CheckMate 714: Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02823574
• Collaborator: (none)
• Enrollment: 425
• Locations: 105
• Arms: 2
• Actual Duration (Months): 64.7
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

A study in patients with metastatic or recurrent squamous cell cancer of the head and neck to evaluate the effectiveness of Nivolumab plus Ipilumumab vs. Nivolumab alone (CheckMate 714)

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Biological: Nivolumab; Biological: Ipilimumab; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 425 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Two Arm Phase 2 Study of Nivolumab in Combination With Ipilimumab Versus Nivolumab in Combination With Ipilimumab Placebo in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)
• Actual Study Start Date: Oct 20, 2016
• Actual Primary Completion Date: Jan 23, 2019
• Actual Study Completion Date: Mar 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab and Ipilimumab Specified dose on specified days	Biological: Nivolumab; Other Names: Opdivo ; Biological: Ipilimumab
Active Comparator: Nivolumab and Ipilimumab-placebo Specified dose on specified days	Biological: Nivolumab; Other Names: Opdivo ; Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.

2. Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

3. Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response.

Secondary Outcome Measures

1. Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.

2. Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

3. Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.

4. Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.

5. Overall Survival (OS) [Approximately up to 30 months (from FPFV to Data base lock)]

   Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

6. Overall Survival (OS) - Platinum Refractory Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

7. Overall Survival (OS) - Platinum Eligible Subgroup [Approximately up to 30 months (from FPFV to Data base lock)]

   Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

8. ORR - Platinum Eligible Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

   ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.

9. ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker [Approximately up to 30 months (from FPFV to Data base lock)]

   ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

10. ORR - Platinum Refractory Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.

11. ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker [Approximately up to 30 months (from FPFV to Data base lock)]

    ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

12. Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

13. Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

14. Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.

15. Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

16. Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

17. Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

18. Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.

19. Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

20. Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

21. Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.

22. Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.

23. Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb

24. Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

25. ORR - Platinum Refractory Subgroup Based on PD-L1 Expression [Approximately up to 30 months (from FPFV to Data base lock)]

    ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

26. Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

27. Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

28. Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

29. ORR - Platinum Eligible Subgroup Based on PD-L1 Expression [Approximately up to 30 months (from FPFV to Data base lock)]

    ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

30. Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

31. Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status [Approximately up to 30 months (from FPFV to Data base lock)]

    The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Confirmed squamous cell head and neck cancer

• Widespread (metastatic) disease, or returned after previous treatment (recurrent)

• Tumor sample must be available for analysis of PDL1 (Programmed death-ligand 1) and HPV [Human Papilloma Virus (oropharynx only)]

• Performance status ECOG 0-1 (Eastern Cooperative Oncology Group)

Exclusion Criteria:

• Previous treatment for metastatic or recurrent disease

• Cancer arising from one of the following primary sites: paranasal sinus, nasopharynx, salivary gland, skin

