First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors
Sponsor
Innovent Biologics (Suzhou) Co. Ltd. (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02937116
Collaborator
(none)
233
1
9
62.4
3.7
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the safety, tolerability and efficacy of IBI308 monotherapy or in combination with chemotherapy in patients with certain types of advanced solid tumors. Another purpose is to determine the pharmacokinetics, pharmacodynamics and immunogenicity of IBI308.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
This is a study which consists of phase 1a study (dose escalation stage) and phase 1b study (expansion stage). Phase 1a study will adopt the classical 3+3 dose escalation design, exploring safety and tolerance of 4 dose cohorts (1mg/kg, 3mg/kg, 200mg and 10mg/kg) and determining the recommended dose for phase 1b study. Phase 1b is expansion study of 8 cohorts which will evaluate anti-tumor efficacy and safety of eight IBI308 monotherapy or in combination with chemotherapy. Cohort A is IBI308 monotherapy for advanced melanoma. Cohort B is IBI308 monotherapy for advanced digestive system carcinoma or neuroendocrine neoplasm after failure or intolerance of first line standard therapy. Cohort C is IBI308 monotherapy for advanced non-small cell lung cancer (NSCLC) after failure or intolerance of first line standard therapy. Cohort D is IBI308 in combination with cisplatin and pemetrexed for treatment naïve locally advanced, recurrent or metastatic non-squamous NSCLC. Cohort E is IBI308 in combination with gemcitabine and cisplatin for treatment-naïve locally advanced, recurrent or metastatic squamous NSCLC. Cohort F is IBI308 in combination with oxaliplatin and capecitabine for treatment naïve locally advanced gastric or gastroesophageal junction adenocarcinoma. Cohort G is IBI308 in combination with etoposide and cisplatin for treatment naïve locally advanced, recurrent or metastatic high grade(G3) neuroendocrine tumor. Cohort H is IBI308 in combination with irinotecan and 5-FU for advanced high grade(G3) neuroendocrine tumor after failure of first line standard therapy. Phase 1a and 1b consist of screening period (28 days before enrollment), treatment period and follow up period (every 3 months until death or the end of study). In phase 1a, dose limiting toxicity (DLT) will be recorded for up to 28 days after the 1st dose of IBI308. Efficacy will be evaluated by RECIST v1.1. Adverse events will be monitored throughout the study. Further exploration of pharmacokinetic/pharmacodynamics and immunogenicity information will be assessed throughout the trial.
Study Design
Study Type:
Interventional
Actual Enrollment
:
233 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label, Multicenter Study of IBI308 in Subjects With Selected Advanced Solid Tumors
Actual Study Start Date
:
Oct 19, 2016
Actual Primary Completion Date
:
Oct 19, 2020
Anticipated Study Completion Date
:
Jan 1, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1a Participants will receive IBI308 1mg/kg, 3mg/kg or 10mg/kg intravenous every 2 weeks, or 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity. Drug: IBI308 |
Drug: IBI308
|
| Experimental: Phase 1b Cohort A Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308 |
Drug: IBI308
|
| Experimental: Phase 1b Cohort B Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308 |
Drug: IBI308
|
| Experimental: Phase 1b Cohort C Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308 |
Drug: IBI308
|
| Experimental: Phase 1b Cohort D Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308/Cisplatinum/Pemetrexed |
Drug: IBI308\Cisplatinum\Pemetrexed
|
| Experimental: Phase 1b Cohort E Participants will receive IBI308 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\gemcitabine\cisplatin |
Drug: IBI308\cisplatin\gemcitabine
|
| Experimental: Phase 1b Cohort F Participants will receive IBI308 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\oxaliplatin\capecitabine |
Drug: IBI308\oxaliplatin\capecitabine
|
| Experimental: Phase 1b Cohort G Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 intravenously and etoposide 100mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles. Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\etoposide\cisplatin |
Drug: IBI308\etoposide\cisplatin
|
| Experimental: Phase 1b Cohort H Participants will receive IBI308 200mg in combination with irinotecan 125mg/m2 intravenously day 1and 8 and 5-FU 1000mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles.Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\irinotecan\5-FU |
Drug: IBI308\irinotecan\5-FU
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing Dose-limiting Toxicities (DLTs) [Up to 28 days in Cycle 1]
- Number of All Study Participants Who Demonstrate a Tumor Response [Through out the study (up to 2 years)]
- Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator [Through out the study (up to 2 years)]
ORR was defined as the percentage of participants in the analysis population who had achieved BOR of CR or PR according to RECIST 1.1.
