Trial Outcomes & Findings for A Study of LY2510924 in Participants With Extensive-Stage Small Cell Lung Carcinoma (NCT NCT01439568)

Last Updated: 2019-07-23

Results Overview

PFS is defined as the time from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For participants who are still alive at the time of analysis and without evidence of tumor progression, PFS will be censored at the date of the most recent objective progression-free observation. For participants who receive subsequent anticancer therapy (except PCI) prior to objective disease progression or death, PFS will be censored at the date of the last objective progression-free observation prior to the date of subsequent therapy.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Randomization to Measured Progressive Disease or Date of Death from Any Cause (Up To 59 Months)

Results posted on

2019-07-23

Participant Flow

Participants who died (any cause) or had disease progression were considered to be study completers.

Participant milestones

Participant milestones
Measure	LY2510924 + Carboplatin + Etoposide LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Overall Study STARTED	47	43
Overall Study Received at Least One Dose of Study Drug	47	43
Overall Study COMPLETED	44	41
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2510924 + Carboplatin + Etoposide LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	2	2

Baseline Characteristics

A Study of LY2510924 in Participants With Extensive-Stage Small Cell Lung Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2510924 + Carboplatin + Etoposide n=47 Participants LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=43 Participants Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Total n=90 Participants Total of all reporting groups
Age, Continuous	63.69 years STANDARD_DEVIATION 9.033 • n=5 Participants	67.07 years STANDARD_DEVIATION 8.328 • n=7 Participants	65.31 years STANDARD_DEVIATION 8.820 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	17 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	45 Participants n=5 Participants	40 Participants n=7 Participants	85 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	43 Participants n=5 Participants	40 Participants n=7 Participants	83 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	47 Participants n=5 Participants	43 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization to Measured Progressive Disease or Date of Death from Any Cause (Up To 59 Months)

Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation.The number of participants censored were LY2510924 + Carboplatin + Etoposide=13 and Carboplatin + Etoposide=7.

Outcome measures

Outcome measures
Measure	LY2510924 + Carboplatin + Etoposide n=47 Participants LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=42 Participants Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Progression Free Survival (PFS)	5.88 Months Interval 4.83 to 6.24	5.85 Months Interval 4.63 to 6.51

SECONDARY outcome

Timeframe: Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause (Up to 59 Months)

Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation.

ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	LY2510924 + Carboplatin + Etoposide n=47 Participants LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=42 Participants Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])	35 Participants	34 Participants

SECONDARY outcome

Timeframe: Randomization to Date of Death from Any Cause (Up To 59 Months)

Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation. The numbers of participants censored were LY2510924 + Carboplatin + Etoposide= 4 and Carboplatin + Etoposide=3.

Overall survival (OS) is defined as the time from the randomization to the date of death from any cause. For participants who are still alive as of the data cutoff date, OS time will be censored on the date of the participant's last contact (last contact for participants in postdiscontinuation is last known alive date in mortality status).

Outcome measures

Outcome measures
Measure	LY2510924 + Carboplatin + Etoposide n=47 Participants LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=42 Participants Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Overall Survival (OS)	9.72 Months Interval 6.64 to 11.7	11.14 Months Interval 8.25 to 14.23

SECONDARY outcome

Timeframe: Date of Response to Date of Progressive Disease (Up To 59 Months)

Population: All participants who received at least one dose of study drug. One participant was excluded from analysis due to protocol violation. The number of participants censored were LY2510924 + Carboplatin + Etoposide=47 and Carboplatin + Etoposide=42.

DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

Outcome measures

Outcome measures
Measure	LY2510924 + Carboplatin + Etoposide n=47 Participants LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=42 Participants Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Duration of Overall Response (DOR)	4.83 Months Interval 3.58 to 5.09	4.67 Months Interval 3.32 to 5.78

