A Safety and Tolerability Study of NC318 in Subjects With... | NCT03665285

Label	Type	Description	Intervention Names
NC318 8mg	Experimental	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC318
NC318 24mg	Experimental	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC318
NC318 80mg	Experimental	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC318
NC318 240mg	Experimental	Phase 1 Dose Escalation/Safety Expansion (Cohort 3): Subjects received NC318 IV at 240mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC318
NC318 400mg	Experimental	Phase 1 Dose Escalation/Safety Expansion (Cohort 4): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Name	Type	Description	Arm Group Labels	Other Names
NC318	Drug	NC318 is an experimental antibody drug that may make the immune response more active against cancer.	Dose Expansion: 400mg Q2W Dose Expansion: 800mg QW

Measure	Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0	The number of participants who have had at least one TEAE during the study.	From enrollment through up to 90 days after end of treatment, an average of 1 year

Measure	Description	Time Frame
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Men and women aged 18 or older.
Willingness to provide written informed consent for the study.
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
Subjects with advanced unresectable and/or metastatic solid tumors.
Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. Note: There is no limit to the number of prior treatment regimens.
Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
Able to provide pretreatment tumor tissue sample at Screening.
Subjects of childbearing potential (defined as female subjects who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as ≥ 12 months of amenorrhea not caused by reversible conditions, diseases, or medications) and non-sterilized male subjects must agree to take appropriate precautions to avoid pregnancy or fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study drug.

Exclusion Criteria:

Inability to comprehend or unwilling to sign the Informed Consent Form.
Screening laboratory values of:
1. Absolute neutrophil count < 1.5 × 10^9/L
2. Platelets < 100 × 10^9/L
3. Hemoglobin < 9 g/dL or < 5.6 mmol/L
4. Serum creatinine > 1.5 × institutional upper limit of normal (ULN)
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 × ULN
6. Total bilirubin > 1.5 × ULN.
7. International normalized ratio (INR) or prothrombin time (PT) > 1.5 × ULN or activated partial thromboplastin time (aPTT) > 1.5 × ULN
Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 7 days before the first administration of study drug.
Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:
1. ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not require chronic use of corticosteroids and must not have had radiation pneumonitis because of a treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with medical monitor approval. Note: Bisphosphonates and denosumab are permitted medications.
2. ≤ 28 days for prior immunotherapy or persistence of active cellular therapy (e.g., chimeric antigen receptor T cell therapy; other cellular therapies must be discussed with the medical monitor to determine eligibility).
3. ≤ 28 days for a prior monoclonal antibody used for anticancer therapy except for denosumab.
4. ≤ 7 days for immune-suppressive-based treatment for any reason. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted. Note: The use of corticosteroids equivalent to prednisone </= 10mg/day is allowed.
5. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices.
6. ≤ 14 days for COVID-19 vaccine.
Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy.
Receipt of a live vaccine within 30 days of planned start of study therapy.
Active autoimmune disease that required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
Known active CNS metastases and/or carcinomatous meningitis.
Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry after treatment with curative intent.
Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
Documented known activating or driver mutations (i.e. EGFR mutations/amplification, BRAF mutations, ALK alterations, etc.) which have not been previously treated with a standard of care targeted therapy.
Subjects with screening QTc interval >470 milliseconds are excluded.
Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate anti-infection treatment.
Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured.
Known history of HIV (HIV 1 or HIV 2 antibodies).
Known allergy or reaction to any component of study drug or formulation components.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study treatment.
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Name	Affiliation	Role
Han Myint, MD	NextCure, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
The Angeles Clinic and Research Institute		Los Angeles	California	90025	United States
Yale University Cancer Center

ID	Title	Description
FG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
FG001	NC318 24mg

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	Mar 3, 2022

ID	Title	Description
BG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG003	NC318 240mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 3): Subjects received NC318 IV at 240mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG004	NC318 400mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 4): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG005	NC318 800mg	Phase 1 Dose Escalation (Cohort 5): Subjects received NC318 IV at 800mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG006	NC318 1600mg	Phase 1 Dose Escalation (Cohort 6): Subjects received NC318 IV at 1600mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG007	Dose Expansion: 400mg Q2W	Phase 2 Dose Expansion (400mg): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG008	Dose Expansion: 800mg QW	Phase 2 Dose Expansion (800mg): Subjects received NC318 IV at 800mg QW for 8 weeks, then Q2W thereafter until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
BG009	Total	Total of all reporting groups

Units	Counts
Participants	BG0004 BG0014 BG00210 BG00312 BG00411 BG0054 BG0064 BG00747 BG00813 BG009109

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

Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0

The number of participants who have had at least one TEAE during the study.

