Study of Quavonlimab (MK-1308) in Combination With Pembro... | NCT03179436

ID	Type	Description
MK-1308-001	Other Identifier	Merck
173820	Registry Identifier	JAPIC-CTI
2019-003703-35	EudraCT Number

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Escalation: Dose Level (DL) 1 Quavonlimab + Pembro: Cohort 1	Experimental	On Cycle 1, Day 1 of the Dose Escalation Phase, advanced solid tumor participants receive a single monotherapy dose lead-in with quavonlimab at dose level 1 (DL1). On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL1 in combination with pembrolizumab (pembro) at pembrolizumab dose level 1 (PDL1) according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.	Biological: Quavonlimab Biological: Pembrolizumab
Escalation: DL 2 Quavonlimab + Pembro: Cohort 2	Experimental	On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL2. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL2 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.	Biological: Quavonlimab Biological: Pembrolizumab
Escalation: DL 3 Quavonlimab + Pembro: Cohort 3	Experimental	On Cycle 1, Day 1 of the Dose Escalation Phase, participants with advanced solid tumors except NSCLC receive a single monotherapy dose lead-in with quavonlimab at DL3. On Cycle 2, Day 1, and for 3 subsequent cycles on Day 1 (Cycles 3 to 5), these participants receive quavonlimab at DL3 in combination with pembrolizumab at PDL1 according to Schedule 1. For all subsequent cycles (starting with Cycle 6), all participants receive pembrolizumab monotherapy according to Schedule 1. Participants will be treated for up to 35 cycles total on study.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Quavonlimab	Biological	Quavonlimab is administered intravenously (IV) during the Dose Escalation Phase and Dose Confirmation Phase at either DL1 or DL2, and is administered IV during the Efficacy Expansion Phase at DL2.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT)	DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.	Up to 6 weeks
Number of Participants With ≥1 Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented.	Up to approximately 77 months
Number of Participants Discontinuing Study Treatment Due to an AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who discontinued study treatment due to an AE are presented.	Up to approximately 26 months
Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

Secondary Outcomes

Measure	Description	Time Frame
Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab	AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. AUC of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For Dose Escalation Phase:

Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor (except NSCLC for Cohorts 2 and 3) by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit

For Dose Confirmation Phase NSCLC Arms (A, B, C, and E):

Have newly diagnosed histologically or cytologically-confirmed stage IIIB/stage IV NSCLC. Epidermal growth factor receptor (EGFR)-and anaplastic lymphoma kinase (ALK) translocation-directed therapy is not indicated as primary therapy. Participant must not have received prior systemic treatment for advanced NSCLC or must have received previous neoadjuvant and adjuvant chemotherapies ≥6 months before dosing of study drug if prior systemic treatment was given for early stage disease

For Dose Confirmation Phase SCLC Arm (Arm D):

Have histologically- or cytologically-confirmed metastatic (Stage III/IV) SCLC with progressive disease after ≥1 platinum-based chemotherapy regimen. Participants with platinum-sensitive disease are eligible
Have measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology
Have Eastern Cooperative Oncology Group (ECOG) Performance Scale status of 0 or 1
A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 of the following conditions applies:
Is not a woman of child bearing potential (WOCBP) OR
Is a WOCBP and using a contraceptive method that is highly effective during the intervention period and for at least 120 days after the last dose of pembrolizumab or pembrolizumab/quavonlimab, whichever comes last
Female participants of childbearing potential must have negative urine or serum pregnancy test within 24 hours for urine and within 72 hours for serum prior to receiving the first dose of study treatment
Male participants with a female partner(s) of child-bearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication and refrain from donating sperm during this period
Must submit an evaluable baseline tumor sample for analysis (either a recent or archival tumor sample)

For Efficacy Expansion Phase Arms F and G:

