Study of IBI308 With Advanced/Metastatic Esophageal Squamous Cell Carcinoma After Failure of First-line Treatment

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03116152
• Collaborator: (none)
• Enrollment: 190
• Location: 1
• Arms: 2
• Actual Duration (Months): 28.7
• Patients Per Site Per Month: 6.6

Study Details

Study Description

Brief Summary

Efficacy and safety evaluation of IBI308 versus paclitaxel/irinotecan in patients with advanced/metastatic esophageal squamous cell carcinoma after failure of first-line treatment: a randomized, open-label, multicenter, phase 2 study

Condition or Disease	Intervention/Treatment	Phase
Esophageal Squamous Cell Carcinoma	Biological: IBI308; Drug: paclitaxel/ irinotecan	Phase 2

Detailed Description

Efficacy and safety evaluation of IBI308 versus paclitaxel/irinotecan in patients with advanced/metastatic esophageal squamous cell carcinoma after failure of first-line treatment: a randomized, open-label, multicenter, phase 2 study (ORIENT-2)

Study Design

• Study Type: Interventional
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety Evaluation of IBI308 Versus Paclitaxel/Irinotecan in Patients With Advanced/Metastatic Esophageal Squamous Cell Carcinoma After Failure of First-line Treatment: a Randomized, Open-label, Multicenter, Phase 2 Study (ORIENT-2)
• Actual Study Start Date: May 10, 2017
• Actual Primary Completion Date: Oct 2, 2019
• Actual Study Completion Date: Oct 2, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IBI308 IBI308 200mg Intravenous drip every three weeks	Biological: IBI308; IBI308 200mg Intravenous drip every three weeks；
Active Comparator: paclitaxel/irinotecan paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks	Drug: paclitaxel/ irinotecan; paclitaxel 175mg/㎡ Intravenous drip every three weeks or irinotecan 180mg/㎡ Intravenous drip every two weeks

Outcome Measures

Primary Outcome Measures

1. Overall Survival [Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)]

   OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.

Secondary Outcome Measures

1. Progression-free Survival [Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)]

   PFS was defined as the time from randomization to the first documented progressive disease (PD) as determined by the investigator, 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. Unequivocal progression of non-target leisions and the appearance of ≥1 new lesions were also considered as PD.

2. Objective Response Rate [Through Final Analysis data cut-off date of 2-August-2019 (up to approximately 26 months)]

   Objective Response Rate (ORR) was defined as the proportion of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment.

3. Duration of Response [Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)]

   Duration of response (DoR) was defined as the time from the date of the first investigator-assessed response (CR or PR) to the date of subsequent investigator-assessed PD or death, whichever is earlier.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Histologically or cytologically confirmed locally advanced unresectable or metastatic esophageal squamous cell carcinoma (excluding mixed adenosquamous carcinoma and other pathological types).

2. Imaging evidence (e.g. CT scan) or clinical evidence (e.g. cytological report of new ascites or pleural effusion) of disease progression during or after first-line chemotherapy; Subjects have to receive at least one dose of first-line treatment, permitting discontinuation or dose reduction of one drug or exchange of fluorouracil drugs used during first-line treatment, and patients discontinuing first-line treatment due to intolerable toxicity are allowed to be enrolled; Neoadjuvant or adjuvant therapy (chemotherapy or chemo-radiotherapy) should be regarded as first-line treatment if there is disease progression during treatment or within 6 months after treatment discontinuation.

3. At least one measurable lesion according to RECIST v1.1.

4. ECOG PS score of 0 or 1.

5. Subjects who have signed the written informed consent form and are able to follow the visit schedule and relevant procedures as specified in the study protocol.

6. Age ≥ 18 and ≤ 75 years.

7. Life expectancy ≥ 12 weeks.

8. Female subjects of childbearing potential or male subjects with sexual partners of childbearing potential should use effective contraception throughout and within 6 months after treatment.

9. Adequate organ and bone marrow functions, defined as follows:

• Hematology: absolute neutrophil count (ANC) ≥ 1.5×10^{9/L; Platelet (PLT) count ≥ 100×10}9/L; Hemoglobin (HGB) ≥ 9.0 g/dL.

• Liver function: serum total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; Serum albumin ≥ 28 g/L.

• Renal function: Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance (Ccr) ≥ 40 mL/min (calculated using the standard Cockcroft -Gault formula):

• Females: CrCl = (140-age) x body weight (kg) x 0.85/(72 x serum creatinine (mg/dL))

• Males: CrCl = (140-age) x body weight (kg) x 1.00/(72 x serum creatinine (mg/dL))

Exclusion Criteria:

1. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody.