The Safety Analysis Set (SAS) will include all the subjects who receive any amount of study drug.

Posted

Count of Participants

Participants

From enrollment through up to 90 days after end of treatment, an average of 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG003	NC318 240mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 3): Subjects received NC318 IV at 240mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG004	NC318 400mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 4): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG005	NC318 800mg	Phase 1 Dose Escalation (Cohort 5): Subjects received NC318 IV at 800mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG006	NC318 1600mg	Phase 1 Dose Escalation (Cohort 6): Subjects received NC318 IV at 1600mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG007	Dose Expansion: 400mg Q2W	Phase 2 Dose Expansion (400mg): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG008	Dose Expansion: 800mg QW	Phase 2 Dose Expansion (800mg): Subjects received NC318 IV at 800mg QW for 8 weeks, then Q2W thereafter until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Units	Counts
Participants	OG0004 OG0014 OG00210 OG003

Title

Denominators

Categories

Title	Measurements
	OG0004 OG0014 OG00210 OG003

Secondary

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC318.

Posted

Count of Participants

Participants

Approximately 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Secondary

Duration of Response (DoR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

To assess antitumor activity/efficacy by evaluating duration of response (DoR), defined as the time from the first documented complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to the first documented progressive disease or death due to any cause, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC318.

Posted

Median

95% Confidence Interval

months

Approximately 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg

Secondary

Disease Control Rate (DCR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

To assess antitumor activity/efficacy by evaluating disease control rate (DCR), defined as the proportion of participants in whom a documented complete response, partial response, or stable disease is observed as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC318.

Posted

Count of Participants

Participants

Approximately 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Secondary

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

To evaluate progression-free survival (PFS), defined as the time from the first dose of NC318 to the first occurrence of documented progressive disease or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC318.

Posted

Median

95% Confidence Interval

months

Approximately 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Secondary

Overall Survival (OS)

To evaluate overall survival (OS), defined as the time from the first dose of NC318 to death due to any cause.

The full analysis set (FAS) includes all subjects enrolled in the study who received at least one full dose of NC318.

Posted

Median

95% Confidence Interval

months

Approximately 1 year

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG003	NC318 240mg

Secondary

Maximum Plasma Concentration (Cmax) of NC318

To evaluate the Maximum Plasma Concentration (Cmax) of NC318

The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis. PK analysis only took place during the dose escalation portion of the study.

Posted

Mean

Standard Deviation

ng/mL

Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG003

Secondary

Area Under the Curve (AUC) of NC318

To evaluate the Area Under the Curve (AUC) of NC318

The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis. PK analysis only took place during the dose escalation portion of the study.

Posted

Mean

Standard Deviation

h*ng/mL

Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG003

Secondary

Half-life (t1/2) of NC318

To evaluate the half-life (t1/2) of NC318

The PK analysis set (PAS) will include all the subjects whose blood samples are collected for PK analysis. PK analysis only took place during the dose escalation portion of the study.

Posted

Mean

Standard Deviation

hours

Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.

ID	Title	Description
OG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
OG003