Have histologically/cytologically-confirmed unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8, not amenable to local therapy
Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 by BICR. Cutaneous lesions and other superficial lesions are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions
Participants with unresectable Stage III or IV disease must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies (combinations with anti-cytotoxic T-lymphocyte associated protein 4 [CTLA-4] agents will not be allowed)
Participants who receive anti-PD-1 therapy as adjuvant treatment following complete resection of Stage III or IV melanoma and have disease recurrence (unresectable loco-regional disease or distant metastases) while on active treatment or within 6 months of stopping anti-PD-1 are eligible
Have submitted pre-trial imaging and provided a baseline tumor sample
Proto-oncogene B-raf (BRAF) V600 mutation-positive melanoma participants should have received targeted therapy for advanced or metastatic disease (eg, BRAF/MEK inhibitor, alone or in combination) prior to enrolling on this study; however, they are not required to progress on this treatment prior to enrollment
BRAF V600E mutation-positive melanoma participants who have NOT received a BRAF inhibitor (either as adjuvant therapy or in the metastatic disease setting) with lactate dehydrogenase (LDH) < local upper limit of normal (ULN), no clinically significant tumor-related symptoms, and absence of rapidly progressing metastatic melanoma. Approximately 10 participants each from Arms F and G will have 2 mandatory biopsies

For Dose Coformulation Phase Arm I:

Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for or refused all treatment known to confer clinical benefit
Meet all requirements for Dose Escalation Phase and Dose Confirmation Phase

For the Coformulation Phase - Arm K (China only):

Have any histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit
Be a Chinese participant residing in China.

Exclusion Criteria:

For all phases of the study: Has received previous treatment with another agent targeting cytotoxic T lymphocyte leukocyte antigen (CTLA)-4

For Dose Confirmation Phase:

Has received previous treatment with another agent targeting programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study therapy, or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
Has received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment
Is currently participating and receiving study therapy in a study of an investigational agent or has participated and received study therapy in a study of an investigational agent or has used an investigational device within 28 days of administration of quavonlimab.
Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years

For Dose Escalation Cohorts (1-3) and Dose Confirmation Arms (A-E):

Has known untreated central nervous system (CNS) metastases. Has known carcinomatous meningitis
Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse events (irAE)
Has had a severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study drug
Has any active infection requiring therapy
Has a history of interstitial lung disease, history of noninfectious pneumonitis that required steroids (or has current pneumonitis), or history of inflammatory bowel disease
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has clinically significant cardiac disease
Has received a live or live attenuated vaccine within 28 days of planned treatment start
Has known history of human immunodeficiency virus (HIV) and/or known active Hepatitis B or C infections, and/or known to be positive for hepatitis B surface antigen (HBsAg)/ hepatitis B virus (HBV) DNA
Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with screening and for up to 120 days following cessation of pembrolizumab or pembrolizumab/quavonlimab
Has not fully recovered from any effects of major surgery without significant detectable infection

For Arm F and G (Efficacy Expansion Phase) and Arm K (Coformulation Phase) ONLY:

Has known active CNS metastases and/or carcinomatous meningitis
Has not had resolution of anti-PD-1 antibody-related AEs, including immune-mediated AEs back to Grade ≤1 or baseline (not applicable to Arm K)
Has not discontinued steroid treatment for an irAE for at least 2 weeks prior to the first dose of study drug (not applicable to Arm K)
Has ocular melanoma (not applicable to Arm K)
Has mucosal melanoma (not applicable to Arm K)
Has had an allogenic tissue/solid organ transplant

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Banner MD Anderson Cancer Center ( Site 0013)		Gilbert	Arizona	85234	United States
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)

PubMed Identifier	Type	Citation	Retractions
33276076	Result	Perets R, Bar J, Rasco DW, Ahn MJ, Yoh K, Kim DW, Nagrial A, Satouchi M, Lee DH, Spigel DR, Kotasek D, Gutierrez M, Niu J, Siddiqi S, Li X, Cyrus J, Chackerian A, Chain A, Altura RA, Cho BC. Safety and efficacy of quavonlimab, a novel anti-CTLA-4 antibody (MK-1308), in combination with pembrolizumab in first-line advanced non-small-cell lung cancer. Ann Oncol. 2021 Mar;32(3):395-403. doi: 10.1016/j.annonc.2020.11.020. Epub 2020 Dec 2.
34371366

