Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC)

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00527735
• Collaborator: (none)
• Enrollment: 334
• Locations: 72
• Arms: 3
• Duration (Months): 46
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of the study is to determine whether ipilimumab given with paclitaxel/carboplatin has clinical benefit when compared with paclitaxel/carboplatin alone in patients with previously untreated lung cancer.

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer; Small Cell Lung Cancer; Carcinoma, Non-Small-Cell Lung	Drug: Ipilimumab; Drug: Placebo; Drug: Paclitaxel; Drug: Carboplatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 334 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double Blind, Parallel, Three Arm Trial Evaluating the Efficacy and Safety of Ipilimumab (BMS-734016) in Combination With Paclitaxel/Carboplatin Compared to Paclitaxel/Carboplatin Alone in Previously Untreated Subjects With Lung Cancer
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ipilimumab/ placebo + paclitaxel + carboplatin (concurrent)	Drug: Ipilimumab; Ipilimumab, 10 mg/kg, administered as a single-dose, intravenously (IV), over 90 minutes depending on randomization every 3 weeks (up to 6 doses). Participants could receive additional maintenance ipilimumab at a dose of 10 mg/kg every 12 weeks starting 24 weeks after the first ipilimumab dose.; Drug: Placebo; Matched placebo for ipilimumab administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants could also receive additional maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first placebo dose.; Drug: Paclitaxel; 175 mg/m^2, administered as a single IV dose over 3 hours every 3 weeks (up to 6 doses). Dose modifications (reductions as well as delays) done as per product label.; Drug: Carboplatin; Area under the concentration curve (AUC)=6, administered as a single IV dose over 30 minutes every 3 weeks (up to 6 doses) as per randomization. Dose modifications (reductions as well as delays) done as per product label.
Experimental: Ipilimumab/ placebo + paclitaxel + carboplatin (sequential)	Drug: Ipilimumab; Ipilimumab, 10 mg/kg, administered as a single-dose, intravenously (IV), over 90 minutes depending on randomization every 3 weeks (up to 6 doses). Participants could receive additional maintenance ipilimumab at a dose of 10 mg/kg every 12 weeks starting 24 weeks after the first ipilimumab dose.; Drug: Placebo; Matched placebo for ipilimumab administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants could also receive additional maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first placebo dose.; Drug: Paclitaxel; 175 mg/m^2, administered as a single IV dose over 3 hours every 3 weeks (up to 6 doses). Dose modifications (reductions as well as delays) done as per product label.; Drug: Carboplatin; Area under the concentration curve (AUC)=6, administered as a single IV dose over 30 minutes every 3 weeks (up to 6 doses) as per randomization. Dose modifications (reductions as well as delays) done as per product label.
Active Comparator: Ipilimumab placebo + paclitaxel + carboplatin	Drug: Placebo; Matched placebo for ipilimumab administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants could also receive additional maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first placebo dose.; Drug: Paclitaxel; 175 mg/m^2, administered as a single IV dose over 3 hours every 3 weeks (up to 6 doses). Dose modifications (reductions as well as delays) done as per product label.; Drug: Carboplatin; Area under the concentration curve (AUC)=6, administered as a single IV dose over 30 minutes every 3 weeks (up to 6 doses) as per randomization. Dose modifications (reductions as well as delays) done as per product label.

Outcome Measures

Primary Outcome Measures

1. Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC) [Tumor assessed at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until immune-related Progressive Disease (irPD) or death (of censored, maximum reached: 16.5 months)]

   irPFS is defined as the time between the randomization date and date of immune-related Progressive Disease (irPD) (at least 25% increase percentage change in total tumor burden, including new lesions) or death, whichever occurs first. For patients with no recorded postbaseline tumor assessments, irPFS is censored at randomization. Participant who die without reported irPD are considered to have progressed on the date of death. For those who remain alive and have no irPD, irPFS is censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.

Secondary Outcome Measures

1. Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria [Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)]

   By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.

2. Overall Survival in Participants With NSCLC [Randomization date to date of death (of censored, maximum reached: 26.5 months)]

   Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.

3. Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC [Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance]

   mWHO criteria define BORR as the number of patients with best overall response of Complete Response (CR) or Partial Response (PR), divided by the total number of participants in the data set (multiplied by 100 for percentage). CR=Complete disappearance of all index lesions; PR=decrease from baseline of >=50% in the sum of products of the 2 largest perpendicular diameters of all index lesions. Independent review committee performed tumor assessment.

4. Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC) [Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance]

   irBORR=number of participants with irBORR of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), divided by total participants in the data set. irCR=Complete disappearance of all index lesions. irPR=Decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index and of all new measurable lesions. Independent review committee performed the tumor assessments.

5. Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC [Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until irPD, progressive disease, or death (maximum reached: 22 months)]

   irDCR is defined as the proportion of participants whose immune-related best overall response is irPR, irCR, or immune-related Stable Disease (irSD) in the analysis data set. irSD=Does not meet criteria for irCR or irPR, in the absence of progressive disease. By mWHO criteria, DCR is defined as the proportion of participants whose best overall response is PR, CR, or SD in the analysis data set. SD=A decrease or tumor stabilization of 1 or more nonindex lesions. Independent review committee assessed response.

6. Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC [Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months)]

   irDoR is defined as the time between the date of response of confirmed irCR or irPR and the date of irPD or death, whichever occurs first. For those participants who remain alive and did progress following response, irDoR was censored on the date of last evaluable tumor assessment. By mWHO criteria, DoR is defined as the time between the date of response of confirmed CR or PR and the date of PD or death, whichever occurs first. For those who remain alive and did not progress following response, DoR was censored on the date of last evaluable tumor assessment.

7. Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade [Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)]

   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. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

8. Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade [At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent]

   CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.

9. irPFS in Participants With SCLC Per irRC [Randomization date to date of irPD or death (maximum reached: 22 months)]

   IRC performed TA.

10. Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade [At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent]

    ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.

11. Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings [At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent]

    Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.

12. Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade [At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment]

    ULN=upper limit of normal. Lipase (U/L) Gr 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Creatine (mg/dL) Grade 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.

13. Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline [Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment]

    An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.

14. Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade [Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)]

    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. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.

15. Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade [At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment]

    CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Gr 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.

16. Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade [At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment]

    ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. ULN=Upper limit of normal among all laboratory ranges. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.

17. Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade [At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment]

    ULN=upper limit of normal. Lipase (U/L) Grade (Gr) 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Gr 2 >1.5 to 2.0*ULN, Gr 3 >2.0 to 5.0*ULN, Gr 4 >5.0*ULN. Creatine (mg/dL) Gr 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.

18. Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria [Randomization date to date of progression or death (of censored, maximum reached: 22 months)]

    By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment.

19. Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings [Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment]

    Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.

20. Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline [Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment]

    An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.

21. Overall Survival in Participants With SCLC [Randomization date to date of death (of censored, maximum reached: 22 months)]

    Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed lung cancer (Stage IIIb/IV nonsmall-cell lung cancer or extensive stage small-cell lung cancer [SCLC])

• Measurable tumor lesion (as long as it is not located in a previously irradiated area) as defined by modified World Health Organization criteria

• Eastern Cooperative Oncology Group performance status of ≤1 at study entry

• Accessible for treatment and follow-up

Exclusion Criteria:

• Brain metastases

• Malignant pleural effusion

• Autoimmune disease

• Motor neuropathy of autoimmune origin

• SCLC-related paraneoplastic syndromes

• Any concurrent malignancy other than nonmelanoma skin cancer; carcinoma in situ of the cervix or breast; or prostate cancer treated with systemic therapy (participants with a previous malignancy but without evidence of disease for 5 years were allowed to enter the study)

• Prior systemic therapy for lung cancer. Prior radiation therapy or locoregional surgeries performed later than at least 3 weeks prior to randomization date were allowed.

