Trial Outcomes & Findings for Sintilimab in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Therapy for Advanced or Metastatic Squamous NSCLC (NCT NCT03629925)

Last Updated: 2023-02-28

Results Overview

PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by BIRRC was reported for each arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

357 participants

Primary outcome timeframe

Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Results posted on

2023-02-28

Participant Flow

primary analysis data cutoff date: 15 October 2019; updated analysis data cutoff date: 25 March 2020

Participant milestones

Participant milestones
Measure	Sintilimab+ Gemcitabine Plus Platinum Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Overall Study STARTED	179	178
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	179	178

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Sintilimab in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line Therapy for Advanced or Metastatic Squamous NSCLC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Total n=357 Participants Total of all reporting groups
Age, Continuous	61.9 Years STANDARD_DEVIATION 7.47 • n=5 Participants	61.0 Years STANDARD_DEVIATION 7.85 • n=7 Participants	61.5 Years STANDARD_DEVIATION 7.66 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	163 Participants n=5 Participants	164 Participants n=7 Participants	327 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	179 Participants n=5 Participants	178 Participants n=7 Participants	357 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	179 Participants n=5 Participants	178 Participants n=7 Participants	357 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
Region of Enrollment China	179 Participants n=5 Participants	178 Participants n=7 Participants	357 Participants n=5 Participants

PRIMARY outcome

Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
PFS(Progression Free Survival)	5.5 months Interval 4.9 to 6.8	4.9 months Interval 4.8 to 5.0

SECONDARY outcome

Timeframe: Through Database Cutoff Date of 15 October 2019 (up to approximately 13 months)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each arm.

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
OS (Overall Survival)	NA Months Median OS and upper and lower limit of 95%CI not reached due to insufficient number of participants with events	NA Months Median OS and upper and lower limit of 95%CI not reached due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by BIRRC was reported as the ORR for each arm.

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
ORR(Objective Response Rate)	44.7 Percentage of Participants Interval 37.27 to 52.29	35.4 Percentage of Participants Interval 28.38 to 42.9

SECONDARY outcome

Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters \[SOD\] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The time from first treatment administration to the first incidence of treatment response was reported as the TTR for each arm.

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=80 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=63 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
TTR (Time to Response)	1.41 Months Interval 1.2 to 11.1	1.41 Months Interval 1.2 to 2.9

SECONDARY outcome

Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD\]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BIRRC was reported as the DCR for each arm.

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
DCR (Disease Control Rate)	86.0 Percentage of Participants Interval 80.08 to 90.75	80.3 Percentage of Participants Interval 73.73 to 85.91

SECONDARY outcome

Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BIRRC assessment. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each arm.

Outcome measures

Outcome measures
Measure	Sintilimab+ Gemcitabine Plus Platinum n=80 Participants Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=63 Participants Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
DOR (Duration of Response)	6.05 Months Interval 4.73 to 9.63	5.06 Months Interval 3.71 to 5.55

Adverse Events

Sintilimab+ Gemcitabine Plus Platinum

Serious events: 90 serious events

Other events: 179 other events

Deaths: 65 deaths

Placebo+Gemcitabine Plus Platinum

Serious events: 80 serious events

Other events: 178 other events

Deaths: 71 deaths

Serious adverse events

Other adverse events

Additional Information

YiBo

Innovent Biologics (Suzhou) Co., Ltd

Phone: +86 13382419112

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 participants at risk Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 participants at risk Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Investigations Platelet count decreased	17.9% 32/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	18.0% 32/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations White blood cell count decreased	3.9% 7/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	4.5% 8/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Neutrophil count decreased	2.8% 5/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	2.8% 5/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Amylase increased	1.7% 3/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Lipase increased	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Infections and infestations Pneumonia	12.3% 22/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.9% 14/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Infections and infestations Enteritis infectious	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Infections and infestations Sepsis	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Haemoptysis	4.5% 8/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	2.2% 4/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.2% 4/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Immune-mediated pneumonitis	1.7% 3/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Anaemia	3.4% 6/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	3.4% 6/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Bone marrow failure	1.7% 3/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Thrombocytopenia	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	1.1% 2/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Pyrexia	2.8% 5/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	1.7% 3/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Asthenia	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Death	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	2.8% 5/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Skin and subcutaneous tissue disorders Rash	2.8% 5/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hyponatraemia	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	1.7% 3/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Hepatobiliary disorders Hepatic function abnormal	1.1% 2/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Alanine aminotransferase increased	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Aspartate aminotransferase increased	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood thyroid stimulating hormone decreased	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Platelet count increased	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood creatine phosphokinase increased	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood creatinine increased	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Cough	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary artery thrombosis	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Bronchostenosis	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Febrile neutropenia	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	1.1% 2/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Leukopenia	0.56% 1/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.00% 0/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Agranulocytosis	0.00% 0/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	0.56% 1/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.