Adverse Events

LY2510924 + Carboplatin + Etoposide

Serious events: 24 serious events

Other events: 47 other events

Deaths: 0 deaths

Carboplatin + Etoposide

Serious events: 13 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	LY2510924 + Carboplatin + Etoposide n=47 participants at risk LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=43 participants at risk Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Blood and lymphatic system disorders Anaemia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Febrile neutropenia	4.3% 2/47 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Cardiac disorders Atrial fibrillation	2.1% 1/47 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Cardiac disorders Cardiac arrest	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Cardiac disorders Myocardial infarction	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Asthenia	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
General disorders Chest pain	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Infections and infestations Peridiverticular abscess	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	10.6% 5/47 • Number of events 6 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Infections and infestations Sepsis	4.3% 2/47 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Hip fracture	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypovolaemia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Biliary neoplasm	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Nervous system disorders Ataxia	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Cerebrovascular accident	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Ruptured cerebral aneurysm	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Syncope	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Psychiatric disorders Mental status changes	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/47 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumothorax	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Vascular disorders Deep vein thrombosis	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Vascular disorders Hypotension	0.00% 0/47 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.

Measure	LY2510924 + Carboplatin + Etoposide n=47 participants at risk LY2510924: 20 milligram (mg) administered once daily as a subcutaneous injection on days 1 to 7 of the 21 day cycle; repeat every 21 days for 6 cycles. Carboplatin: 5 milligram/millimeter/per minute (mg/mL/min) area under the curve (AUC) administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered intravenously on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.	Carboplatin + Etoposide n=43 participants at risk Carboplatin: 5 mg/mL/min area under the curve administered intravenously on day 1 of the 21 day cycle; repeat every 21 days for 6 cycles. Etoposide: 100 milligram square meter (mg/m\^2) administered on days 1 to 3 of the 21 day cycle; repeat every 21 days for 6 cycles.
Blood and lymphatic system disorders Anaemia	59.6% 28/47 • Number of events 94 All participants who received at least one dose of study drug.	48.8% 21/43 • Number of events 81 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukocytosis	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	27.7% 13/47 • Number of events 18 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 6 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	59.6% 28/47 • Number of events 43 All participants who received at least one dose of study drug.	51.2% 22/43 • Number of events 49 All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	36.2% 17/47 • Number of events 56 All participants who received at least one dose of study drug.	39.5% 17/43 • Number of events 52 All participants who received at least one dose of study drug.
Cardiac disorders Tachycardia	6.4% 3/47 • Number of events 4 All participants who received at least one dose of study drug.	4.7% 2/43 • Number of events 2 All participants who received at least one dose of study drug.
Eye disorders Vision blurred	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Gastrointestinal disorders Constipation	38.3% 18/47 • Number of events 20 All participants who received at least one dose of study drug.	41.9% 18/43 • Number of events 22 All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	25.5% 12/47 • Number of events 16 All participants who received at least one dose of study drug.	20.9% 9/43 • Number of events 11 All participants who received at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	10.6% 5/47 • Number of events 10 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 4 All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	48.9% 23/47 • Number of events 44 All participants who received at least one dose of study drug.	44.2% 19/43 • Number of events 36 All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	31.9% 15/47 • Number of events 21 All participants who received at least one dose of study drug.	18.6% 8/43 • Number of events 10 All participants who received at least one dose of study drug.
General disorders Asthenia	12.8% 6/47 • Number of events 7 All participants who received at least one dose of study drug.	14.0% 6/43 • Number of events 7 All participants who received at least one dose of study drug.
General disorders Chest pain	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
General disorders Fatigue	61.7% 29/47 • Number of events 46 All participants who received at least one dose of study drug.	58.1% 25/43 • Number of events 46 All participants who received at least one dose of study drug.
General disorders Injection site erythema	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
General disorders Injection site pain	19.1% 9/47 • Number of events 11 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
General disorders Mucosal inflammation	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
General disorders Oedema peripheral	14.9% 7/47 • Number of events 11 All participants who received at least one dose of study drug.	23.3% 10/43 • Number of events 10 All participants who received at least one dose of study drug.
General disorders Pain	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 5 All participants who received at least one dose of study drug.
General disorders Pyrexia	10.6% 5/47 • Number of events 9 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	6.4% 3/47 • Number of events 5 All participants who received at least one dose of study drug.	11.6% 5/43 • Number of events 5 All participants who received at least one dose of study drug.
