Clinical trial NCT02488629
Conditions: Head and Neck Squamous Cell Carcinoma
Keywords: Head and neck squamous cell carcinoma
Sponsor: SynCore Biotechnology Co., Ltd.
Start date: 2015-09-01; Completion date: 2017-12-01
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
To evaluate the safety and efficacy of SCB01A in head and neck cancer.

Detailed description:
The study is designed to evaluate the safety and efficacy of SCB01A in patients with recurrent or metastatic squamous cell carcinoma in head and neck.

Arms: arm 1: This study is a single arm, open-label, Phase II trial
Interventions: intervention 1: SCB01A
Intervention descriptions: intervention 1: This study is a single arm, open-label, Phase II trial

Protocol documents:
Prot_000.pdf: 
Confidential 
Page 1 of 82 
Protocol Number: SCB01A-21 
An Open-Label, Phase II Study to Evaluate SCB01A in 
Patients with Recurrent or Metastatic Squamous Cell Head 
and Neck Cancer who have Received Platinum-Based 
Treatment
Author(s): 
SynCore Biotechnology Co., Ltd. 
Investigational Product: 
SCB01A 
Development Phase: 
Phase II 
Version/Date: 
Version 3.0 /25 Jul 2016 
SynCore Biotechnology Co., Ltd. 
No. 84 Chung-Shan Rd., 
Chung-Shan Village, 
Tung-Shan Shine, ILan, 
Taiwan, R.O.C. 
The information contained in this document is confidential and is the property of SynCore 
Biotechnology Co. Ltd.  This information should not be reproduced, revealed, or sent to third 
parties other than the Independent Ethics Committee / Institutional Review Board, Regulatory 
Authorities, and the Investigator’s research support staff for the conduct of the study, without the 
proper written authorisation of SynCore Biotechnology Co. Ltd. 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
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Page 2 of 82 
 
INVESTIGATOR SIGNATURE PAGE 
 
STUDY ACKNOWLEDGEMENT 
 
An Open-Label, Phase II Study to Evaluate SCB01A in Patients with Recurrent or 
Metastatic Squamous Cell Head and Neck Cancer who have Received Platinum-Based 
Treatment  
 
 
 SCB01A 
 
Amendment 3 
25 Jul 2016 
 
INVESTIGATOR STATEMENT 
I have read the protocol, including all appendices and the current Investigator’s 
Brochure (IB), and I agree that it contains all necessary details for me and my staff to 
conduct this study as described. I will conduct this study as outlined herein and will 
make a reasonable effort to complete the study within the time designated. 
I will provide all study personnel under my supervision copies of the protocol and 
access to all information provided by SynCore Biotechnology. I will discuss this 
material with them to ensure that they are fully informed about the drugs and the 
study. 
I will conduct the trial in accordance with the guidelines of Good Clinical Practice 
(GCP) including the archiving of essential documents, the Declaration of Helsinki, 
any applicable local health authority, and Institutional Review Board (IRB) 
requirements. 
 
 
 
 
Investigator Name (Printed) 
 
Institution 
 
 
 
 
Signature 
 
Date 
 
 
Please retain the original for your study files. 
 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 3 of 82 
Signature Page for Sponsor 
 
 
Protocol Number:  SCB01A-21 
 
Protocol Title:  An Open-Label, Phase II Study to Evaluate SCB01A in Patients with 
Recurrent or Metastatic Squamous Cell Head and Neck Cancer who have Received 
Platinum-Based Treatment 
 
SynCoreBio Approval(s): 
 
Muh-Hwan Su 
 
 
 
General Manager 
 
 
 
SynCore Biotechnology Co., Ltd. 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
Hui-Hung Wang 
 
 
 
Head of Project management 
 
 
 
SynCore Biotechnology Co., Ltd. 
 
 
 
 
Signature 
 
Date 
 
 
 
 
Chien-Chang Su 
 
 
 
Project Manager 
 
 
 
SynCore Biotechnology Co., Ltd. 
 
 
 
 
Signature 
 
Date 
 
 
 
 
Shoung-Hui Tsai 
 
 
 
Quality Assurance  
 
 
 
SynCore Biotechnology Co., Ltd. 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 
Ronelle Heath  
 
 
 
Biostatistician, Data Management 
 
 
 
Novotech Australia PTY LTD 
 
 
 
 
Signature 
 
Date 
 
 
 
 
 


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Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
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Page 4 of 82 
SUMMARY OF MAJOR PROTOCOL AMENDMENT CHANGES 
Amendment 3 
In addition to the major changes listed below, minor editorial changes were made 
throughout the document to correct typographical errors, and to improve consistency 
and clarity.  
 
Page 
Version: 2.0  (Date: Apr-8-2015) 
Version: 3.0  (Date: 25-Jul-2016) 
Reason/Rationale for 
the change 
1 
Version/Date: Version 2.0/ 08-
Apr-2015 
Version/Date: Version 3.0/ 2-
Mar-2016 
Version change 
2 
Signature Page for Sponsor: 
Chien-Chih Ou 
Head of Project Management 
SynCore Biotechnology Co., Ltd. 
 
Chi-Ling Liu 
Project Manager 
 
SynCore Biotechnology Co., Ltd. 
 
Ya-Tang Liao 
Quality Assurance 
SynCore Biotechnology Co., Ltd. 
Signature Page for Sponsor: 
Hui-Hung Wang 
Head of Project Management 
SynCore Biotechnology Co., Ltd. 
 