Secondary Outcome Measures
- PFS According to RECIST 1.1 as Assessed by Investigator [Through out the study (up to 2 years)]
- DOR According to RECIST 1.1 as Assessed by Investigator [Through out the study (up to 2 years)]
- TTR According to RECIST 1.1 as Assessed by Investigator [Through out the study (up to 2 years)]
- OS for Participants [Through out the study]
- Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) [Cycle 1: pre-dose, post-dose at 0, 1, and 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
- Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants [Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
- Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants [Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
- The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration [Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
- Volume of Distribution of IBI308 in Plasma After Single Dose Administration [Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
- Clearance of IBI308 in Plasma After Single Dose Administration [Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
-
Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil count >= 1.5* 109 cells/litre (L); 2) Platelets >=100 x 109 cells/L; 3) Hemoglobin
= 9 gram/deciliter (g/dL); 4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 * upper limit of normal (ULN) for participants without hepatic cell cancer and hepatic metastasis, ALT and AST <= 5 * ULN for participants with hepatic cell cancer or hepatic metastasis; 5) Total bilirubin (TBIL) < 1.5 * ULN for participants without hepatic cell cancer, hepatic metastasis and confirmed/suspicious Gilbert syndrome, TBIL < 3 * ULN for participants with hepatic cell cancer, hepatic metastasis or confirmed/suspicious Gilbert syndrome; 6) Creatinine determined by serum creatinine levels <=1.5 * ULN or a calculated creatinine clearance of >= 50 mL/min/1.73 m^2; 7) urine protein -~+, 24 hour urine < 1 gram for participants with urine protein ++ or above; 8) activated partial thromboplastin time and international normalized ratio <= 1.5 * ULN; 9) thyroid stimulating hormone and free thyroxine 4 within normal range
-
Tumor type
-
Phase 1a: advanced solid tumors after failure of standard therapy
-
Phase 1b Cohort A: cytologically or histologically confirmed advanced melanoma
-
Phase 1b Cohort B: cytologically or histologically confirmed advanced malignancies of the digestive system after failure of at least 1 line of standard therapy
-
Phase 1b Cohort C: cytologically or histologically confirmed advanced NSCLC without known epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement after failure of 1st line standard therapy
-
Phase 1b Cohort D: treatment naive cytologically or histologically confirmed inoperable locally advanced (stage IIIB) or advanced (stage IV) nsNSCLC without known EGFR mutation and ALK rearrangement, participants with disease recurrence or progression within 6 months after completion of prior platinum doublet-based chemotherapy regimen as neoadjuvant or adjuvant therapy are not eligible
-
Phase 1b Cohort E: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic squamous NSCLC without known EGFR mutation and ALK rearrangement. Participants with Stage IIIB NSCLC who progressed within 6 months after completion of platinum-based chemotherapy are not eligible.
-
Phase 1b Cohort F: Histologically confirmed locally advanced, recurrent or metastatic gastric or esophagogastric junction adenocarcinoma without known HER2 amplification.
-
Phase 1b Cohort G: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic high grade(G3) neuroendocrine tumor with Ki-67>20%.
-
Phase 1b Cohort H: Cytologically or histologically confirmed advanced high grade(G3) neuroendocrine tumor with Ki-67>20% after failure of first line standard therapy. Participants progressed within 6 months after completion of adjuvant or neoadjuvant chemotherapy are eligible.
