Evaluate the Efficacy and Safety of IBI305 in Patients With Advanced or Recurrent Non-squamous NSCLC

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02954172
• Collaborator: WuXi CDS Clinical Research (Shanghai) Co.Ltd. (Other)
• Enrollment: 450
• Location: 1
• Arms: 2
• Actual Duration (Months): 35.4
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

A randomized, double blind, multicenter phase3 study .

Condition or Disease	Intervention/Treatment	Phase
NSCLC	Drug: Bevacizumab in Combination With Paclitaxel/Carboplatin; Drug: IBI305 in Combination with Paclitaxel/Carboplatin	Phase 3

Detailed Description

A randomized, double blind, multicenter phase3 study in chemotherapy naive patients with stage IIIB,IV or recurrent NSCLC of non-squamous. the study will randomize about 436 patients at a 1:1 ratio to 2 treatment arms. The study is divided 4 phase, screening, combination treatment, maintenance and follow up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Study to Evaluate the Efficacy and Safety of IBI305 in Combination With Paclitaxel/Carboplatin Versus Bevacizumab in Combination With Paclitaxel/Carboplatin in Treatment-naïve Patients With Advanced or Recurrent Non-squamous NSCLC
• Actual Study Start Date: Nov 28, 2016
• Actual Primary Completion Date: Oct 19, 2018
• Actual Study Completion Date: Nov 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bevacizumab in Combination With Paclitaxel/Carboplatin Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug: Bevacizumab in Combination With Paclitaxel/Carboplatin; Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg; Other Names: Avastin
Active Comparator: IBI305 in Combination with Paclitaxel/Carboplatin Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug: IBI305 in Combination with Paclitaxel/Carboplatin; Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg; Other Names: Bevacizumab Biosimilar

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate [18 weeks]

   ORR（objective response rate）was defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Overall Response (OR) = CR + PR.

Secondary Outcome Measures

1. Overall Survival Time [18.020 months]

   OS was defined as the time from randomization to death due to any cause.

2. Progression-free Survival [18 months]

   Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Independent Radiological Review Committee.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. signed inform consent form(ICF)

2. Age ≥ 18 years and ≤ 75 years, male or female

3. Histologically or cytologically documented inoperable, local advanced (stage IIIB), metastatic (stage IV), or recurrent non-squamous NSCLC; Mixed tumors should be categorized according to the predominant cell type

4. Histologically confirmed epidermal growth factor receptor (EGFR) wild type or insensitive mutation

5. At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1

6. Eastern Cooperative Oncology Group(ECOG) performance status of 0 or 1

7. Life expectancy ≥ 6 months

8. Laboratory results:

9. Adequate hematologic function, defined as absolute neutrophil count ≥1.5×10^{9 /L, platelet count ≥100 ×10}9 /L, hemoglobin ≥90g/L;

10. 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, or AST and ALT levels ≤ 5 times ULN for patients with hepatic metastasis;

11. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 ml / min (Cockcroft-Gault formula) and proteinuria < 2+;

12. Coagulation function is adequate, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times normal upper limit (ULN), PTT or aPTT ≤ 1.5 times ULN;

13. Expected protocol compliance

14. Patients of childbearing potential must agree to use effective contraceptive measures during study treatment and for 6 months after receiving last study treatment (e.g. abstinence, sterilization surgery, oral contraceptives, contraception by progesterone injection or subcutaneous).

Exclusion Criteria:

1. Prior chemotherapy or target therapy with another systemic anti-cancer agent (e.g., monoclonal antibody, tyrosine kinase inhibitor) for the treatment of the patient's current stage of disease (Stage IIIB not amenable for combined modality treatment, stage IV or recurrent disease). Prior surgery and irradiation is permitted, provided that the criteria outlined in the protocol for both treatments are met. Disease progressed within 6 months after adjuvant therapy must be excluded.

2. Mixed non-small cell and small cell carcinoma, or mixed adenosquamous carcinomas with predominant squamous cell

3. Histologically or cytologically confirmed EGFR sensitive mutation type, unknown EGFR status for any reason is allowed in this study.