Chien-Chang Su 
Project Manager 
SynCore Biotechnology Co., Ltd. 
 
Shoung-Hui Tsai 
Quality Assurance 
SynCore Biotechnology Co., Ltd. 
Personnel change 
3 
Study Rationale: 
The research data available to date 
indicate 
that 
SCB01A 
is 
a 
promising anticancer agent with a 
vascular disrupting activity that 
has the potential for treatment of 
various malignancies, particularly 
for patients with drug resistance to 
existing therapies.  The drug has 
been trialed in human patients in 
an ongoing dose-escalation phase I 
study and shown to be safe for up 
to 2 cycles of 16 mg/m2 (each 
cycle consists of one intravenous 
[i.v.] administration of SCB01A 
via a central line every 3 weeks).  
In the phase I study, partial 
response (PR) (shrinkage of tumor 
size to 50%) was observed in 
cycle 9 (3 mg/m2) of one patient 
with right buccal squamous cell 
carcinoma 
and 
15/23 
(65%) 
patients had stable disease (SD) 
for more than 2 cycles.  A 
pre-clinical study of SCB01A 
showed that the concentration at 
which tubulin inhibition occurred 
was 200 nM.  Pharmacokinetic 
(PK) results demonstrated that 
average serum concentration of 
Study Rationale: 
The research data available to date 
indicate that SCB01A is a 
promising anticancer agent with a 
vascular disrupting activity that 
has the potential for treatment of 
various malignancies, particularly 
for patients with drug resistance to 
existing therapies.  The drug has 
been trailed in human patients in a 
dose-escalation phase I study and 
shown to be safe for up to 2 cycles 
of 24 mg/m2 (each cycle consists 
of one intravenous [i.v.] 
administration of SCB01A via a 
central line every 3 weeks).  In the 
phase I study, partial response 
(PR) (shrinkage of tumor size to 
50%) was observed in cycle 9 (3 
mg/m2) of one patient with right 
buccal squamous cell carcinoma 
and 19/33 (58%) patients had 
stable disease (SD) for more than 
2 cycles.  A pre-clinical study of 
SCB01A showed that the 
concentration at which tubulin 
inhibition occurred was 200 nM.  
Pharmacokinetic (PK) results 
demonstrated that average serum 
concentration of SCB01A reached 
To update the maximum 
tolerance dose and study 
information from finished 
phase I study 


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SCB01A reached 600 nM at 
16 mg/m2 suggesting 
that 
the 
current dose is safe and close to its 
probable 
efficacious 
concentration.  The aim of this 
Phase II study with SCB01A is to 
determine the effect of SCB01A in 
patients 
with 
squamous 
cell 
carcinoma of head and neck who 
have failed previous platinum 
based therapies. 
1000 nM at 24 mg/m2 suggesting 
that the current dose is safe and 
beyond its probable efficacious 
concentration. Based on both 
observed PK profile in Phase I 
study and also simulation data, 
the administration of SCB01A 
at 18 and 24 mg/m2 in D1 and 
D8 of a 21-days cycle will 
extend the duration of effective 
concentration in blood. One 
subject in the 24 mg/m2 cohort 
revealed that a higher blood 
concentration of SCB01A was 
not linked to the elevated 
incidence of adverse events. 
Besides, the severe peripheral 
neuropathy of one subject was 
clinically judged as probably 
related to SCB01A but also 
may be involved in other 
causes including underlying 
diabetic mellitus and previous 
cytotoxic medication. Another 
subject in the 32 mg/m2 cohort 
demonstrated that resolution of 
lower limb weakness after one 
week indicating the reversal of 
adverse events. 
The aim of this Phase II study 
with SCB01A is to determine the 
effect of SCB01A in patients with 
squamous cell carcinoma of head 
and neck who have failed previous 
platinum based therapies. 
4 
Study Design 
Run-in Phase 
During the run-in phase, three 
patients will be enrolled and will 
receive 
3 cycles 
of 
i.v. 
administration of SCB01A at a 
dose of 3.25 mg/m2 on Days 1 and 
8 of each cycle in a 3-week cycle 
(Dose 1).  If one of the three 
patients 
experiences 
a 
dose 
limiting toxicity (DLT) during the 
first 3 cycles, an additional three 
patients will be enrolled at the 
same dose level (Dose 1).  
 
Patients enrolled in the run-in 
phase must either complete 3 
Study Design 
Run-in Phase 
During the run-in phase, three 
patients will be enrolled to receive 
3 cycles of i.v. SCB01A at a dose 
of 3.25 mg/m2 (Dose 1) on Days 1 
and 8 of each cycle in a 3-week 
cycle (Dose 1).  If 1 or more of the 
three patients experiences a dose 
limiting toxicity (DLT) during the 
first 3 cycles, an additional three 
patients will be enrolled at the 
same dose level. If 0/3 or 1/6 i.e 
≤1 of subjects experience DLT at 
the given dose level, subject can 
be enrolled in the next higher dose 
cohort, and this process will 
To 
update 
the 
study 
procedures: 
a. Add 3 more dose 
levels in run-in 
phase; 
b. Clarify the dose 
escalation 
and 
de-escalation 
procedures 
in 
run-in phase; 


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cycles of study treatment or 
experience a DLT to be included 
in the Full Analysis Set (FAS) for 
the statistical analyses.  During the 
run-in phase, patients who do not 
complete the 3 cycles of study 
treatment, 
and 
who 
do 
not 
experience 
a 
DLT, 
will 
be 
replaced.  
continue until >1/6 of subjects 
experience DLT at certain dose 
level or the maximum dose in this 
protocol, 24 mg/ m2 (Dose 4) is 
reached. 
 