2. Concurrent participation in another interventional clinical study, except for observational (non-interventional) clinical studies or in the follow-up phase of an interventional study.

3. Receipt of any investigational products within 4 weeks prior to the first dose of study treatment.

4. Receipt of the last dose of anti-tumor therapy (chemotherapy, targeted therapy, tumor immunotherapy, tumor embolization) within 3 weeks prior to the first dose of study treatment.

5. Radiotherapy within 4 weeks prior to the first dose of study treatment.

6. Receipt of immunosuppressive agents within 4 weeks prior to the first dose of study treatment, excluding topical glucocorticoids for intranasal, inhalation or other routes of administration, or physiological doses of systemic glucocorticoids (i.e., no more than 10 mg/day prednisone or equivalent doses of other glucocorticoids).

7. Receipt of a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or planned receipt of a live attenuated vaccine during the study.

8. Subjects who have undergone major surgical procedures (craniotomy, thoracotomy or laparotomy) within 4 weeks prior to the first dose of study treatment or have unhealed wound, ulcers or bone fracture.

9. Presence of toxicities induced by previous anti-tumor therapy that have not recovered to Grade 0 or 1 as assessed per NCI CTCAE 4.03 (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) prior to the first dose of study treatment, excluding alopecia, and non-clinically significant and asymptomatic laboratory abnormalities.

10. Known symptomatic metastases to central nervous system (CNS) and/or carcinomatous meningitis. Subjects previously treated for brain metastasis are eligible for the study provided the brain metastasis has remained stable for at least 4 weeks before first dose of study treatment; Neurological symptoms must be recovered to grade 0 or 1 as per NCI CTCAE version 4.03.

11. Active, known or suspected autoimmune diseases (refer to Appendix 6) or a history of such disease in the past 2 years (patients with vitiligo, psoriasis, alopecia or Grave's disease requiring no systemic treatment in the past 2 years, patients with hypothyroidism requiring only thyroid hormone replacement therapy and patients with type I diabetes requiring only insulin replacement therapy can be enrolled).

12. Known history of primary immunodeficiency.

13. Known active tuberculosis (TB).

14. Known history of allotransplantation and allogeneic hematopoietic stem cell transplantation.

15. Known hypersensitivity to any component of the monoclonal antibody, paclitaxel or irinotecan formulation.

16. Uncontrolled concurrent diseases, including but not limited to:

• HIV infection (HIV antibody positive).

• Active or clinically uncontrolled severe infections.

• Symptomatic congestive heart failure (New York Heart Association Class II-IV) or symptomatic or poorly controlled arrhythmia.

• Uncontrolled arterial hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg) despite standard treatment.

• Any arterial thromboembolism events within 6 months prior to inclusion for treatment, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attacks.

• Significant malnutrition, if intravenous nutrient solution supplement is required; Except for malnutrition corrected for more than 4 weeks before first dose of study treatment.

• Tumor invasion into surrounding vital organs (e.g., aorta and trachea) or a risk for esophagotracheal fistula or esophagopleural fistula.

• Post esophageal or intratracheal stenting.

• History of deep vein thrombosis (DVT), pulmonary embolism, or any other serious thromboembolism within 3 months prior to enrollment (implanted venous access port or catheter-related thrombosis, or superficial venous thrombosis is not considered as "serious"thromboembolism).

• Uncontrolled metabolic disorders or other non-malignant organic or systemic diseases or reactions secondary to cancer, which can result in high medical risks and/or uncertainty in survival evaluations.

• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh class B or even more severe cirrhosis.

• History of intestinal obstruction or the following diseases: inflammatory bowel disease or extensive bowel resection (partial colectomy or extensive resection of the small intestine, concurrent chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.

• Other acute or chronic diseases, mental disorders or abnormal laboratory findings that may lead to the following results: increase risks associated with study participation in the study or use of the study drug, or interfere with the interpretation of study results, and render the patient ineligible for the study at the investigator's discretion.

1. Known acute or chronic active hepatitis B (HBsAg positive and HBV DNA ≥200 IU/mL or ≥ 10^3 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and positive for HCV RNA test).

2. History of gastrointestinal perforation and/or fistula within 6 months prior to study inclusion.

3. Presence of interstitial lung disease.

4. Clinically uncontrollable effusion of the third space, such as pleural effusion and ascites that can not be controlled by drainage or other methods before enrollment.