4. Known hemoptysis within 3 months prior to screening with blood volume more than 2.5 mL each time

5. Evidence of tumor invading major blood vessels on imaging. The investigator or the local radiologist must exclude evidence of tumor that is fully contiguous with, surrounding, or extending into the lumen of a major blood vessel (e.g., pulmonary artery or superior vena cava)

6. Evidence of brain metastasis, spinal cord compression or carcinomatous meningitis history with clinical symptoms. For stable patients with no symptom, could be admitted if fulfill all below criteria: measurable lesion(s) out of CNS, no metastasis at mesocephalon, annular protuberance, medulla oblongata and spinal cord; no history of intracranial bleeding.

7. Radical radiotherapy to the thorax with curative intent within 28 days prior to enrollment; palliative radiotherapy for bone lesions outside the thoracic region within 2 weeks prior to first dose of study treatment.

8. Serious, non-healing wound, active ulcer, or untreated bone fracture, or major surgical procedure within 28 days prior to randomization or anticipation of need for major surgery during the course of the study.

9. Minor surgery (Including insertion of an indwelling catheter) within 48 hours prior to first dose of study treatment

10. Recent or current (within 10 days prior to first dose of study treatment) receive treatment of Aspirin (> 325 mg/day) or other non-steroidal anti-inflammatory drugs (NSAID) known to inhibit platelet function (within 10 days prior to first dose of study treatment)

11. Recent or current receive treatment of oral all doses of oral or parenteral anticoagulants or thrombolytic agent. Prophylactic use of anticoagulants is permitted.

12. History or evidence of inherited bleeding diathesis or coagulopathy or thrombus

13. Uncontrolled hypertension (SBP>140 mmHg and/or diastolic blood pressure>90 mmHg), prior history of hypertensive crisis and hypertensive encephalopathy

14. Clinically significant cardiovascular disease but not limited to active infections; unstable angina; stroke or transient cerebral ischemia (within 6 months prior to screening); myocardial infarction (within 6 months prior to screening) ; congestive heart-failure (New York Heart Association (NYHA) class≥ II) ; serious cardiac arrhythmia, hepatic, renal or metabolic disease requiring medication during the study.

15. History of peptic ulcer, gastrointestinal perforation, erosive esophagitis, erosive gastritis, inflammatory bowel disease or diverticulitis, abdominal fistula or intra-abdominal abscess within 6 months prior to screening

16. Patient diagnosed with a tracheo-esophageal fistula

17. Clinically significant third space effusion (e.g., uncontrolled ascites or pleural effusion by extraction or other treatment)

18. Pulmonary fibrosis or active pneumonia showed by CT at baseline

19. Active malignancy other than non-small cell lung cancer (NSCLC), treated carcinoma in situ of the cervix, superficial basal cell or squamous cell carcinoma, radical surgery of localized prostate cancer, radical surgery of ductal carcinoma in situ within 5 years prior to randomization

20. Known autoimmune disease

21. Known positive HbsAg and hepatitis B virus (HBV)-DNA drop test in peripheral blood ≥ 1 x 10^{3 copy number/L or 200 IU/mL; If HBsAg positive and HBV-DNA drop test in peripheral blood < 1 x 10}3 copy number/L or 200 IU/mL, patient is considered to be eligible by investigator only when chronic hepatitis B in the plateau and do not increase the risk

22. Known positive HIV or hepatitis C virus (HCV) or syphilis

23. Known allergic disease or allergic physique

24. Treatment with any other investigational agent or participation in another clinical trial within 30 days prior to screening

25. Known alcoholism or drug abuse

26. Pregnant or anticipation of pregnant during the study or lactating women

27. Known hypersensitivity to bevacizumab or any of its excipients and/or any of the chemotherapy agents

28. Other conditions that the investigator thinks unsuitable in this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Center; Sun Yat sen University;	Guangzhou	Guangdong	China	510060

Sponsors and Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.
• WuXi CDS Clinical Research (Shanghai) Co.Ltd.