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Dec 2, 2022

Arm/Group Information

ID	Title	Description
BG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
BG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
BG002	Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
BG003	Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).
BG004	Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months).
BG005	Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).
BG006	Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).
BG007	Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).
BG008	Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin	On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.
BG009	Arm G: MK-1308 25 mg Q6W	On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months.
BG010	Arm I: MK-1308A Q6W (Co-form)	On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.
BG011	Arm K: MK-1308A Q6W (Co-form)	On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.
BG012	Total	Total of all reporting groups

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

Percentage of Participants With ≥1 Dose Limiting Toxicity (DLT)

DLT was defined as toxicity that is possibly, probably, or definitely related to study therapy and may result in a change in the given dose. DLTs include Grade (Gr)4 non-hematologic toxicity (not laboratory); Gr 4 hematologic toxicity lasting ≥7 days (except thrombocytopenia); most non-hematologic AEs ≥ Gr 3 in severity; any Gr 3 or Gr 4 non-hematologic laboratory value that requires clinically significant medical intervention, leads to hospitalization, persists for >1 week, or results in a drug-induced liver injury; Gr 3 or Gr 4 febrile neutropenia; a prolonged delay in initiating Cycle 2 or 3 of Dose Escalation or Cycle 2 of Dose Confirmation due to treatment-related toxicity; any treatment-related toxicity that causes the participant to discontinue treatment during the DLT observation period, and Gr 5 toxicity.

The DLT evaluable population consists of all participants who received ≥1 dose of study treatment who finished the DLT observation period in the dose escalation or dose confirmation phase. Per protocol, no analysis was planned for the efficacy expansion phase (Arms F and G), coformulation phase (Arms I and K) and cross over phase (MK-1308 25 mg and Pembrolizumab 400 mg).

Posted

Number

80% Confidence Interval

Percentage of Participants

Up to 6 weeks

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG002	Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG003	Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).
OG004	Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W

Units	Counts
Participants	OG00013 OG00115 OG0027 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.0(0.0 to 10.9) OG00113.3(4.9 to 26.6) OG0020.0(0.0 to 18.2) OG003

Primary

Number of Participants With ≥1 Adverse Event (AE)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, no analysis was planned for the cross over phase. The number of participants who experienced an AE are presented.

All participants who received at least one dose of study intervention

Posted

Count of Participants

Participants

Up to approximately 77 months

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Primary

Number of Participants Discontinuing Study Treatment Due to an AE

All participants who received at least one dose of study intervention.

Posted

Count of Participants

Participants

Up to approximately 26 months

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Primary

Efficacy Expansion: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Based on Adjusted Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per adjusted Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR in the concurrent randomized subset as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.

All participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 72 months

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W

Secondary

Area Under the Plasma Concentration Time Curve (AUC) of Pembrolizumab

AUC was defined as a measure of pembrolizumab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. AUC of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Participants who complied with the protocol sufficiently to ensure that their data will be likely to show the effects of treatment, according to the underlying scientific model and had available data from at least 1 dose of study intervention.

Posted

Geometric Mean

Geometric Coefficient of Variation

day*μg/mL

At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Maximum Concentration (Cmax) of Pembrolizumab

Cmax was defined as the maximum concentration of pembrolizumab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmax of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Minimum Concentration (Cmin) of Pembrolizumab

Cmin was defined as the minimum or "trough" concentration of pembrolizumab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for participants in arm G and cross over phase. Cmin of pembrolizumab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 2 and 3, Day 1 on Cycle 4. Arms A, B, C, D, E: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2, 3. Arm F: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Predose and Postdose on Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Posted

Median

Full Range

μg/mL

At designated time points up to - Cohorts 1-3: Day 1 Cycle 4, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F: Day 21 Cycle 3, Arm I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Area Under the Plasma Concentration Time Curve (AUC) of Quavonlimab (MK-1308)