• Grade 2 peripheral neuropathy (motor or sensory)

• Known HIV or hepatitis B or C infection

• Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or noncancer-related illnesses). However, use of corticosteroids was allowed if used as premedication for paclitaxel infusion or for treating immune-related adverse events or adrenal insufficiencies.

• Inadequate hematologic function defined by an absolute neutrophil count <1,500/mm^{3, a platelet count <100,000/mm}3, or hemoglobin level <9 g/dL.

• Inadequate hepatic function defined by a total bilirubin level >2.0 times the upper limit of normal (ULN), or ≥2.5 times the ULN if liver metastases are present, aspartate aminotransferase and alanine aminotransferase levels ≥2.5 times the ULN or ≥5 times the ULN if liver metastases are present.

• Inadequate renal function defined by a serum creatinine level ≥2.5 times the ULN

• Inadequate creatinine clearance defined as less than 50 mL/min.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Birmingham Hematology & Oncology Assoc. Llc	Birmingham	Alabama	United States	35235
2	Mayo Clinic	Scottsdale	Arizona	United States	85259
3	Acrc/Arizona Clinical Research Center, Inc.	Tucson	Arizona	United States	85715
4	Compassionate Cancer Care Medical Group	Corona	California	United States	92879
5	Compassionate Cancer Care Medical Group, Inc.	Fountain Valley	California	United States	92708
6	The Angeles Clinic & Research Institute, Inc	Los Angeles	California	United States	90025
7	Oncology Care Medical Associates	Montebello	California	United States	90640
8	Compassionate Cancer Care Medical Group	Riverside	California	United States	92501
9	Sharp Clinical Oncology Research	San Diego	California	United States	92123
10	M D Anderson Cancer Center- Orlando	Orlando	Florida	United States	32806
11	Georgia Cancer Specialists	Atlanta	Georgia	United States	30341
12	University Of Chicago Medical Center	Chicago	Illinois	United States	60637
13	Local Institution	Park Ridge	Illinois	United States	60068
14	Kentucky Cancer Clinic	Hazard	Kentucky	United States	41701
15	The John R. Marsh Cancer Center	Hagerstown	Maryland	United States	21740
16	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
17	The Cancer Center	Minneapolis	Minnesota	United States	55455
18	Nevada Cancer Institute	Las Vegas	Nevada	United States	89135
19	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
20	Local Institution	New York	New York	United States	10017
21	Cmc-Northeast/ Northeast Oncology Associates	Concord	North Carolina	United States	28025
22	Gabrail Cancer Center	Canton	Ohio	United States	44718
23	Hematology Oncology Consultants, Inc	Columbus	Ohio	United States	43235
24	St. Mary Medical Center	Langhorne	Pennsylvania	United States	19047
25	Guthrie Clinical Research	Sayre	Pennsylvania	United States	18840
26	Santee Hematology/Oncology	Sumter	South Carolina	United States	29150
27	Southwest Cancer Treatment And Research Center	Lubbock	Texas	United States	79415
28	Local Institution	Belfort		France	90016
29	Local Institution	Caen		France	14076
30	Local Institution	Marseille Cedex 9		France	13274
31	Local Institution	Rennes Cedex 9		France	35033
32	Local Institution	Bochum		Germany	44791
33	Local Institution	Coswig		Germany	01640
34	Local Institution	Ebensfeld		Germany	96250
35	Local Institution	Grosshansdorf		Germany	22927
36	Local Institution	Halle (Saale)		Germany	06120
37	Local Institution	Hamburg		Germany	21075
38	Local Institution	Koeln		Germany	51109
39	Local Institution	Leipzig		Germany	04103
40	Local Institution	Mainz		Germany	55131
41	Local Institution	Muenchen		Germany	81675
42	Local Institution	Hyderabad	Andhra Pradesh	India	500082
43	Local Institution	Navrangpura, Ahmedabad	Gujarat	India	380009
44	Local Institution	Manipal	Karnataka	India	576104
45	Local Institution	Trivandrum	Kerala	India	695011
46	Local Institution	Vellore		India	632004
47	Local Institution	Genova		Italy	16132
48	Local Institution	Siena		Italy	53100
49	Local Institution	Torino		Italy	10143
50	Local Institution	Gdansk		Poland	80-952
51	Local Institution	Krakow		Poland	31-826
52	Local Institution	Olsztyn		Poland	10-513
53	Local Institution	Szczecin		Poland	70-891
54	Local Institution	Arkhangelsk		Russian Federation	163045
55	Local Institution	Chelyabinsk		Russian Federation	454087
56	Local Institution	Ivanovo		Russian Federation	153013
57	Local Institution	Moscow		Russian Federation	105077
58	Local Institution	Moscow		Russian Federation	115478
59	Local Institution	Moscow		Russian Federation	125284
60	Local Institution	Pyatigorsk		Russian Federation	357502
61	Local Institution	Saint-Petersburg		Russian Federation	190005
62	Local Institution	Sochi		Russian Federation	354057
63	Local Institution	St. Petersburg		Russian Federation	194044
64	Local Institution	St. Petersburg		Russian Federation	194291
65	Local Institution	St. Petersburg		Russian Federation	197022
66	Local Institution	St. Petersburg		Russian Federation	198255
67	Local Institution	Dnipropetrovsk		Ukraine	49102
68	Local Institution	Donetsk		Ukraine	83092
69	Local Institution	Kharkov		Ukraine	46023
70	Local Institution	Lviv		Ukraine	79031
71	Local Institution	Ternopol		Ukraine	46023
72	Local Institution	Uzhgorod		Ukraine	88014

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT00527735
• Other Study ID Numbers: CA184-041
• First Posted: Sep 11, 2007
• Last Update Posted: Jul 18, 2018
• Last Verified: Jun 1, 2018

• Keywords provided by Bristol-Myers Squibb: Non Small Cell Lung Cancer (NSCLC); Small Cell Lung Cancer (SCLC)
• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Ipilimumab

Study Results

Participant Flow

Pre-assignment Detail	Of 334 participants enrolled in this study, 331 received treatment. One patient with nonsmall-cell lung cancer, randomized to the sequential arm but mistakenly treated with concurrent therapy, is included in the sequential arm for efficacy results and in the concurrent arm for safety results.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until progressive disease (PD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Period Title: Overall Study
STARTED	113	109	109
COMPLETED	5	2	2
NOT COMPLETED	108	107	107