-
At least 1 measurable site of disease per RECIST v1.1
Exclusion Criteria:
-
Prior treatment of any antibody of PD-1 or PD-L1
-
Prior treatment of ipilimumab, unless all the following requirements are met:
-
Full resolution of ipilimumab related adverse effects (including immune related adverse effects) and no treatment for these adverse events (AEs) for at least 4 weeks prior to the time of enrollment
-
Minimum of 12 weeks from the first dose of ipilimumab and >6 weeks from the last dose
-
No history of severe immune related adverse effects from ipilimumab (CTCAE Grade 4; CTCAE Grade 3 requiring treatment >4 weeks)
-
Unequivocal PD following a dose of ipilimumab
-
HIV infection
-
Active HBV or HCV infection
-
Uncontrolled complication including but not limited to :
-
Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias or congestive heart failure
-
History of stroke, myocardial infarction or intracranial hemorrhage within 6 months prior to the enrolment
-
History or risk of autoimmune disease
-
Known interstitial lung disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The fifth medical center of the PLA general hospital | Beijing | China |
Sponsors and Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier:
NCT02937116
Other Study ID Numbers:
- CIBI308A101
First Posted:
Oct 18, 2016
Last Update Posted:
Feb 21, 2021
Last Verified:
Feb 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor of the Digestive System or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Period Title: Overall Study | ||||||||||||
| STARTED | 3 | 3 | 3 | 3 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 3 | 3 | 3 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
Baseline Characteristics
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor of the Digestive System or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Total of all reporting groups |
| Overall Participants | 3 | 3 | 3 | 3 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 | 233 |
| Age (Years) [Mean (Standard Deviation) ] | |||||||||||||
| Mean (Standard Deviation) [Years] |
44.33
(17.010)
|
46
(15.524)
|
48
(6.557)
|
50
(16.093)
|
49.13
(13.061)
|
52.27
(11.280)
|
55.35
(11.201)
|
60.52
(6.539)
|
62.30
(6.951)
|
58.20
(8.600)
|
62.86
(4.140)
|
49.29
(11.912)
|
54.54
(11.291)
|
| Sex: Female, Male (Count of Participants) | |||||||||||||
| Female |
1
33.3%
|
2
66.7%
|
3
100%
|
1
33.3%
|
7
31.8%
|
30
34.5%
|
6
16.2%
|
5
23.8%
|
1
5%
|
2
10%
|
1
14.3%
|
2
28.6%
|
61
26.2%
|
| Male |
2
66.7%
|
1
33.3%
|
0
0%
|
2
66.7%
|
15
68.2%
|
57
65.5%
|
31
83.8%
|
16
76.2%
|
19
95%
|
18
90%
|
6
85.7%
|
5
71.4%
|
172
73.8%
|
| Race (NIH/OMB) (Count of Participants) | |||||||||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
22
100%
|
87
100%
|
37
100%
|
21
100%
|
20
100%
|
20
100%
|
7
100%
|
7
100%
|
233
100%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||||||||||||
| China |
3
100%
|
3
100%
|
3
100%
|
3
100%
|
22
100%
|
87
100%
|
37
100%
|
21
100%
|
20
100%
|
20
100%
|
7
100%
|
7
100%
|
233
100%
|
Outcome Measures
| Title | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) |
|---|---|
| Description | |
| Time Frame | Up to 28 days in Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 who received ≥1 dose of study treatment and either 1) had a DLT in Cycle 1 or 2) received ≥90% of the prescribed dose of Sintilimab in Cycle 1 and completed all safety evaluations ≥28 days after the first administration of Sintilimab without experiencing DLT. Per protocol, cohort A to H were not analyzed. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Number [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of All Study Participants Who Demonstrate a Tumor Response |
|---|---|
| Description | |
| Time Frame | Through out the study (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Number [Participants] |
0
0%
|
1
33.3%
|
0
0%
|
1
33.3%
|
1
4.5%
|
13
14.9%
|
5
13.5%
|
13
61.9%
|
11
55%
|
17
85%
|
3
42.9%
|
1
14.3%
|
| Title | Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator |
|---|---|
| Description | ORR was defined as the percentage of participants in the analysis population who had achieved BOR of CR or PR according to RECIST 1.1. |
| Time Frame | Through out the study (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 0 | 0 | 0 | 0 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Number (95% Confidence Interval) [percentage of participants] |
4.5
150%
|
14.9
496.7%
|
13.5
450%
|
61.9
2063.3%
|
55.0
250%
|
85.0
97.7%
|
42.9
115.9%
|
14.3
68.1%
|
| Title | PFS According to RECIST 1.1 as Assessed by Investigator |
|---|---|
| Description | |
| Time Frame | Through out the study (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 0 | 0 | 0 | 0 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Median (95% Confidence Interval) [Days] |
62.0
|
66.0
|
84.0
|
377.0
|
194.0
|
230.0
|
NA
|
NA
|
| Title | DOR According to RECIST 1.1 as Assessed by Investigator |
|---|---|
| Description | |
| Time Frame | Through out the study (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 0 | 0 | 0 | 0 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Median (95% Confidence Interval) [Days] |
NA
|
NA
|
368.0
|
NA
|
170.5
|
181.0
|
NA
|
NA
|
| Title | TTR According to RECIST 1.1 as Assessed by Investigator |
|---|---|
| Description | |
| Time Frame | Through out the study (up to 2 years) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 0 | 0 | 0 | 0 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Median (95% Confidence Interval) [Days] |
63.0
|
64.0
|
63.0
|
63.0
|
62.0
|
63.0
|
62.0
|
62.0
|
| Title | OS for Participants |
|---|---|
| Description | |
| Time Frame | Through out the study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants from cohort A to H that received ≥1 dose of study treatment. Per protocol, Part A1 to A4 (dose-escalation) was not analyzed for efficacy. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 0 | 0 | 0 | 0 | 22 | 87 | 37 | 21 | 20 | 20 | 7 | 7 |
| Median (95% Confidence Interval) [Days] |
518.0
|
342.0
|
431.0
|
566.0
|
461.0
|
NA
|
NA
|
NA
|