AUC was defined as a measure of quavonlimab exposure that was calculated as the product of plasma drug concentration and time after drug administration. AUC determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. AUC of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Posted

Geometric Mean

Geometric Coefficient of Variation

day*μg/mL

At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Maximum Concentration (Cmax) of Quavonlimab

Cmax was defined as the maximum concentration of quavonlimab observed in plasma. Cmax determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmax of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001

Secondary

Minimum Concentration (Cmin) of Quavonlimab

Cmin was defined as the minimum or "trough" concentration of quavonlimab observed after its administration and just prior to the administration of a subsequent dose. Cmin determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase. Cmin of quavonlimab is presented. Blood sampling was taken for Cohorts 1-3: Predose and Postdose on Days 1, 8, 15 on Cycles 1, 2 and 3. Arms A, B, C, D, E: Days 1, 8, 15 on Cycles 1, 2, 3. Arms F, G and I: Predose and Postdose on Day 1 and 21 on Cycles 1, 2, 3. Arm K: Days 1, 2, 8, 15, 21 on Cycles 1, 2; Days 1, 21 on Cycle 3. Each cycle is 21 days.

Posted

Median

Full Range

μg/mL

At designated time points up to - Cohorts 1-3: Day 15 Cycle 3, Arms A, B, C, D, E: Day 15 Cycle 3, Arm F, G, I: Day 21 Cycle 3, Arm K: Day 21 Cycle 3. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Number of Participants With Pembrolizumab Anti-drug Antibodies (ADAs)

Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with pembrolizumab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for arm G and cross over phase.

Participants with at least one ADA sample available after treatment with pembrolizumab

Posted

Count of Participants

Participants

Cohorts 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycles 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Number of Participants With Quavonlimab Anti-drug Antibodies (ADAs)

Non-Treatment emergent (TE) ADA refers to presence of ADAs (as determined by assay) in the absence of treatment with quavonlimab (i.e., at predose). Evaluable participants (used as the denominator for analysis) are the total number of negative, inconclusive, and positive participants (non-treatment emergent, treatment emergent and treatment boosted (TB)). Inconclusive participants are the number of participants with no positive ADA samples present and the drug concentration in the last sample above the drug tolerance level. ADA determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Per protocol, no analysis was planned for the cross over phase.

Participants with at least one ADA sample available after treatment with quavonlimab

Posted

Count of Participants

Participants

Cohort 1-3: Predose and day 1 of cycles 2, 3, 5, 6, 7, 9 and every 4 cycles up to 35 cycles. Arms A-E: Predose and day 1 of cycle 1-5, 6, 8 and every 4 cycles up to 35 cycles. Arms F, G, I, K: Predose and day 1 of cycles 1, 2, 3, 4. Each cycle is 21 days.

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Dose Escalation, Dose Confirmation, Coformulation: ORR as Assessed by Investigator Based on Adjusted RECIST v1.1

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, no analysis was planned for the cross over phase.

All participants with a baseline scan that demonstrated measurable disease and who were administered at least 1 dose of study intervention.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 72 months

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).

Secondary

Efficacy Expansion: Duration of Response (DOR) as Assessed by BICR Based on Adjusted RECIST v1.1

DOR was defined as the time from first documented evidence of complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. Per protocol, only data for arms F and G were presented for this endpoint.

Participants who received at least one dose of study intervention who had either a CR or PR.

Posted

Median

Full Range

Months

Up to approximately 72 months

ID	Title	Description
OG000	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).
OG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W

