Phase II Study of MEDI4736, Tremelimumab, and MEDI4736 in... | NCT02319044

NCT02319044

Status Module

Name	Class
PRA Health Sciences	INDUSTRY

Description Module

Detailed Description

This is a randomized, open-label, multi-center, global, Phase II study to determine the efficacy and safety of MEDI4736 + tremelimumab combination therapy, MEDI4736 monotherapy and tremelimumab monotherapy in the treatment of patients with recurrent or metastatic PD-L1-negative squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease, that must have contained a platinum agent.

Patients will be randomized in a stratified manner according to prognostic factors, including human papillomavirus (HPV) status and smoking status to achieve a balance between treatments for each of the factors. Patients will be randomized in a 1:1:2 fashion to receive MEDI4736 monotherapy, tremelimumab monotherapy, or MEDI4736 + tremelimumab combination.

All treatments will be administered beginning on Day 0 for 12 months or until confirmed progression of disease; unless, in the Investigator's opinion, the patient continues to receive benefit from the treatment), initiation of alternative cancer therapy, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Patients with confirmed progression of disease who, in the Investigator's opinion, continue to receive benefit from their assigned investigational product and who meet the criteria for treatment in the setting of progression of disease may continue to receive their assigned investigational product treatment for a maximum of 12 months after consultation with the Sponsor and at the Investigator's discretion. The monotherapy arms (tremelimumab and MEDI4736) should be discontinued if there is confirmed progression of disease following a previous response in target lesions (complete response or partial response).

Tumor assessments will be performed using computed tomography or magnetic resonance imaging. Efficacy for all patients will be assessed by objective tumor assessments every 8 weeks (q8w) for the first 48 weeks (relative to the date of the first infusion) then q12w in patients who have disease control after 12 months until confirmed objective disease progression.

Following completion or discontinuation of treatment, patients will enter a follow-up period.

Label	Type	Description	Intervention Names
MEDI4736	Experimental	MEDI4736 monotherapy	Drug: MEDI4736
Tremelimumab	Experimental	Tremelimumab monotherapy	Drug: Tremelimumab
MEDI4736 + Tremelimumab	Experimental	MEDI4736 + Tremelimumab combination therapy	Drug: MEDI4736 + Tremelimumab

Name	Type	Description	Arm Group Labels	Other Names
MEDI4736	Drug	MEDI4736 monotherapy	MEDI4736
Tremelimumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate at 6 Months	Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses	After 6 months
Objective Response Rate at 12 Months	Objective response rate (per RECIST 1.1 as assessed by blinded independent central review [BICR]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors [RECIST] 1.1. criteria are: Complete response [CR] = disappearance of all target lesions since baseline; and partial response [PR] = at least a 30% decrease in the sum of the diameters of target lesions.	After 12 months

Secondary Outcomes

Measure	Description	Time Frame
Best Objective Response	The best response a patient has had during their time in the study	After 12 months
Duration of Response - Participants Remaining in Response	Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years;
Written informed consent obtained from the patient/legal representative;
Histologically confirmed recurrent or metastatic SCCHN; tumor progression or recurrence during or after treatment with only 1 systemic palliative regimen for recurrent or metastatic disease that must have contained a platinum agent; Patients who have only received chemo-radiation with curative intent for treatment of their locally advanced disease or recurrent disease are not eligible. Patients who received concurrent chemo-radiation as part of treatment of their recurrent disease are also not eligible.
Written consent to provide newly acquired tumor tissue (preferred) or archival tissue for the purpose of establishing PD-L1 status.
Confirmed PD-L1-negative SCCHN by Ventana SP263;
WHO/ECOG performance status of 0 or 1;
At least 1 measurable lesion at baseline;
No prior exposure to immune-mediated therapy;
Adequate organ and marrow function; Evidence of post-menopausal status or negative urinary or serum pregnancy test.