5. History of other primary malignancies, excluding:

• A malignancy with complete remission for at least 2 years before enrollment and requiring no other treatment during the study;

• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of relapse;

• Adequately treated carcinoma in situ without evidence of relapse.

1. Pregnant or breastfeeding women.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Fifth Medical Center of PLA Ceneral Hospital	Beijing	Beijing	China	10071

Sponsors and Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 19, 2019

More Information

Publications

None provided.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03116152
• Other Study ID Numbers: CIBI308A201
• First Posted: Apr 14, 2017
• Last Update Posted: Feb 3, 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: Carcinoma; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Paclitaxel; Irinotecan

Study Results

Participant Flow

Pre-assignment Detail	253 enrolled. 190 randomized. Non-randomized reasons: 55 no longer met study criteria, 4 withdrew consent, 4 other. 181 treated (94 sintilimab, 87 chemotherapy).

Arm/Group Title	Sintilimab	Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks	paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks
Period Title: Overall Study
STARTED	95	95
Treated	94	87
COMPLETED	4	0
NOT COMPLETED	91	95

Baseline Characteristics

Arm/Group Title	Sintilimab	Chemotherapy	Total
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks	paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks	Total of all reporting groups
Overall Participants	95	95	190
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	74 77.9%	75 78.9%	149 78.4%
>=65 years	21 22.1%	20 21.1%	41 21.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.8 (7.23)	59.4 (7.06)	59.1 (7.13)
Sex: Female, Male (Count of Participants)
Female	7 7.4%	11 11.6%	18 9.5%
Male	88 92.6%	84 88.4%	172 90.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	95 100%	95 100%	190 100%
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%
Region of Enrollment (participants) [Number]
China	95 100%	95 100%	190 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented.
Time Frame	Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)

Outcome Measure Data

Analysis Population Description

The efficacy analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab	Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks	paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks
Measure Participants	95	95
Median (95% Confidence Interval) [month]	7.23	6.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sintilimab, Chemotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.032
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.701
	Confidence Interval	(2-Sided) 95%; 0.504 to 0.972
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Progression-free Survival
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) as determined by the investigator, 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. Unequivocal progression of non-target leisions and the appearance of ≥1 new lesions were also considered as PD.
Time Frame	Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)

Outcome Measure Data

Analysis Population Description

The efficacy analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab	Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg intravenous drip every three weeks	paclitaxel 175mg/㎡ intravenous drip every three weeks； irinotecan 180mg/㎡ intravenous drip every two weeks
Measure Participants	95	95
Median (95% Confidence Interval) [month]	1.58	2.86

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sintilimab, Chemotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.979
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.002
	Confidence Interval	(2-Sided) 95%; 0.722 to 1.391
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Objective Response Rate
Description	Objective Response Rate (ORR) was defined as the proportion of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment.
Time Frame	Through Final Analysis data cut-off date of 2-August-2019 (up to approximately 26 months)

Outcome Measure Data

Analysis Population Description

The efficacy analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab	Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks	paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks
Measure Participants	95	95
Number (95% Confidence Interval) [Percentage of Participants]	12.6 13.3%	6.3 6.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sintilimab, Chemotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentages
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95%; -2.2 to 15.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Duration of Response
Description	Duration of response (DoR) was defined as the time from the date of the first investigator-assessed response (CR or PR) to the date of subsequent investigator-assessed PD or death, whichever is earlier.
Time Frame	Through Final Analysis data cutoff date of 2-August-2019 (up to approximately 26 months)

Outcome Measure Data

Analysis Population Description

The efficacy analysis population consisted of all randomized participants.

Arm/Group Title	Sintilimab	Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks	paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks
Measure Participants	95	95
Median (95% Confidence Interval) [month]	8.28	6.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sintilimab, Chemotherapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.345
	Comments
	Method	Log Rank
	Comments

