Trial Outcomes & Findings for A Study to Evaluate Safety and Efficacy of HS-10296 as First-Line Treatment in Patients (NCT NCT03849768)

NCT ID: NCT03849768

Last Updated: 2023-01-20

Results Overview

PFS was defined as the time from the date of first dose until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by investigators. Progression is defined 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.

• Recruitment status: UNKNOWN
• Study phase: PHASE3
• Target enrollment: 429 participants
• Primary outcome timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, approximately 2 years.
• Results posted on: 2023-01-20

Participant Flow

A total of 429 participants were randomized to at 53 study sites.

Participant milestones

Measure	HS-10296 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Overall Study STARTED	214	215
Overall Study COMPLETED	121	181
Overall Study NOT COMPLETED	93	34

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study to Evaluate Safety and Efficacy of HS-10296 as First-Line Treatment in Patients

Baseline characteristics by cohort

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Total n=429 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	155 Participants n=5 Participants	139 Participants n=7 Participants	294 Participants n=5 Participants
Age, Categorical >=65 years	59 Participants n=5 Participants	76 Participants n=7 Participants	135 Participants n=5 Participants
Age, Continuous	58.1 years STANDARD_DEVIATION 9.59 • n=5 Participants	60.6 years STANDARD_DEVIATION 9.72 • n=7 Participants	59.3 years STANDARD_DEVIATION 9.72 • n=5 Participants
Sex: Female, Male Female	134 Participants n=5 Participants	135 Participants n=7 Participants	269 Participants n=5 Participants
Sex: Female, Male Male	80 Participants n=5 Participants	80 Participants n=7 Participants	160 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	214 Participants n=5 Participants	215 Participants n=7 Participants	429 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	0 Participants n=7 Participants	0 Participants n=5 Participants
Smoking status Never smoked	156 Participants n=5 Participants	144 Participants n=7 Participants	300 Participants n=5 Participants
Smoking status smoked	58 Participants n=5 Participants	71 Participants n=7 Participants	129 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, approximately 2 years.

PFS was defined as the time from the date of first dose until the date of radiological disease progression or until death due to any cause, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, as assessed by investigators. Progression is defined 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.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Progression Free Survival (PFS)	19.3 months Interval 17.8 to 20.8	9.9 months Interval 8.3 to 12.6

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study.（up to 24 months）

ORR is defined as the percentage of patients who have at least 1 response of CR or PR prior to any evidence of progression. Target lesions and assessed by CT per RECIST v1.1 (Complete Response(CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.).

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Percentage of Participants With Objective Response Rate (ORR)	73.8 percentage of participants Interval 67.4 to 79.6	72.1 percentage of participants Interval 65.6 to 78.0

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study. (up to 24 months)

DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression assessed up to 24 months.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Assess the Anti-tumor Activity: Duration of Response (DoR)	18.1 months Interval 15.2 to This outcome measure data was not available at the analysis cut-off due to insufficient number of participants with events.	8.3 months Interval 6.9 to 11.1

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study.

The DCR is defined as the proportion of patients with a best overall response of CR, PR, or SD assessed up to 24 months.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Assess the Anti-tumor Activity: Disease Control Rate (DCR)	93.0 percentage Interval 88.7 to 96.0	96.7 percentage Interval 93.4 to 98.7

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study.（up to 24 months）

DepOR is defined as the percentage change in tumor shrinkage, based on longest diameter or reconstructed volume, observed at the lowest point (nadir) compared with baseline.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Assess the Anti-tumor Activity: Depth of Response (DepOR)	-44.95 percentage of change from baseline Standard Deviation 21.961	-41.95 percentage of change from baseline Standard Deviation 19.966

SECONDARY outcome

Timeframe: Continuously throughout the study until 28 days after HS-10296 discontinuation.From first dose of study drug up to 28 days after last dose of study drug taken (up to data cut-off (15 Jan 2021)),approximately 2 years.

