A Study of Combination Therapies With Viagenpumatucel-L (... | NCT02439450

Label	Type	Description	Intervention Names
Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive	Experimental	Patients naïve to checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.	Biological: Viagenpumatucel-L Drug: Nivolumab
Arm 6: Viagenpumatucel-L + pembrolizumab	Experimental	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first.	Biological: Viagenpumatucel-L Drug: Pembrolizumab
Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor	Experimental	Patients with prior checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.

Name	Type	Description	Arm Group Labels	Other Names
Viagenpumatucel-L	Biological	Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig	Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive

Measure	Description	Time Frame
Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03.	The number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.	Up to 3 years

Eligibility Module

Eligibility Criteria

INCLUSION CRITERIA:

Non-small cell lung adenocarcinoma or squamous cell carcimona
At least one site of measurable disease by RECIST 1.1
Arm 5: Received at least one prior line of therapy, but no more than three prior lines of therapy, for incurable (i.e. unresectable) or metastatic NSCLC. Up to one prior line of FDA-approved checkpoint inhibitor therapy is permitted (must have received at least 4 months of treatment) --OR--
Arm 6: Received front line immunotherapy (with or without chemotherapy) for incurable or metastatic NSCLC and did not progress clinically or radiographically per RECIST 1.1 at the most recent imaging assessment, and will begin maintenance immunotherapy with standard of care pembrolizumab ± pemetrexed.
Life expectancy ≥18 weeks
Arm 5: Disease progression at study entry --OR--
Arm 6: Documented Stable Disease, Partial Response, Complete Response (SD/PR/CR) per RECIST 1.1 after a minimum of 9 to 12 weeks of front line immunotherapy (with or without chemotherapy).
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
Central nervous system (CNS) metastases may be permitted but must be treated and neurologically stable
Adequate laboratory parameters
Willing and able to comply with the protocol and sign informed consent
Female patients who are of childbearing potential and fertile male patients must agree to use an effective form of contraception throughout study participation
Willing to provide archival or fresh tumor biopsy at Screening, and fresh tumor biopsy at Week 10 when feasible.
Arm 5: Suitable for treatment with nivolumab per package insert --OR--
Arm 6: Suitable for front line maintenance treatment with pembrolizumab ± pemetrexed per the current approved package inserts.

EXCLUSION CRITERIA:

Arm 5: Received systemic anticancer therapy within 21 days prior to first dose of study drug
Human immunodeficiency virus (HIV), hepatitis B or C, or severe/uncontrolled infections or concurrent illness, unrelated to the tumor, requiring active therapy
Any condition requiring concurrent systemic immunosuppressive therapy
Known immunodeficiency disorders, either primary or acquired
Known leptomeningeal disease
Active malignancies within 12 months with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
Pregnant or breastfeeding
Prior participation in a clinical study of viagenpumatucel-L (HS-110)
Administration of a live vaccine within 30 days prior to first dose of study drug
Active, known or suspected autoimmune disease
Significant cardiovascular disease
Refractory to prior immunotherapy (clinical or radiographic progression after 12 weeks or less of immunotherapy).

Name	Affiliation	Role
Daniel Morgensztern, MD	Washington University School of Medicine in St. Louis	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Arizona Cancer Center		Tucson	Arizona	85724	United States
UC San Diego

ID	Title	Description
FG000	Arm 5: Viagenpumatucel-L + Nivolumab CPI Naïve	Patients naïve to CPI therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.

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	May 24, 2019

Arm/Group Information

ID	Title	Description
BG000	Arm 5: Viagenpumatucel-L + Nivolumab CPI Naïve	Patients naïve to CPI therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
BG001	Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor	Patients with prior CPI therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
BG002	Arm 6: Viagenpumatucel-L + Pembrolizumab	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
BG003	Arm 6: Viagenpumatucel-L + Pembrolizumab +/- Pemetrexed	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab ± pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab ± pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Pemetrexed: The recommended dose of ALIMTA (pemetrexed) when administered with carboplatin and pembrolizumab for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous infusion over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles. Pembrolizumab should be administered prior to ALIMTA when given on the same day.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00047 BG00168 BG0022 BG0034 BG004121

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Arm/Group Information

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Primary

Phase 1b: Frequency of Treatment Emergent Adverse Events (TEAEs) as Assessed by CTCAE v4.03.

The number and percent of patients with a given TEAE will be summarized overall and by system organ class and preferred term by treatment group. The number and percent of patients with TEAEs will be tabulated by maximum severity.