• Any non-squamous subtype

• Active autoimmune disease

• Positive test for hepatitis B, C or HIV (Human Immunodeficiency Virus) virus

• Previous treatment with checkpoint inhibitor drugs

• Active CNS metastases or carcinomatous meningitis

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85724-5024
2	City Of Hope	Duarte	California	United States	91010
3	Los Angeles Cancer Network	Los Angeles	California	United States	90017
4	Ucla Department Of Medicine	Los Angeles	California	United States	90095
5	Torrance Health Association	Redondo Beach	California	United States	90277
6	Sutter Cancer Center	Sacramento	California	United States	95816
7	Ucsf	San Francisco	California	United States	94158
8	Coastal Integrative Cancer Care	San Luis Obispo	California	United States	93401
9	Central Coast Med Oncology	Santa Maria	California	United States	93454
10	Yale University School Of Medicine	New Haven	Connecticut	United States	06520
11	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
12	Winship Cancer Institute	Atlanta	Georgia	United States	30322
13	Dekalb Medical Center	Decatur	Georgia	United States	30033
14	University Of Chicago	Chicago	Illinois	United States	60637
15	Ft. Wayne Med Onco-Hema Inc	Fort Wayne	Indiana	United States	46845
16	University Of Louisville	Louisville	Kentucky	United States	40202
17	Oncology Associated Of Western Kentucky	Paducah	Kentucky	United States	42003
18	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
19	Mass General Hospital	Boston	Massachusetts	United States	02215
20	Mayo Clinic	Rochester	Minnesota	United States	55905
21	Mission Hospital, Inc	Asheville	North Carolina	United States	28801
22	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45219
23	Vanderbilt University Medical Center	Cleveland	Ohio	United States	44106
24	Oregon Health & Science University	Portland	Oregon	United States	97239
25	UPMC	Pittsburgh	Pennsylvania	United States	15232
26	Donald Guthrie Foundation	Sayre	Pennsylvania	United States	18840
27	Ut Southwestern Medical Center	Dallas	Texas	United States	75390
28	University Of Washington	Seattle	Washington	United States	98109
29	Centro de Investigacion Pergamino SA- Clinica Pergamino	Pergamino	Buenos Aires	Argentina
30	Hospital Italiano De Buenos Aires	Buenos Aires		Argentina	C1181ACH
31	Local Institution	Gent		Belgium	9000
32	Local Institution	Sint-Niklaas		Belgium	9100
33	Local Institution	Yvoir		Belgium	5530
34	Local Institution	Belo Horizonte	Minas Gerais	Brazil	30130-090
35	Local Institution	Ipatinga	Minas Gerais	Brazil	35160-158
36	Local Institution	Curitiba	Parana	Brazil	81480-580
37	Local Institution	Caxias do Sul	RIO Grande DO SUL	Brazil	95070-560
38	Local Institution	Ijui	RIO Grande DO SUL	Brazil	98700-000
39	Local Institution	Porto Alegre	RIO Grande DO SUL	Brazil	90035-903
40	Local Institution	Barretos	Sao Paulo	Brazil	14784-400
41	Local Institution	Santo Andre	Sao Paulo	Brazil	09060-870
42	Local Institution	Sao Jose do Rio Preto	SAO Paulo	Brazil	15090-000
43	Local Institution	Rio de Janeiro		Brazil	20231-050
44	Local Institution	Sao Paulo		Brazil	04039-004
45	Local Institution	Sao Paulo		Brazil	05403-010
46	Cross Cancer Institute.	Edmonton	Alberta	Canada	T6G 1Z2
47	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6
48	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
49	Centre Hospitalier De L'Universite De Montreal	Montreal	Quebec	Canada	H2X 3E4
50	CHU de Quebec - Universite Laval - Hopital de l'Enfant Jesus	Quebec		Canada	G1J 1Z4
51	Fundacion Arturo Lopez Perez	Santiago	Metropolitana	Chile
52	Klinika komplexni onkologicke pece	Brno		Czechia	656 53
53	Klinika onkologie a radioterapie	Hradec Kralove		Czechia	500 05
54	Onkologicka klinika	Olomouc		Czechia	779 00
55	Local Institution	Helsinki		Finland	00290
56	Chu Amiens - Groupe Hospitalier Sud	Amiens Cedex 1		France	80054
57	Local Institution	Bordeaux		France	33075
58	Centre Jean Perrin	Clermont Ferrand cedex 01		France	63011
59	Local Institution	Clichy		France	92110
60	Centre Leon Berard	Lyon Cedex 08		France	69373
61	Hopital De La Timone	Marseille Cedex 5		France	13385
62	Local Institution	Nice		France	06189
63	Local Institution	Rennes Cedex		France	35042
64	Local Institution	Villejuif		France	94805
65	Local Institution	Dublin 8	Dublin	Ireland
66	Local Institution	Milano		Italy	20133
67	Istituto Nazionale Tumori Fondazione Pascale	Napoli		Italy	80131
68	Local Institution	Merida	Yucatan	Mexico	97070
69	Local Institution	Merida	Yucatan	Mexico	97138
70	Local Institution	Oaxaca		Mexico	68040
71	Local Institution	Amsterdam		Netherlands	1066 CX
72	Vu Medical Centre	Amsterdam		Netherlands	1081 HV
73	Local Institution	Groningen		Netherlands	9713 GZ
74	Local Institution	Bergen		Norway	5021
75	Local Institution	Oslo		Norway	0379
76	Centrul Medical Sanador	Bucharest		Romania	010991
77	CF Clinical Hospital Cluj-Napoca	Cluj-Napoca		Romania	400015
78	Sf. Nectarie Oncology Center	Craiova		Romania	200347
79	Institutul Regional de Oncologie Iasi	Iasi		Romania	700483
80	County Emergency Hospital Suceava	Suceava		Romania	720237
81	Local Institution	Moscow		Russian Federation	121309
82	Local Institution	Ryazan		Russian Federation	390011
83	Local Institution	Port Elizabeth	Eastern Cape	South Africa	6045
84	Local Institution	Pretoria	Gauteng	South Africa	0084
85	Local Institution	Sandton	Gauteng	South Africa	2199
86	Local Institution	Cape Town	Western CAPE	South Africa	7700
87	Local Institution	A Coruna		Spain	15009
88	Local Institution	Barcelona		Spain	08035
89	Local Institution	Barcelona		Spain	08036
90	Local Institution	Madrid		Spain	28041
91	Local Institution	Marbella		Spain	29603
92	Local Institution	San Sabastian Gipuzkoa		Spain	20014
93	Local Institution	Goteborg		Sweden	413 45
94	Local Institution	Lund		Sweden	221 85
95	Local Institution	Stockholm		Sweden	171 76
96	Local Institution	Adana		Turkey	01250
97	Local Institution	Antalya		Turkey	07070
98	Local Institution	Izmir		Turkey	35340
99	Local Institution	Aberdeen	Aberdeenshire	United Kingdom	AB25 2ZN
100	Local Institution	London	Greater London	United Kingdom	SW3 6JJ
101	Local Institution	Wirral	Merseyside	United Kingdom	L63 4JY
102	Royal Marsden Hospital	Sutton	Surrey	United Kingdom	SM2 5PT
103	Local Institution	Cardiff		United Kingdom	CF14 2TL
104	Local Institution	Glasgow		United Kingdom	G12 0YN
105	Local Institution	Newcastle Upon Tyne		United Kingdom	NE7 7DN

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

• Study Protocol - May 25, 2018
• Statistical Analysis Plan - May 30, 2018

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02823574
• Other Study ID Numbers: CA209-714; 2016-001645-64
• First Posted: Jul 6, 2016
• Last Update Posted: Apr 21, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Nivolumab; Ipilimumab

Study Results

Participant Flow

Pre-assignment Detail	425 participants were randomized, 423 treated.