Investigators

• Principal Investigator: Li Zhang, Doctor, Sun Yat-sen University

Study Documents (Full-Text)

• Statistical Analysis Plan - Nov 14, 2018
• Study Protocol - Nov 5, 2018

More Information

Publications

None provided.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT02954172
• Other Study ID Numbers: CIBI305A301
• First Posted: Nov 3, 2016
• Last Update Posted: Dec 8, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Additional relevant MeSH terms: Carcinoma, Non-Small-Cell Lung; Paclitaxel; Albumin-Bound Paclitaxel; Bevacizumab; Carboplatin

Study Results

Participant Flow

Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin	IBI305 in Combination With Paclitaxel/Carboplatin
Arm/Group Description	Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
Period Title: Overall Study
STARTED	226	224
COMPLETED	220	221
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin	IBI305 in Combination With Paclitaxel/Carboplatin	Total
Arm/Group Description	Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Total of all reporting groups
Overall Participants	220	221	441
Age (years) [Mean (Standard Deviation) ]
Mean (SD)	57.6 (8.69)	57.2 (9.28)	57.4 (8.98)
Sex: Female, Male (Count of Participants)
Female	83 37.7%	79 35.7%	162 36.7%
Male	137 62.3%	142 64.3%	279 63.3%
Race/Ethnicity, Customized (Count of Participants)
Han	217 98.6%	211 95.5%	428 97.1%
Others	4 1.8%	9 4.1%	13 2.9%
Region of Enrollment (participants) [Number]
China	220 100%	221 100%	441 100%
Height (centimeter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter]	164.93 (8.166)	164.03 (7.829)	164.48 (8.003)
Weight (kilogram) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram]	62.16 (10.844)	62.14 (10.272)	62.15 (10.550)

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate
Description	ORR（objective response rate）was defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Overall Response (OR) = CR + PR.
Time Frame	18 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin	IBI305 in Combination With Paclitaxel/Carboplatin
Arm/Group Description	Drug Bevacizumab 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
Measure Participants	220	221
Number [percentage of participants]	46.4 21.1%	44.3 20%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab in Combination With Paclitaxel/Carboplatin, IBI305 in Combination With Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Equivalence
	Comments	the equivalence margin of the ORR ratio was set at (0.75, 1.33).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 90%; 0.756 to 1.077
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Survival Time
Description	OS was defined as the time from randomization to death due to any cause.
Time Frame	18.020 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin	IBI305 in Combination With Paclitaxel/Carboplatin
Arm/Group Description	Drug Bevacizumab 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
Measure Participants	220	221
Median (95% Confidence Interval) [month]	NA	18.020

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab in Combination With Paclitaxel/Carboplatin, IBI305 in Combination With Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.7066
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Progression-free Survival
Description	Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Independent Radiological Review Committee.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin	IBI305 in Combination With Paclitaxel/Carboplatin
Arm/Group Description	Drug Bevacizumab 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg	Drug IBI30515mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
Measure Participants	220	221
Median (95% Confidence Interval) [months]	8.260	8.430

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bevacizumab in Combination With Paclitaxel/Carboplatin, IBI305 in Combination With Paclitaxel/Carboplatin
	Comments
	Type of Statistical Test	Equivalence
	Comments
Statistical Test of Hypothesis	p-Value	0.3497
	Comments
	Method	Log Rank
	Comments