Exclusion Criteria:

Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck;
Received more than 1 regimen for recurrent or metastatic disease
Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment;
Receipt of any investigational anticancer therapy within 28 days or 5 half-lives;
Receipt of last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, mAbs, etc) within 21 days prior to the first dose of study treatment;
Major surgical procedure within 28 days prior to the first dose of Investigational Product;
Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criterion;
Current or prior use of immunosuppressive medication within 14 days before the first dose of their assigned Investigational Product;
History of allogeneic organ transplantation;
Active or prior documented autoimmune or inflammatory disorders;
Uncontrolled intercurrent illness;
another primary malignancy
Patients with history of brain metastases, spinal cord compression, or a history of leptomeningeal carcinomatosis;
History of active primary immunodeficiency;
Known history of previous tuberculosis;
Active infection including hepatitis B, hepatitis C or human immunodeficiency virus (HIV);
Receipt of live, attenuated vaccine within 30 days prior to the first dose of Investigational Product;
Pregnant or breast-feeding female patients;
Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia's Correction
Known allergy or hypersensitivity to Investigational Product.
Any condition that, in the opinion of the Investigator, would interfere with evaluation of the IP or interpretation of patient safety or study results

Name	Affiliation	Role
Magdalena Wrona	Medical Scientist AstraZeneca Magdalena.Wrona@astrazeneca.com	Study Director
Lillian Siu, MD	Princess Margaret Hospital in Toronto, Ontario	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Birmingham	Alabama	35294	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
30383184	Derived	Siu LL, Even C, Mesia R, Remenar E, Daste A, Delord JP, Krauss J, Saba NF, Nabell L, Ready NE, Brana I, Kotecki N, Zandberg DP, Gilbert J, Mehanna H, Bonomi M, Jarkowski A, Melillo G, Armstrong JM, Wildsmith S, Fayette J. Safety and Efficacy of Durvalumab With or Without Tremelimumab in Patients With PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol. 2019 Feb 1;5(2):195-203. doi: 10.1001/jamaoncol.2018.4628.

Label	URL
Redacted Protocol	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	MEDI4736 AND TREMELIMUMAB COMBINATION	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
FG001	MEDI4736

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
BG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
BG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020 BG003

Age, Continuous

Full analysis set - all randomized patients

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00062(26 to 81) BG00162(23 to 82) BG002

Sex: Female, Male

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00020 BG00113 BG002

Race (NIH/OMB)

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Ethnic group - Hispanic or Latino

Title	Measurements
	BG0008 BG0012 BG002

Negative PD-L1 status

Programmed cell death ligand 1 status identification performed at screening

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
PD-L1 negative patients	BG000133 BG001

HPV status

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Positive	BG00039 BG00118 BG002

Use of nicotine (other than cigarettes)

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG0001 BG0011 BG002

Smoking/nicotine status by nicotine user

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Current smoker >10 pack years	BG00022 BG0017 BG002

WHO/ECOG performance status at study entry

Full analysis set - all randomized patients

Count of Participants

Participants

Title

Denominators

Categories

(0) Normal activity

Title	Measurements
	BG00040 BG00122 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Objective Response Rate at 6 Months

Objective response rate, primary analysis, based on BICR assessments according to RECIST v1.1. The number (%) of patients with a response excludes unconfirmed responses

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

95% Confidence Interval

% participants

After 6 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)

Units	Counts
Participants	OG000130 OG00165 OG00263

Title

Denominators

Categories

Title	Measurements
	OG0007.7(3.75 to 13.69) OG0019.2(3.46 to 19.02) OG0021.6(0.04 to 8.53)

Primary

Objective Response Rate at 12 Months

Objective response rate (per RECIST 1.1 as assessed by blinded independent central review [BICR]) is defined as the number (%) of patients with a confirmed complete response or confirmed partial response and will be based on all treated patients who are PD-L1-positive with measurable disease at baseline per BICR. Response Evaluation Criteria in Solid Tumors [RECIST] 1.1. criteria are: Complete response [CR] = disappearance of all target lesions since baseline; and partial response [PR] = at least a 30% decrease in the sum of the diameters of target lesions.

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

95% Confidence Interval

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab

Secondary

Best Objective Response

The best response a patient has had during their time in the study

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)
OG003	Total

Secondary

Duration of Response - Participants Remaining in Response

Participants remaining in response - based on BICR assessments according to RECIST v1.1. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off.