Patients enrolled in the run-in 
phase must either complete 3 
cycles of study treatment or 
experience a DLT to be included 
in the Full Analysis Set (FAS) for 
the statistical analyses.  During the 
run-in phase, patients who do not 
complete the 3 cycles of study 
treatment, 
and 
who 
do 
not 
experience 
a 
DLT, 
will 
be 
replaced. 
 
Rules for dose escalation for the 
run-in phase of the study are listed 
as following: 
1. Dosing will start at 3.25 
mg/m2 (Dose 1) in the 1st 
Cohort and can be escalated to 
12 mg/m2 (Dose 2), 18 mg/m2 
(Dose 3) and 24 mg/m2 (Dose 
4). If ≤1 subjects have DLT in 
a cohort of 24 mg/m2 (Dose 4), 
the 24 mg/m2 (Dose 4) will be 
determined as the Optimal 
Dose. 
2. If =1/3 subjects in a cohort 
have DLT(s), three more 
subjects to be enrolled at the 
same dose level or if  ≤1 
subjects (i.e 0/3 or 1/6) 
experience DLT then subjects 
can be enrolled into the next 
higher dose level as per 
below: 
Dose Level 3.25 mg/m2 
(Dose 1): Note: Dose 1 
cohort has been completed 
and no DLT seen, thus 
enrolment to start at Dose 
level 2 under current 
Protocol Amendement 3. 
a) Dose Level 12 mg/m2 
(Dose 2): If 1 patient 
experiences DLT then 3 


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additional patients to be 
enrolled in the same dose 
level. If the total DLT 
from 6 patients in the 
same dose level is ≤1 then 
move to the next higher 
dose level. If >1 patients 
have DLT then 3 patients 
to be enrolled at reduced 
dose of 10mg/ m2 (Dose 
1a). If 1 patient 
experiences DLT then 3 
additional patients to be 
enrolled in the same dose 
level. If ≤1 patient has 
DLT then dose level 
10mg/ m2 (Dose 1a) will 
be considered Optimal 
Dose. If >1 patients have 
DLT then dose will be 
further reduced to 5 
mg/m2 (Dose 0a) for the 
next 3 patients enrolled in 
the study. If 1 patient 
experiences DLT then 3 
additional patients to be 
enrolled in the same dose 
level. If ≤1 has patient 
DLT then dose level 5 
mg/m2 (Dose 0a) will be 
considered Optimal Dose. 
If >1 patients have DLT 
then 3.5 mg/m2 (Dose 1) 
will be considered MTD.   
b) Dose Level 18 mg/m2 
(Dose 3): If 1 patient 
experiences DLT then 3 
additional patients to be 
enrolled in the same dose 
level. If the total DLT 
from 6 patients in the 
same dose level is ≤1 then 
move to the next higher 
dose level. If >1  patient 
has DLT then 3 patients to 
be enrolled at reduced 
dose of 15mg/ m2 (Dose 


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2a). If 1 patient 
experiences DLT then 3 
additional patients to be 
enrolled in the same dose 
level. If ≤1 patient has 
DLT then dose level 
15mg/ m2 (Dose 2a) will 
be considered Optimal 
Dose. If >1 patient have 
DLT then 12 mg/m2 (Dose 
2) will be considered 
MTD.   
c) Dose Level 24 mg/m2 
(Dose 4): If 1 patient 
experiences DLT then 
enrol 3 additional patients 
in the same dose level. If 
the total DLT from 6 
patients at the same dose 
level is ≤1 then Dose 
Level 24 mg/m2 (Dose 4) 
will be the Optimal Dose. 
If >1 patient have DLT 
then 3 patients to be 
enrolled at the reduced 
dose of 21mg/ m2 (Dose 
3a). If 1 patient 
experiences DLT then 3 
additional patients to be 
enrolled in the same dose 
level. If ≤1 patient has 
DLT then dose level 
21mg/ m2 (Dose 3a) will 
be considered Optimal 
Dose. If >1 patients have 
DLT then 18 mg/m2 (Dose 
3) will be considered 
MTD.   
 
Phase II 
In the phase II of the study 
additional patients will be enrolled 
to evaluate the Optimal Dose as 
established by review of the safety 
committee.  
a) Stage 1: In stage 1 of 
phase II, 7 subjects to be 


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enrolled and dosed at the 
optimal dose level as 
established by the safety 
review committee. Note: 
In case only 3 patients 
were enrolled in the 
optimal dose cohort of the 
run-in phase then 10 
patients to be enrolled in 
stage 1 thus enrolling total 
13 subjects in the optimal 
dose level. 
b) Stage 2: Once all subjects 
have completed their 
treatment cycle in stage 1 
then a review by safety 
committee will be 
conducted to confirm if 
stage 2 can be initiated. If 
confirmed then stage 2 of 
the study will enrol 
additional 21 subjects who 
will be dosed at the same 
Optimal Dose level 
identified for stage 1.  
 
