Efficacy and Safety Evaluation of Sintilimab in Patients With Advanced or Metastatic Non-squamous NSCLC

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd. (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03607539
• Collaborator: (none)
• Enrollment: 397
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 34.3
• Patients Per Site Per Month: 11.6

Study Details

Study Description

Brief Summary

Efficacy and Safety Evaluation of IBI308 in Patients with advanced or metastatic Non-squamous NSCLC

Condition or Disease	Intervention/Treatment	Phase
Lung Neoplasms	Drug: Sintilimab; Drug: Pemetrexed; Drug: Platinum; Drug: Placebos	Phase 3

Detailed Description

Sintilimab is expected to increase the PFS from 6 months to 9.2 months. Anti-PD-1 therapy in Chinese non-squamous NSCLC naïve patients will be investigated in this clinical trial.

Additionally the correlation between PD-L1 expression and the response to Sintilimab treatment in Chinese non-squamous NSCLC as well as the role of iRECIST in immune checkpoint inhibitor treatment evaluation will also be assessed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 397 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blinded, Phase III Study of Pemetrexed Plus Platinum Chemotherapy With or Without Sintilimab (IBI308) in First Line Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (Orient-11)
• Actual Study Start Date: Aug 23, 2018
• Actual Primary Completion Date: Nov 15, 2019
• Anticipated Study Completion Date: Jul 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sintilimab in combination with pemetrexed and platinum Injection; dosage form: 10ml: 100mg; frequency: 200mgQ3W (qualer 3 weeks); duration: randomization to the date of the first documented tumor progression per RECIST v1.1 criteria Sintilimab 200mg + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintains	Drug: Sintilimab; 10 mL:100 mg，200mg，Q3W (qualer 3 weeks), day1, I.V.; Other Names: IBI308 ; Drug: Pemetrexed; 500mg/m^2; Q3W (qualer 3 weeks), day1, I.V.; Drug: Platinum; Q3W (qualer 3 weeks), day1, I.V.; first 4 cycles.
Placebo Comparator: Sitilimab Placebo Comparator placebo 2 vials + pemetrexed/ platinum 4 cycles then Sintilimab 200mg + pemetrexed maintains	Drug: Pemetrexed; 500mg/m^2; Q3W (qualer 3 weeks), day1, I.V.; Drug: Platinum; Q3W (qualer 3 weeks), day1, I.V.; first 4 cycles.; Drug: Placebos; 10 mL:100 mg，200mg，Q3W (qualer 3 weeks), day1, I.V.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Independent Radiographic Review Committee (IRRC) [Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)]

   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

Secondary Outcome Measures

1. Overall Survival (OS) [Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)]

   The analysis population consisted of all randomized participants.

2. Objective Response Rate (ORR) by IRRC Assessment [Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)]

   ORR was defined as the percentage of participants in the analysis population who had 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, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR

3. Disease Control Rate (DCR) by IRRC Assessment [Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)]

4. Time to Response (TTR) by IRRC Assessment [Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 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, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The time from first treatment administration to the first incidence of treatment response was reported as the TTR

5. Duration of Response (DOR) by IRRC Assessment [From time of first documented evidence of CR or PR trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria

1. Sign written informed consent before any trial-related processes are implemented;

2. Age ≥ 18 years and <75 years;

3. Life expectancy exceeds 3 months;

4. The investigator confirmed at least one measurable lesion according to RECIST 1.1.

A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if it is confirmed to have progressed;

1. According to the International Lung Cancer Research Association and the American Association for the Classification of Cancer Classification, the 8th edition of the TNM (Tumor Node Metastasis) staging of lung cancer, a histologically or cytologically confirmed locally advanced (IIIB/IIIC phase) that cannot be treated surgically and cannot undergo radical concurrent chemoradiotherapy, Patients with metastatic or recurrent (stage IV) non-squamous NSCLC;

2. Confirmed for patients with EGFR (Epidermal growth factor receptor) or ALK (Anaplastic lymphoma kinase) targeted therapy (documentary evidence of no tumor EGFR-sensitive mutations and no ALK gene rearrangement)