Adverse Events

Time Frame	through study completion, an average of 2 year
Arm/Group Title	Bevacizumab in Combination With Paclitaxel/Carboplatin		IBI305 in Combination With Paclitaxel/Carboplatin
Arm/Group Description	Drug Bevacizumab15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg		Drug IBI305 15mg/kg in combination with Paclitaxel/Carboplatin 6 cycles then maintains at 7.5 mg/kg
All Cause Mortality
	Bevacizumab in Combination With Paclitaxel/Carboplatin		IBI305 in Combination With Paclitaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/226 (2.2%)		6/224 (2.7%)
Serious Adverse Events
	Bevacizumab in Combination With Paclitaxel/Carboplatin		IBI305 in Combination With Paclitaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	85/226 (37.6%)		75/224 (33.5%)
Blood and lymphatic system disorders
Febrile neutropenia	7/226 (3.1%)		4/224 (1.8%)
Anaemia	8/226 (3.5%)		4/224 (1.8%)
Anemia	8/226 (3.5%)		4/224 (1.8%)
Bone marrow failure	0/226 (0%)		2/224 (0.9%)
Cardiac disorders
Congestive heart-failure	0/226 (0%)		2/224 (0.9%)
Ventricular premature contraction	1/226 (0.4%)		2/224 (0.9%)
Atrial fibrillation	1/226 (0.4%)		2/224 (0.9%)
Myocardial infarction	0/226 (0%)		1/224 (0.4%)
Cardiopulmonary failure	0/226 (0%)		1/224 (0.4%)
Acute myocardial infarction	0/226 (0%)		1/224 (0.4%)
Sinus tachycardia	0/226 (0%)		0/224 (0%)
Wolfe-parkinson-white syndrome	1/226 (0.4%)		0/224 (0%)
Supraventricular tachycardia	1/226 (0.4%)		0/224 (0%)
Hydropericardium	1/226 (0.4%)		0/224 (0%)
Eye disorders
Angle-closure glaucoma	0/226 (0%)		1/224 (0.4%)
Uveitis	0/226 (0%)		1/224 (0.4%)
Meibomianitis	1/226 (0.4%)		0/224 (0%)
Retinal hemorrhage	1/226 (0.4%)		0/224 (0%)
Gastrointestinal disorders
Vomiting	4/226 (1.8%)		0/224 (0%)
Nausea	1/226 (0.4%)		1/224 (0.4%)
Pancreatitis	0/226 (0%)		1/224 (0.4%)
Diarrhea	0/226 (0%)		1/224 (0.4%)
Emesis	4/226 (1.8%)		0/224 (0%)
Esophageal obstruction	1/226 (0.4%)		0/224 (0%)
Saprodontia	1/226 (0.4%)		0/224 (0%)
General disorders
Fever	3/226 (1.3%)		2/224 (0.9%)
Hepatobiliary disorders
Hepatic disease	0/226 (0%)		1/224 (0.4%)
Immune system disorders
Anaphylaxis occurs almost instantaneously	0/226 (0%)		1/224 (0.4%)
Hypersensitivity	1/226 (0.4%)		0/224 (0%)
Infections and infestations
Lung infection	7/226 (3.1%)		11/224 (4.9%)
Pneumonia	3/226 (1.3%)		3/224 (1.3%)
Upper respiratory tract infection	3/226 (1.3%)		1/224 (0.4%)
pulmonary infection	7/226 (3.1%)		11/224 (4.9%)
Infectious Pneumonia	3/226 (1.3%)		3/224 (1.3%)
upper respiratory infection	3/226 (1.3%)		1/224 (0.4%)
Respiratory tract infection	0/226 (0%)		1/224 (0.4%)
pharyngitis	0/226 (0%)		1/224 (0.4%)
urinary tract infection	0/226 (0%)		1/224 (0.4%)
gastroenteritis	1/226 (0.4%)		1/224 (0.4%)
Device associated infection	0/226 (0%)		1/224 (0.4%)
Herpes zoster	1/226 (0.4%)		0/224 (0%)
The anus infection	1/226 (0.4%)		0/224 (0%)
Anal abscess	1/226 (0.4%)		0/224 (0%)
Phthisis	1/226 (0.4%)		0/224 (0%)
Sepsis	1/226 (0.4%)		0/224 (0%)
Gingivitis	1/226 (0.4%)		0/224 (0%)
Injury, poisoning and procedural complications
Tracheorrhagia	1/226 (0.4%)		0/224 (0%)
Fracture	1/226 (0.4%)		0/224 (0%)
Investigations
Platelet count decreased	27/226 (11.9%)		24/224 (10.7%)
White blood cell count decreased	10/226 (4.4%)		7/224 (3.1%)
Neutrophil count decreased	13/226 (5.8%)		6/224 (2.7%)
Fever infection	1/226 (0.4%)		0/224 (0%)
Decreased platelet count	27/226 (11.9%)		24/224 (10.7%)
Lower white blood cell count	10/226 (4.4%)		7/224 (3.1%)
Neutrophils count decreased	13/226 (5.8%)		6/224 (2.7%)
Alanine aminotransferase is elevated	1/226 (0.4%)		2/224 (0.9%)