Baseline Characteristics

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin	Total
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (concurrent). The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes every 3 weeks. Participants who experienced clinical benefit on treatment phase without intolerable toxicity were allowed to continue in the maintenance phase, receiving additional ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until immune-related progressive disease (irPD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (sequential). The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes every 3 weeks. Participants who experienced clinical benefit on treatment phase without intolerable toxicity were allowed to continue in the maintenance phase, receiving additional ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who experienced clinical benefit on treatment phase without intolerable toxicity could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.	Total of all reporting groups
Overall Participants	113	110	111	334
Age, Customized (Number) [Number]
Younger than 65 years	79 69.9%	73 66.4%	76 68.5%	228 68.3%
65 years and older	34 30.1%	37 33.6%	35 31.5%	106 31.7%
Sex: Female, Male (Count of Participants)
Female	27 23.9%	29 26.4%	29 26.1%	85 25.4%
Male	86 76.1%	81 73.6%	82 73.9%	249 74.6%
Age Customized, by Disease Type (Number) [Number]
Younger than 65 years (NSCLC patients)	44 38.9%	44 40%	40 36%	128 38.3%
65 years and older (NSCLC patients)	26 23%	24 21.8%	26 23.4%	76 22.8%
Younger than 65 years (SCLC patients)	35 31%	29 26.4%	36 32.4%	100 29.9%
65 years and older (SCLC patients)	8 7.1%	13 11.8%	9 8.1%	30 9%
Gender, by Disease Type (Number) [Number]
Female (NSCLC patients)	17 15%	19 17.3%	17 15.3%	53 15.9%
Male (NSCLC patients)	53 46.9%	49 44.5%	49 44.1%	151 45.2%
Female (SCLC patients)	10 8.8%	10 9.1%	12 10.8%	32 9.6%
Male (SCLC patients)	33 29.2%	32 29.1%	33 29.7%	98 29.3%
Disease Stage at Study Entry (Number) [Number]
Stage IIIB (NSCLC patients)	11 9.7%	7 6.4%	17 15.3%	35 10.5%
Stage IV (NSCLC patients)	59 52.2%	61 55.5%	49 44.1%	169 50.6%
Extensive (SCLC patients)	43 38.1%	42 38.2%	44 39.6%	129 38.6%
Recurrent disease (SCLC patients)	0 0%	0 0%	1 0.9%	1 0.3%
Cell Type (Number) [Number]
Adenocarcinoma (NSCLC patients)	35 31%	30 27.3%	38 34.2%	103 30.8%
Bronchoalveolar carcinoma (NSCLC patients)	1 0.9%	1 0.9%	0 0%	2 0.6%
Large-cell carcinoma (NSCLC patients)	6 5.3%	11 10%	7 6.3%	24 7.2%
Other (NSCLC patients)	6 5.3%	4 3.6%	3 2.7%	13 3.9%
Squamous-cell carcinoma (NSCLC patients)	21 18.6%	21 19.1%	15 13.5%	57 17.1%
Unknown (NSCLC patients)	1 0.9%	1 0.9%	3 2.7%	5 1.5%
Other (SCLC patients)	2 1.8%	2 1.8%	0 0%	4 1.2%
Small-cell carcinoma (SCLC patients)	41 36.3%	38 34.5%	45 40.5%	124 37.1%
Unknown (SCLC patients)	0 0%	1 0.9%	0 0%	1 0.3%
Not reported (SCLC patients)	0 0%	1 0.9%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
Description	irPFS is defined as the time between the randomization date and date of immune-related Progressive Disease (irPD) (at least 25% increase percentage change in total tumor burden, including new lesions) or death, whichever occurs first. For patients with no recorded postbaseline tumor assessments, irPFS is censored at randomization. Participant who die without reported irPD are considered to have progressed on the date of death. For those who remain alive and have no irPD, irPFS is censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.
Time Frame	Tumor assessed at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until immune-related Progressive Disease (irPD) or death (of censored, maximum reached: 16.5 months)

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until immune-related progressive disease (irPD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	70	68	66
Median (95% Confidence Interval) [Months]	5.52	5.68	4.63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1302
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.806
	Confidence Interval	(2-Sided) 95%; 0.553 to 1.174
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0473
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.724
	Confidence Interval	(2-Sided) 95%; 0.495 to 1.059
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
Description	By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment.
Time Frame	Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)

Outcome Measure Data

Analysis Population Description

All NSCLC participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	70	68	66
Mean (95% Confidence Interval) [Months]	4.11	5.13	4.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2502
	Comments
	Method	One-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.882
	Confidence Interval	(2-Sided) 95%; 0.612 to 1.271
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0240
	Comments
	Method	One-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.691
	Confidence Interval	(2-Sided) 95%; 0.478 to 0.999
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Overall Survival in Participants With NSCLC
Description	Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.
Time Frame	Randomization date to date of death (of censored, maximum reached: 26.5 months)

Outcome Measure Data

Analysis Population Description

All NSCLC participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	70	68	66
Median (95% Confidence Interval) [Months]	9.69	12.22	8.28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4759
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.988
	Confidence Interval	(2-Sided) 95%; 0.669 to 1.460
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2340
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.866
	Confidence Interval	(2-Sided) 95%; 0.587 to 1.278
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC
Description	mWHO criteria define BORR as the number of patients with best overall response of Complete Response (CR) or Partial Response (PR), divided by the total number of participants in the data set (multiplied by 100 for percentage). CR=Complete disappearance of all index lesions; PR=decrease from baseline of >=50% in the sum of products of the 2 largest perpendicular diameters of all index lesions. Independent review committee performed tumor assessment.
Time Frame	Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance

Outcome Measure Data

Analysis Population Description

All participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	113	110	111
BORR (mWHO criteria) NSCLC cohort (n=70, 68, 66)	21.4 18.9%	32.4 29.5%	13.6 12.3%
BORR (mWHO criteria) SCLC cohort (n=43, 42, 45)	32.6 28.8%	57.1 51.9%	48.9 44.1%

5. Secondary Outcome

Title	Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)
Description	irBORR=number of participants with irBORR of immune-related Complete Response (irCR) or immune-related Partial Response (irPR), divided by total participants in the data set. irCR=Complete disappearance of all index lesions. irPR=Decrease, relative to baseline, of 50% or greater in the sum of the products of the 2 largest perpendicular diameters of all index and of all new measurable lesions. Independent review committee performed the tumor assessments.
Time Frame	Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance

Outcome Measure Data

Analysis Population Description

All participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	113	110	111
irBORR ( irRC) NSCLC cohort (n=70, 68, 66)	21.4 18.9%	32.4 29.5%	18.2 16.4%
irBORR (irRC) SCLC cohort (n=43, 42, 45)	48.8 43.2%	71.4 64.9%	53.3 48%

6. Secondary Outcome

Title	Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC
Description	irDCR is defined as the proportion of participants whose immune-related best overall response is irPR, irCR, or immune-related Stable Disease (irSD) in the analysis data set. irSD=Does not meet criteria for irCR or irPR, in the absence of progressive disease. By mWHO criteria, DCR is defined as the proportion of participants whose best overall response is PR, CR, or SD in the analysis data set. SD=A decrease or tumor stabilization of 1 or more nonindex lesions. Independent review committee assessed response.
Time Frame	Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance until irPD, progressive disease, or death (maximum reached: 22 months)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	113	110	111
irDCR (irRC) NSCLC cohort (n=70, 68, 66)	70.0 61.9%	86.8 78.9%	81.8 73.7%
DCR (mWHO criteria) NSCLC cohort (n=70, 68, 66)	57.1 50.5%	77.9 70.8%	72.7 65.5%
rDCR (irRC) SCLC cohort (n=43, 42, 45)	81.4 72%	92.9 84.5%	95.6 86.1%
DCR (mWHO criteria) SCLC cohort (n=43, 42, 45)	69.8 61.8%	81.0 73.6%	93.3 84.1%

7. Secondary Outcome

Title	Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC
Description	irDoR is defined as the time between the date of response of confirmed irCR or irPR and the date of irPD or death, whichever occurs first. For those participants who remain alive and did progress following response, irDoR was censored on the date of last evaluable tumor assessment. By mWHO criteria, DoR is defined as the time between the date of response of confirmed CR or PR and the date of PD or death, whichever occurs first. For those who remain alive and did not progress following response, DoR was censored on the date of last evaluable tumor assessment.
Time Frame	Date of irCR or irPR to date of irPD or death (maximum reached: 14.2 months)

Outcome Measure Data

Analysis Population Description

All participants who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	113	110	111
irDoR (irRC) NSCLC cohort (n=70, 63, 62)	6.70	5.55	4.01
DoR (mWHO criteria) NSCLC cohort (n=70, 63, 62)	5.42	5.55	4.01
irDoR (irRC) SCLC cohort (n=43, 42, 45)	5.95	5.78	4.21
DoR (mWHO criteria) SCLC cohort (n=43, 42, 45)	7.62	5.78	4.21