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)

Secondary

Time to Response

Time to response in patients with objective response based on BICR assessments according to RECIST 1.1

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)
OG003	Total

Secondary

Time to Onset of Response From First Dose

Time to onset of response in patients with objective response based on BICR assessments according to RECIST 1.1

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Median

Full Range

Months

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)
OG003	Total

Secondary

Disease Control Rate (DCR)

Disease control rate (DCR) at 6 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

% participants

After 6 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab

Secondary

Disease Control Rate (DCR)

Disease control rate (DCR) at 12 months based on BICR assessments according to RECIST v1.1. DCR at 6 months was evaluated using 2 different approaches to the length of stable disease (SD). -Method 1: Patients who had a best objective response of complete response (CR) or partial response (PR) within 24 weeks or had demonstrated SD for a minimum interval of 24 weeks following randomization. -Method 2: Patients who had a best objective response of CR or PR in the first 24 weeks or who had demonstrated SD for a minimum interval of 16 weeks following randomization.

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab

Secondary

Progression-free Survival (PFS)

Progression status at 6 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.

Full analysis set - all randomized patients

Posted

Number

% participants

After 6 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)

Secondary

Progression-free Survival (PFS)

Progression status at 12 months based on BICR assessments according to RECIST v1.1 at time of Progression Free Survival (PFS) analysis. Progression was defined as the time from the data of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. -Target Lesions, Non Target Lesions and New Lesions are not necessarily mutually exclusive categories. -Progression death refers to death in the absence of RECIST 1.1 progression.

Full analysis set - all randomized patients

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)

Secondary

Overall Survival

Survival status at time of overall survival analysis. 'Still in survival follow-up' includes patients known to be alive at data cut-off. 'Terminated prior to death' includes patients with unknown survival status or patients who were lost to follow-up.

Full analysis set - all randomized patients

Posted

Number

% participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)
OG003	Total

Secondary

Quality of Life

Improvement in quality of life was assessed using European Organisation for Research and Treatment of Cancer (EORTC) questionnaires: -The impact of treatment on Health-Related Quality of Life, functioning, and symptoms was evaluated using the EORTC QLQ-C30 v3. -Head and neck cancer-specific symptoms were evaluated using the EORTC QLQ-H&N35. The symptom and QoL/function improvement rate was defined as the number (%) of patients with 2 consecutive assessments at least 14 days apart that showed a clinically meaningful improvement (a decrease from baseline score ≥10 or EORTC QLQ-C30 scales) in that symptom/function from baseline. For QLQ-H&N35A a minimum clinically meaningful change was defined as a change in the score from baseline of >10 for scales/items

Full analysis set - all randomized patients

Posted

Number

95% Confidence Interval

% patients

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002

Secondary

Duration of Response

Duration of objective response in patients with objective response based on BICR assessments according to RECIST v1.1. Duration of response was the time from the first documentation of Complete response/Partial response (which was subsequently confirmed) until the date of progression, death, or the last evaluable RECIST assessment for patients that did not progress. An ongoing response was defined as a patient who had documented objective response and was still alive and progression-free at the time of the data cut-off (per RECIST v1.1 as assessed by BICR).

Evaluable analysis set - all patients who received at least one dose of study treatment, who had a baseline tumor assessment, and had measurable disease

Posted

Number

Participants

After 12 months

ID	Title	Description
OG000	MEDI4736 + Tremelimumab	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment
OG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)
OG002	Tremelimumab

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	MEDI4736 AND TREMELIMUMAB COMBINATION	MEDI4736 (20 mg/kg) + Tremelimumab (1 mg/kg) combination therapy administered via intravenous infusion every 4 weeks for up to 4 months (4 doses), then MEDI4736 (10 mg/kg) as a single agent every 2 weeks to complete 12 months of treatment	86	133	59	133	110	133
EG001	MEDI4736	MEDI4736 (10 mg/kg) monotherapy administered via intravenous infusion every 2 weeks for up to 12 months (up to 26 doses)	44	67	18	65	52	65
EG002	Tremelimumab	Tremelimumab (10 mg/kg) monotherapy administered via intravenous infusion every 4 weeks for 7 doses, then every 12 weeks for 2 additional doses for up to 12 months (up to 9 doses)	51	67	25	65	59	65