5 
Figure 1 Schematic Study 
Design 
 
 
Figure 
1 
Schematic 
Study 
Design 
To update the schematic 
study design 
 
6 
A safety committee will 
be 
established to: 
1. Evaluate all AEs, and 
laboratory safety data for the 
run-in phase; 
2. Decide on the recommended 
dose regimen of SCB01A for 
Phase II (Dose 1 or Dose 2). 
A safety committee will 
be 
established to: 
1. Evaluate all AEs, and 
laboratory safety data for the 
run-in phase; 
2. Decide on the recommended 
dose regimen of SCB01A for 
Phase II (Optimal Dose). 
To revise the of function 
of safety committee in 
defining Optimal Dose 
7 
Number of Planned Patients: 
Up to 40 patients will be enrolled, 
consisting of 3 to 6 patients in the 
run-in phase; 7 to 10 patients at 
Dose 1 or 13 patients at Dose 2 in 
stage 1 of Phase II and 21 patients 
Number of Planned Patients: 
Up to 64 patients will be enrolled, 
consisting up to 30 patients in the 
run-in phase; 7 to 10 patients at 
Stage 1 of Phase II at the ‘Optimal 
Dose’ and 21 patients in Stage 2 
To update the definition 
of optimal dose 


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in Stage 2 of Phase II.  During the 
run-in phase, any patients who do 
not complete the 3 cycles of study 
treatment, and do not experience a 
DLT, will be replaced, while no 
patients will be replaced during 
Phase II. 
of Phase II assuming replacement 
of 20% of patients in the run-in 
Phase.  During the run-in phase, 
any patients who do not complete 
the 3 cycles of study treatment, 
and do not experience a DLT, will 
be replaced, while no patients will 
be replaced during Phase II. 
8 
Investigational Product: 
Name: SCB01A 
Dose and Route of Administration 
 
Dose 1: one i.v. administration 
of 3.25 mg/m2 SCB01A on 
Days 1 and 8 of a 3-week 
cycle; or 
 
Dose 2: one i.v. administration 
of 6.5 mg/m2 SCB01A on Day 
1 of a 3-week cycle. 
Investigational Product: 
Name: SCB01A 
Dose and Route of Administration 
will be one of the following: 
 
Dose 1: one i.v. administration 
of 3.25 mg/m2 SCB01A on 
Days 1 and 8 of a 3-week 
cycle; or 
 
Dose 0a : one i.v. 
administration of 5 mg/m2 
SCB01A on Days 1 and 8 of a 
3-week cycle; or 
 
Dose 1a : one i.v. 
administration of 10 mg/m2 
SCB01A on Days 1 and 8 of a 
3-week cycle; or 
 
Dose 2: one i.v. administration 
of 12 mg/m2 SCB01A on 
Days 1 and 8 of a 3-week 
cycle  
 
Dose 2a : one i.v. 
administration of 15 mg/m2 
SCB01A on Days 1 and 8 of a 
3-week cycle; or 
 
Dose 3: one i.v. administration 
of 18 mg/m2 SCB01A on 
Days 1 and 8 of a 3-week 
cycle; or 
 
Dose 3a : one i.v. 
administration of 21 mg/m2 
SCB01A on Days 1 and 8 of a 
3-week cycle; or 
 
Dose 4: one i.v. administration 
of 24 mg/m2 SCB01A on 
Days 1 and 8 of a 3-week 
cycle or 
 
To revise the proposed 
study dose 
9 
According to a PP approach, all 
enrolled patients who meet the 
eligibility criteria and do not 
present major deviations during 
the study will be included in the 
analyses.  Inferential analysis 
results will be expressed as point 
estimates 
and 
their 
95% 
Both according to FAS and PP 
approaches (all enrolled patients 
who meet the eligibility criteria 
and 
do 
not 
present 
major 
deviations during the study) will 
be included in the analyses.  The 
conclusion will be summarized 
according to analyses of PP 
To revise the proposed 
statistical methods  