8. Secondary Outcome

Title	Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade
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. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame	Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who received at least 1 dose of blinded active or placebo ipilimumab with or without paclitaxel/carboplatin. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	71	67	65
Deaths (total)	52 46%	50 45.5%	51 45.9%
Deaths within 30 days of last dose of study drug	11 9.7%	7 6.4%	8 7.2%
Deaths within 70 days of last dose of study drug	21 18.6%	16 14.5%	18 16.2%
SAEs (total)	49 43.4%	36 32.7%	33 29.7%
SAEs, Grade 3	17 15%	16 14.5%	9 8.1%
SAEs, Grade 4	10 8.8%	4 3.6%	5 4.5%
SAEs, Grade 5	20 17.7%	15 13.6%	18 16.2%
SAEs, Drug-related	20 17.7%	13 11.8%	11 9.9%
SAEs, Drug-related Grade 5	2 1.8%	1 0.9%	2 1.8%
AEs leading to discontinuation (disc) (total)	28 24.8%	19 17.3%	15 13.5%
AEs leading to disc, Drug-related (all)	16 14.2%	7 6.4%	8 7.2%
AEs leading to disc, Drug-related Grade 3	9 8%	6 5.5%	4 3.6%
AEs leading to disc, Drug-related Grade 4	1 0.9%	0 0%	0 0%
AEs leading to disc, Drug-related Grade 5	1 0.9%	0 0%	1 0.9%
AEs (total)	71 62.8%	64 58.2%	64 57.7%
AEs, Grades 3 and 4	40 35.4%	36 32.7%	26 23.4%
AEs, Drug-related Any Grade	56 49.6%	56 50.9%	54 48.6%
AEs, Drug-related Grades 3 and 4	29 25.7%	26 23.6%	24 21.6%
AEs, Drug-related Grade 5	2 1.8%	1 0.9%	2 1.8%

9. Secondary Outcome

Title	Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
Description	CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.
Time Frame	At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study hematology test result available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	71	67	65
White blood cell count, Grades 3 and 4	7.7 6.8%	6.2 5.6%	3.2 2.9%
Hemoglobin, Any grade	90.8 80.4%	98.5 89.5%	90.2 81.3%
Hemoglobin, Grades 3 and 4	10.8 9.6%	6.2 5.6%	6.3 5.7%
ANC, Grades 3 and 4	7.7 6.8%	1.5 1.4%	9.5 8.6%
Platelets, Grades 3 and 4	1.5 1.3%	3.1 2.8%	9.5 8.6%

10. Secondary Outcome

Title	irPFS in Participants With SCLC Per irRC
Description	IRC performed TA.
Time Frame	Randomization date to date of irPD or death (maximum reached: 22 months)

Outcome Measure Data

Analysis Population Description

All participants with SCLC who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress and did not experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	43	42	45
Mean (95% Confidence Interval) [Months]	5.68	6.44	5.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1098
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.751
	Confidence Interval	(2-Sided) 95%; 0.475 to 1.188
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0282
	Comments
	Method	1-sided log rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.640
	Confidence Interval	(2-Sided) 95%; 0.403 to 1.1016
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade
Description	ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.
Time Frame	At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study liver function measurement available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	65	65	62
Alanine aminotransferase (ALT), Grade 1	24 21.2%	15 13.6%	19 17.1%
ALT, Grade 2	2 1.8%	4 3.6%	3 2.7%
ALT, Grades 3 and 4	1 0.9%	1 0.9%	1 0.9%
Aspartate aminotransferase (AST), Grade 1	16 14.2%	18 16.4%	20 18%
AST, Grade 2	0 0%	2 1.8%	0 0%
AST, Grades 3 and 4	1 0.9%	1 0.9%	1 0.9%
Total bilirubin, Grade 1	1 0.9%	3 2.7%	2 1.8%
Total bilirubin, Grade 2	3 2.7%	2 1.8%	1 0.9%
Total bilirubin, Grades 3 and 4	0 0%	0 0%	0 0%
Alkaline phosphatase, Grade 1	24 21.2%	28 25.5%	24 21.6%
Alkaline phosphatase, Grade 2	1 0.9%	2 1.8%	3 2.7%
Alkaline phosphatase, Grades 3 and 4	0 0%	1 0.9%	1 0.9%

12. Secondary Outcome

Title	Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
Description	Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.
Time Frame	At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study measurement available.One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	71	67	65
Vital sign measurements	0 0%	0 0%	0 0%
Physical examination findings	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade
Description	ULN=upper limit of normal. Lipase (U/L) Gr 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Creatine (mg/dL) Grade 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.
Time Frame	At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

Outcome Measure Data

Analysis Population Description

All participants with NSCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study pancreatic enzyme laboratory test measurement available. One NSCLC participant randomized to the sequential arm is included in the concurrent arm for safety evaulations.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	71	67	65
Lipase, Grades 3 and 4	7.7 6.8%	6.2 5.6%	3.2 2.9%
Amylase, Grades 3 and 4	1.5 1.3%	4.6 4.2%	1.6 1.4%

14. Secondary Outcome

Title	Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline
Description	An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.
Time Frame	Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

Outcome Measure Data

Analysis Population Description

Participants with at least 1 HAHA measurement prior to and at least 1 after the first ipilimumab dose and with an increase in HAHA measurement from baseline.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Measure Participants	61	56
Number [Participants]	2 1.8%	1 0.9%

15. Secondary Outcome

Title	Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade
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. Drug-related=possibly, probably, or certainly related to and of unknown relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
Time Frame	Weeks 4, 7, 10, 16, 19, and 24; at end of treatment; and at follow-up (70 days from last dose)

Outcome Measure Data

Analysis Population Description

All participants with SCLC who received at least 1 dose of blinded active or placebo ipilimumab with or without paclitaxel/carboplatin.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	42	42	44
Deaths (total)	37 32.7%	31 28.2%	35 31.5%
Deaths within 30 days of last dose of study drug	6 5.3%	2 1.8%	1 0.9%
Deaths within 70 days of last dose of study drug	13 11.5%	7 6.4%	8 7.2%
SAEs (total)	25 22.1%	21 19.1%	20 18%
SAEs, Grade 3	7 6.2%	6 5.5%	4 3.6%
SAEs, Grade 4	3 2.7%	4 3.6%	4 3.6%
SAEs, Grade 5	12 10.6%	7 6.4%	7 6.3%
SAEs, Drug-related	10 8.8%	12 10.9%	6 5.4%
SAEs, Drug-related Grade 5	1 0.9%	0 0%	0 0%
AEs leading to discontinuation (disc) (total)	14 12.4%	13 11.8%	12 10.8%
AEs leading to disc, Drug-related (all)	9 8%	7 6.4%	7 6.3%
AEs leading to disc, Drug-related Grade 3	3 2.7%	3 2.7%	4 3.6%
AEs leading to disc, Drug-related Grade 4	2 1.8%	2 1.8%	0 0%
AEs leading to disc, Drug-related Grade 5	1 0.9%	0 0%	0 0%
AEs (total)	41 36.3%	40 36.4%	43 38.7%
AEs, Grades 3 and 4	19 16.8%	22 20%	19 17.1%
AEs, Grade 5	12 10.6%	7 6.4%	7 6.3%
AEs, Drug-related (all)	36 31.9%	40 36.4%	40 36%
AEs, Drug-related,Grades 3 and 4	18 15.9%	21 19.1%	13 11.7%
AEs, Drug-related, Grade 5	1 0.9%	0 0%	0 0%

16. Secondary Outcome

Title	Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
Description	CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Gr 1:<LLN to 3.0*10^9/L, Gr 2:<3.0 to 2.0*10^9/L, Gr 3:<2.0 to 1.0*10^9/L, Gr 4:<1.0*10^9/L. ANC Gr 1:<LLN to 1.5*10^9/L, Gr 2:<1.5 to 1.0*10^9/L, Gr 3:<1.0 to 0.5*10^9/L, Gr 4:<0.5*10^9/L. Platelet count Gr 1:LLN to 75.0*10^9/L, Gr 2:<75.0 to 50.0*10^9/L, Gr 3:<50.0 to 25.0*10^9/L, Gr 4:<25.0 to 10^9/L. Hemoglobin Gr 1:<LLN to 10.0 g/dL, Gr 2:<10.0 to 8.0 g/dL, Gr 3:<8.0 to 6.5 g/dL, Gr 4:<6.5 g/dL.
Time Frame	At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment