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Period Title: Pre-Treatment Period
STARTED	159	82	123	61
COMPLETED	158	82	122	61
NOT COMPLETED	1	0	1	0
Period Title: Pre-Treatment Period
STARTED	158	82	122	61
COMPLETED	19	16	14	10
NOT COMPLETED	139	66	108	51

Baseline Characteristics

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup	Total
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W	Total of all reporting groups
Overall Participants	159	82	123	61	425
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	119 74.8%	63 76.8%	79 64.2%	40 65.6%	301 70.8%
>=65 years	40 25.2%	19 23.2%	44 35.8%	21 34.4%	124 29.2%
Sex: Female, Male (Count of Participants)
Female	29 18.2%	18 22%	18 14.6%	14 23%	79 18.6%
Male	130 81.8%	64 78%	105 85.4%	47 77%	346 81.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 6.3%	7 8.5%	6 4.9%	6 9.8%	29 6.8%
Not Hispanic or Latino	56 35.2%	23 28%	66 53.7%	25 41%	170 40%
Unknown or Not Reported	93 58.5%	52 63.4%	51 41.5%	30 49.2%	226 53.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	3 1.9%	1 1.2%	0 0%	1 1.6%	5 1.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 1.3%	3 3.7%	2 1.6%	1 1.6%	8 1.9%
White	141 88.7%	75 91.5%	120 97.6%	58 95.1%	394 92.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	13 8.2%	3 3.7%	1 0.8%	1 1.6%	18 4.2%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
Description	ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
Number (95% Confidence Interval) [percentage of participants]	13.2 8.3%	18.3 22.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment A - Platinum Refractory Subgroup, Treatment B - Platinum Refractory Subgroup
	Comments	Treatment A over Treatment B
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2897
	Comments
	Method	Mantel Haenszel
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95.5%; 0.33 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory Responders

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	21	15
Median (95% Confidence Interval) [Months]	NA	11.07

3. Primary Outcome

Title	Time to Response (TTR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
Description	Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed response.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum refractory responders

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	21	15
Median (Full Range) [Months]	2.56	1.51

4. Secondary Outcome

Title	Objective Response Rate (ORR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
Description	ORR is defined as best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
Number (95% Confidence Interval) [percentage of participants]	20.3 12.8%	29.5 36%

5. Secondary Outcome

Title	Duration of Response (DOR) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum eligible subgroup responders

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	25	18
Median (95% Confidence Interval) [Months]	NA	NA

6. Secondary Outcome

Title	Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Refractory Subgroup
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory subgroup all randomized

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
Median (95% Confidence Interval) [Months]	2.60	2.60

7. Secondary Outcome

Title	Progression Free Survival (PFS) as Determined by Blinded Independent Central Review (BIRC) - Platinum Eligible Subgroup
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Eligible subgroup all randomized

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
Median (95% Confidence Interval) [Months]	2.76	2.83

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants

Arm/Group Title	Treatment A	Treatment B
Arm/Group Description	Participants in both Platinum Refractory Subgroup and Platinum Eligible Subgroup treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants in both Platinum Refractory Subgroup and Platinum Eligible Subgroup treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	282	143
Median (95% Confidence Interval) [Months]	9.99	12.02

9. Secondary Outcome

Title	Overall Survival (OS) - Platinum Refractory Subgroup
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
Median (95% Confidence Interval) [Months]	9.95	9.59

10. Secondary Outcome

Title	Overall Survival (OS) - Platinum Eligible Subgroup
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
Median (95% Confidence Interval) [Months]	9.99	13.08

11. Secondary Outcome

Title	ORR - Platinum Eligible Subgroup Based on HPV p-16 Status
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
Positive	20.0 12.6%	41.2 50.2%
Negative	20.5 12.9%	25.0 30.5%

12. Secondary Outcome

Title	ORR - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Biomarker
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
TMB < 7	10.2 6.4%	30.8 37.6%
TMB ≥ 7	34.2 21.5%	28.6 34.9%
TMB < 10	17.3 10.9%	28.6 34.9%
TMB ≥ 10	31.3 19.7%	33.3 40.6%
TMB Not Reported	23.1 14.5%	28.6 34.9%

13. Secondary Outcome

Title	ORR - Platinum Refractory Subgroup Based on HPV p-16 Status
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
OROPHARYNGEAL HPV P-16 POSITIVE	26.7 16.8%	31.3 38.2%
OROPHARYNGEAL HPV P-16 NEGATIVE/ NON-OROPHARYNGEAL	10.1 6.4%	15.2 18.5%

14. Secondary Outcome

Title	ORR - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Biomarker
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
TMB < 7	9.0 5.7%	20.5 25%
TMB ≥ 7	20.9 13.1%	14.3 17.4%
TMB < 10	9.9 6.2%	18.4 22.4%
TMB ≥ 10	31.6 19.9%	18.2 22.2%
TMB Not Reported	12.2 7.7%	18.2 22.2%

15. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Refractory Subgroup Based on HPV p-16 Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All treated participants in the Platinum Refractory subgroup with a response

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	21	15
HPV p-16 Positive	NA	11.14
HPV p-16 Negative	NA	8.21

16. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All treated participants in the Platinum Refractory subgroup with a response

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	21	15
TMB: <7	NA	11.14
TMB ≥ 7	NA	4.90
TMB: <10	NA	11.14
TMB: ≥ 10	NA	NA
TMB: Not Reported	NA	8.08

17. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on HPV p-16 Status
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory subgroup all randomized

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
Postive	4.11	4.24
Negative	2.27	2.60
No Reported	1.84

18. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory subgroup all randomized

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
TMB: < 7	1.45	2.50
TMB: ≥ 7	2.76	1.54
TMB: < 10	1.58	2.50
TMB: ≥ 10	2.83	1.41
TMB: Not Reported	2.83	2.92

19. Secondary Outcome

Title	Overall Survival (OS) - Platinum Refractory Subgroup Based on HPV p-16 Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
Positive	13.93	NA
Negative	9.66	9.59
Not Reported	1.84

20. Secondary Outcome

Title	Overall Survival (OS) - Platinum Refractory Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Refractory Subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
TMB: <7	5.98	8.77
TMB: ≥ 7	11.37	7.16
TMB: < 10	7.52	8.31
TMB: ≥10	6.51	9.26
Not Reported	13.86	14.78

21. Secondary Outcome

Title	Overall Survival (OS) - Platinum Eligible Subgroup Based on HPV p-16 Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W
Measure Participants	123	61
Positive	18.63	NA
Negative	8.90	9.59

22. Secondary Outcome

Title	Overall Survival (OS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All Randomized Participants - Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
TMB: <7	7.56	NA
TMB: ≥ 7	16.30	13.08
TMB: < 10	9.99	12.16
TMB: ≥10	16.30	16.46
Not Reported	8.21	9.59

23. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum eligible subgroup all randomized

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
TMB: < 7	2.66	2.92
TMB: ≥ 7	5.82	2.83
TMB: < 10	2.66	2.99
TMB: ≥ 10	20.44	2.76
TMB: Not Reported	2.71	2.79

24. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on HPV p-16 Status
Description	the time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum eligible subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
Postive	4.60	4.37
Negative	2.63	2.83

25. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Eligible Subgroup Based on HPV p-16 Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first.
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All treated participants in the Platinum Eligible subgroup with a response

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	25	18
Positive	11.01	NA
Negative	NA	NA

26. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Eligible Subgroup Based on Tumor Mutation Burden (TMB) Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor Mutational Burden (TMB) refers to the number of nonsynonymous somatic mutations that exist within a tumor's genome as measured by the Foundation One CDx panel at Foundation Medicine. The analysis was done on subjects with baseline tumor mutation burden by a cutoff of 7 mutations/megabase (mut/Mb) and 10 mut/Mb
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All treated participants in the Platinum eligible subgroup with a response

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	25	18
TMB: <7	10.97	12.42
TMB ≥ 7	NA	NA
TMB: <10	11.01	12.42
TMB: ≥ 10	NA	NA
TMB: Not Reported	NA	NA

27. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Refractory Subgroup Based on PD-L1 Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

All treated participants in the Platinum refractory subgroup with a response

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	21	15
PD-L1: ≥ 1%	NA	8.34
PD-L1: < 25%	NA	11.07
PD-L1: ≥ 25%	NA	8.34
PD-L1: <50%	NA	11.14
PD-L1: > 50%	11.01	6.24
PD-L1: 1 - < 25%	NA	NA
PD-L1: Unquantifiable	NA

28. Secondary Outcome

Title	ORR - Platinum Refractory Subgroup Based on PD-L1 Expression
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
<1%	7.7 4.8%	25.8 31.5%
PD-L1: ≥ 1%	17.4 10.9%	15.2 18.5%
PD-L1: < 25%	9.4 5.9%	17.5 21.3%
PD-L1: ≥ 25%	33.3 20.9%	25.0 30.5%
PD-L1: <50%	11.6 7.3%	19.7 24%
PD-L1: > 50%	33.3 20.9%	18.2 22.2%
PD-L1: 1 - < 25%	10.8 6.8%	7.7 9.4%
without quantifiable PD-L1 expression at baseline	NA NaN	NA NaN

29. Secondary Outcome

Title	Overall Survival (OS) - Platinum Refractory Subgroup Based on PD-L1 Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum refractory subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
<1%	9.53	12.29
PD-L1: ≥ 1%	10.32	9.02
PD-L1: < 25%	9.95	8.77
PD-L1: ≥ 25%	NA	10.23
PD-L1: <50%	9.95	10.71
PD-L1: > 50%	NA	7.33
PD-L1: 1 - < 25%	10.32	7.56
Without quantifiable PD-L1 expression at baseline	6.93	NA

30. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Refractory Subgroup Based on PD-L1 Status
Description	The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Refractory subgroup