Aspartate aminotransferase was elevated	1/226 (0.4%)		2/224 (0.9%)
Gamma-glutamyl transferase is elevated	0/226 (0%)		1/224 (0.4%)
Haemoglobin reduction	1/226 (0.4%)		0/224 (0%)
Blood bilirubin is elevated	1/226 (0.4%)		0/224 (0%)
Metabolism and nutrition disorders
Hypoproteinemia	0/226 (0%)		1/224 (0.4%)
hyponatremia	0/226 (0%)		1/224 (0.4%)
Reduced food intake	1/226 (0.4%)		0/224 (0%)
Musculoskeletal and connective tissue disorders
Gout joint inflammation	1/226 (0.4%)		0/224 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Central nervous system metastasis	0/226 (0%)		1/224 (0.4%)
lymphangitis carcinomatosa	1/226 (0.4%)		0/224 (0%)
Nervous system disorders
Cerebral infarction	2/226 (0.9%)		1/224 (0.4%)
Epilepsy	0/226 (0%)		1/224 (0.4%)
Brain stem infarction	0/226 (0%)		1/224 (0.4%)
Cerebrovascular disorders	0/226 (0%)		1/224 (0.4%)
Cerebral hemorrhage	1/226 (0.4%)		0/224 (0%)
Neurophlegmon	1/226 (0.4%)		0/224 (0%)
Lacunar infarction	1/226 (0.4%)		0/224 (0%)
Intracranial hemorrhage	1/226 (0.4%)		0/224 (0%)
Product Issues
Fever	3/226 (1.3%)		2/224 (0.9%)
death	0/226 (0%)		2/224 (0.9%)
Debilitation	0/226 (0%)		1/224 (0.4%)
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	0/226 (0%)		3/224 (1.3%)
Hemoptysis	4/226 (1.8%)		1/224 (0.4%)
Bronchorrhagia	1/226 (0.4%)		2/224 (0.9%)
Respiratory distress	0/226 (0%)		1/224 (0.4%)
Breathing difficulties	1/226 (0.4%)		0/224 (0%)
Expectoration	1/226 (0.4%)		0/224 (0%)
Pneumothorax	2/226 (0.9%)		0/224 (0%)
Asphyxia	1/226 (0.4%)		0/224 (0%)
Pleural effusion	1/226 (0.4%)		0/224 (0%)
Skin and subcutaneous tissue disorders
Drug eruption	0/226 (0%)		1/224 (0.4%)
Vascular disorders
Distal embolization	0/226 (0%)		1/224 (0.4%)
Limb vein thrombosis	0/226 (0%)		1/224 (0.4%)
Hypertension	1/226 (0.4%)		0/224 (0%)
Other (Not Including Serious) Adverse Events
	Bevacizumab in Combination With Paclitaxel/Carboplatin		IBI305 in Combination With Paclitaxel/Carboplatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	222/226 (98.2%)		216/224 (96.4%)
Blood and lymphatic system disorders
Anaemia	54/226 (23.9%)		53/224 (23.7%)
Gastrointestinal disorders
Constipation	50/226 (22.1%)		44/224 (19.6%)
Nausea	52/226 (23%)		31/224 (13.8%)
Vomiting	24/226 (10.6%)		22/224 (9.8%)
Diarrhea	30/226 (13.3%)		20/224 (8.9%)
Gastroesophageal reflux disease	13/226 (5.8%)		4/224 (1.8%)
General disorders
Fever	33/226 (14.6%)		20/224 (8.9%)
Fatigue	13/226 (5.8%)		8/224 (3.6%)
Pain	14/226 (6.2%)		8/224 (3.6%)
Infections and infestations
Upper respiratory tract infection	21/226 (9.3%)		23/224 (10.3%)
Investigations
White blood cell count decreased	179/226 (79.2%)		161/224 (71.9%)
Neutrophil count decreased	169/226 (74.8%)		158/224 (70.5%)
Platelet count decreased	98/226 (43.4%)		113/224 (50.4%)
AST increased	14/226 (6.2%)		24/224 (10.7%)
ALT increased	17/226 (7.5%)		23/224 (10.3%)
Gamma-glutamyltransferase increased	4/226 (1.8%)		13/224 (5.8%)
Lymphocytes decreased	15/226 (6.6%)		10/224 (4.5%)
Metabolism and nutrition disorders
decreased appetite	18/226 (8%)		18/224 (8%)
Hypokalemia	11/226 (4.9%)		17/224 (7.6%)
Musculoskeletal and connective tissue disorders
Pain in extremity	16/226 (7.1%)		18/224 (8%)
Arthralgia	14/226 (6.2%)		7/224 (3.1%)
Nervous system disorders
Hypoesthesia	24/226 (10.6%)		25/224 (11.2%)
Psychiatric disorders
Sleeplessness	15/226 (6.6%)		16/224 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	16/226 (7.1%)		17/224 (7.6%)
Productive cough	13/226 (5.8%)		7/224 (3.1%)
Vascular disorders
Hypertension	25/226 (11.1%)		25/224 (11.2%)

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.