Investigations Aspartate aminotransferase increased	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	4.7% 2/43 • Number of events 2 All participants who received at least one dose of study drug.
Investigations Blood alkaline phosphatase increased	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	2.1% 1/47 • Number of events 1 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 4 All participants who received at least one dose of study drug.
Investigations Blood lactate dehydrogenase increased	4.3% 2/47 • Number of events 3 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Investigations Blood magnesium decreased	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Investigations Blood uric acid increased	8.5% 4/47 • Number of events 4 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	6.4% 3/47 • Number of events 6 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 6 All participants who received at least one dose of study drug.
Investigations Neutrophil count increased	6.4% 3/47 • Number of events 6 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 2 All participants who received at least one dose of study drug.
Investigations Platelet count decreased	6.4% 3/47 • Number of events 7 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 6 All participants who received at least one dose of study drug.
Investigations Weight decreased	12.8% 6/47 • Number of events 6 All participants who received at least one dose of study drug.	14.0% 6/43 • Number of events 7 All participants who received at least one dose of study drug.
Investigations White blood cell count increased	10.6% 5/47 • Number of events 9 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 2 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	27.7% 13/47 • Number of events 15 All participants who received at least one dose of study drug.	25.6% 11/43 • Number of events 13 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	17.0% 8/47 • Number of events 9 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	6.4% 3/47 • Number of events 4 All participants who received at least one dose of study drug.	4.7% 2/43 • Number of events 7 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 5 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypokalaemia	12.8% 6/47 • Number of events 11 All participants who received at least one dose of study drug.	11.6% 5/43 • Number of events 5 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypomagnesaemia	10.6% 5/47 • Number of events 12 All participants who received at least one dose of study drug.	16.3% 7/43 • Number of events 10 All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyponatraemia	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	16.3% 7/43 • Number of events 11 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	8.5% 4/47 • Number of events 5 All participants who received at least one dose of study drug.	14.0% 6/43 • Number of events 6 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	19.1% 9/47 • Number of events 10 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Bone pain	10.6% 5/47 • Number of events 12 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 4 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	6.4% 3/47 • Number of events 4 All participants who received at least one dose of study drug.	14.0% 6/43 • Number of events 6 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	8.5% 4/47 • Number of events 5 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 6 All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	10.6% 5/47 • Number of events 6 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 4 All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 4 All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	12.8% 6/47 • Number of events 7 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Headache	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	18.6% 8/43 • Number of events 8 All participants who received at least one dose of study drug.
Nervous system disorders Syncope	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Nervous system disorders Tremor	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Psychiatric disorders Anxiety	6.4% 3/47 • Number of events 3 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 5 All participants who received at least one dose of study drug.
Psychiatric disorders Confusional state	8.5% 4/47 • Number of events 4 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Psychiatric disorders Insomnia	23.4% 11/47 • Number of events 12 All participants who received at least one dose of study drug.	18.6% 8/43 • Number of events 9 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	23.4% 11/47 • Number of events 14 All participants who received at least one dose of study drug.	27.9% 12/43 • Number of events 16 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	29.8% 14/47 • Number of events 17 All participants who received at least one dose of study drug.	23.3% 10/43 • Number of events 13 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	14.9% 7/47 • Number of events 7 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Haemoptysis	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 5 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.3% 2/47 • Number of events 2 All participants who received at least one dose of study drug.	7.0% 3/43 • Number of events 3 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	10.6% 5/47 • Number of events 5 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	8.5% 4/47 • Number of events 4 All participants who received at least one dose of study drug.	2.3% 1/43 • Number of events 1 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	42.6% 20/47 • Number of events 27 All participants who received at least one dose of study drug.	39.5% 17/43 • Number of events 19 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	8.5% 4/47 • Number of events 5 All participants who received at least one dose of study drug.	4.7% 2/43 • Number of events 2 All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	8.5% 4/47 • Number of events 6 All participants who received at least one dose of study drug.	9.3% 4/43 • Number of events 4 All participants who received at least one dose of study drug.
Vascular disorders Flushing	8.5% 4/47 • Number of events 5 All participants who received at least one dose of study drug.	0.00% 0/43 All participants who received at least one dose of study drug.
Vascular disorders Hypotension	8.5% 4/47 • Number of events 5 All participants who received at least one dose of study drug.	11.6% 5/43 • Number of events 5 All participants who received at least one dose of study drug.