothyroidism - Grade 2	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Nasal congestion - Grade 1	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Neutrophil count decreased - Grade 3	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Platelet count decreased - Grade 1	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Postnasal drip - Grade 1	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Sinus Pressure - Grade 1	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Upper respiratory Infection - Grade 2	Immune system disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Lung Infection - Grade 3	Infections and infestations	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Sepsis - Grade 3	Infections and infestations	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Skin infection - Grade 1	Infections and infestations	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Facial trauma - Grade 1	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Incision wound injury - Grade 1	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Infusion related reaction	Injury, poisoning and procedural complications	Systematic Assessment	EG0001 events1 affected4 at risk EG0012 events2 affected10 at risk
Infusion site reaction - Grade 1	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Right shoulder injury - Grade 1	Injury, poisoning and procedural complications	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Bloating - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Dehydration - Grade 2	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Dehydration - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk
Hyperglycemia - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0012 events2 affected10 at risk
Weight loss - Grade 1	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0013 events3 affected10 at risk
Brachial plexus impingement - Grade 1	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected10 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017672	Nitrogen Compounds
D017671	Platinum Compounds
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000600	Amino Acids, Dicarboxylic
D003841	Deoxycytidine
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort I (Nivolumab, Cisplatin, Pemetrexed Disodium)	Patients with non-squamous lung cancer receive nivolumab IV over 30 minutes, cisplatin IV over 60-120 minutes, and pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity Nivolumab: Given IV Cisplatin: Given IV Pemetrexed Disodium: Given IV	0	4	0	4	1	4
EG001	Cohort II (Nivolumab, Cisplatin, Gemcitabine Hydrochloride)	Patients with squamous lung cancer receive nivolumab IV over 30 minutes on day 1, cisplatin IV over 60-120 minutes on day 1, and gemcitabine hydrochloride IV over 1 hour on days 1 and 8. Courses repeat every 3 weeks for up to 9 weeks in the absence of disease progression or unacceptable toxicity. Nivolumab: Given IV Gemcitabine Hydrochloride: Given IV	2	10	1	10	10	10

ID	Term
D000077594	Nivolumab
D002945	Cisplatin
C044245	1,2-diaminocyclohexaneplatinum II citrate
D000068437	Pemetrexed
D000093542	Gemcitabine