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	Cohort 1: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumors received 25 mg quavonlimab (MK-1308) monotherapy followed by 25 mg quavonlimab in combination with 200 mg pembrolizumab (pembro) every 3 weeks (Q3W) for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).	13	14	2	14	14	14
EG001	Cohort 2: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 75 mg quavonlimab monotherapy followed by 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).	18	18	10	17	16	17
EG002	Cohort 3: MK-1308 200 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose escalation phase, participants with advanced solid tumor except non-small cell lung cancer (NSCLC) received 200 mg quavonlimab monotherapy followed by 200 mg quavonlimab in combination with 200 mg pembrolizumab Q3W for cycles 2-5. Participants then received 200 mg pembrolizumab monotherapy Q3W starting on Cycle 6, for up to 35 cycles total (up to approximately 24 months).	7	8	4	8	8	8
EG003	Arm A: MK-1308 25 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).	33	40	20	40	38	40
EG004	Arm B: MK-1308 25 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 25 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 25 mg quavonlimab every 6 weeks (Q6W). Participants were treated for up to 35 cycles total (up to approximately 24 months).	31	40	14	40	38	40
EG005	Arm C: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).	32	41	23	40	38	40
EG006	Arm D: MK-1308 75 mg Q6W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase, participants with advanced/metastatic small cell lung cancer (SCLC) received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. On all subsequent cycles, participants received 200 mg pembrolizumab Q3W and 75 mg quavonlimab Q6W. Participants were treated for 35 cycles total (up to approximately 24 months).	35	40	16	40	37	40
EG007	Arm E: MK-1308 75 mg Q3W + Pembro. 200 mg Q3W	On cycle 1, day 1 of the dose confirmation phase and during all subsequent cycles, participants with NSCLC received 75 mg quavonlimab in combination with 200 mg pembrolizumab Q3W. Participants were treated for 35 cycles total (up to approximately 24 months).	9	14	10	14	13	14
EG008	Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin	On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) refractory melanoma received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.	86	111	31	111	102	111
EG009	Arm F: MK-1308 25 mg Q6W + Pembro. 400 mg Q6W Co-admin After Crossover	Participants who demonstrated radiographically confirmed progressive disease in Arm G and switched over to combination therapy received 25 mg quavonlimab in combination with 400 mg pembrolizumab. Both quavonlimab and pembrolizumab were administered Q6W for 24 months.	17	21	4	21	17	21
EG010	Arm G: MK-1308 25 mg Q6W	On cycle 1, day 1 of the efficacy expansion phase and during all subsequent cycles, participants with PD-1/PD-L1 refractory melanoma received 25 mg quavonlimab Q6W for up to 24 months.	16	40	9	40	31	40
EG011	Arm I: MK-1308A Q6W (Co-form)	On cycle 1, day 1 of the coformulation (Co-form) phase and during all subsequent cycles, participants with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.	22	29	15	29	26	29
EG012	Arm K: MK-1308A Q6W (Co-form)	On cycle 1, day 1 of the coformulation phase and during all subsequent cycles, participants in mainland China with advanced/metastatic solid tumors received 400 mg pembrolizumab co-formulated with 25 mg quavonlimab (MK-1308A) Q6W for 24 months.	15	20	4	20	16	20