3. The Eastern Cancer Cooperative Group (ECOG) has a performance score of 0 or 1;

4. Have not received any systematic anti-tumor treatment for advanced disease; The patient may have received adjuvant chemotherapy as long as the disease relapses at least 6 months after the last dose of chemotherapy is completed;

5. Adequate hematologic function, defined as absolute neutrophil count ≥1.5×10^{9 /L, platelet count ≥100 ×10}9 /L, hemoglobin ≥9g/dL (no blood transfusion or erythropoietin (EPO) within 7 days) Dependency);

6. Adequate liver function, defined as total bilirubin levels ≤ 1.5 times normal upper limit (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN in all patients, or for recorded liver Patients with metastasis, AST and ALT levels ≤ 5 times ULN;

7. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN or measured or calculated creatinine clearance ≥ 60 ml / min (Cockcroft-Gault formula);

8. Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times normal upper limit (ULN); if the subject is receiving anticoagulant therapy, as long as the PT is used in anticoagulant drugs Within the scope;

9. Female subjects of childbearing age should be negative for urine or serum pregnancy test within 72 hours prior to the first study drug administration (Day 1, Day 1). If the urine pregnancy test results are positive or cannot be confirmed as negative, a blood pregnancy test is required.

10. If there is a risk of conception, male and female patients are required to use high-efficiency contraception (ie, an annual failure rate of less than 1%) and continue until at least 180 days after stopping the trial treatment; Note: If abstinence is the usual lifestyle of the subject and the preferred method of contraception, abstinence can be accepted as a method of contraception.

Exclusion criteria:

1. Histological squamous cell-dominated NSCLC; Mixed cell types must distinguish between dominant cell morphology, and if small cell types are present, the subject is not eligible for inclusion;

2. Currently participating in interventional clinical research or treatment, or receiving other research drugs or using research equipment within 4 weeks before the first dose;

3. Previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or against another stimulatory or synergistic inhibition of T cell receptors [eg CTLA-4 (Cytotoxic T lymphocyte antigen-4), OX-40 (also called CD134, cluster of differentiation134), CD137] agent;

4. Received a traditional Chinese medicine with anti-tumor effect, or an immunomodulatory drug (thymosin, interferon, interleukin) within 2 weeks before the first dose, or received major surgery within 3 weeks before the first dose;

5. Pulmonary radiation therapy of >30 Gy within 6 months prior to the first dose;

6. Completed palliative radiotherapy within 7 days prior to the first dose;

7. Clinical active diverticulitis, abdominal abscess, gastrointestinal obstruction and peritoneal metastasis;

8. Have received a physical organ or blood system transplant;

9. There is clinically uncontrollable pleural effusion/peritoneal effusion;

10. known to have severe allergic reactions (≥3 grade) to the active ingredients of Sintilimab, pemetrexed, cisplatin, carboplatin and or any excipients;

11. Active autoimmune diseases requiring systemic treatment (eg, using a disease-modifying drug, corticosteroid or immunosuppressant) within 2 years prior to the first dose. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatments;

12. Diagnosis of immunodeficiency or study of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study.

Physiological doses of corticosteroids (≤10 mg/day of prednisone or equivalent) are permitted;

1. Has not fully recovered from the toxicity and/or complications caused by any intervention before starting treatment (ie, ≤1 or reaching baseline, excluding fatigue or alopecia);

2. Other malignant tumors were diagnosed within 5 years prior to the first dose, with the exception of radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radically resected carcinoma in situ;

3. Active central nervous system (CNS) metastasis and / or cancerous meningitis. Patients with treated brain metastases who have remained clinically stable for at least 2 weeks and have no new or advanced brain metastases may be enrolled and discontinued hormone therapy 3 days prior to the first study drug. Patients with known untreated, asymptomatic brain metastases can be enrolled, but regular imaging assessments of the brain must be performed.