Posted

Count of Participants

Participants

Up to 3 years

ID	Title	Description
OG000	Arm 5: Viagenpumatucel-L + Nivolumab CPI Naive	Patients naïve to checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
OG001	Arm 6: Viagenpumatucel-L + Pembrolizumab	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
OG002	Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor	Patients with prior checkpoint inhibitor (CPI) therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.
OG003	Arm 6: Viagenpumatucel-L + Pembrolizumab + Pemetrexed	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab + pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab + pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Pemetrexed: The recommended dose of ALIMTA (pemetrexed) when administered with carboplatin and pembrolizumab for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous infusion over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles. Pembrolizumab should be administered prior to ALIMTA when given on the same day.

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Participants	OG00047 OG00168 OG0022 OG003

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	OG00047 OG00166 OG0022 OG003

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	Arm 5: Viagenpumatucel-L + Nivolumab CPI Naïve	Patients naïve to CPI therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.	39	47	13	47	47	47
EG001	Arm 5: Viagenpumatucel-L + Nivolumab CPI Progressor	Patients with prior CPI therapy will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/ 0.5 mL for 18 weeks and bi-weekly nivolumab infusions. After 18 weeks of treatment, patients will continue on monotherapy standard of care nivolumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Nivolumab: Nivolumab 240mg IV q2weeks for 18 weeks or until disease progression or unacceptable toxicity. After the completion of 18 weeks of combination therapy, patients may receive either nivolumab dosing schedule listed in the current approved package insert (every 2 weeks or every 4 weeks) per Investigator discretion.	60	68	16	68	66	68
EG002	Arm 6: Viagenpumatucel-L + Pembrolizumab	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.	2	2	0	2	2	2
EG003	Arm 6: Viagenpumatucel-L + Pembrolizumab + Pemetrexed	HS-110 dosing to be initiated at/before the start of the 3rd maintenance treatment cycle, or within 19 weeks of front-line pembrolizumab monotherapy. Patients will receive a combination of weekly HS-110 administered as 5 intradermal 0.1 mL injections at a dose of 1 × 107 viable cells/0.5 mL for 13 weeks in combination with SOC pembrolizumab + pemetrexed every 3 weeks. Following the 13-week priming period, HS-110 injections will be administered for boosting every 3 weeks in combination with SOC pembrolizumab + pemetrexed until confirmed disease progression or unacceptable toxicity, whichever occurs first. Viagenpumatucel-L: Vaccine derived from irradiated human lung cancer cells genetically engineered to continually secrete gp96-Ig Pembrolizumab: The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. Pemetrexed: The recommended dose of ALIMTA (pemetrexed) when administered with carboplatin and pembrolizumab for the initial treatment of NSCLC in patients with a creatinine clearance (calculated by Cockcroft-Gault equation) of 45 mL/min or greater is 500 mg/m2 administered as an intravenous infusion over 10 minutes prior to carboplatin on Day 1 of each 21-day cycle for 4 cycles. Pembrolizumab should be administered prior to ALIMTA when given on the same day.	3	4	1	4	4	4