Outcome Measure Data

Analysis Population Description

All participants with SCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study hematology test result available.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	42	42	44
White blood cells, Grade 1 (n=39, 42, 43)	7 6.2%	11 10%	13 11.7%
White blood cells, Grade 2 (n= 39, 42, 43)	10 8.8%	9 8.2%	7 6.3%
White blood cells, Grades 3 (n= 39, 42, 43)	0 0%	2 1.8%	0 0%
White blood cells, Grade 4 (n= 39, 42, 43)	0 0%	0 0%	0 0%
Absolute neutrophil count, Grade 1 (n= 39, 42, 43)	8 7.1%	8 7.3%	8 7.2%
Absolute neutrophil count, Grade 2 (n= 39, 42, 43)	8 7.1%	9 8.2%	91 82%
Absolute neutrophil count, Grade 3 (n= 39, 42, 43)	2 1.8%	2 1.8%	1 0.9%
Absolute neutrophil count, Grade 4 (n= 39, 42, 43)	1 0.9%	2 1.8%	0 0%
Platelet count, Grade 1 (n= 39, 42, 43)	15 13.3%	18 16.4%	23 20.7%
Platelet count, Grade 2 (n= 39, 42, 43)	2 1.8%	3 2.7%	3 2.7%
Platelet count, Grade 3 (n= 39, 42, 43)	1 0.9%	2 1.8%	1 0.9%
Platelet count, Grade 4 (n= 39, 42, 43)	0 0%	1 0.9%	0 0%
Hemoglobin, Grade 1 (n= 39, 42, 43)	26 23%	24 21.8%	25 22.5%
Hemoglobin, Grade 2 (n= 39, 42, 43)	8 7.1%	10 9.1%	11 9.9%
Hemoglobin, Grade 3 (n= 39, 42, 43)	2 1.8%	2 1.8%	3 2.7%
Hemoglobin, Grade 4 (n= 39, 42, 43)	0 0%	2 1.8%	0 0%

17. Secondary Outcome

Title	Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade
Description	ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. ULN=Upper limit of normal among all laboratory ranges. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN.
Time Frame	At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

Outcome Measure Data

Analysis Population Description

All participants with SCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study liver function test result available.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	42	42	44
ALT, Grade 1	12 10.6%	12 10.9%	8 7.2%
ALT, Grade 2	2 1.8%	3 2.7%	1 0.9%
ALT, Grades 3 & 4	7 6.2%	2 1.8%	0 0%
AST, Grade 1	11 9.7%	13 11.8%	12 10.8%
AST, Grade 2	4 3.5%	1 0.9%	2 1.8%
AST, Grades 3 & 4	5 4.4%	3 2.7%	0 0%
Total bilirubin, Grade 1	4 3.5%	5 4.5%	3 2.7%
Total bilirubin, Grade 2	1 0.9%	0 0%	0 0%
Total bilirubin, Grades 3 & 4	1 0.9%	0 0%	0 0%
ALK, Grade 1	15 13.3%	14 12.7%	16 14.4%
ALK, Grade 2	1 0.9%	3 2.7%	2 1.8%
ALK, Grades 3 & 4	0 0%	0 0%	0 0%

18. Secondary Outcome

Title	Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade
Description	ULN=upper limit of normal. Lipase (U/L) Grade (Gr) 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Gr 2 >1.5 to 2.0*ULN, Gr 3 >2.0 to 5.0*ULN, Gr 4 >5.0*ULN. Creatine (mg/dL) Gr 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN.
Time Frame	At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment

Outcome Measure Data

Analysis Population Description

All participants with SCLC who received at least 1 dose of ipilimumab and/or chemotherapy and had at least 1 on-study pancreatic enzyme or other laboratory test measurement available.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (concurrent). The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes every 3 weeks as part of induction. Participants could also receive additional maintenance ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin (sequential). The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes every 3 weeks as part of induction. Participants could also receive additional maintenance ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	42	42	44
Lipase, Grades 3 and 4	7.7 6.8%	16.7 15.2%	11.6 10.5%
Amylase, Grades 3 and 4	5.1 4.5%	4.8 4.4%	4.7 4.2%
Creatinine, Grades 3 and 4	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
Description	By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment.
Time Frame	Randomization date to date of progression or death (of censored, maximum reached: 22 months)

Outcome Measure Data

Analysis Population Description

All participants with SCLC who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	43	42	45
Mean (95% Confidence Interval) [Months]	3.89	5.22	5.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3846
	Comments
	Method	1-sided Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.933
	Confidence Interval	(2-Sided) 95%; 0.588 to 1.481
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3700
	Comments
	Method	1-sided Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.927
	Confidence Interval	(2-Sided) 95%; 0.591 to 1.453
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
Description	Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area.
Time Frame	Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment

Outcome Measure Data

Analysis Population Description

All participants with SCLC who received at least 1 dose of ipilimumab/placebo and/or chemotherapy and had at least 1 on-study measurement available.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	42	42	44
Vital sign measurements	0 0%	0 0%	0 0%
Physical examination findings	0 0%	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline
Description	An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline.
Time Frame	Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

Outcome Measure Data

Analysis Population Description

Participants with SCLC who had at least 1 HAHA measurement prior to and at least 1 after the first ipilimumab dose and with an increase in HAHA measurement from baseline.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Ipilimumab + Paclitaxel/Carboplatin (Sequential)
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.
Measure Participants	38	41
Positive at any timepoint (n=42, 42)	2 1.8%	3 2.7%
Positive postbaseline (n=38, 41)	2 1.8%	0 0%

22. Secondary Outcome

Title	Overall Survival in Participants With SCLC
Description	Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive.
Time Frame	Randomization date to date of death (of censored, maximum reached: 22 months)

Outcome Measure Data

Analysis Population Description

All participants with SCLC who were randomized to a treatment group.