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Angina pectoris	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Bradycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Cardiac arrest	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Cardiac failure	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Tracheo-oesophageal fistula	Congenital, familial and genetic disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Hypothyroidism	Endocrine disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Lymphocytic hypophysitis	Endocrine disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Autoimmune colitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Colitis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0008 events5 affected133 at risk EG0010 events0 affected65 at risk EG0027 events5 affected65 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0023 events2 affected65 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Large intestine perforation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Mouth haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events3 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Oral cavity fistula	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Pneumatosis intestinalis	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Death	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Face oedema	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
General physical health deterioration	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0022 events1 affected65 at risk
Abdominal infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Abscess	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Bacteraemia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Bronchitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Cellulitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Clostridium difficile colitis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0022 events1 affected65 at risk
Device related sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Localised infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Lung infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected133 at risk EG0011 events1 affected65 at risk EG0021 events1 affected65 at risk
Lymph gland infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Mastoiditis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Pneumonia	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG00010 events9 affected133 at risk EG0011 events1 affected65 at risk EG0022 events1 affected65 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0022 events2 affected65 at risk
Pseudomonal sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events1 affected65 at risk EG0020 events0 affected65 at risk
Sepsis	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0021 events1 affected65 at risk
Septic rash	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Superinfection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Foreign body aspiration	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Gastrostomy tube site complication	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Tracheal obstruction	Injury, poisoning and procedural complications	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Platelet count decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0005 events4 affected133 at risk EG0011 events1 affected65 at risk EG0021 events1 affected65 at risk
Failure to thrive	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Hypernatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Malnutrition	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Fistula	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Pain in jaw	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Depressed level of consciousness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0012 events2 affected65 at risk EG0020 events0 affected65 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Presyncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Syncope	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0002 events1 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Device dislocation	Product Issues	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Agitation	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Confusional state	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Delirium	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Depression	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Autoimmune nephritis	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Urinary retention	Renal and urinary disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Apnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected133 at risk EG0011 events1 affected65 at risk EG0022 events2 affected65 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0021 events1 affected65 at risk
Increased bronchial secretion	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected133 at risk EG0010 events0 affected65 at risk EG0022 events2 affected65 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0011 events1 affected65 at risk EG0020 events0 affected65 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0000 events0 affected133 at risk EG0010 events0 affected65 at risk EG0021 events1 affected65 at risk
Exsanguination	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0010 events0 affected65 at risk EG0020 events0 affected65 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 19.1	Systematic Assessment	EG00020 events20 affected133 at risk EG00114 events11 affected65 at risk EG00212 events11 affected65 at risk
Tachycardia	Cardiac disorders	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected133 at risk EG0010 events0 affected65 at risk EG0024 events4 affected65 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected133 at risk EG0012 events2 affected65 at risk EG0024 events4 affected65 at risk
Hypothyroidism	Endocrine disorders	MedDRA 19.1	Systematic Assessment	EG00015 events15 affected133 at risk EG0019 events9 affected65 at risk EG0026 events6 affected65 at risk