Arm/Group Title	Treatment A - Platinum Refractory Subgroup	Treatment B - Platinum Refractory Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	159	82
<1%	2.60	2.96
PD-L1: ≥ 1%	2.66	0.82
PD-L1: < 25%	2.60	2.73
PD-L1: ≥ 25%	2.79	1.54
PD-L1: <50%	2.60	2.73
PD-L1: > 50%	2.79	1.54
PD-L1: 1 - < 25%	2.66	2.60
Without Quantifiable PD-L1 expression at Baseline	1.87	1.71

31. Secondary Outcome

Title	Duration of Response (DOR) - Platinum Eligible Subgroup Based on PD-L1 Status
Description	The time between the date of first confirmed response to the date of the first documented tumor progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Eligible Responders

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	25	18
PD-L1: ≥ 1%	NA	NA
PD-L1: < 25%	NA	12.42
PD-L1: ≥ 25%	NA	NA
PD-L1: <50%	13.67	12.42
PD-L1: > 50%	NA	NA
PD-L1: 1 - < 25%	11.01	4.81
PD-L1: Unquantifiable	NA	NA

32. Secondary Outcome

Title	ORR - Platinum Eligible Subgroup Based on PD-L1 Expression
Description	ORR is defined as the best overall response (BOR) of a complete response (CR) or partial response (PR) divided by the number of randomized participants for each treatment group. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
<1%	15.7 9.9%	21.7 26.5%
PD-L1: ≥ 1%	21.5 13.5%	30.3 37%
PD-L1: < 25%	14.9 9.4%	24.3 29.6%
PD-L1: ≥ 25%	31.0 19.5%	31.6 38.5%
PD-L1: <50%	16.7 10.5%	24.4 29.8%
PD-L1: > 50%	30.0 18.9%	33.3 40.6%
PD-L1: 1 - < 25%	13.9 8.7%	28.6 34.9%
Without quantifiable PD-L1 expression at baseline	NA NaN	NA NaN

33. Secondary Outcome

Title	Overall Survival (OS) - Platinum Eligible Subgroup Based on PD-L1 Status
Description	Overall survival was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum Eligible Subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
<1%	12.62	13.08
PD-L1: ≥ 1%	7.56	12.16
PD-L1: < 25%	8.90	11.17
PD-L1: ≥ 25%	12.39	NA
PD-L1: <50%	9.43	9.92
PD-L1: > 50%	9.40	NA
PD-L1: 1 - < 25%	6.16	8.48
Without quantifiable PD-L1 expression at baseline	NA	NA

34. Secondary Outcome

Title	Progression Free Survival (PFS) - Platinum Eligible Subgroup Based on PD-L1 Status
Description	The time from randomization to the date of first documented disease progression, or death due to any cause, whichever occurs first. Tumor PD-L1 expression was defined as the percent of tumor cell membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC assay
Time Frame	Approximately up to 30 months (from FPFV to Data base lock)

Outcome Measure Data

Analysis Population Description

Platinum eligible subgroup

Arm/Group Title	Treatment A - Platinum Eligible Subgroup	Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
Measure Participants	123	61
<1%	2.66	2.32
PD-L1: ≥ 1%	2.89	2.99
PD-L1: < 25%	2.45	2.73
PD-L1: ≥ 25%	5.75	2.99
PD-L1: <50%	2.56	2.73
PD-L1: > 50%	4.21	2.99
PD-L1: 1 - < 25%	1.51	3.10
Without quantifiable PD-L1 expression at baseline	6.47	13.73