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Acute Myocardial Infarction	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG0030 events0 affected4 at risk
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Cardiac failure congestive	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Cardiac tamponade	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Supraventricular tachycardia	Cardiac disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Dysphagia	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Chest Pain	General disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Death	General disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Non-cardiac chest pain	General disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Oedema peripheral	General disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0012 events2 affected68 at risk EG0020 events0 affected2 at risk EG003
Pyrexia	General disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0012 events2 affected68 at risk EG0020 events0 affected2 at risk EG003
Complicated appendicitis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Sepsis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Upper respiratory tract infection	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Polyarthritis	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Embolic stroke	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Transient ischaemic attack	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Haematuria	Renal and urinary disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Haematoma	Vascular disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	Non-systematic Assessment	EG00010 events7 affected47 at risk EG00111 events7 affected68 at risk EG0020 events0 affected2 at risk EG0033 events2 affected4 at risk
Thrombocytopenia	Blood and lymphatic system disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Atrial fibrillation	Cardiac disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Palpitations	Cardiac disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Vertigo	Ear and labyrinth disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Dry eye	Eye disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Eye pruritus	Eye disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Ocular hyperaemia	Eye disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Abdominal distention	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Abdominal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0018 events8 affected68 at risk EG0020 events0 affected2 at risk EG003
Constipation	Gastrointestinal disorders	Non-systematic Assessment	EG0007 events7 affected47 at risk EG00110 events10 affected68 at risk EG0020 events0 affected2 at risk EG003
Diarrhoea	Gastrointestinal disorders	Non-systematic Assessment	EG0007 events7 affected47 at risk EG00111 events11 affected68 at risk EG0020 events0 affected2 at risk EG003
Dry mouth	Gastrointestinal disorders	Non-systematic Assessment	EG0006 events6 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Gastrointestinal pain	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	Non-systematic Assessment	EG0007 events7 affected47 at risk EG00111 events11 affected68 at risk EG0020 events0 affected2 at risk EG003
Retching	Gastrointestinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Stomatitis	Gastrointestinal disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Vomiting	Gastrointestinal disorders	Non-systematic Assessment	EG0005 events5 affected47 at risk EG0016 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Chest pain	General disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Chills	General disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Fatigue	General disorders	Non-systematic Assessment	EG00013 events13 affected47 at risk EG00126 events23 affected68 at risk EG0020 events0 affected2 at risk EG003
Mucosal inflammation	General disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Malaise	General disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Oedema peripheral	General disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0016 events4 affected68 at risk EG0021 events1 affected2 at risk EG003
Pyrexia	General disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0016 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Conjunctivitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Diverticulitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Laryngitis	Infections and infestations	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Pneumonia	Infections and infestations	Non-systematic Assessment	EG0003 events2 affected47 at risk EG0017 events7 affected68 at risk EG0020 events0 affected2 at risk EG003
Sinusitis	Infections and infestations	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Upper respiratory tract infection	Infections and infestations	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0013 events3 affected68 at risk EG0020 events0 affected2 at risk EG003
Fall	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0015 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Alanine aminotransferase increased	Investigations	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Aspartate aminotransferase increased	Investigations	Non-systematic Assessment	EG00011 events7 affected47 at risk EG0019 events7 affected68 at risk EG0020 events0 affected2 at risk EG003
Blood alkaline phosphatase increased	Investigations	Non-systematic Assessment	EG0005 events4 affected47 at risk EG00110 events7 affected68 at risk EG0020 events0 affected2 at risk EG003
Blood creatinine increased	Investigations	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0012 events2 affected68 at risk EG0020 events0 affected2 at risk EG003
Blood urea increased	Investigations	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Lymphocyte count decreased	Investigations	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Platelet count decreased	Investigations	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Weight decreased	Investigations	Non-systematic Assessment	EG0004 events4 affected47 at risk EG00110 events10 affected68 at risk EG0020 events0 affected2 at risk EG003
White blood cell count decreased	Investigations	Non-systematic Assessment	EG0004 events3 affected47 at risk EG0012 events2 affected68 at risk EG0020 events0 affected2 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	Non-systematic Assessment	EG0006 events6 affected47 at risk EG00111 events11 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0006 events4 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0009 events7 affected47 at risk EG0017 events7 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0019 events9 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0006 events6 affected47 at risk EG0018 events8 affected68 at risk EG0020 events0 affected2 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	Non-systematic Assessment	EG0005 events5 affected47 at risk EG00110 events8 affected68 at risk EG0020 events0 affected2 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0008 events8 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0006 events6 affected47 at risk EG0018 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0015 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Dizziness	Nervous system disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0016 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Headache	Nervous system disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG00111 events9 affected68 at risk EG0020 events0 affected2 at risk EG003
Paresthesia	Nervous system disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Anxiety	Psychiatric disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0016 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Depression	Psychiatric disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Insomnia	Psychiatric disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0016 events6 affected68 at risk EG0020 events0 affected2 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0007 events7 affected47 at risk EG00111 events10 affected68 at risk EG0020 events0 affected2 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0006 events5 affected47 at risk EG00114 events12 affected68 at risk EG0021 events1 affected2 at risk EG003
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0014 events4 affected68 at risk EG0020 events0 affected2 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0019 events8 affected68 at risk EG0020 events0 affected2 at risk EG003
Nasal congestion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0004 events4 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0013 events3 affected68 at risk EG0020 events0 affected2 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0003 events2 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Upper airway cough syndrome	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Wheezing	Respiratory, thoracic and mediastinal disorders	Non-systematic Assessment	EG0001 events1 affected47 at risk EG0017 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0005 events5 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Nail ridging	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0000 events0 affected47 at risk EG0010 events0 affected68 at risk EG0021 events1 affected2 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0007 events5 affected47 at risk EG00111 events11 affected68 at risk EG0020 events0 affected2 at risk EG003
Rash	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0006 events6 affected47 at risk EG0015 events5 affected68 at risk EG0020 events0 affected2 at risk EG003
Rash maculopapular	Skin and subcutaneous tissue disorders	Non-systematic Assessment	EG0006 events4 affected47 at risk EG0011 events1 affected68 at risk EG0020 events0 affected2 at risk EG003
Hot flush	Vascular disorders	Non-systematic Assessment	EG0003 events3 affected47 at risk EG0010 events0 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypertension	Vascular disorders	Non-systematic Assessment	EG0002 events2 affected47 at risk EG0017 events7 affected68 at risk EG0020 events0 affected2 at risk EG003
Hypotension	Vascular disorders	Non-systematic Assessment	EG0005 events4 affected47 at risk EG0018 events6 affected68 at risk EG0020 events0 affected2 at risk EG003

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
D009369	Neoplasms

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000600	Amino Acids, Dicarboxylic