Adverse Events

Time Frame	Through the Analysis data cutoff date of 2-October-2019 (up to approximately 26 months). The cutoff date for the primary efficacy analysis was 02 August 2019 when 150 OS events were actually observed. Upon the observation, the study follow-up was extended for another 2 months. The safety data was cut off as of 2-October-2019. AEs were collected till 90 days after the last dose.
Adverse Event Reporting Description	All-Cause Mortality assessed for all the participants who Started the study and Serious and Other (Not Including Serious) Adverse Events were assessed in all participants who received ≥1 dose of study treatment. 181 treated (94 sintilimab, 87chemotherapy).
Arm/Group Title	Sintilimab		Chemotherapy
Arm/Group Description	Sintilimab (IBI308) 200mg Intravenous drip every three weeks		paclitaxel 175mg/㎡ Intravenous drip every three weeks； irinotecan 180mg/㎡ Intravenous drip every two weeks
All Cause Mortality
	Sintilimab		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/95 (76.8%)		82/95 (86.3%)
Serious Adverse Events
	Sintilimab		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/94 (43.6%)		23/87 (26.4%)
Blood and lymphatic system disorders
Anaemia	2/94 (2.1%)		1/87 (1.1%)
Bone marrow failure	0/94 (0%)		6/87 (6.9%)
Cardiac disorders
Cardiac failure	1/94 (1.1%)		0/87 (0%)
Pericardial effusion	1/94 (1.1%)		0/87 (0%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	5/94 (5.3%)		1/87 (1.1%)
Dysphagia	2/94 (2.1%)		0/87 (0%)
Gastrointestinal haemorrhage	2/94 (2.1%)		0/87 (0%)
Gastric fistula	1/94 (1.1%)		0/87 (0%)
Gastropleural fistula	1/94 (1.1%)		0/87 (0%)
Ileus	1/94 (1.1%)		0/87 (0%)
Oesophageal obstruction	1/94 (1.1%)		0/87 (0%)
Oesophageal stenosis	1/94 (1.1%)		0/87 (0%)
Vomiting	1/94 (1.1%)		1/87 (1.1%)
Diarrhoea	0/94 (0%)		2/87 (2.3%)
Nausea	0/94 (0%)		1/87 (1.1%)
General disorders
Pyrexia	2/94 (2.1%)		0/87 (0%)
Accidental death	1/94 (1.1%)		0/87 (0%)
Pain	1/94 (1.1%)		0/87 (0%)
Chest pain	0/94 (0%)		1/87 (1.1%)
Hepatobiliary disorders
Hepatic function abnormal	4/94 (4.3%)		0/87 (0%)
Infections and infestations
Pneumonia	6/94 (6.4%)		0/87 (0%)
Lung infection	5/94 (5.3%)		4/87 (4.6%)
Biliary tract infection	1/94 (1.1%)		1/87 (1.1%)
Pneumonia bacterial	1/94 (1.1%)		0/87 (0%)
Pneumonia fungal	1/94 (1.1%)		0/87 (0%)
Upper respiratory tract infection	1/94 (1.1%)		1/87 (1.1%)
Injury, poisoning and procedural complications
Extradural haematoma	1/94 (1.1%)		0/87 (0%)
Radiation pneumonitis	1/94 (1.1%)		0/87 (0%)
Traumatic intracranial haemorrhage	1/94 (1.1%)		0/87 (0%)
Investigations
Amylase increased	1/94 (1.1%)		0/87 (0%)
Platelet count decreased	1/94 (1.1%)		1/87 (1.1%)
Neutrophil count decreased	0/94 (0%)		1/87 (1.1%)
Metabolism and nutrition disorders
Decreased appetite	1/94 (1.1%)		1/87 (1.1%)
Diabetic ketosis	1/94 (1.1%)		0/87 (0%)
Hypercalcaemia	1/94 (1.1%)		0/87 (0%)
Hyperglycaemia	1/94 (1.1%)		0/87 (0%)
Hypokalaemia	1/94 (1.1%)		0/87 (0%)
Hyponatraemia	1/94 (1.1%)		0/87 (0%)
Malnutrition	0/94 (0%)		1/87 (1.1%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/94 (1.1%)		0/87 (0%)
Arthralgia	0/94 (0%)		1/87 (1.1%)
Nervous system disorders
Cerebrovascular accident	1/94 (1.1%)		0/87 (0%)
Transient ischaemic attack	0/94 (0%)		1/87 (1.1%)
Renal and urinary disorders