Adverse Events

Time Frame	Approximately up to 30 months (from FPFV to Data base lock)
Arm/Group Title	Treatment A - Platinum Refractory Subgroup		Treatment B - Platinum Refractory Subgroup		Treatment A - Platinum Eligible Subgroup		Treatment B - Platinum Eligible Subgroup
Arm/Group Description	Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W		Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) that has recurred during or less than 6 months after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W		Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W		Participants with histologically confirmed Squamous Cell Carcinoma of the Head and Neck (SCCHN) who are platinum naive or have recurred 6 months or more after completion of previous platinum-based chemotherapy. Treated with Nivolumab 3 mg/kg Q2W + Ipilimumab-Placebo Q6W
All Cause Mortality
	Treatment A - Platinum Refractory Subgroup		Treatment B - Platinum Refractory Subgroup		Treatment A - Platinum Eligible Subgroup		Treatment B - Platinum Eligible Subgroup
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/158 (63.9%)		48/82 (58.5%)		80/122 (65.6%)		32/61 (52.5%)
Serious Adverse Events
	Treatment A - Platinum Refractory Subgroup		Treatment B - Platinum Refractory Subgroup		Treatment A - Platinum Eligible Subgroup		Treatment B - Platinum Eligible Subgroup
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	100/158 (63.3%)		46/82 (56.1%)		88/122 (72.1%)		33/61 (54.1%)
Blood and lymphatic system disorders
Anaemia	1/158 (0.6%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Febrile bone marrow aplasia	2/158 (1.3%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Lymph node pain	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Neutropenia	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Cardiac disorders
Acute myocardial infarction	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Cardiac arrest	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Cardiac failure congestive	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Myocardial infarction	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Pericardial effusion	2/158 (1.3%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Ear and labyrinth disorders
Vestibular disorder	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Endocrine disorders
Adrenal insufficiency	0/158 (0%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Adrenocortical insufficiency acute	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Hypophysitis	0/158 (0%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Gastrointestinal disorders
Abdominal distension	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Abdominal pain upper	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Ascites	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Autoimmune colitis	5/158 (3.2%)		1/82 (1.2%)		2/122 (1.6%)		1/61 (1.6%)
Colitis	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Constipation	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Diarrhoea	4/158 (2.5%)		1/82 (1.2%)		4/122 (3.3%)		0/61 (0%)
Duodenitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Dysphagia	2/158 (1.3%)		0/82 (0%)		5/122 (4.1%)		0/61 (0%)
Gastric ulcer	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Gastrointestinal haemorrhage	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Haematemesis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hernial eventration	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Impaired gastric emptying	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Mouth haemorrhage	2/158 (1.3%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Mouth ulceration	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Nausea	0/158 (0%)		2/82 (2.4%)		0/122 (0%)		0/61 (0%)
Oesophageal fistula	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Palatal disorder	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Pancreatitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Small intestinal perforation	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Stomatitis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Vomiting	5/158 (3.2%)		3/82 (3.7%)		2/122 (1.6%)		0/61 (0%)
General disorders
Adverse event	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Chest pain	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Death	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Drug intolerance	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Face oedema	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Fatigue	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
General physical health deterioration	0/158 (0%)		0/82 (0%)		3/122 (2.5%)		0/61 (0%)
Generalised oedema	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Hyperthermia	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Impaired healing	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Inflammation	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Malaise	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Mucosal inflammation	1/158 (0.6%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Pain	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Pyrexia	1/158 (0.6%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Sudden death	0/158 (0%)		0/82 (0%)		3/122 (2.5%)		0/61 (0%)
Swelling	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Hepatobiliary disorders
Autoimmune hepatitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Cholecystitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hepatotoxicity	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Immune-mediated hepatitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Immune system disorders
Drug hypersensitivity	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Infections and infestations
Abscess neck	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Bacteraemia	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Cellulitis	2/158 (1.3%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Device related infection	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Empyema	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Encephalitis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Endocarditis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Epiglottitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Gastroenteritis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hepatic infection bacterial	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Herpes zoster	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Infective myositis	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Influenza	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Lower respiratory tract infection	1/158 (0.6%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Ludwig angina	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Lung infection	5/158 (3.2%)		1/82 (1.2%)		2/122 (1.6%)		1/61 (1.6%)