| Title | Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t) |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, and 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available AUC 0-t data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis.. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [h*ug/ml] |
4800
(8.2)
|
12300
(35.2)
|
39800
(14.5)
|
10800
(49.3)
|
| Title | Maximum Concentration (Cmax) of Sintilimab in Solid Tumor Participants |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available Cmax data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ug/ml] |
21.9
(11.3)
|
69.7
(12.2)
|
220
(13.4)
|
54.6
(50.5)
|
| Title | Time to Maximum Concentration (Tmax) of Sintilimab in Solid Tumor Participants |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available Tmax data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Median (Full Range) [hours] |
1.05
|
2.07
|
2.27
|
1.93
|
| Title | The Half-life (t1/2) of IBI308 in Plasma After Single Dose Administration |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available T1/2 data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [Days] |
17
(7.3)
|
12.7
(44.6)
|
12.5
(26.4)
|
16.1
(32.6)
|
| Title | Volume of Distribution of IBI308 in Plasma After Single Dose Administration |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available volume of distribution data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [L] |
5.02
(24.0)
|
5.14
(18.7)
|
5.95
(10.5)
|
7.2
(45.0)
|
| Title | Clearance of IBI308 in Plasma After Single Dose Administration |
|---|---|
| Description | |
| Time Frame | Cycle 1: pre-dose, post-dose at 0, 1, 6 hours, and Days 2, 3, 8, 15, and 22, and 29 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants in Parts A1 to A4 receiving a single dose of drug during Cycle 1 (28 days) and having available clearance data. Per protocol, participants in cohort A to H were not included in the escalating dose PK analysis. |
| Arm/Group Title | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. |
| Measure Participants | 3 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [ml/h] |
8.53
(20.7)
|
11.7
(33.3)
|
13.7
(15.9)
|
12.9
(61.1)
|
Adverse Events
| Time Frame | Up to approximately 90 days (through Final Database cut-off date of 30-Oct-2017) for Phase Ia (Part A1 to A4); Up to approximately 90 days (through Final Database cut-off date of 17-Apr-2019) for Phase Ib (Cohort A to F); Up to approximately 90 days (through Final Database cut-off date of 30-Sep-2019) for Phase Ib (Cohort G to H); | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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 | Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | ||||||||||||
| Arm/Group Description | 1mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 3mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 10mg/kg intravenous Q2W, will be continued until disease progression or unacceptable toxicity. | 200mg intravenous Q3W, will be continued until disease progression or unacceptable toxicity. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg in combination with Cisplatin 75mg/m2 intravenously Day 1 and Etoposide 100mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | Subjects received sintilimab 200mg intravenously Day 1 in combination with Irinotecan 125mg/m2 intravenously Day 1 and 8, and 5-FU 1000mg/m2 intravenously Day 1-3 every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 2/3 (66.7%) | 3/3 (100%) | 1/3 (33.3%) | 12/22 (54.5%) | 57/87 (65.5%) | 25/37 (67.6%) | 9/21 (42.9%) | 8/20 (40%) | 3/20 (15%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/22 (0%) | 18/87 (20.7%) | 11/37 (29.7%) | 3/21 (14.3%) | 9/20 (45%) | 6/20 (30%) | 2/7 (28.6%) | 1/7 (14.3%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Bone marrow failure | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Supraventricular tachycardia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||
| Hypothyroidism | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Upper gastrointestinal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 3/87 (3.4%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Intestinal obstruction | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Oesophageal stenosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Diarrhoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Functional gastrointestinal disorder | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Autoimmune colitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pancreatitis acute | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| General disorders | ||||||||||||||||||||||||
| Pyrexia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 2/87 (2.3%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Death | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Drug-induced liver injury | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gallbladder pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Jaundice | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hepatic function abnormal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Infections and infestations | ||||||||||||||||||||||||
| Biliary tract infection | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Lung infection | 1/3 (33.3%) | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 5/37 (13.5%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Soft tissue infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pyopneumothorax | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Femoral neck fracture | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tracheal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Investigations | ||||||||||||||||||||||||
| Blood bilirubin increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Amylase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 3/20 (15%) | 4/20 (20%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Neutrophil count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Decreased appetite | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Cancer pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Uterine leiomyoma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||