4. There is a history of (non-infectious) pneumonia requiring steroid therapy or the presence of interstitial lung disease 1 year before the first dose;

5. There are active infections that require systemic treatment;

6. Subjects who are unable or unwilling to receive folic acid or vitamin B12 supplementation;

7. There are known cases of mental illness or substance abuse that may have an impact on compliance with the test requirements;

8. A history of human immunodeficiency virus (HIV) infection (ie, HIV 1/2 antibody positive) is known.

9. Untreated active hepatitis B;

Note: Controlled (treated) hepatitis B subjects also meet the inclusion criteria if the following criteria are met:

At least 4 weeks of HBV (Hepatitis B virus) antiviral therapy must have been received prior to the first dose of study drug, and the HBV viral load is <1000 copies/ml (200 IU/ml). Subjects who are receiving HBV therapy and have a viral load of <1000 copies/ml (200 IU/ml) should receive antiviral therapy throughout the study treatment period.

For subjects with anti-HBc (hepatitis B core antigen)(+), HBsAg(-), anti-HBs(-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but viral reactivation is closely monitored;

1. Active HCV (Hepatitis C virus)-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection);

2. Vaccination of live vaccine within 30 days before the first dose (1st cycle, 1st day); Note: Inactivated virus vaccines for seasonal influenza, injectable drugs are permitted; however, live attenuated influenza vaccines (such as FluMist®) are not allowed for intranasal administration;

3. There may be a history of illness or disease evidence, treatment or laboratory abnormalities that may interfere with the subject's full participation in the study, or the investigator believes that participating in the study is not in the best interests of the subject, including dialysis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-Sen University Cancer Center	Guangzhou		China

Sponsors and Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.

Investigators

• Principal Investigator: Li Zhang, Doctor, SunYat-senUniversity

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 9, 2019

More Information

Publications

None provided.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03607539
• Other Study ID Numbers: CIBI308C302
• First Posted: Jul 31, 2018
• Last Update Posted: Feb 16, 2021
• Last Verified: Jan 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lung Neoplasms; Pemetrexed

Study Results

Participant Flow

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Period Title: Overall Study
STARTED	266	131
COMPLETED	0	0
NOT COMPLETED	266	131

Baseline Characteristics

Arm/Group Title	Sintilimab Combination	Placebo Combination	Total
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w	Total of all reporting groups
Overall Participants	266	131	397
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.9 (8.35)	59.5 (8.73)	59.8 (8.47)
Sex: Female, Male (Count of Participants)
Female	62 23.3%	32 24.4%	94 23.7%
Male	204 76.7%	99 75.6%	303 76.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	266 100%	131 100%	397 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Programmed Cell Death-Ligand(PD-L1) Tumor Proportion Score(TPS) (Count of Participants)
PD-L1 <1% (measured by the tumor proportion score [TPS])	85 32%	44 33.6%	129 32.5%
PD-L1 ≥ 1% (measured by the tumor proportion score[TPS])	181 68%	87 66.4%	268 67.5%
Platinum Chemotherapy (Count of Participants)
Cisplatin	71 26.7%	33 25.2%	104 26.2%
Carboplatin	195 73.3%	98 74.8%	293 73.8%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Independent Radiographic Review Committee (IRRC)
Description	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
Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Median (95% Confidence Interval) [Months]	8.9	5.0

2. Secondary Outcome

Title	Overall Survival (OS)
Description	The analysis population consisted of all randomized participants.
Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Median (95% Confidence Interval) [Months]	NA	NA

3. Secondary Outcome

Title	Objective Response Rate (ORR) by IRRC Assessment
Description	ORR was defined as the percentage of participants in the analysis population who had 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, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by IRC was reported as the ORR
Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Number (95% Confidence Interval) [Percentage of Participants]	51.9 19.5%	29.8 22.7%

4. Secondary Outcome

Title	Disease Control Rate (DCR) by IRRC Assessment
Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Number (95% Confidence Interval) [Percentage of Participants]	86.8 32.6%	75.6 57.7%

5. Secondary Outcome

Title	Time to Response (TTR) by IRRC Assessment
Description	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, which was modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The time from first treatment administration to the first incidence of treatment response was reported as the TTR
Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Median (Full Range) [Months]	1.51	2.63

6. Secondary Outcome

Title	Duration of Response (DOR) by IRRC Assessment
Time Frame	From time of first documented evidence of CR or PR trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab Combination	Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w	Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
Measure Participants	266	131
Median (95% Confidence Interval) [Months]	NA	5.52