Constipation	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00019 events18 affected133 at risk EG0019 events9 affected65 at risk EG0028 events8 affected65 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00042 events27 affected133 at risk EG00114 events12 affected65 at risk EG00219 events14 affected65 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00015 events14 affected133 at risk EG0019 events8 affected65 at risk EG0027 events6 affected65 at risk
Nausea	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00024 events18 affected133 at risk EG0018 events7 affected65 at risk EG00222 events18 affected65 at risk
Vomiting	Gastrointestinal disorders	MedDRA 19.1	Systematic Assessment	EG00013 events9 affected133 at risk EG0014 events4 affected65 at risk EG00211 events9 affected65 at risk
Asthenia	General disorders	MedDRA 19.1	Systematic Assessment	EG00024 events21 affected133 at risk EG00112 events10 affected65 at risk EG00211 events8 affected65 at risk
Fatigue	General disorders	MedDRA 19.1	Systematic Assessment	EG00029 events25 affected133 at risk EG00123 events19 affected65 at risk EG00212 events12 affected65 at risk
Mucosal inflammation	General disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0014 events4 affected65 at risk EG0022 events1 affected65 at risk
Oedema peripheral	General disorders	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected133 at risk EG0013 events2 affected65 at risk EG0022 events2 affected65 at risk
Pain	General disorders	MedDRA 19.1	Systematic Assessment	EG0005 events5 affected133 at risk EG0010 events0 affected65 at risk EG0028 events8 affected65 at risk
Pyrexia	General disorders	MedDRA 19.1	Systematic Assessment	EG00019 events16 affected133 at risk EG0015 events5 affected65 at risk EG00216 events12 affected65 at risk
Weight decreased	Investigations	MedDRA 19.1	Systematic Assessment	EG00018 events18 affected133 at risk EG0015 events5 affected65 at risk EG0029 events8 affected65 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00027 events25 affected133 at risk EG00111 events10 affected65 at risk EG00211 events10 affected65 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00010 events6 affected133 at risk EG0010 events0 affected65 at risk EG0026 events6 affected65 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0008 events7 affected133 at risk EG0017 events6 affected65 at risk EG0023 events3 affected65 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0002 events2 affected133 at risk EG0014 events4 affected65 at risk EG0022 events2 affected65 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0003 events2 affected133 at risk EG0011 events1 affected65 at risk EG0024 events4 affected65 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00010 events7 affected133 at risk EG0013 events3 affected65 at risk EG0025 events5 affected65 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG0006 events5 affected133 at risk EG0015 events5 affected65 at risk EG0025 events5 affected65 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 19.1	Systematic Assessment	EG00010 events10 affected133 at risk EG0016 events4 affected65 at risk EG0025 events5 affected65 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00013 events13 affected133 at risk EG0011 events1 affected65 at risk EG0023 events3 affected65 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG00010 events9 affected133 at risk EG0015 events5 affected65 at risk EG0021 events1 affected65 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0004 events4 affected133 at risk EG0011 events1 affected65 at risk EG0026 events5 affected65 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 19.1	Systematic Assessment	EG0008 events4 affected133 at risk EG0014 events4 affected65 at risk EG0028 events6 affected65 at risk
Dizziness	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0005 events4 affected133 at risk EG0013 events3 affected65 at risk EG0026 events5 affected65 at risk
Headache	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0007 events6 affected133 at risk EG0017 events6 affected65 at risk EG0027 events7 affected65 at risk
Paraesthesia	Nervous system disorders	MedDRA 19.1	Systematic Assessment	EG0003 events3 affected133 at risk EG0015 events5 affected65 at risk EG0021 events1 affected65 at risk
Anxiety	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0001 events1 affected133 at risk EG0013 events3 affected65 at risk EG0024 events4 affected65 at risk
Insomnia	Psychiatric disorders	MedDRA 19.1	Systematic Assessment	EG0009 events9 affected133 at risk EG0013 events3 affected65 at risk EG0023 events2 affected65 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG00014 events14 affected133 at risk EG0018 events8 affected65 at risk EG0028 events7 affected65 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG00016 events14 affected133 at risk EG00110 events10 affected65 at risk EG00212 events12 affected65 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 19.1	Systematic Assessment	EG0005 events4 affected133 at risk EG0016 events6 affected65 at risk EG0026 events5 affected65 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG0006 events5 affected133 at risk EG0015 events5 affected65 at risk EG0021 events1 affected65 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00015 events14 affected133 at risk EG0016 events6 affected65 at risk EG0024 events4 affected65 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.1	Systematic Assessment	EG00011 events10 affected133 at risk EG0013 events3 affected65 at risk EG0026 events5 affected65 at risk
Hypertension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG00011 events8 affected133 at risk EG0017 events6 affected65 at risk EG0021 events1 affected65 at risk
Hypotension	Vascular disorders	MedDRA 19.1	Systematic Assessment	EG0007 events7 affected133 at risk EG0010 events0 affected65 at risk EG0025 events5 affected65 at risk

ID	Term
D012008	Recurrence
D006258	Head and Neck Neoplasms

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009371	Neoplasms by Site
D009369	Neoplasms