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confidence intervals (CIs).  To be 
consistent with the sample size 
calculation, the 90% CI will also 
be presented.  Analyses will be 
carried out using SAS® Software, 
version 
9.3 
or 
higher 
(SAS 
Institute, Cary, North Carolina, 
USA). 
population. 
Inferential analysis 
results will be expressed as point 
estimates 
and 
their 
95% 
confidence intervals (CIs).  To be 
consistent with the sample size 
calculation, the 90% CI will also 
be presented.  Analyses will be 
carried out using SAS® Software, 
version 
9.3 
or 
higher 
(SAS 
Institute, Cary, North Carolina, 
USA). 
10 
Duration of the Study: 
The planned duration of the entire 
study is approximately 24 months 
with an enrolment period of 6 
months. 
Duration of the Study: 
The planned duration of the entire 
study is approximately 30 months 
with an enrolment period of 12 
months. 
To update the duration of 
the study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Table of Contents 
1. 
Introduction ........................................................................................................ 35 
1.1. 
Background .................................................................................................. 35 
1.2. 
Rationale for the Study ................................................................................ 36 
2. 
Study Objectives ................................................................................................. 37 
2.1. 
Run-In Phase: ............................................................................................... 37 
2.2. 
Phase II: ....................................................................................................... 37 
3. 
Investigational Plan ........................................................................................... 38 
3.1. 
Description of Overall Study Design and Plan ............................................ 38 
3.2. 
Run-In Phase ................................................................................................ 40 
3.2.1 
Screening Evaluations ....................................................................................... 40 
3.2.2 
Cycle 1, Day 1 (C1D1) ...................................................................................... 41 
3.2.3 
Cycle 1, Day 8 (C1D8) ±1 day .......................................................................... 41 
3.2.4 
Cycle 1, Day 15 (C1D15) ±2 days ..................................................................... 42 
3.2.5 
Cycle 2, Day 1 (C2D1) ±1 day .......................................................................... 42 
3.2.6 
Cycle 2, Day 8 (C2D8) ±1 day .......................................................................... 42 
3.2.7 
Cycle 2, Day 15 (C2D15) ±2 days ..................................................................... 42 
3.2.8 
Cycle 3, Day 1 (C3D1) ±1 day .......................................................................... 42 
3.2.9 
Cycle 3, Day 8 (C3D8) ±1 day .......................................................................... 43 
3.2.10 
Cycle 3, Day 15 (C3D15) ±2 days ................................................................ 43 
3.2.11 
3.2.11 Cycle 4, Days 1 and 8 (C4D1 and C4D8) .......................................... 43 
3.3. 
Phase II ......................................................................................................... 43 
3.3.1 
Screening Evaluations ....................................................................................... 43 
3.3.2 
Cycle 1, Day 1 (C1D1) (Optimal Dose)) ........................................................... 43 
3.3.3 
Cycle 1, Day 8 (C1D8) ±1 day (Optimal Dose) ................................................ 44 
3.3.4 
Cycle 1, Day 15 (C1D15) ±2 days (Optimal Dose) ........................................... 44 
3.3.5 
Cycle 2, Day 1 (C2D1) ±1 day (Optimal Dose) ................................................ 44 
3.3.6 
Cycle 2, Day 8 (C2D8) ±1 day (Optimal Dose) ................................................ 45 
3.3.7 
Cycle 2, Day 15 (C2D15) ±2 days ( Optimal Dose) .......................................... 45 
3.3.8 
Cycles >2, Day 1 ±1 day (Optimal Dose) .......................................................... 45 
3.3.9 
Cycles >2, Day 8 ±1 day ( Optimal Dose) ......................................................... 45 
3.3.10 
Cycles >2, Day 15 ±2 days ( Optimal Dose) ................................................. 45 
3.4. 
End of Treatment (EOT) Evaluation/Early Withdrawal .............................. 45 
3.5. 
Follow-up ..................................................................................................... 46 
3.6. 
Unscheduled Visit ........................................................................................ 46 
3.7. 
Study Design, Including the Choice of Control Groups .............................. 46 
3.8. 
Selection of Study Population ...................................................................... 46 
3.8.1. 
Inclusion Criteria: .................................................................................... 46 
3.8.2. 
Exclusion Criteria: ................................................................................... 47 
3.9. 
Removal of Patients from Treatment or Assessment ................................... 48 
3.9.1. 
Early Discontinuation of the Study .......................................................... 48 
3.9.2. 
Early Discontinuation of Individual Patients ........................................... 48 
4. 
Treatments .......................................................................................................... 48 


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4.1. 
Identity of Investigational Product (IP) ....................................................... 48 
4.2. 
Study Drug Packaging and Labeling ........................................................... 49 
4.3. 
Study Drug Storage Conditions ................................................................... 49 
4.4. 
Study Drug Dose Preparation and Administration ...................................... 49 
4.5. 
Study Drug Accountability .......................................................................... 49 
4.6. 
Method of Assigning Patients to Treatment Groups .................................... 49 
4.7. 
Selection of Doses in the Study ................................................................... 49 
4.8. 
Selection and Timing of Dose for each Patient ........................................... 50 
4.9. 
Dose Adjustment and Toxicity Management .............................................. 50 
4.10. Blinding ........................................................................................................ 50 
4.11. Prior and Concomitant Therapy ................................................................... 50 
4.12. Prohibited Medications ................................................................................ 51 
4.13. Treatment Compliance ................................................................................. 51 
5. 
Study Assessments and Procedures .................................................................. 51 
5.1. 
Safety Procedures and Assessments ............................................................ 51 
5.1.1. 
Medical History......................................................................................... 51 
5.1.2. 
Physical Examination ................................................................................ 52 
5.1.3. 
BSA Calculation ....................................................................................... 52 
5.1.4. 
Vital Signs ................................................................................................. 53 
5.2. 
ECOG Performance Status .......................................................................... 53 
5.3. 
12-lead ECG ................................................................................................. 53 
5.4. 
DCE-MRI ..................................................................................................... 54 
5.5. 
Safety Laboratory Assessments ................................................................... 54 
5.6. 
Bioanalytical Assessments ........................................................................... 55 
5.7. 
EORTC QLQ-C30 ....................................................................................... 55 
5.8. 
EORTC QLQ H&N35 ................................................................................. 55 
5.9. 
Nerve Conduction Velocity ......................................................................... 56 
5.10. Appropriateness of Measurements ............................................................... 56 
6. 
Safety and Efficacy Variables ........................................................................... 56 
6.1. 
Efficacy Measurements ................................................................................ 56 
6.2. 
Dose Limiting Toxicity (DLT) .................................................................... 56 
6.3. 
Safety Measurements ................................................................................... 57 
6.4. 
Pharmacokinetic Measurements .................................................................. 57 
6.5. 
Bioanalytical Measurements ........................................................................ 57 
6.6. 
Health outcomes measurements ................................................................... 58 
7. 
Adverse Events Definitions and Reporting ...................................................... 58 
7.1. 
Adverse Events ............................................................................................ 58 
7.1.1. 
Intensity Assessment ................................................................................ 59 
7.1.2. 
Causality Assessment ............................................................................... 59 
7.2. 
Adverse Event Reporting ............................................................................. 60 
7.3. 
Serious Adverse Events (SAEs) ................................................................... 60 