| Renal hydrocele | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Haemoptysis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Interstitial lung disease | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pneumonitis | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pulmonary embolism | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Respiratory failure | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Cough | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
Other (Not Including Serious) Adverse Events |
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| Solid Tumors: Sintilimab 1mg/kg Q2W (Part A1) | Solid Tumors: Sintilimab 3mg/kg Q2W (Part A2) | Solid Tumors: Sintilimab 10mg/kg Q2W (Part A3) | Solid Tumors: Sintilimab 200mg/kg Q3W (Part A4) | MEL: Sintilimab 200mg Q3W (Cohort A) | Malignant Tumor or Neuroendocrine Tumor: Sintilimab 200mg Q3W (Cohort B) | NSCLC: Sintilimab 200mg Q3W (Cohort C) | nsNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort D) | scNSCLC: Sintilimab 200mg Q3W + Chemotherapy (Cohort E) | Gastric or Gastroesophageal Junction Adenocarcinoma: Sintilimab 200mg Q3W + Chemotherapy (Cohort F) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort G) | Neuroendocrine Tumors: Sintilimab 200mg Q3W + Chemotherapy (Cohort H) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 18/22 (81.8%) | 82/87 (94.3%) | 35/37 (94.6%) | 19/21 (90.5%) | 20/20 (100%) | 20/20 (100%) | 7/7 (100%) | 7/7 (100%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anaemia | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/22 (9.1%) | 37/87 (42.5%) | 10/37 (27%) | 9/21 (42.9%) | 17/20 (85%) | 12/20 (60%) | 6/7 (85.7%) | 4/7 (57.1%) | ||||||||||||
| Coagulopathy | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Iron deficiency anaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Leukopenia | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Neutrophilia | 1/3 (33.3%) | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thrombocytopenia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Arrhythmia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Atrioventricular block first degree | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Bundle branch block right | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Cardiac failure | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Palpitations | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Sinus bradycardia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/22 (4.5%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Sinus tachycardia | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 3/87 (3.4%) | 8/37 (21.6%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Supraventricular extrasystoles | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Ventricular arrhythmia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Ventricular extrasystoles | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/22 (4.5%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||
| Hypoacusis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tinnitus | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||
| Goitre | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hyperthyroidism | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 5/87 (5.7%) | 2/37 (5.4%) | 0/21 (0%) | 1/20 (5%) | 1/20 (5%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Hypothyroidism | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/22 (9.1%) | 4/87 (4.6%) | 2/37 (5.4%) | 1/21 (4.8%) | 2/20 (10%) | 6/20 (30%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Thyroid mass | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thyroiditis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Eye disorders | ||||||||||||||||||||||||
| Conjunctival hyperaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Eyelid oedema | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Xerophthalmia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 3/21 (14.3%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Abdominal distension | 0/3 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 2/21 (9.5%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Abdominal pain | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Abdominal pain upper | 1/3 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/22 (0%) | 6/87 (6.9%) | 1/37 (2.7%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Constipation | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 2/22 (9.1%) | 10/87 (11.5%) | 4/37 (10.8%) | 3/21 (14.3%) | 2/20 (10%) | 2/20 (10%) | 1/7 (14.3%) | 3/7 (42.9%) | ||||||||||||
| Diarrhoea | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 6/87 (6.9%) | 0/37 (0%) | 4/21 (19%) | 2/20 (10%) | 2/20 (10%) | 1/7 (14.3%) | 4/7 (57.1%) | ||||||||||||
| Dyspepsia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 2/7 (28.6%) | ||||||||||||
| Dysphagia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Flatulence | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gastric dilatation | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Gastric ulcer | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Haemorrhoids | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Hyperchlorhydria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 2/21 (9.5%) | 0/20 (0%) | 2/20 (10%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Loose tooth | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Mouth ulceration | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 3/7 (42.9%) | ||||||||||||
| Nausea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 3/87 (3.4%) | 3/37 (8.1%) | 9/21 (42.9%) | 8/20 (40%) | 3/20 (15%) | 2/7 (28.6%) | 6/7 (85.7%) | ||||||||||||
| Retching | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Subileus | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Toothache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Upper gastrointestinal haemorrhage | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Vomiting | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 4/87 (4.6%) | 0/37 (0%) | 7/21 (33.3%) | 6/20 (30%) | 3/20 (15%) | 2/7 (28.6%) | 4/7 (57.1%) | ||||||||||||