Lymph node abscess	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Oral infection	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Peritonitis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Pneumococcal sepsis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Pneumonia	13/158 (8.2%)		3/82 (3.7%)		8/122 (6.6%)		4/61 (6.6%)
Pneumonia pseudomonal	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Sepsis	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Sepsis syndrome	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Septic shock	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Sinusitis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Skin infection	0/158 (0%)		1/82 (1.2%)		1/122 (0.8%)		1/61 (1.6%)
Staphylococcal bacteraemia	0/158 (0%)		2/82 (2.4%)		0/122 (0%)		0/61 (0%)
Staphylococcal scalded skin syndrome	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Subcutaneous abscess	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Tracheitis	2/158 (1.3%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Tracheobronchitis	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Tracheostomy infection	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Upper respiratory tract infection	0/158 (0%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Urinary tract infection	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Viral myocarditis	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Viral upper respiratory tract infection	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Injury, poisoning and procedural complications
Fall	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Femur fracture	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Foot fracture	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Hand fracture	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Head injury	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Infusion related reaction	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Overdose	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Post procedural haemorrhage	0/158 (0%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Toxicity to various agents	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Tracheal haemorrhage	0/158 (0%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Upper limb fracture	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Investigations
Creatinine renal clearance decreased	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Platelet count decreased	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Weight decreased	1/158 (0.6%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Metabolism and nutrition disorders
Dehydration	4/158 (2.5%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Diabetes mellitus	0/158 (0%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Electrolyte imbalance	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Failure to thrive	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Feeding disorder	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Hypercalcaemia	6/158 (3.8%)		2/82 (2.4%)		1/122 (0.8%)		1/61 (1.6%)
Hyperglycaemia	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hyperkalaemia	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Hypernatraemia	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hypokalaemia	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Hyponatraemia	2/158 (1.3%)		2/82 (2.4%)		0/122 (0%)		1/61 (1.6%)
Malnutrition	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/158 (0.6%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Joint range of motion decreased	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Neck pain	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Osteonecrosis	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Pathological fracture	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Spinal pain	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Cancer pain	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Hepatocellular carcinoma	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Malignant neoplasm progression	59/158 (37.3%)		24/82 (29.3%)		46/122 (37.7%)		16/61 (26.2%)
Metastases to bone	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Tumour associated fever	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Tumour haemorrhage	2/158 (1.3%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Tumour pain	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Nervous system disorders
Carotid aneurysm rupture	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Cerebral ischaemia	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Cerebrovascular accident	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Nervous system disorder	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Neuropathy peripheral	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Syncope	1/158 (0.6%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Product Issues
Device dislocation	0/158 (0%)		0/82 (0%)		0/122 (0%)		2/61 (3.3%)
Device leakage	2/158 (1.3%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Psychiatric disorders
Insomnia	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Renal and urinary disorders
Acute kidney injury	2/158 (1.3%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Renal failure	1/158 (0.6%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Respiratory, thoracic and mediastinal disorders
Autoimmune lung disease	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Chronic obstructive pulmonary disease	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Dyspnoea	4/158 (2.5%)		3/82 (3.7%)		4/122 (3.3%)		1/61 (1.6%)
Haemoptysis	0/158 (0%)		0/82 (0%)		3/122 (2.5%)		0/61 (0%)
Hypoxia	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Laryngeal dyspnoea	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Laryngeal haemorrhage	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		1/61 (1.6%)