Safety was assessed by AEs, which included abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.) if the abnormality induced clinical signs or symptoms, needed active intervention, interruption or discontinuation of study medication or was clinically significant. A treatment-emergent AE (TEAE) was defined as an AE observed after starting administration of the study drug. AEs were considered serious (SAEs) if the AE resulted in death, was life threatening, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, resulted in congenital anomaly, or birth defect or required inpatient hospitalization or led to prolongation of hospitalization.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Number of Participants With Adverse Events (AEs)/Serious Adverse Events (SAEs)	211 Participants	213 Participants

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study. (up to 24 months)

Participants had at least one delay in planned treatment due to treatment emergent adverse events.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Number of Participants With Dose Interruptions	36 Participants	53 Participants

SECONDARY outcome

Timeframe: From baseline, then every 6 weeks, until disease progression or discontinuation from study. (up to 24 months)

Participants had at least one reduction in planned treatment dosage due to treatment emergent adverse events. Every participant took 2 pills of HS

-10296 + 1 pill of placebo(experimental arm) or 2pills of placebo + 1pill of Gefitinib (control arm). When a dose reduction was decided by INV, the set of "2 pills of placebo" was decreased resulting in no reduction of active compound in control arm, compliance with dose modification for AEs in Gefitinib's label which includes interruption, discontinuation but reduction.

Outcome measures

Measure	HS-10296 n=214 Participants 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 Participants 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Number of Participants With Dose Reductions	9 Participants	10 Participants

Adverse Events

HS-10296

Serious events: 47 serious events

Other events: 211 other events

Deaths: 54 deaths

Gefitinib

Serious events: 46 serious events

Other events: 213 other events

Deaths: 69 deaths

Serious adverse events

Measure	HS-10296 n=214 participants at risk 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 participants at risk 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Infections and infestations Pneumonia	2.8% 6/214 • Number of events 6 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	3.7% 8/215 • Number of events 8 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Infection	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Paronychia	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Sepsis	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Bronchitis	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Herpes zoster	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Appendicitis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Urinary tract infection	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Skin infections	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Hepatobiliary disorders Hepatic function abnormal	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	4.2% 9/215 • Number of events 9 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Hepatobiliary disorders Drug-induced liver injury	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.93% 2/215 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Hepatobiliary disorders Liver function injury	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	1.4% 3/215 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.93% 2/215 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Spontaneous pneumothorax	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.4% 3/214 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Increased alanine aminotransferase	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	1.9% 4/215 • Number of events 4 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Increased aspartate aminotransferase	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	1.9% 4/215 • Number of events 4 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Increased aminotransferases	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Decreased white blood cell count	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Decreased neutrophil count	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Intracranial hemorrhage	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Epilepsy	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Cerebral infarction	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Headache	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Cerebral hemorrhage	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Hypoglycemia	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Cerebral thrombosis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Atrial fibrillation	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Acute cardiac failure	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Coronary atherosclerosis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Acute myocardial infarction	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Pericardial effusion	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Cardiorespiratory arrest	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Ureteral stones	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Impairment of renal function	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Difficulty urinating	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Nephrolithiasis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Injury, poisoning and procedural complications Humeral fracture	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Injury, poisoning and procedural complications Fall	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Injury, poisoning and procedural complications Complications of hepatobiliary surgery	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Musculoskeletal and connective tissue disorders Back pain	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Injury, poisoning and procedural complications Pathological fracture	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
General disorders Death	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
General disorders Pyrexia	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
General disorders Sudden cardiac death	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Decreased appetite	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hypoproteinemia	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hyponatremia	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Diabetes mellitus	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Diarrhea	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Gastritis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Nervous system disorders Completed suicide	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/214 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.47% 1/215 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Vascular disorders Venous thrombosis of extremities	1.4% 3/214 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Vascular disorders Deep vein thrombosis	0.93% 2/214 • Number of events 2 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Vascular disorders Thrombophlebitis	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Liver cancer	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Eye disorders Cataract	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Eye disorders Rhegmatogenous retinal detachment	0.47% 1/214 • Number of events 1 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	0.00% 0/215 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.