Adverse Events

Time Frame	Trough Database Cutoff Date of 15-Nov-2019 (Up to approximately 16 months)
Adverse Event Reporting Description	The incidence (frequency) and severity (according to NCI CTCAE Version 4.03) of adverse events (AEs). Population: All participants receiving ≥1 dose of randomized study drug. 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.
Arm/Group Title	Sintilimab Combination		Placebo Combination
Arm/Group Description	Sintilimab 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then sintilimab 200mg, pemetrexed 500mg/m2 IV infusion q3w		Placebo 200mg, pemetrexed 500mg/m2, cisplatin 75mg/m2 or carboplatin AUC 5 IV infusion q3w for 4 cycles, then placebo, pemetrexed 500mg/m2 IV infusion q3w
All Cause Mortality
	Sintilimab Combination		Placebo Combination
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/266 (19.2%)		39/131 (29.8%)
Serious Adverse Events
	Sintilimab Combination		Placebo Combination
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/266 (28.2%)		39/131 (29.8%)
Blood and lymphatic system disorders
Anaemia	12/266 (4.5%)		4/131 (3.1%)
Thrombocytopenia	2/266 (0.8%)		0/131 (0%)
Febrile neutropenia	1/266 (0.4%)		0/131 (0%)
Lymphadenopathy	1/266 (0.4%)		0/131 (0%)
Cardiac disorders
Atrial fibrillation	2/266 (0.8%)		0/131 (0%)
Cardiac failure	2/266 (0.8%)		1/131 (0.8%)
Cardiovascular disorder	1/266 (0.4%)		0/131 (0%)
Immune-mediated myocarditis	1/266 (0.4%)		0/131 (0%)
Pericardial effusion	1/266 (0.4%)		0/131 (0%)
Supraventricular tachycardia	1/266 (0.4%)		0/131 (0%)
Palpitations	0/266 (0%)		1/131 (0.8%)
Pericarditis constrictive	0/266 (0%)		1/131 (0.8%)
Gastrointestinal disorders
Nausea	3/266 (1.1%)		0/131 (0%)
Abdominal pain	2/266 (0.8%)		0/131 (0%)
Upper gastrointestinal haemorrhage	2/266 (0.8%)		0/131 (0%)
Vomiting	2/266 (0.8%)		0/131 (0%)
Diarrhoea	1/266 (0.4%)		0/131 (0%)
Pancreatitis acute	1/266 (0.4%)		0/131 (0%)
Haemorrhoids	0/266 (0%)		1/131 (0.8%)
General disorders
Asthenia	1/266 (0.4%)		0/131 (0%)
Chest discomfort	1/266 (0.4%)		0/131 (0%)
Chest pain	1/266 (0.4%)		0/131 (0%)
Oedema peripheral	1/266 (0.4%)		0/131 (0%)
Pyrexia	1/266 (0.4%)		1/131 (0.8%)
Hepatobiliary disorders
Hepatic function abnormal	5/266 (1.9%)		0/131 (0%)
Infections and infestations
Pneumonia	7/266 (2.6%)		6/131 (4.6%)
Erysipelas	1/266 (0.4%)		0/131 (0%)
Febrile infection	1/266 (0.4%)		0/131 (0%)
Gastrointestinal infection	1/266 (0.4%)		0/131 (0%)
Herpes zoster	1/266 (0.4%)		0/131 (0%)
Purulent pericarditis	1/266 (0.4%)		0/131 (0%)
Respiratory tract infection	1/266 (0.4%)		0/131 (0%)
Enteritis infectious	0/266 (0%)		1/131 (0.8%)
Infectious pleural effusion	0/266 (0%)		1/131 (0.8%)
Myelitis	0/266 (0%)		1/131 (0.8%)
Peripheral nerve infection	0/266 (0%)		1/131 (0.8%)
Pharyngitis	0/266 (0%)		1/131 (0.8%)
Upper respiratory tract infection	0/266 (0%)		2/131 (1.5%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/266 (0%)		1/131 (0.8%)