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7.4. 
Serious Adverse Event Reporting ................................................................ 61 
7.5. 
Pregnancies .................................................................................................. 62 
8. 
Statistical Methods and Determination of Sample Size .................................. 63 
8.1. 
Statistical and Analytical Plans .................................................................... 63 
8.2. 
Determination of Sample Size ..................................................................... 63 
8.3. 
Populations for Analysis .............................................................................. 63 
8.4. 
Safety Analysis ............................................................................................ 64 
8.5. 
Efficacy Analysis ......................................................................................... 65 
8.6. 
PK Analysis ................................................................................................. 65 
8.7. 
Health Outcomes Assessments .................................................................... 65 
8.8. 
Interim Analysis ........................................................................................... 66 
9. 
Study Management ............................................................................................ 66 
9.1. 
Regulatory Guidelines ................................................................................. 66 
9.2. 
Ethics ............................................................................................................ 66 
9.2.1. 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC)66 
9.2.2. 
Ethical Conduct of the Study ................................................................... 66 
9.3. 
Patient Information and Consent ................................................................. 66 
9.4. 
Confidentiality and Disclosure .................................................................... 67 
9.5. 
Indemnification ............................................................................................ 67 
9.6. 
Discontinuation of the Study by the Sponsor .............................................. 67 
9.7. 
Study Documentation ................................................................................... 67 
9.8. 
Data Handling and Record Retention .......................................................... 68 
9.8.1. 
Source Documents ................................................................................... 68 
9.8.2. 
Recording and Collection of Data ............................................................ 68 
9.8.3. 
Clinical Data Management ...................................................................... 68 
9.8.4. 
Archiving ................................................................................................. 69 
9.9. 
Monitoring ................................................................................................... 69 
9.10. Protocol Amendments, other Changes in Study Conduct ............................ 69 
9.10.1. 
Protocol Amendments .............................................................................. 69 
9.10.2. 
Other Changes in Study Conduct ............................................................. 69 
9.11. Quality Control and Quality Assurance ....................................................... 69 
9.12. Publication Policy ........................................................................................ 70 
10. 
References ....................................................................................................... 71 
11. 
Appendices ...................................................................................................... 72 
11.1. Appendix 1 –  Reference List of Known Inhibitors of CYP1A2 and 
CYP2D6 Inhibitors .................................................................................................. 72 
11.2. Appendix 2 – Declaration of Helsinki ....................................................... 74 
11.3. Appendix 3– Questionnaires EORTC QLQ C30 and QLQ H&N35 ......... 78 
 
Tables 


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Table 1: 
Study Schedule, Run-in phase (Dose 1, 0a, 1a, 2, 2a, 3, 3a, and 4 
SCB01A) 
…………………………………………………………………………..31 
Table 2: 
Study Schedule, Phase II, Stage 1 and Stage 2, Optimal dose SCB01A . 33 
Table 3: 
ECOG Performance Status Scale ............................................................. 53 
 
 
 
 
Figures 
 
Figure 1: 
Schematic Study Design .......................................................................... 23 
Figure 2: 
Schematic Study Design .......................................................................... 39 
 


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LIST OF ABBREVIATIONS: 
 
Abbreviation 
Definition 
AE(s) 
Adverse Event(s) 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANC 
Absolute Neutrophil Count 
AST 
Aspartate Aminotransferase 
AUC0-inf 
Area Under the Plasma Concentration-time Curve from Time Zero to 
Infinite Time 
AUC0-t 
Area Under the Plasma Concentration-time Curve from Time Zero to 
Time t 
BSA 
Body Surface Area 
CEC 
Circulating Endothelial Cells 
CEP 
Circulating Endothelial Progenitor  
Ck 
Creatine Kinase 
CL 
Clearance 
Cmax 
Maximum Plasma Concentration 
CR 
Complete Response 
CRO 
Clinical Research Organization 
CT 
Computerized Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCE-MRI 
Dynamic Contrast-Enhanced MRI 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EORTC QLQ 
European Organization for Research and Treatment of Cancer Quality 
of Life Questionnaire 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GGT 
Gammy Glutamyltransferase 
Hb 
Hemoglobin 
HDL 
High-density Lipoprotein 
HPLC/MS-MS 
High-Performance 
Liquid 
Chromatography/Tandem 
Mass 
Spectrometry 
HPV 
Human Papillomavirus 


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Abbreviation 
Definition 
Hct 
Hematocrit 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IHC 
Immunohistochemistry 
IND 
Investigational New Drug 
INR 
International Normalized Ratio 
IP 
Investigational Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
Kel 
Elimination Constant 
LDL 
Low-density Lipoprotein 
MedDRA 
Medical Dictionary for Regulatory Activities 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MRI 
Magnetic Resonance Imaging 
MRT 
Mean Residence Time 
NCV 
Nerve Conduction Velocity 
PK 
Pharmacokinetic 
PP 
Per-Protocol 
PR 
Partial Response 
PT 
Prothrombin 
RBC 
Red Blood Cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE(s) 
Serious Adverse Event(s) 
SD 
Stable Disease 
SOP 
Standard Operating Procedure 
t1/2 
Half-life 
TEAE 
Treatment Emergent Adverse Event 
TG 
Triglycerides 
Tmax 
Time to Maximum Concentration 
ULN 
Upper Limit of Normal 
Vd 
Volume of Distribution 
VEGF 
Vascular Endothelial Growth Factor 