Arm/Group Title	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)	Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)	Placebo + Paclitaxel/Carboplatin
Arm/Group Description	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until PD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.	During induction, participants received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
Measure Participants	43	42	45
Median (95% Confidence Interval) [Months]	3.89	5.22	5.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4132
	Comments
	Method	1-sided Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.947
	Confidence Interval	(2-Sided) 95%; 0.585 to 1.536
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent), Ipilimumab + Paclitaxel/Carboplatin (Sequential), Placebo + Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1287
	Comments
	Method	1-sided Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.753
	Confidence Interval	(2-Sided) 95%; 0.461 to 1.232
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Ipilimubab+Paclitaxel/Carboplatin (Concurrent) NSCLC		Placebo/Ipilimumab+ Paclitaxel/Carboplatin (Sequential) NSCLC		Placebo + Paclitaxel/Carboplatin NSCLC		Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) SCLC		Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) SCLC		Placebo + Paclitaxel/Carboplatin SCLC
Arm/Group Description	During induction, participants with nonsmall-cell lung cancer (NSCLC) received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered intravenously (IV) as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered intravenously (IV) over 90 minutes every 12 weeks starting 24 weeks after the first dose until immune-related progressive disease (irPD), drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.		During induction, participants with NSCLC received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.		During induction, participants with NSCLC received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.		During induction, participants with small-cell lung cancer (SCLC) received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 4 doses consisted of active ipilimumab with paclitaxel/carboplatin, and the last 2 doses consisted of placebo ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until irPD, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.		During induction, participants with SCLC received up to 6 doses of blinded ipilimumab with paclitaxel/carboplatin on a 3-week schedule. The initial 2 doses consisted placebo ipilimumab with paclitaxel/carboplatin followed by 4 doses of active ipilimumab with paclitaxel/carboplatin. Ipilimumab, 10 mg/kg, was administered IV as a single dose over 90 minutes. Participants who did not progress or experience intolerable toxicity during the treatment phase were allowed to continue in the maintenance phase, receiving additional (blinded) ipilimumab at a dose of 10 mg/kg administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose until progressive disease, drug intolerance, withdrawal of consent, pregnancy, death, loss to follow up, or study closure.		During induction, participants with SCLC received up to 6 doses of placebo ipilimumab with paclitaxel/carboplatin every 3 weeks. Matched placebo for ipilimumab was administered as a single dose IV over 90 minutes every 3 weeks (up to 6 doses) as part of induction. Participants who did not progress or experience intolerable toxicity during the treatment phase could continue in the maintenance phase, receiving maintenance placebo administered IV over 90 minutes every 12 weeks starting 24 weeks after the first dose.
All Cause Mortality
	Ipilimubab+Paclitaxel/Carboplatin (Concurrent) NSCLC		Placebo/Ipilimumab+ Paclitaxel/Carboplatin (Sequential) NSCLC		Placebo + Paclitaxel/Carboplatin NSCLC		Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) SCLC		Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) SCLC		Placebo + Paclitaxel/Carboplatin SCLC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ipilimubab+Paclitaxel/Carboplatin (Concurrent) NSCLC		Placebo/Ipilimumab+ Paclitaxel/Carboplatin (Sequential) NSCLC		Placebo + Paclitaxel/Carboplatin NSCLC		Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) SCLC		Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) SCLC		Placebo + Paclitaxel/Carboplatin SCLC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/71 (69%)		36/67 (53.7%)		33/65 (50.8%)		25/42 (59.5%)		21/42 (50%)		20/44 (45.5%)
Blood and lymphatic system disorders
ANAEMIA	4/71 (5.6%)		4/67 (6%)		1/65 (1.5%)		0/42 (0%)		2/42 (4.8%)		2/44 (4.5%)
FEBRILE NEUTROPENIA	2/71 (2.8%)		1/67 (1.5%)		2/65 (3.1%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
LEUKOCYTOSIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
NEUTROPENIA	3/71 (4.2%)		0/67 (0%)		3/65 (4.6%)		0/42 (0%)		3/42 (7.1%)		3/44 (6.8%)
PANCYTOPENIA	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
THROMBOCYTOPENIA	1/71 (1.4%)		0/67 (0%)		2/65 (3.1%)		0/42 (0%)		3/42 (7.1%)		1/44 (2.3%)
LEUKOPENIA	1/71 (1.4%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Cardiac disorders
PERICARDIAL EFFUSION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ACUTE MYOCARDIAL INFARCTION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ATRIAL FIBRILLATION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CARDIAC FAILURE	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
TACHYARRHYTHMIA	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
ANGINA PECTORIS	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
MYOCARDIAL INFARCTION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CARDIAC FAILURE CONGESTIVE	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
CARDIO-RESPIRATORY ARREST	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
VENTRICULAR FIBRILLATION	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
Congenital, familial and genetic disorders
TRACHEO-OESOPHAGEAL FISTULA	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ICHTHYOSIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Ear and labyrinth disorders
VERTIGO	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Endocrine disorders
HYPOPITUITARISM	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPOPHYSITIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Eye disorders
OPTIC ISCHAEMIC NEUROPATHY	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
MACULAR CYST	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Gastrointestinal disorders
NAUSEA	0/71 (0%)		1/67 (1.5%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
COLITIS	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
CONSTIPATION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
DYSPHAGIA	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
VOMITING	0/71 (0%)		2/67 (3%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		2/44 (4.5%)
GASTROOESOPHAGEAL REFLUX DISEASE	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ILEAL PERFORATION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
SALIVARY GLAND CALCULUS	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
ABDOMINAL DISTENSION	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
DIARRHOEA	7/71 (9.9%)		5/67 (7.5%)		4/65 (6.2%)		1/42 (2.4%)		2/42 (4.8%)		1/44 (2.3%)
DUODENAL ULCER	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ENTERITIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
GASTROINTESTINAL PERFORATION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
OESOPHAGEAL DISORDER	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PANCREATITIS	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
ABDOMINAL HERNIA	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
EROSIVE OESOPHAGITIS	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
GASTRITIS EROSIVE	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
GASTROINTESTINAL HAEMORRHAGE	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
RECTAL HAEMORRHAGE	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