| General disorders | ||||||||||||||||||||||||
| Asthenia | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/22 (4.5%) | 23/87 (26.4%) | 5/37 (13.5%) | 7/21 (33.3%) | 5/20 (25%) | 2/20 (10%) | 1/7 (14.3%) | 4/7 (57.1%) | ||||||||||||
| Chest discomfort | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 2/21 (9.5%) | 3/20 (15%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Chest pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Chills | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Face oedema | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Fatigue | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 2/7 (28.6%) | ||||||||||||
| Oedema peripheral | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 2/21 (9.5%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Peripheral swelling | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pyrexia | 1/3 (33.3%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/3 (33.3%) | 4/22 (18.2%) | 15/87 (17.2%) | 6/37 (16.2%) | 6/21 (28.6%) | 6/20 (30%) | 3/20 (15%) | 1/7 (14.3%) | 2/7 (28.6%) | ||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Hepatic function abnormal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 3/37 (8.1%) | 0/21 (0%) | 1/20 (5%) | 3/20 (15%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 2/20 (10%) | 7/7 (100%) | 1/7 (14.3%) | ||||||||||||
| Immune system disorders | ||||||||||||||||||||||||
| Hypersensitivity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Infections and infestations | ||||||||||||||||||||||||
| Abdominal infection | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gastroenteritis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Herpes zoster | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Influenza | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Lung infection | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 3/37 (8.1%) | 3/21 (14.3%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pneumonia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 1/21 (4.8%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Respiratory tract infection | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Rhinitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Sebaceous gland infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Skin infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Soft tissue infection | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tonsillitis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Upper respiratory tract infection | 3/3 (100%) | 2/3 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 5/87 (5.7%) | 3/37 (8.1%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Urinary tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 5/87 (5.7%) | 3/37 (8.1%) | 3/21 (14.3%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Viral upper respiratory tract infection | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 1/20 (5%) | 2/20 (10%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Investigations | ||||||||||||||||||||||||
| Alanine aminotransferase increased | 2/3 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 3/22 (13.6%) | 22/87 (25.3%) | 7/37 (18.9%) | 7/21 (33.3%) | 1/20 (5%) | 5/20 (25%) | 0/7 (0%) | 3/7 (42.9%) | ||||||||||||
| Amylase increased | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Aspartate aminotransferase increased | 2/3 (66.7%) | 0/3 (0%) | 2/3 (66.7%) | 3/3 (100%) | 5/22 (22.7%) | 28/87 (32.2%) | 6/37 (16.2%) | 6/21 (28.6%) | 2/20 (10%) | 5/20 (25%) | 2/7 (28.6%) | 4/7 (57.1%) | ||||||||||||
| Bilirubin conjugated increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/22 (13.6%) | 2/87 (2.3%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood albumin decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 6/87 (6.9%) | 5/37 (13.5%) | 2/21 (9.5%) | 3/20 (15%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood bilirubin increased | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 5/22 (22.7%) | 14/87 (16.1%) | 2/37 (5.4%) | 0/21 (0%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood bilirubin unconjugated increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/22 (9.1%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood cholesterol increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood creatine phosphokinase increased | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 2/87 (2.3%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood glucose increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 3/21 (14.3%) | 1/20 (5%) | 1/20 (5%) | 1/7 (14.3%) | 2/7 (28.6%) | ||||||||||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/22 (13.6%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 4/20 (20%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Blood potassium decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood potassium increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood pressure increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood thyroid stimulating hormone decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 4/37 (10.8%) | 4/21 (19%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood thyroid stimulating hormone increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 5/22 (22.7%) | 3/87 (3.4%) | 6/37 (16.2%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood triglycerides increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/22 (18.2%) | 4/87 (4.6%) | 3/37 (8.1%) | 2/21 (9.5%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood urea increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 3/37 (8.1%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Blood uric acid increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 6/87 (6.9%) | 4/37 (10.8%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| C-reactive protein increased | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Creatinine