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Abbreviation 
Definition 
WBC 
White Blood Cell 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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SYNOPSIS 
 
Title of Study: 
An Open-Label, Phase II Study to Evaluate SCB01A in Patients with 
Recurrent or Metastatic Squamous Cell Head and Neck Cancer who 
have Received Platinum-Based Treatment  
Sponsor: 
SynCore Biotechnology Co., Ltd. No. 84 Chung-Shan Rd., Chung-Shan 
Village, Tung-Shan Shine, ILan, Taiwan, R.O.C. 
Principal/ 
Coordinating 
Investigator: 
Dr. Cheng-Hsu Wang, Director, Keelung Chang Gung Cancer Center,  
Keelung Chang Gung Memorial Hospital, Keelung, Taiwan 
Investigational 
Product (IP): 
SCB01A 
Protocol 
Number: 
SCB01A-21 
Indication: 
Recurrent or metastatic squamous cell carcinoma of head and neck 
Phase of 
Development: 
Phase II 
Study Centers: 
4–8 sites in Taiwan 
Study Rationale: From pre-clinical pharmacology and phase I clinical study SCB01A has 
demonstrated promising anticancer action with a vascular disrupting 
activity that has the potential for treatment of various malignancies, 
particularly for patients with drug resistance.  The drug has been studied 
in human patients in a dose-escalation phase I study and has shown to be 
safe for up to 2 cycles of 24 mg/m2 (each cycle consisting of one 
intravenous [i.v.] administration of SCB01A via a central line every 
3 weeks).  In the phase I study, partial response (PR) (shrinkage of tumor 
size to 50%) was observed in cycle 9 (3 mg/m2) of one patient with right 
buccal squamous cell carcinoma and 19/33 (58%) patients had stable 
disease (SD) for more than 2 cycles.   
Pre-clinical study of SCB01A showed that the concentration at which 
tubulin inhibition occurred was 200 nM.  Pharmacokinetic (PK) results 
demonstrated that average serum concentration of SCB01A reached 
1000 nM at 24 mg/m2 suggesting that the current dose is safe and beyond 
its probable efficacious concentration. Based on both observed PK 
profile in Phase I study and also simulation data, the administration of 
SCB01A at 18 and 24 mg/m2 in D1 and D8 of a 21-days cycle will 
extend the duration of effective concentration in blood. One subject in 
the 24 mg/m2 cohort revealed that a higher blood concentration of 
SCB01A was not linked to the elevated incidence of adverse events. 
Besides, the severe peripheral neuropathy of one subject was clinically 
judged as probably related to SCB01A but also may be involved in other 
causes including underlying diabetic mellitus and previous cytotoxic 
medication. Another subject in the 32 mg/m2 cohort demonstrated that 
resolution of lower limb weakness after one week indicating the reversal 
of adverse events. 
The aim of this study is to determine the effect of SCB01A in patients 


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with squamous cell carcinoma of head and neck who have failed 
previous platinum based therapies. 
Study 
Objectives: 
Objective: 
 
The study is designed with a run-in phase and the continuation phase 
(Phase II) is to evaluate the safety and efficacy of SCB01A in patients 
with recurrent or metastatic squamous cell carcinoma of head and neck. 
Run-in phase 
Primary Objective:  
To determine the optimal dose for 3 cycles of i.v. administration of 
SCB01A on Days 1 and 8 of each cycle in a 3-week cycle  
  
Secondary Objective: 
To evaluate the safety and toxicity for 3 cycles of i.v. administration of 
SCB01A on Days 1 and 8 of each cycle in a 3-week cycle 
  
Phase II  
Primary Objective: 
To assess the disease control rate (DCR) at the end of the 9th week 
(3 cycles, each cycle consists of 21 days) after treatment with SCB01A, 
according to the Response Evaluation Criteria in Solid Tumors 
(RECIST) version 1.1. 
  
Secondary Objectives: 
        To assess the overall survival (OS) rate at 36 weeks after first 
treatment with SCB01A in patients with recurrent or metastatic 
squamous cell head and neck cancer who have previously been 
treated with platinum therapy. 
        To assess the progression-free survival (PFS) 
        To assess the PK profile of SCB01A of patients in the run-in phase. 
       To assess health outcomes using patient-reported European 
Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire-C30 (EORTC QLQ-C30) and EORTC QLQ H&N35 
questionnaires. 
        To assess biomarkers relevant to the efficacy and mechanism of 
action of SCB01A. 
        To explore the possible association between biomarkers and clinical 
outcomes 
Study Design: 
Multicenter, open-label, phase II study of SCB01A administered to 
patients with recurrent or metastatic squamous cell carcinoma of head 
and neck. The study will be conducted in two parts.  
 
 
 
 
Run-in Phase I (Dose Escalation Phase):  


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The first part of the study involves dose-escalation, in which successive 
cohorts of three patients (expanded to six patients in the event of a dose-
limiting toxicity) will receive escalating doses of SCB01A until 24 
mg/m2. Dose escalation assessment will be based on tolerability observed 
during 3 cycles of treatment. An Optimal Dose will be agreed upon.  
 