Spinal compression fracture	0/266 (0%)		1/131 (0.8%)
Investigations
Platelet count decreased	12/266 (4.5%)		8/131 (6.1%)
Lymphocyte count decreased	3/266 (1.1%)		0/131 (0%)
Neutrophil count decreased	3/266 (1.1%)		2/131 (1.5%)
White blood cell count decreased	3/266 (1.1%)		2/131 (1.5%)
Acid base balance abnormal	1/266 (0.4%)		0/131 (0%)
Alanine aminotransferase increased	1/266 (0.4%)		0/131 (0%)
Aspartate aminotransferase increased	1/266 (0.4%)		0/131 (0%)
Eosinophil count increased	1/266 (0.4%)		0/131 (0%)
Gamma-glutamyltransferase increased	1/266 (0.4%)		0/131 (0%)
Haemoglobin decreased	1/266 (0.4%)		0/131 (0%)
Troponin I increased	1/266 (0.4%)		0/131 (0%)
Blood bilirubin increased	0/266 (0%)		1/131 (0.8%)
Metabolism and nutrition disorders
Hypoalbuminaemia	1/266 (0.4%)		0/131 (0%)
Hypophagia	1/266 (0.4%)		0/131 (0%)
Diabetes mellitus	0/266 (0%)		1/131 (0.8%)
Hypokalaemia	0/266 (0%)		1/131 (0.8%)
Hypoproteinaemia	0/266 (0%)		1/131 (0.8%)
Musculoskeletal and connective tissue disorders
Muscular weakness	1/266 (0.4%)		0/131 (0%)
Myositis	1/266 (0.4%)		0/131 (0%)
Intervertebral disc disorder	1/266 (0.4%)		0/131 (0%)
Nervous system disorders
Brain oedema	1/266 (0.4%)		0/131 (0%)
Cerebral haemorrhage	1/266 (0.4%)		0/131 (0%)
Cerebral artery embolism	0/266 (0%)		1/131 (0.8%)
Cerebral infarction	0/266 (0%)		2/131 (1.5%)
Cerebrovascular accident	0/266 (0%)		1/131 (0.8%)
Haemorrhage intracranial	0/266 (0%)		1/131 (0.8%)
Psychiatric disorders
Confusional state	1/266 (0.4%)		0/131 (0%)
Respiratory, thoracic and mediastinal disorders
Immune-mediated pneumonitis	6/266 (2.3%)		1/131 (0.8%)
Pneumonitis	5/266 (1.9%)		0/131 (0%)
Haemoptysis	3/266 (1.1%)		0/131 (0%)
Pleural effusion	3/266 (1.1%)		0/131 (0%)
Interstitial lung disease	2/266 (0.8%)		1/131 (0.8%)
Respiratory failure	2/266 (0.8%)		0/131 (0%)
Asphyxia	1/266 (0.4%)		0/131 (0%)
Bronchitis chronic	1/266 (0.4%)		0/131 (0%)
Hiccups	1/266 (0.4%)		0/131 (0%)
Obstructive airways disorder	1/266 (0.4%)		0/131 (0%)
Pneumothorax	1/266 (0.4%)		0/131 (0%)
Dyspnoea	0/266 (0%)		1/131 (0.8%)
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	1/266 (0.4%)		0/131 (0%)
Toxic epidermal necrolysis	1/266 (0.4%)		0/131 (0%)
Dermatomyositis	0/266 (0%)		1/131 (0.8%)
Vascular disorders
Embolism arterial	1/266 (0.4%)		0/131 (0%)
Superior vena cava syndrome	0/266 (0%)		1/131 (0.8%)
Other (Not Including Serious) Adverse Events
	Sintilimab Combination		Placebo Combination
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	265/266 (99.6%)		131/131 (100%)
Blood and lymphatic system disorders
Anaemia	197/266 (74.1%)		103/131 (78.6%)
Endocrine disorders
Hypothyroidism	28/266 (10.5%)		14/131 (10.7%)
Hyperthyroidism	15/266 (5.6%)		4/131 (3.1%)
Gastrointestinal disorders
Nausea	108/266 (40.6%)		55/131 (42%)