Laryngeal obstruction	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Laryngeal oedema	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Lung disorder	0/158 (0%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Nasal obstruction	0/158 (0%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Obstructive airways disorder	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Pharyngeal oedema	0/158 (0%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Pleural effusion	3/158 (1.9%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Pneumonia aspiration	2/158 (1.3%)		0/82 (0%)		3/122 (2.5%)		1/61 (1.6%)
Pneumonitis	1/158 (0.6%)		1/82 (1.2%)		2/122 (1.6%)		0/61 (0%)
Pneumothorax	0/158 (0%)		1/82 (1.2%)		1/122 (0.8%)		0/61 (0%)
Pulmonary embolism	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		1/61 (1.6%)
Respiratory distress	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Respiratory failure	3/158 (1.9%)		0/82 (0%)		2/122 (1.6%)		1/61 (1.6%)
Skin and subcutaneous tissue disorders
Pruritus	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Rash	2/158 (1.3%)		0/82 (0%)		1/122 (0.8%)		0/61 (0%)
Rash maculo-papular	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Vascular disorders
Embolism	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Haemorrhage	1/158 (0.6%)		1/82 (1.2%)		2/122 (1.6%)		0/61 (0%)
Hypovolaemic shock	0/158 (0%)		1/82 (1.2%)		0/122 (0%)		0/61 (0%)
Lymphoedema	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Peripheral venous disease	0/158 (0%)		0/82 (0%)		2/122 (1.6%)		0/61 (0%)
Superior vena cava syndrome	1/158 (0.6%)		0/82 (0%)		0/122 (0%)		0/61 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A - Platinum Refractory Subgroup		Treatment B - Platinum Refractory Subgroup		Treatment A - Platinum Eligible Subgroup		Treatment B - Platinum Eligible Subgroup
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	139/158 (88%)		74/82 (90.2%)		116/122 (95.1%)		53/61 (86.9%)
Blood and lymphatic system disorders
Anaemia	40/158 (25.3%)		32/82 (39%)		28/122 (23%)		14/61 (23%)
Lymphopenia	10/158 (6.3%)		3/82 (3.7%)		0/122 (0%)		0/61 (0%)
Endocrine disorders
Hyperthyroidism	12/158 (7.6%)		4/82 (4.9%)		11/122 (9%)		1/61 (1.6%)
Hypothyroidism	27/158 (17.1%)		6/82 (7.3%)		21/122 (17.2%)		11/61 (18%)
Gastrointestinal disorders
Abdominal pain	7/158 (4.4%)		5/82 (6.1%)		10/122 (8.2%)		4/61 (6.6%)
Constipation	24/158 (15.2%)		13/82 (15.9%)		26/122 (21.3%)		9/61 (14.8%)
Diarrhoea	34/158 (21.5%)		16/82 (19.5%)		26/122 (21.3%)		14/61 (23%)
Dry mouth	10/158 (6.3%)		3/82 (3.7%)		9/122 (7.4%)		3/61 (4.9%)
Dysphagia	15/158 (9.5%)		9/82 (11%)		16/122 (13.1%)		6/61 (9.8%)
Nausea	30/158 (19%)		18/82 (22%)		28/122 (23%)		10/61 (16.4%)
Vomiting	18/158 (11.4%)		10/82 (12.2%)		12/122 (9.8%)		5/61 (8.2%)
Abdominal pain upper	7/158 (4.4%)		0/82 (0%)		4/122 (3.3%)		5/61 (8.2%)
Dyspepsia	6/158 (3.8%)		0/82 (0%)		7/122 (5.7%)		3/61 (4.9%)
General disorders
Asthenia	25/158 (15.8%)		14/82 (17.1%)		12/122 (9.8%)		7/61 (11.5%)
Face oedema	9/158 (5.7%)		3/82 (3.7%)		7/122 (5.7%)		2/61 (3.3%)
Fatigue	29/158 (18.4%)		21/82 (25.6%)		45/122 (36.9%)		22/61 (36.1%)
Mucosal inflammation	8/158 (5.1%)		3/82 (3.7%)		8/122 (6.6%)		2/61 (3.3%)
Oedema peripheral	7/158 (4.4%)		5/82 (6.1%)		10/122 (8.2%)		0/61 (0%)
Pyrexia	15/158 (9.5%)		8/82 (9.8%)		13/122 (10.7%)		5/61 (8.2%)
Chills	2/158 (1.3%)		0/82 (0%)		7/122 (5.7%)		0/61 (0%)
Infections and infestations
Lung infection	9/158 (5.7%)		2/82 (2.4%)		5/122 (4.1%)		1/61 (1.6%)
Nasopharyngitis	2/158 (1.3%)		1/82 (1.2%)		5/122 (4.1%)		4/61 (6.6%)
Oral candidiasis	9/158 (5.7%)		2/82 (2.4%)		1/122 (0.8%)		2/61 (3.3%)
Injury, poisoning and procedural complications
Fall	1/158 (0.6%)		1/82 (1.2%)		2/122 (1.6%)		4/61 (6.6%)
Investigations
Alanine aminotransferase increased	7/158 (4.4%)		4/82 (4.9%)		6/122 (4.9%)		5/61 (8.2%)
Aspartate aminotransferase increased	9/158 (5.7%)		4/82 (4.9%)		11/122 (9%)		3/61 (4.9%)
Blood alkaline phosphatase increased	6/158 (3.8%)		8/82 (9.8%)		9/122 (7.4%)		3/61 (4.9%)
Blood creatinine increased	10/158 (6.3%)		9/82 (11%)		7/122 (5.7%)		4/61 (6.6%)
Lipase increased	10/158 (6.3%)		2/82 (2.4%)		9/122 (7.4%)		4/61 (6.6%)
Weight decreased	19/158 (12%)		9/82 (11%)		23/122 (18.9%)		5/61 (8.2%)
Amylase increased	4/158 (2.5%)		4/82 (4.9%)		9/122 (7.4%)		3/61 (4.9%)
Metabolism and nutrition disorders
Decreased appetite	21/158 (13.3%)		15/82 (18.3%)		25/122 (20.5%)		7/61 (11.5%)
Hypercalcaemia	18/158 (11.4%)		10/82 (12.2%)		11/122 (9%)		4/61 (6.6%)
Hyperglycaemia	4/158 (2.5%)		4/82 (4.9%)		5/122 (4.1%)		4/61 (6.6%)
Hyperkalaemia	7/158 (4.4%)		7/82 (8.5%)		0/122 (0%)		1/61 (1.6%)
Hypokalaemia	5/158 (3.2%)		2/82 (2.4%)		11/122 (9%)		3/61 (4.9%)
Hypomagnesaemia	8/158 (5.1%)		6/82 (7.3%)		9/122 (7.4%)		6/61 (9.8%)
Hyponatraemia	11/158 (7%)		11/82 (13.4%)		11/122 (9%)		5/61 (8.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	14/158 (8.9%)		6/82 (7.3%)		16/122 (13.1%)		7/61 (11.5%)
Back pain	9/158 (5.7%)		10/82 (12.2%)		11/122 (9%)		5/61 (8.2%)
Neck pain	19/158 (12%)		9/82 (11%)		8/122 (6.6%)		9/61 (14.8%)
Musculoskeletal pain	9/158 (5.7%)		2/82 (2.4%)		4/122 (3.3%)		3/61 (4.9%)
Myalgia	4/158 (2.5%)		3/82 (3.7%)		8/122 (6.6%)		3/61 (4.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	3/158 (1.9%)		1/82 (1.2%)		2/122 (1.6%)		4/61 (6.6%)
Nervous system disorders
Headache	14/158 (8.9%)		4/82 (4.9%)		12/122 (9.8%)		6/61 (9.8%)
Dizziness	8/158 (5.1%)		2/82 (2.4%)		5/122 (4.1%)		3/61 (4.9%)
Psychiatric disorders
Insomnia	13/158 (8.2%)		6/82 (7.3%)		5/122 (4.1%)		5/61 (8.2%)
Anxiety	9/158 (5.7%)		3/82 (3.7%)		2/122 (1.6%)		3/61 (4.9%)
Respiratory, thoracic and mediastinal disorders
Cough	20/158 (12.7%)		8/82 (9.8%)		19/122 (15.6%)		8/61 (13.1%)
Dyspnoea	17/158 (10.8%)		11/82 (13.4%)		19/122 (15.6%)		9/61 (14.8%)
Productive cough	8/158 (5.1%)		2/82 (2.4%)		6/122 (4.9%)		5/61 (8.2%)
Skin and subcutaneous tissue disorders
Dry skin	10/158 (6.3%)		4/82 (4.9%)		5/122 (4.1%)		1/61 (1.6%)
Pruritus	32/158 (20.3%)		5/82 (6.1%)		23/122 (18.9%)		9/61 (14.8%)
Rash	31/158 (19.6%)		9/82 (11%)		18/122 (14.8%)		6/61 (9.8%)
Erythema	5/158 (3.2%)		4/82 (4.9%)		7/122 (5.7%)		1/61 (1.6%)
Vascular disorders
Hypotension	6/158 (3.8%)		2/82 (2.4%)		5/122 (4.1%)		6/61 (9.8%)
Hypertension	2/158 (1.3%)		2/82 (2.4%)		5/122 (4.1%)		4/61 (6.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.