renal clearance increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Electrocardiogram T wave abnormal | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Electrocardiogram abnormal | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Electrocardiogram low voltage | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Gamma-glutamyltransferase increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 8/87 (9.2%) | 10/37 (27%) | 4/21 (19%) | 4/20 (20%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Glucose urine present | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Granulocyte count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Heart rate increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 4/37 (10.8%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Lipase increased | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/22 (9.1%) | 10/87 (11.5%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Lymphocyte count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Mean cell haemoglobin concentration decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 4/21 (19%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Neutrophil count decreased | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 2/22 (9.1%) | 5/87 (5.7%) | 3/37 (8.1%) | 10/21 (47.6%) | 16/20 (80%) | 10/20 (50%) | 5/7 (71.4%) | 4/7 (57.1%) | ||||||||||||
| Neutrophil count increased | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Occult blood positive | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Platelet count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 7/87 (8%) | 2/37 (5.4%) | 2/21 (9.5%) | 14/20 (70%) | 16/20 (80%) | 2/7 (28.6%) | 0/7 (0%) | ||||||||||||
| Platelet count increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 2/7 (28.6%) | ||||||||||||
| Procalcitonin increased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Protein urine present | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Red blood cell count decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 2/21 (9.5%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Red blood cells urine positive | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/22 (13.6%) | 2/87 (2.3%) | 0/37 (0%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thyroid function test abnormal | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 18/87 (20.7%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 3/20 (15%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||||||||||
| Thyroxine decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thyroxine free decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thyroxine free increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Thyroxine increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 2/21 (9.5%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tri-iodothyronine decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/22 (9.1%) | 0/87 (0%) | 4/37 (10.8%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tri-iodothyronine free decreased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 4/37 (10.8%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tri-iodothyronine free increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 2/87 (2.3%) | 3/37 (8.1%) | 2/21 (9.5%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Urine ketone body present | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Weight decreased | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/22 (0%) | 6/87 (6.9%) | 5/37 (13.5%) | 1/21 (4.8%) | 3/20 (15%) | 1/20 (5%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Weight increased | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 8/87 (9.2%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| White blood cell count decreased | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 5/22 (22.7%) | 14/87 (16.1%) | 4/37 (10.8%) | 7/21 (33.3%) | 18/20 (90%) | 10/20 (50%) | 5/7 (71.4%) | 5/7 (71.4%) | ||||||||||||
| White blood cell count increased | 1/3 (33.3%) | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 3/37 (8.1%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| White blood cells urine positive | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Abnormal loss of weight | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Decreased appetite | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 5/87 (5.7%) | 6/37 (16.2%) | 8/21 (38.1%) | 8/20 (40%) | 2/20 (10%) | 3/7 (42.9%) | 6/7 (85.7%) | ||||||||||||
| Glucose tolerance impaired | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hypercholesterolaemia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hyperglycaemia | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 2/22 (9.1%) | 5/87 (5.7%) | 3/37 (8.1%) | 2/21 (9.5%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hyperkalaemia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hypernatraemia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hypertriglyceridaemia | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 3/37 (8.1%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hyperuricaemia | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 7/87 (8%) | 2/37 (5.4%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 3/7 (42.9%) | 2/7 (28.6%) | ||||||||||||
| Hypoalbuminaemia | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 14/87 (16.1%) | 5/37 (13.5%) | 1/21 (4.8%) | 5/20 (25%) | 0/20 (0%) | 2/7 (28.6%) | 3/7 (42.9%) | ||||||||||||
| Hypocalcaemia | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 10/87 (11.5%) | 1/37 (2.7%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||||||||||
| Hypochloraemia | 0/3 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||||||||||
| Hypokalaemia | 3/3 (100%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 11/87 (12.6%) | 2/37 (5.4%) | 1/21 (4.8%) | 2/20 (10%) | 3/20 (15%) | 3/7 (42.9%) | 1/7 (14.3%) | ||||||||||||
| Hypomagnesaemia | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 2/7 (28.6%) | 0/7 (0%) | ||||||||||||