General disorders
GENERAL PHYSICAL HEALTH DETERIORATION	2/71 (2.8%)		1/67 (1.5%)		0/65 (0%)		2/42 (4.8%)		0/42 (0%)		0/44 (0%)
MULTI-ORGAN FAILURE	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
PYREXIA	1/71 (1.4%)		3/67 (4.5%)		0/65 (0%)		4/42 (9.5%)		0/42 (0%)		0/44 (0%)
ASTHENIA	1/71 (1.4%)		1/67 (1.5%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
OEDEMA PERIPHERAL	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CHEST PAIN	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
PAIN	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
DEATH	2/71 (2.8%)		4/67 (6%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
FATIGUE	1/71 (1.4%)		2/67 (3%)		1/65 (1.5%)		1/42 (2.4%)		1/42 (2.4%)		1/44 (2.3%)
LOCALISED OEDEMA	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
SUDDEN DEATH	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
DISEASE PROGRESSION	5/71 (7%)		1/67 (1.5%)		4/65 (6.2%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
DROWNING	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Hepatobiliary disorders
AUTOIMMUNE HEPATITIS	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HEPATITIS	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
HEPATITIS ACUTE	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
BILIARY COLIC	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HEPATOTOXICITY	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
BILE DUCT STENOSIS	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Immune system disorders
HYPERSENSITIVITY	1/71 (1.4%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ANAPHYLACTIC REACTION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Infections and infestations
GASTROENTERITIS SHIGELLA	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
SEPSIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		1/42 (2.4%)		1/44 (2.3%)
SIALOADENITIS	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
URINARY TRACT INFECTION	1/71 (1.4%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ERYSIPELAS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
GASTROENTERITIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CELLULITIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
FEBRILE INFECTION	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
GASTROINTESTINAL INFECTION	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
PSEUDOMONAL SEPSIS	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
BRONCHITIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CLOSTRIDIUM DIFFICILE COLITIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
SEPTIC SHOCK	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
MENINGITIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
LOBAR PNEUMONIA	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PLEURAL INFECTION BACTERIAL	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PNEUMONIA	5/71 (7%)		2/67 (3%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		2/44 (4.5%)
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
FEMUR FRACTURE	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PROCEDURAL PAIN	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HIP FRACTURE	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		2/42 (4.8%)		1/42 (2.4%)		0/44 (0%)
WEIGHT DECREASED	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ASPARTATE AMINOTRANSFERASE INCREASED	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		2/42 (4.8%)		1/42 (2.4%)		0/44 (0%)
HEPATIC ENZYME INCREASED	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
Metabolism and nutrition disorders
METABOLIC ACIDOSIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
DEHYDRATION	2/71 (2.8%)		2/67 (3%)		4/65 (6.2%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CACHEXIA	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HYPERGLYCAEMIA	1/71 (1.4%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPERCALCAEMIA	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
MALNUTRITION	0/71 (0%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPOKALAEMIA	1/71 (1.4%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
ACIDOSIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPOCALCAEMIA	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPONATRAEMIA	1/71 (1.4%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS	0/71 (0%)		1/67 (1.5%)		3/65 (4.6%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PAIN IN EXTREMITY	0/71 (0%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PATHOLOGICAL FRACTURE	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MALIGNANT PLEURAL EFFUSION	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
METASTATIC NEOPLASM	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
TUMOUR PAIN	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
LUNG NEOPLASM	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
MALIGNANT NEOPLASM PROGRESSION	2/71 (2.8%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PERICARDIAL EFFUSION MALIGNANT	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
LUNG CANCER METASTATIC	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
NEOPLASM PROGRESSION	3/71 (4.2%)		1/67 (1.5%)		3/65 (4.6%)		4/42 (9.5%)		2/42 (4.8%)		3/44 (6.8%)
NON-SMALL CELL LUNG CANCER	0/71 (0%)		2/67 (3%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
METASTASES TO CENTRAL NERVOUS SYSTEM	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
SQUAMOUS CELL CARCINOMA	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
LUNG NEOPLASM MALIGNANT	4/71 (5.6%)		4/67 (6%)		5/65 (7.7%)		4/42 (9.5%)		6/42 (14.3%)		5/44 (11.4%)
Nervous system disorders
SYNCOPE	1/71 (1.4%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
CEREBRAL HAEMORRHAGE	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
DYSARTHRIA	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HEADACHE	0/71 (0%)		2/67 (3%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYDROCEPHALUS	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
ATAXIA	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
EPILEPSY	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CERVICAL CORD COMPRESSION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CONVULSION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
GRAND MAL CONVULSION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PERIPHERAL SENSORIMOTOR NEUROPATHY	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
BASAL GANGLIA HAEMORRHAGE	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
MONOPLEGIA	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
NEUROPATHY PERIPHERAL	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PERIPHERAL MOTOR NEUROPATHY	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PERIPHERAL SENSORY NEUROPATHY	0/71 (0%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
OCCIPITAL NEURALGIA	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Psychiatric disorders
CONFUSIONAL STATE	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Renal and urinary disorders
RENAL FAILURE ACUTE	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY FAILURE	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PLEURAL EFFUSION	3/71 (4.2%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
PNEUMOTHORAX	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
PULMONARY EMBOLISM	4/71 (5.6%)		2/67 (3%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
BRONCHITIS CHRONIC	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
BRONCHOSPASM	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
OBSTRUCTIVE AIRWAYS DISORDER	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HAEMOPTYSIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
PNEUMONIA ASPIRATION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
MEDIASTINAL DISORDER	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PULMONARY HAEMORRHAGE	0/71 (0%)		0/67 (0%)		3/65 (4.6%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