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG0030 events0 affected40 at risk EG0040 events0 affected40 at risk EG0050 events0 affected40 at risk EG0060 events0 affected40 at risk EG0070 events0 affected14 at risk EG0083 events3 affected111 at risk EG0090 events0 affected21 at risk EG0100 events0 affected40 at risk EG0110 events0 affected29 at risk EG0120 events0 affected20 at risk
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Mesenteric lymphadenitis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Atrioventricular block complete	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Cardiogenic shock	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Tachyarrhythmia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Vestibular disorder	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypophysitis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Retinal detachment	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Diverticular perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Enterocolitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Large intestine perforation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Subileus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Death	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Incarcerated hernia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Biliary obstruction	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Appendicitis perforated	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Arthritis infective	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Bronchopulmonary aspergillosis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
COVID-19 pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Clostridium difficile infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Encephalitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Meningitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Oesophageal candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pulmonary sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Septic shock	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Spinal cord infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Urosepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Animal bite	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Radiation oesophagitis	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Troponin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0022 events1 affected8 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Osteolysis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Metastases to central nervous system	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Autonomic nervous system imbalance	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Brain oedema	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cerebral haematoma	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cerebral infarction	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Guillain-Barre syndrome	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Metabolic encephalopathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Seizure	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Delirium	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Nephritis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Urinary tract obstruction	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Urinoma	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Embolism	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Multiple organ dysfunction syndrome	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cholestasis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected14 at risk EG0012 events2 affected17 at risk EG0022 events2 affected8 at risk EG0031 events1 affected40 at risk EG0043 events3 affected40 at risk EG0059 events8 affected40 at risk EG0065 events5 affected40 at risk EG0073 events2 affected14 at risk EG00812 events11 affected111 at risk EG0094 events4 affected21 at risk EG0109 events8 affected40 at risk EG0114 events3 affected29 at risk EG01213 events5 affected20 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected17 at risk EG0023 events3 affected8 at risk EG003
Hypophysitis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0013 events3 affected17 at risk EG0020 events0 affected8 at risk EG003
Lacrimation increased	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Vision blurred	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Aphthous ulcer	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events3 affected14 at risk EG0013 events3 affected17 at risk EG0021 events1 affected8 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events3 affected14 at risk EG0012 events2 affected17 at risk EG0023 events3 affected8 at risk EG003
Diarrhoea haemorrhagic	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected17 at risk EG0021 events1 affected8 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Gingival pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Inguinal hernia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0023 events3 affected8 at risk EG003
Obstruction gastric	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events2 affected14 at risk EG0015 events5 affected17 at risk EG0022 events2 affected8 at risk EG003
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0022 events2 affected8 at risk EG003
Catheter site pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Chest discomfort	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Chills	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Early satiety	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0007 events7 affected14 at risk EG0013 events3 affected17 at risk EG0022 events2 affected8 at risk EG003
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Influenza like illness	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Localised oedema	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Malaise	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0022 events2 affected8 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Contrast media allergy	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Cystitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Gingivitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Oral candidiasis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Oral herpes	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Sinusitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Tinea infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Animal bite	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dental restoration failure	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Foot fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Ammonia increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected14 at risk EG0014 events3 affected17 at risk EG0022 events2 affected8 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected17 at risk EG0022 events2 affected8 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0022 events2 affected8 at risk EG003
Blood corticotrophin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
C-reactive protein increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Cortisol increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0011 events1 affected17 at risk EG0022 events2 affected8 at risk EG003
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Platelet count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0014 events3 affected17 at risk EG0021 events1 affected8 at risk EG003
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected14 at risk EG0013 events3 affected17 at risk EG0023 events3 affected8 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Glucose tolerance impaired	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected17 at risk EG0023 events2 affected8 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected17 at risk EG0022 events1 affected8 at risk EG003
Hypophagia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected14 at risk EG0012 events2 affected17 at risk EG0022 events1 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0011 events1 affected17 at risk EG0021 events1 affected8 at risk EG003
Joint range of motion decreased	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Muscle rigidity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Seborrhoeic keratosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected14 at risk EG0012 events2 affected17 at risk EG0021 events1 affected8 at risk EG003
Ataxia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0012 events2 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Presyncope	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected17 at risk EG0020 events0 affected8 at risk EG003
Seizure	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Somnolence	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Depression	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hydronephrosis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Urinary tract inflammation	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Urinary tract pain	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Gynaecomastia	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Vulvovaginal burning sensation	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0021 events1 affected8 at risk EG003
Chylothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0013 events3 affected17 at risk EG0021 events1 affected8 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0013 events3 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypercapnia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0012 events2 affected17 at risk EG0020 events0 affected8 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected14 at risk EG0018 events6 affected17 at risk EG0020 events0 affected8 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0016 events4 affected17 at risk EG0021 events1 affected8 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0004 events3 affected14 at risk EG0013 events2 affected17 at risk EG0020 events0 affected8 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0013 events2 affected17 at risk EG0020 events0 affected8 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0002 events1 affected14 at risk EG0011 events1 affected17 at risk EG0020 events0 affected8 at risk EG003
Thrombocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Amylase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected14 at risk EG0010 events0 affected17 at risk EG0020 events0 affected8 at risk EG003