Other adverse events
Measure	Sintilimab+ Gemcitabine Plus Platinum n=179 participants at risk Sintilimab 200mg IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.	Placebo+Gemcitabine Plus Platinum n=178 participants at risk Placebo IV, Gemcitabine 1.0 g/m\^2 IV and Cisplatin 75 mg/m\^2 or Carboplatin AUC 5 mg/ml/min IV Q3W.
Investigations White blood cell count decreased	88.8% 159/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	86.0% 153/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Neutrophil count decreased	83.2% 149/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	82.0% 146/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Platelet count decreased	72.6% 130/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	70.2% 125/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Aspartate aminotransferase increased	24.0% 43/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	19.7% 35/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Alanine aminotransferase increased	23.5% 42/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	24.7% 44/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Weight decreased	19.6% 35/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	13.5% 24/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Lymphocyte count decreased	9.5% 17/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.9% 14/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood creatinine increased	8.9% 16/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.3% 13/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Amylase increased	7.8% 14/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	3.4% 6/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood albumin decreased	6.7% 12/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	3.9% 7/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood glucose increased	6.1% 11/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.9% 14/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Gamma-glutamyltransferase increased	5.6% 10/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	6.7% 12/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Weight increased	5.6% 10/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	5.1% 9/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Investigations Blood bilirubin increased	5.0% 9/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	6.2% 11/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Blood and lymphatic system disorders Anaemia	93.3% 167/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	90.4% 161/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Gastrointestinal disorders Nausea	39.7% 71/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	41.0% 73/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Gastrointestinal disorders Vomiting	32.4% 58/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	34.3% 61/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Gastrointestinal disorders Constipation	30.7% 55/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	25.3% 45/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Gastrointestinal disorders Diarrhoea	14.0% 25/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	10.7% 19/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Gastrointestinal disorders Abdominal distension	7.8% 14/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	9.0% 16/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Decreased appetite	31.8% 57/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	29.8% 53/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypophagia	15.6% 28/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	8.4% 15/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypokalaemia	14.5% 26/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	9.6% 17/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hyponatraemia	14.5% 26/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	18.5% 33/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypoalbuminaemia	14.0% 25/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	11.8% 21/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypoproteinaemia	12.3% 22/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	8.4% 15/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypocalcaemia	6.1% 11/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	3.9% 7/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hypochloraemia	5.0% 9/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.3% 13/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Metabolism and nutrition disorders Hyperglycaemia	4.5% 8/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	7.3% 13/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Asthenia	33.5% 60/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	33.7% 60/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Pyrexia	29.1% 52/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	26.4% 47/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Chest discomfort	7.3% 13/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	5.6% 10/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
General disorders Oedema peripheral	5.0% 9/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	1.7% 3/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Haemoptysis	15.1% 27/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	12.4% 22/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Cough	9.5% 17/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	10.7% 19/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Productive cough	5.0% 9/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	5.1% 9/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.4% 6/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	6.7% 12/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Respiratory, thoracic and mediastinal disorders Hiccups	3.4% 6/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	5.1% 9/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Skin and subcutaneous tissue disorders Rash	23.5% 42/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	14.6% 26/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.
Skin and subcutaneous tissue disorders Pruritus	12.3% 22/179 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.	5.6% 10/178 • Through database cutoff date of 25 March 2020 (up to approximately 18 months) All adverse events, including serious adverse events, will be collected since the consent form is signed until 90th day after last administration of investigation products, either observed by investigator or by the spontaneous reported by subjects.