DYSPNOEA	4/71 (5.6%)		2/67 (3%)		2/65 (3.1%)		2/42 (4.8%)		1/42 (2.4%)		1/44 (2.3%)
LUNG DISORDER	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Skin and subcutaneous tissue disorders
ERYTHEMA MULTIFORME	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
RASH	1/71 (1.4%)		1/67 (1.5%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
RASH MACULAR	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
TOXIC EPIDERMAL NECROLYSIS	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		1/44 (2.3%)
DERMATITIS EXFOLIATIVE	0/71 (0%)		0/67 (0%)		0/65 (0%)		1/42 (2.4%)		0/42 (0%)		0/44 (0%)
Vascular disorders
ARTERIAL THROMBOSIS	0/71 (0%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
HYPOTENSION	1/71 (1.4%)		1/67 (1.5%)		2/65 (3.1%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
PERIPHERAL ISCHAEMIA	1/71 (1.4%)		0/67 (0%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
THROMBOPHLEBITIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
DEEP VEIN THROMBOSIS	1/71 (1.4%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
VENOUS THROMBOSIS	0/71 (0%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPERTENSION	0/71 (0%)		0/67 (0%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Other (Not Including Serious) Adverse Events
	Ipilimubab+Paclitaxel/Carboplatin (Concurrent) NSCLC		Placebo/Ipilimumab+ Paclitaxel/Carboplatin (Sequential) NSCLC		Placebo + Paclitaxel/Carboplatin NSCLC		Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent) SCLC		Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential) SCLC		Placebo + Paclitaxel/Carboplatin SCLC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	63/71 (88.7%)		63/67 (94%)		59/65 (90.8%)		36/42 (85.7%)		39/42 (92.9%)		41/44 (93.2%)
Blood and lymphatic system disorders
ANAEMIA	22/71 (31%)		15/67 (22.4%)		19/65 (29.2%)		13/42 (31%)		12/42 (28.6%)		10/44 (22.7%)
NEUTROPENIA	11/71 (15.5%)		15/67 (22.4%)		15/65 (23.1%)		11/42 (26.2%)		8/42 (19%)		6/44 (13.6%)
THROMBOCYTOPENIA	10/71 (14.1%)		13/67 (19.4%)		12/65 (18.5%)		5/42 (11.9%)		6/42 (14.3%)		7/44 (15.9%)
LEUKOPENIA	6/71 (8.5%)		4/67 (6%)		7/65 (10.8%)		6/42 (14.3%)		4/42 (9.5%)		2/44 (4.5%)
Cardiac disorders
TACHYCARDIA	4/71 (5.6%)		1/67 (1.5%)		0/65 (0%)		0/42 (0%)		0/42 (0%)		3/44 (6.8%)
Eye disorders
VISION BLURRED	5/71 (7%)		2/67 (3%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
Gastrointestinal disorders
NAUSEA	22/71 (31%)		27/67 (40.3%)		22/65 (33.8%)		11/42 (26.2%)		13/42 (31%)		13/44 (29.5%)
ABDOMINAL PAIN UPPER	4/71 (5.6%)		3/67 (4.5%)		2/65 (3.1%)		1/42 (2.4%)		1/42 (2.4%)		1/44 (2.3%)
CONSTIPATION	13/71 (18.3%)		10/67 (14.9%)		15/65 (23.1%)		5/42 (11.9%)		4/42 (9.5%)		9/44 (20.5%)
DYSPHAGIA	1/71 (1.4%)		5/67 (7.5%)		3/65 (4.6%)		1/42 (2.4%)		1/42 (2.4%)		2/44 (4.5%)
VOMITING	19/71 (26.8%)		14/67 (20.9%)		13/65 (20%)		5/42 (11.9%)		5/42 (11.9%)		4/44 (9.1%)
ABDOMINAL PAIN	4/71 (5.6%)		1/67 (1.5%)		8/65 (12.3%)		0/42 (0%)		4/42 (9.5%)		1/44 (2.3%)
DIARRHOEA	21/71 (29.6%)		20/67 (29.9%)		14/65 (21.5%)		12/42 (28.6%)		14/42 (33.3%)		7/44 (15.9%)
DYSPEPSIA	5/71 (7%)		1/67 (1.5%)		4/65 (6.2%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
STOMATITIS	1/71 (1.4%)		1/67 (1.5%)		0/65 (0%)		4/42 (9.5%)		1/42 (2.4%)		3/44 (6.8%)
General disorders
PYREXIA	17/71 (23.9%)		11/67 (16.4%)		7/65 (10.8%)		6/42 (14.3%)		6/42 (14.3%)		5/44 (11.4%)
ASTHENIA	14/71 (19.7%)		20/67 (29.9%)		11/65 (16.9%)		4/42 (9.5%)		7/42 (16.7%)		8/44 (18.2%)
CHILLS	4/71 (5.6%)		1/67 (1.5%)		6/65 (9.2%)		2/42 (4.8%)		1/42 (2.4%)		0/44 (0%)
OEDEMA PERIPHERAL	8/71 (11.3%)		6/67 (9%)		6/65 (9.2%)		0/42 (0%)		3/42 (7.1%)		4/44 (9.1%)
CHEST PAIN	9/71 (12.7%)		8/67 (11.9%)		11/65 (16.9%)		4/42 (9.5%)		12/42 (28.6%)		9/44 (20.5%)
PAIN	7/71 (9.9%)		8/67 (11.9%)		7/65 (10.8%)		3/42 (7.1%)		6/42 (14.3%)		5/44 (11.4%)
FATIGUE	26/71 (36.6%)		24/67 (35.8%)		24/65 (36.9%)		15/42 (35.7%)		15/42 (35.7%)		19/44 (43.2%)
Infections and infestations
PNEUMONIA	7/71 (9.9%)		1/67 (1.5%)		1/65 (1.5%)		3/42 (7.1%)		1/42 (2.4%)		0/44 (0%)
Investigations
ALANINE AMINOTRANSFERASE INCREASED	4/71 (5.6%)		6/67 (9%)		2/65 (3.1%)		4/42 (9.5%)		4/42 (9.5%)		0/44 (0%)
WEIGHT DECREASED	10/71 (14.1%)		10/67 (14.9%)		5/65 (7.7%)		6/42 (14.3%)		7/42 (16.7%)		3/44 (6.8%)
HAEMOGLOBIN DECREASED	3/71 (4.2%)		5/67 (7.5%)		2/65 (3.1%)		0/42 (0%)		1/42 (2.4%)		0/44 (0%)
ASPARTATE AMINOTRANSFERASE INCREASED	4/71 (5.6%)		5/67 (7.5%)		3/65 (4.6%)		4/42 (9.5%)		5/42 (11.9%)		0/44 (0%)
Metabolism and nutrition disorders
DECREASED APPETITE	13/71 (18.3%)		10/67 (14.9%)		11/65 (16.9%)		9/42 (21.4%)		8/42 (19%)		11/44 (25%)
DEHYDRATION	4/71 (5.6%)		5/67 (7.5%)		3/65 (4.6%)		1/42 (2.4%)		2/42 (4.8%)		3/44 (6.8%)
HYPERGLYCAEMIA	4/71 (5.6%)		2/67 (3%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
HYPERCALCAEMIA	4/71 (5.6%)		0/67 (0%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
HYPOMAGNESAEMIA	5/71 (7%)		1/67 (1.5%)		6/65 (9.2%)		1/42 (2.4%)		2/42 (4.8%)		1/44 (2.3%)
HYPOKALAEMIA	4/71 (5.6%)		6/67 (9%)		5/65 (7.7%)		1/42 (2.4%)		2/42 (4.8%)		0/44 (0%)
HYPONATRAEMIA	3/71 (4.2%)		2/67 (3%)		4/65 (6.2%)		1/42 (2.4%)		1/42 (2.4%)		0/44 (0%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	18/71 (25.4%)		11/67 (16.4%)		10/65 (15.4%)		13/42 (31%)		23/42 (54.8%)		15/44 (34.1%)
PAIN IN EXTREMITY	7/71 (9.9%)		9/67 (13.4%)		5/65 (7.7%)		5/42 (11.9%)		6/42 (14.3%)		4/44 (9.1%)
MUSCULOSKELETAL PAIN	3/71 (4.2%)		7/67 (10.4%)		7/65 (10.8%)		1/42 (2.4%)		2/42 (4.8%)		6/44 (13.6%)
BONE PAIN	5/71 (7%)		5/67 (7.5%)		6/65 (9.2%)		4/42 (9.5%)		4/42 (9.5%)		6/44 (13.6%)
BACK PAIN	11/71 (15.5%)		6/67 (9%)		9/65 (13.8%)		2/42 (4.8%)		3/42 (7.1%)		3/44 (6.8%)
MYALGIA	11/71 (15.5%)		9/67 (13.4%)		2/65 (3.1%)		3/42 (7.1%)		5/42 (11.9%)		5/44 (11.4%)
Nervous system disorders
DIZZINESS	9/71 (12.7%)		7/67 (10.4%)		5/65 (7.7%)		1/42 (2.4%)		2/42 (4.8%)		2/44 (4.5%)
HEADACHE	8/71 (11.3%)		9/67 (13.4%)		8/65 (12.3%)		3/42 (7.1%)		10/42 (23.8%)		5/44 (11.4%)
DYSGEUSIA	7/71 (9.9%)		2/67 (3%)		3/65 (4.6%)		0/42 (0%)		2/42 (4.8%)		1/44 (2.3%)
NEUROPATHY PERIPHERAL	12/71 (16.9%)		10/67 (14.9%)		19/65 (29.2%)		6/42 (14.3%)		12/42 (28.6%)		5/44 (11.4%)
PERIPHERAL MOTOR NEUROPATHY	1/71 (1.4%)		0/67 (0%)		3/65 (4.6%)		0/42 (0%)		3/42 (7.1%)		1/44 (2.3%)
PERIPHERAL SENSORY NEUROPATHY	7/71 (9.9%)		14/67 (20.9%)		9/65 (13.8%)		10/42 (23.8%)		15/42 (35.7%)		14/44 (31.8%)
Psychiatric disorders
ANXIETY	2/71 (2.8%)		2/67 (3%)		7/65 (10.8%)		1/42 (2.4%)		1/42 (2.4%)		1/44 (2.3%)
DEPRESSION	4/71 (5.6%)		2/67 (3%)		2/65 (3.1%)		0/42 (0%)		0/42 (0%)		2/44 (4.5%)
INSOMNIA	8/71 (11.3%)		5/67 (7.5%)		5/65 (7.7%)		2/42 (4.8%)		3/42 (7.1%)		2/44 (4.5%)
Respiratory, thoracic and mediastinal disorders
HYPOXIA	5/71 (7%)		1/67 (1.5%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
EPISTAXIS	2/71 (2.8%)		2/67 (3%)		5/65 (7.7%)		1/42 (2.4%)		2/42 (4.8%)		0/44 (0%)
COUGH	16/71 (22.5%)		18/67 (26.9%)		12/65 (18.5%)		9/42 (21.4%)		8/42 (19%)		8/44 (18.2%)
HAEMOPTYSIS	6/71 (8.5%)		4/67 (6%)		4/65 (6.2%)		4/42 (9.5%)		3/42 (7.1%)		4/44 (9.1%)
PRODUCTIVE COUGH	3/71 (4.2%)		0/67 (0%)		0/65 (0%)		4/42 (9.5%)		0/42 (0%)		0/44 (0%)
DYSPHONIA	4/71 (5.6%)		2/67 (3%)		2/65 (3.1%)		1/42 (2.4%)		4/42 (9.5%)		1/44 (2.3%)
DYSPNOEA	21/71 (29.6%)		11/67 (16.4%)		17/65 (26.2%)		16/42 (38.1%)		12/42 (28.6%)		17/44 (38.6%)
OROPHARYNGEAL PAIN	0/71 (0%)		1/67 (1.5%)		4/65 (6.2%)		2/42 (4.8%)		2/42 (4.8%)		1/44 (2.3%)
Skin and subcutaneous tissue disorders
ERYTHEMA	4/71 (5.6%)		2/67 (3%)		1/65 (1.5%)		0/42 (0%)		0/42 (0%)		0/44 (0%)
PRURITUS	14/71 (19.7%)		7/67 (10.4%)		4/65 (6.2%)		10/42 (23.8%)		9/42 (21.4%)		2/44 (4.5%)
RASH	24/71 (33.8%)		9/67 (13.4%)		6/65 (9.2%)		16/42 (38.1%)		12/42 (28.6%)		3/44 (6.8%)
DRY SKIN	4/71 (5.6%)		5/67 (7.5%)		1/65 (1.5%)		1/42 (2.4%)		0/42 (0%)		1/44 (2.3%)
ALOPECIA	27/71 (38%)		32/67 (47.8%)		31/65 (47.7%)		24/42 (57.1%)		29/42 (69%)		28/44 (63.6%)
Vascular disorders
HYPOTENSION	4/71 (5.6%)		1/67 (1.5%)		8/65 (12.3%)		0/42 (0%)		2/42 (4.8%)		0/44 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.