Other adverse events

Measure	HS-10296 n=214 participants at risk 110mg PO once daily HS-10296: Drug: HS-10296 110 mg/55 mg + placebo The initial dose of HS-10296 110 mg once daily can be reduced to 55 mg once daily under specific circumstances. A cycle of treatment is defined as 21 days of once daily treatment. Number of Cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.	Gefitinib n=215 participants at risk 250mg PO once daily Gefitinib: Drug: Gefitinib 250 mg + placebo The initial dose of Gefitinib 250 mg once daily cannot be reduced. A cycle of treatment is defined as 21 days of once daily treatment. Number of cycles: as long as patients are continuing to show clinical benefit, as judged by the Investigator, and in the absence of discontinuation criteria.
Investigations Weight loss	6.5% 14/214 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	16.3% 35/215 • Number of events 35 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Blood bilirubin increased	8.4% 18/214 • Number of events 18 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	15.8% 34/215 • Number of events 34 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations γ-glutamyl transferase increased	8.9% 19/214 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	14.0% 30/215 • Number of events 30 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Blood creatine phosphokinase increased	35.5% 76/214 • Number of events 76 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	9.3% 20/215 • Number of events 20 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations QT interval prolonged	10.7% 23/214 • Number of events 23 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	8.8% 19/215 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Platelet count decreased	22.0% 47/214 • Number of events 47 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	7.9% 17/215 • Number of events 17 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Blood lactate dehydrogenase increased	12.1% 26/214 • Number of events 26 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	6.5% 14/215 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Skin and subcutaneous tissue disorders Erythra	23.4% 50/214 • Number of events 50 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	41.4% 89/215 • Number of events 89 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Skin and subcutaneous tissue disorders Pruritus	6.5% 14/214 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	12.1% 26/215 • Number of events 26 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Dental ulcer	10.3% 22/214 • Number of events 22 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	9.8% 21/215 • Number of events 21 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Nausea	10.7% 23/214 • Number of events 23 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	9.3% 20/215 • Number of events 20 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Emesis	12.1% 26/214 • Number of events 26 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.1% 11/215 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Infections and infestations Upper respiratory infection	19.2% 41/214 • Number of events 41 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	12.1% 26/215 • Number of events 26 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hypokalemia	8.9% 19/214 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	15.3% 33/215 • Number of events 33 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hypoalbuminemia	7.0% 15/214 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	10.7% 23/215 • Number of events 23 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Blood and lymphatic system disorders Anemia	20.1% 43/214 • Number of events 43 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	9.8% 21/215 • Number of events 21 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Bound bilirubin increased	3.3% 7/214 • Number of events 7 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	9.8% 21/215 • Number of events 21 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Blood in urine	6.5% 14/214 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	7.4% 16/215 • Number of events 16 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Serum creatinine increased i	5.1% 11/214 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	6.5% 14/215 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations White blood cells in urine	4.2% 9/214 • Number of events 9 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.6% 12/215 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Weight gain	7.9% 17/214 • Number of events 17 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.1% 11/215 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Blood urea increased	7.5% 16/214 • Number of events 16 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.1% 11/215 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Serum alkaline phosphatase increased	7.0% 15/214 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	4.7% 10/215 • Number of events 10 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Decreased lymphocyte count	5.1% 11/214 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	2.3% 5/215 • Number of events 5 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Investigations Increased Serum creatine phosphokinase MB	6.1% 13/214 • Number of events 13 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	1.4% 3/215 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Constipation	9.3% 20/214 • Number of events 20 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	7.0% 15/215 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Gastroesophageal reflux disease	1.4% 3/214 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.1% 11/215 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Abdominal pain	9.3% 20/214 • Number of events 20 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	1.4% 3/215 • Number of events 3 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Gastrointestinal disorders Pneumonia	7.0% 15/214 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.6% 12/215 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hypocalcemia	8.9% 19/214 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.6% 12/215 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders hyperuricemia	8.9% 19/214 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	4.7% 10/215 • Number of events 10 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Metabolism and nutrition disorders Hypertriglyceridemia	6.1% 13/214 • Number of events 13 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	3.3% 7/215 • Number of events 7 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
General disorders weak	5.6% 12/214 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	7.9% 17/215 • Number of events 17 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
General disorders Influenza like illness	3.3% 7/214 • Number of events 7 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.1% 11/215 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Cardiac disorders Sinus bradycardia	3.7% 8/214 • Number of events 8 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.6% 12/215 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Respiratory, thoracic and mediastinal disorders Cough	8.4% 18/214 • Number of events 18 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	6.0% 13/215 • Number of events 13 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Proteinuria	8.4% 18/214 • Number of events 18 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	8.8% 19/215 • Number of events 19 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Renal and urinary disorders Hematuria	5.1% 11/214 • Number of events 11 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	8.4% 18/215 • Number of events 18 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Musculoskeletal and connective tissue disorders Physical pain	7.0% 15/214 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	2.8% 6/215 • Number of events 6 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Vascular disorders High blood pressure	7.0% 15/214 • Number of events 15 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	5.6% 12/215 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.
Psychiatric disorders Insomnia	5.6% 12/214 • Number of events 12 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.	6.5% 14/215 • Number of events 14 • Serious and Other (Not Including Serious)Adverse Events (AEs) were collected from first dose of study drug up to 28days after last dose of study drug taken (up to data cut-off (15 Jan 2021)), approximately 2 years.

Additional Information

Alison Li

Jiangsu Hansoh Pharmaceutical Group Co., Ltd.

Phone: 86-21-51211850

Email: Alison.li@hspharm.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place