Vomiting	77/266 (28.9%)		41/131 (31.3%)
Constipation	71/266 (26.7%)		42/131 (32.1%)
Diarrhoea	35/266 (13.2%)		15/131 (11.5%)
Abdominal distension	18/266 (6.8%)		12/131 (9.2%)
General disorders
Asthenia	87/266 (32.7%)		42/131 (32.1%)
Pyrexia	56/266 (21.1%)		19/131 (14.5%)
Oedema peripheral	21/266 (7.9%)		9/131 (6.9%)
Chest discomfort	15/266 (5.6%)		5/131 (3.8%)
Hepatobiliary disorders
Hepatic function abnormal	20/266 (7.5%)		5/131 (3.8%)
Infections and infestations
Upper respiratory tract infection	27/266 (10.2%)		12/131 (9.2%)
Pneumonia	22/266 (8.3%)		15/131 (11.5%)
Urinary tract infection	13/266 (4.9%)		8/131 (6.1%)
Investigations
Neutrophil count decreased	189/266 (71.1%)		82/131 (62.6%)
White blood cell count decreased	180/266 (67.7%)		84/131 (64.1%)
Platelet count decreased	113/266 (42.5%)		41/131 (31.3%)
Aspartate aminotransferase increased	109/266 (41%)		51/131 (38.9%)
Alanine aminotransferase increased	108/266 (40.6%)		51/131 (38.9%)
Lymphocyte count decreased	34/266 (12.8%)		10/131 (7.6%)
Gamma-glutamyltransferase increased	33/266 (12.4%)		14/131 (10.7%)
Blood glucose increased	27/266 (10.2%)		8/131 (6.1%)
Weight increased	24/266 (9%)		4/131 (3.1%)
Amylase increased	22/266 (8.3%)		13/131 (9.9%)
Blood creatinine increased	22/266 (8.3%)		11/131 (8.4%)
Weight decreased	22/266 (8.3%)		23/131 (17.6%)
Blood alkaline phosphatase increased	17/266 (6.4%)		7/131 (5.3%)
Haemoglobin decreased	16/266 (6%)		6/131 (4.6%)
Blood thyroid stimulating hormone increased	15/266 (5.6%)		5/131 (3.8%)
Metabolism and nutrition disorders
Decreased appetite	101/266 (38%)		41/131 (31.3%)
Hypoalbuminaemia	53/266 (19.9%)		22/131 (16.8%)
Hypokalaemia	28/266 (10.5%)		12/131 (9.2%)
Hyponatraemia	28/266 (10.5%)		16/131 (12.2%)
Hypophagia	20/266 (7.5%)		13/131 (9.9%)
Hypoproteinaemia	16/266 (6%)		14/131 (10.7%)
Hyperglycaemia	15/266 (5.6%)		6/131 (4.6%)
Hypercholesterolaemia	14/266 (5.3%)		10/131 (7.6%)
Hypertriglyceridaemia	12/266 (4.5%)		7/131 (5.3%)
Musculoskeletal and connective tissue disorders
Back pain	12/266 (4.5%)		7/131 (5.3%)
Pain in extremity	10/266 (3.8%)		7/131 (5.3%)
Nervous system disorders
Dizziness	28/266 (10.5%)		8/131 (6.1%)
Headache	15/266 (5.6%)		5/131 (3.8%)
Hypoaesthesia	12/266 (4.5%)		8/131 (6.1%)
Psychiatric disorders
Insomnia	30/266 (11.3%)		9/131 (6.9%)
Renal and urinary disorders
Proteinuria	28/266 (10.5%)		13/131 (9.9%)
Haematuria	12/266 (4.5%)		9/131 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	33/266 (12.4%)		16/131 (12.2%)
Productive cough	19/266 (7.1%)		17/131 (13%)
Hiccups	16/266 (6%)		6/131 (4.6%)
Dyspnoea	14/266 (5.3%)		9/131 (6.9%)
Tachypnoea	14/266 (5.3%)		8/131 (6.1%)
Haemoptysis	11/266 (4.1%)		8/131 (6.1%)
Skin and subcutaneous tissue disorders
Rash	38/266 (14.3%)		18/131 (13.7%)
Vascular disorders
Hypertension	14/266 (5.3%)		4/131 (3.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.