| Hyponatraemia | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 10/87 (11.5%) | 4/37 (10.8%) | 1/21 (4.8%) | 2/20 (10%) | 0/20 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||||||||||
| Hypophosphataemia | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 5/87 (5.7%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 1/7 (14.3%) | 1/7 (14.3%) | ||||||||||||
| Hypoproteinaemia | 2/3 (66.7%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/22 (0%) | 13/87 (14.9%) | 1/37 (2.7%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Malnutrition | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 1/21 (4.8%) | 2/20 (10%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Metabolic alkalosis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 2/21 (9.5%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Back pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/22 (9.1%) | 9/87 (10.3%) | 5/37 (13.5%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Musculoskeletal pain | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Myalgia | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pain in extremity | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Haemangioma | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||
| Cholinergic syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Dizziness | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 3/21 (14.3%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 3/7 (42.9%) | ||||||||||||
| Headache | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 2/21 (9.5%) | 2/20 (10%) | 1/20 (5%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Hypoaesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 2/20 (10%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Paraesthesia | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Poor quality sleep | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Syncope | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||
| Breath holding | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Insomnia | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/22 (4.5%) | 0/87 (0%) | 4/37 (10.8%) | 3/21 (14.3%) | 3/20 (15%) | 1/20 (5%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||
| Acute kidney injury | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 1/21 (4.8%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Haematuria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Oliguria | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Proteinuria | 2/3 (66.7%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/22 (4.5%) | 22/87 (25.3%) | 5/37 (13.5%) | 1/21 (4.8%) | 4/20 (20%) | 2/20 (10%) | 2/7 (28.6%) | 3/7 (42.9%) | ||||||||||||
| Urethral pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Cough | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/22 (4.5%) | 7/87 (8%) | 5/37 (13.5%) | 1/21 (4.8%) | 1/20 (5%) | 1/20 (5%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Dyspnoea | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Epistaxis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 3/21 (14.3%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Haemoptysis | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 3/37 (8.1%) | 1/21 (4.8%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Interstitial lung disease | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Oropharyngeal pain | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 1/37 (2.7%) | 3/21 (14.3%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pleural effusion | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 1/37 (2.7%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pneumonitis | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 1/7 (14.3%) | 0/7 (0%) | ||||||||||||
| Productive cough | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 1/7 (14.3%) | ||||||||||||
| Respiratory failure | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Tachypnoea | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 2/37 (5.4%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Dermatitis allergic | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Drug eruption | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Eczema | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Night sweats | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 3/21 (14.3%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 1/20 (5%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Pruritus | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Rash | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 7/87 (8%) | 5/37 (13.5%) | 5/21 (23.8%) | 4/20 (20%) | 5/20 (25%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Rash maculo-papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Skin exfoliation | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Urticaria papular | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 1/20 (5%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Vitiligo | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/22 (18.2%) | 0/87 (0%) | 0/37 (0%) | 1/21 (4.8%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Vascular disorders | ||||||||||||||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/22 (0%) | 0/87 (0%) | 0/37 (0%) | 0/21 (0%) | 0/20 (0%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hypertension | 2/3 (66.7%) | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 0/22 (0%) | 6/87 (6.9%) | 0/37 (0%) | 2/21 (9.5%) | 6/20 (30%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
| Hypotension | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/22 (0%) | 1/87 (1.1%) | 0/37 (0%) | 0/21 (0%) | 2/20 (10%) | 0/20 (0%) | 0/7 (0%) | 0/7 (0%) | ||||||||||||
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.
Results Point of Contact
| Name/Title | Yi Bo |
|---|---|
| Organization | Innovent Biologics (Suzhou) Co., Ltd. (seal) |
| Phone | +8613382419112 |
| jessica.yi@innoventbio.com |
Responsible Party:
Innovent Biologics (Suzhou) Co. Ltd.
ClinicalTrials.gov Identifier:
NCT02937116
Other Study ID Numbers:
- CIBI308A101
First Posted:
Oct 18, 2016
Last Update Posted:
Feb 21, 2021
Last Verified:
Feb 1, 2021