Nephrolithiasis	1/94 (1.1%)		0/87 (0%)
Renal impairment	1/94 (1.1%)		1/87 (1.1%)
Urinary tract obstruction	0/94 (0%)		1/87 (1.1%)
Reproductive system and breast disorders
Asphyxia	0/94 (0%)		1/87 (1.1%)
Respiratory, thoracic and mediastinal disorders
Pneumonitis	6/94 (6.4%)		0/87 (0%)
Acquired tracheo-oesophageal fistula	1/94 (1.1%)		2/87 (2.3%)
Cough	1/94 (1.1%)		0/87 (0%)
Pneumonia aspiratio	1/94 (1.1%)		0/87 (0%)
Hydrothorax	0/94 (0%)		1/87 (1.1%)
Vascular disorders
Circulatory collapse	1/94 (1.1%)		0/87 (0%)
Thrombosis	0/94 (0%)		1/87 (1.1%)
Other (Not Including Serious) Adverse Events
	Sintilimab		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	88/94 (93.6%)		78/87 (89.7%)
Blood and lymphatic system disorders
Anaemia	46/94 (48.9%)		43/87 (49.4%)
Bone marrow failure	0/94 (0%)		6/87 (6.9%)
Endocrine disorders
Hypothyroidism	13/94 (13.8%)		2/87 (2.3%)
Gastrointestinal disorders
Constipation	19/94 (20.2%)		14/87 (16.1%)
Nausea	12/94 (12.8%)		31/87 (35.6%)
Vomiting	12/94 (12.8%)		21/87 (24.1%)
Diarrhoea	12/94 (12.8%)		32/87 (36.8%)
Abdominal pain	6/94 (6.4%)		8/87 (9.2%)
General disorders
Asthenia	16/94 (17%)		23/87 (26.4%)
Pyrexia	13/94 (13.8%)		6/87 (6.9%)
Pain	5/94 (5.3%)		5/87 (5.7%)
Hepatobiliary disorders
Hepatic function abnormal	10/94 (10.6%)		5/87 (5.7%)
Infections and infestations
Lung infection	7/94 (7.4%)		7/87 (8%)
Investigations
Weight decreased	28/94 (29.8%)		15/87 (17.2%)
White blood cell count decreased	13/94 (13.8%)		45/87 (51.7%)
Aspartate aminotransferase increased	12/94 (12.8%)		6/87 (6.9%)
Alanine aminotransferase increased	10/94 (10.6%)		6/87 (6.9%)
Amylase increased	10/94 (10.6%)		1/87 (1.1%)
Lymphocyte count decreased	11/94 (11.7%)		11/87 (12.6%)
Neutrophil count decreased	10/94 (10.6%)		32/87 (36.8%)
Gamma-glutamyltransferase increased	9/94 (9.6%)		3/87 (3.4%)
Platelet count decreased	9/94 (9.6%)		12/87 (13.8%)
Blood alkaline phosphatase increased	7/94 (7.4%)		2/87 (2.3%)
Blood bilirubin increased	6/94 (6.4%)		3/87 (3.4%)
Lipase increased	5/94 (5.3%)		0/87 (0%)
Neutrophil count increased	6/94 (6.4%)		2/87 (2.3%)
White blood cell count increased	6/94 (6.4%)		3/87 (3.4%)
Metabolism and nutrition disorders
Hypoproteinaemia	23/94 (24.5%)		8/87 (9.2%)
Decreased appetite	14/94 (14.9%)		17/87 (19.5%)
Hypoalbuminaemia	15/94 (16%)		9/87 (10.3%)
Hyponatraemia	11/94 (11.7%)		7/87 (8%)
Hypocalcaemia	10/94 (10.6%)		1/87 (1.1%)
Hypokalaemia	9/94 (9.6%)		10/87 (11.5%)
Hypochloraemia	9/94 (9.6%)		2/87 (2.3%)
Hypercholesterolaemia	6/94 (6.4%)		4/87 (4.6%)
Hypercalcaemia	5/94 (5.3%)		4/87 (4.6%)
Hyperglycaemia	5/94 (5.3%)		4/87 (4.6%)
Musculoskeletal and connective tissue disorders
Back pain	2/94 (2.1%)		6/87 (6.9%)
Nervous system disorders
Headache	5/94 (5.3%)		2/87 (2.3%)
Hypoaesthesia	2/94 (2.1%)		6/87 (6.9%)
Psychiatric disorders
Insomnia	5/94 (5.3%)		4/87 (4.6%)
Renal and urinary disorders
Proteinuria	8/94 (8.5%)		8/87 (9.2%)
Respiratory, thoracic and mediastinal disorders
Cough	23/94 (24.5%)		7/87 (8%)
Pneumonitis	10/94 (10.6%)		1/87 (1.1%)
Productive cough	6/94 (6.4%)		1/87 (1.1%)
Skin and subcutaneous tissue disorders
Alopecia	0/94 (0%)		13/87 (14.9%)
Vascular disorders
Hypertension	5/94 (5.3%)		2/87 (2.3%)

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.