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG0031 affected12 at risk EG0040 affected11 at risk EG0050 affected4 at risk EG0061 affected4 at risk EG0070 affected47 at risk EG0080 affected13 at risk
Cardiac tamponade	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Death nos	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Disease Progression	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Fatigue	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Sepsis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Soft tissue infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Wound infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hip fracture	Injury, poisoning and procedural complications	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Failure to thrive	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Endometrial cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Hepatocellular carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Ovarian cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Brain oedema	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Encephalitis autoimmune	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hemiparesis	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Seizure	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Spinal cord compression	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Device occlusion	Product Issues	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pelvic Pain	Reproductive system and breast disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Acute respiratory distress syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Laryngeal obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypertension	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0023 affected10 at risk EG0033 affected12 at risk EG0044 affected11 at risk EG0051 affected4 at risk EG0061 affected4 at risk EG0076 affected47 at risk EG0084 affected13 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0022 affected10 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Diplopia	Eye disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Extraocular muscle paresis	Eye disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Eye pain	Eye disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Vision blurred	Eye disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0012 affected4 at risk EG0022 affected10 at risk EG003
Abdominal pain lower	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Abdominal pain UPPER	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Ascites	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0024 affected10 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected4 at risk EG0024 affected10 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0024 affected10 at risk EG003
Oesophageal stenosis	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected10 at risk EG003
Chest pain	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Chills	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Face oedema	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Fatigue	General disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0024 affected10 at risk EG003
Influenza like illness	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Oedema peripheral	General disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Pain	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pyrexia	General disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Supraclavicular fossa pain	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Swelling	General disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Bile duct obstruction	Hepatobiliary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Bronchitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
COVID-19	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Candida infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Chorioretinitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Cystitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Gingivitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Oesophageal candidiasis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Osteomyelitis	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pneumonia	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Skin infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Tooth infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Wound infection	Infections and infestations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Amylase increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0022 affected10 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Blood calcium increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Blood creatine increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Blood creatinine increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
International normalised ratio increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Lipase increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0022 affected10 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Platelet count decreased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Transaminases increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Weight decreased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Weight increased	Investigations	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Acidosis	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Hyperphosphataemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0021 affected10 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0022 affected10 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Cancer Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Tumour Pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Burning sensation	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Depressed level of consciousness	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Dizziness	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0023 affected10 at risk EG003
Dysaesthesia	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Fine motor skill dysfunction	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Headache	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0012 affected4 at risk EG0020 affected10 at risk EG003
Neuralgia	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Tremor	Nervous system disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Depression	Psychiatric disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Suicidal ideation	Psychiatric disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0002 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Cold sweat	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0002 affected4 at risk EG0010 affected4 at risk EG0024 affected10 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0001 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Embolism	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0011 affected4 at risk EG0020 affected10 at risk EG003
Extremity necrosis	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Flushing	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hot flush	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypertension	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003
Hypotension	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0021 affected10 at risk EG003
Peripheral embolism	Vascular disorders	MedDRA 21	Non-systematic Assessment	EG0000 affected4 at risk EG0010 affected4 at risk EG0020 affected10 at risk EG003

ID	Term
D008175	Lung Neoplasms
D001943	Breast Neoplasms
D000077195	Squamous Cell Carcinoma of Head and Neck
D016889	Endometrial Neoplasms
D008545	Melanoma
D002295	Carcinoma, Transitional Cell
D018281	Cholangiocarcinoma
D009362	Neoplasm Metastasis

ID	Term
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases
D002294	Carcinoma, Squamous Cell
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D006258	Head and Neck Neoplasms
D014594	Uterine Neoplasms
D005833	Genital Neoplasms, Female
D014565	Urogenital Neoplasms
D014591	Uterine Diseases
D005831	Genital Diseases, Female
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D000091662	Genital Diseases
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D000230	Adenocarcinoma
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	NC318 8mg	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	0	4	2	4	4	4
EG001	NC318 24mg	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	2	4	3	4	4	4
EG002	NC318 80mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	0	10	4	10	10	10
EG003	NC318 240mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 3): Subjects received NC318 IV at 240mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	4	12	8	12	12	12
EG004	NC318 400mg	Phase 1 Dose Escalation/Safety Expansion (Cohort 4): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	3	11	4	11	10	11
EG005	NC318 800mg	Phase 1 Dose Escalation (Cohort 5): Subjects received NC318 IV at 800mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	1	4	1	4	4	4
EG006	NC318 1600mg	Phase 1 Dose Escalation (Cohort 6): Subjects received NC318 IV at 1600mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	1	4	3	4	4	4
EG007	Dose Expansion: 400mg Q2W	Phase 2 Dose Expansion (400mg): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	7	47	16	47	42	47
EG008	Dose Expansion: 800mg QW	Phase 2 Dose Expansion (800mg): Subjects received NC318 IV at 800mg QW for 8 weeks, then Q2W thereafter until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	6	13	5	13	12	13