 During the run-in phase, three patients will be enrolled and will receive 
3 cycles of i.v. administration of SCB01A at a dose of 3.25 mg/m2 (Dose 
1) on Days 1 and 8 of each cycle in a 3-week cycle (Dose 1).  If 1 of the 
three patients experiences a dose limiting toxicity (DLT) during the first 
3 cycles, an additional three patients will be enrolled at the same dose 
level. If 0/6 or 1/6 i.e ≤1 of subjects experienced DLT at the given dose 
level, the dose of the subsequent cohort will be increased to the next 
level, then this process will continue until >1/6 of subjects experience 
DLT at certain dose level or the maximum dose in this protocol, 24 mg/ 
m2 (Dose 4) is reached. 
 
Patients enrolled in the run-in phase must either complete 3 cycles of 
study treatment or experience a DLT to be included in the Full Analysis 
Set (FAS) for the statistical analyses.  During the run-in phase, patients 
who do not complete the 3 cycles of study treatment, and who do not 
experience a DLT, will be replaced. 
 
Rules for dose escalation for the run-in phase of the study are listed as 
following: 
1. Dose level will start at 3.25 mg/m2 (Dose 1) in the 1st Cohort and can 
be escalated to 12 mg/m2 (Dose 2), 18 mg/m2 (Dose 3) and 24 mg/m2 
(Dose 4). If ≤1 subjects have DLT in a cohort of 24 mg/m2 (Dose 4), 
the 24 mg/m2 (Dose 4) will be determined as the Optimal Dose. 
2. If =1/3 subjects in a cohort have DLT(s), enrol three more subjects 
at the same dose level or if  ≤1 subjects (i.e., 0/3 or 1/6) experience 
DLT then subjects can be enrolled into the next higher dose level as 
per below: 
a) Dose Level 3.25 mg/m2 (Dose 1): This dose level has been 
completed as part of protocol amendment #2 and ≤1 patient 
experienced DLT. Patients will be enrolled in the next dose level 
based on results from 3.25 mg/m2 (Dose 1) Cohort. 
b) Dose Level 12 mg/m2 (Dose 2): If 1 patient experiences DLT 
then 3 additional patients to be enrolled in the same dose level. 
If the total DLT from 6 patients at the same dose level is ≤1, 
then the study to move to the next higher dose level. If >1 
patients have DLT, then 3 patients to be enrolled at the reduced 
dose of 10 mg/ m2 (Dose 1a).  
c) Dose level 10 mg/ m2 (Dose 1a): If 1 patient experiences DLT 
then 3 additional patients to be enrolled in the same dose level. 
If ≤1 patient has DLT then dose level 10mg/ m2 (Dose 1a) will 
be considered Optimal Dose. If >1 patients have DLT then dose 
will be further reduced to 5 mg/m2 (Dose 0a) for the next 3 
patients enrolled in the study. 


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d) Dose level 5 mg/m2 (Dose 0a): If 1 patient experiences DLT 
then we enrol 3 additional patient in the same dose level. If ≤1 
has patient DLT then dose level 5 mg/m2 (Dose 0a) will be 
considered Optimal Dose. If >1 patients have DLT then 3.5 
mg/m2 (Dose 1) will be considered MTD. 
e) Dose Level 18 mg/m2 (Dose 3): If 1 patient experiences DLT 
then we enrol 3 additional patient in the same dose level. If the 
total DLT from 6 patients in the same dose level is ≤1 then we 
move to the next higher dose level.  
f) Dose Level 15 mg/m2 (Dose 2a):  If >1 patient have DLT in 
Dose 3,  then 3 patients to be enrolled at a reduced dose of 
15mg/ m2 (Dose 2a). If 1 patient experiences DLT then 3 
additional patients to be enrolled in the same dose level. If ≤1 
patient has DLT then dose level 15mg/ m2 (Dose 2a) will be 
considered Optimal Dose. If >1 patients have DLT then 12 
mg/m2 (Dose 2) will be considered MTD.  
g) Dose Level 24 mg/m2 (Dose 4): If 1 patient experiences DLT 
then 3 additional patients to be enrolled in the same dose level. 
If the total DLT from 6 patients at the same dose level is ≤1 
then Dose Level 24 mg/m2 (Dose 4) will be the Optimal Dose.  
h) Dose Level 21mg/m2 (Dose 3a): If >1 patient has DLT in Dose 
4, then 3 patients to be enrolled at reduced dose of 21mg/ m2 
(Dose 3a). If 1 patient experiences DLT then 3 additional patient 
to be enrolled in the same dose level. If ≤1 patient has DLT then 
dose level 21mg/ m2 (Dose 3a) will be considered Optimal Dose. 
If >1 patients have DLT then 18 mg/m2 (Dose 3) will be 
considered MTD.   
 
Phase II :  
In the phase II of the study additional patients will be enrolled to 
evaluate the Optimal Dose as established by review of the safety 
committee.  
 
Stage 1: In stage 1 of phase II, 7 subjects will be enrolled and dosed at 
the optimal dose level as established by the safety review committee. 
Note: In case only 3 patients were enrolled in the optimal dose cohort of 
the run-in phase then 10 patients will be enrolled in stage 1 thus 
enrolling total 13 subjects in the optimal dose level. 
Stage 2: Once all subjects have completed their treatment cycle in stage 
1 then a review by safety committee will be conducted to confirm if 
stage 2 can be initiated. If confirmed then stage 2 of the study will enrol 
additional 21 subjects who will be dosed at the same Optimal Dose level 
identified for stage 1 
No patients will be replaced in the continuation phase (Phase II). 


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Figure 1: 
Schematic Study Design 
 
All patients will be treated until the occurrence of progressive disease, 
intolerable adverse events (AEs)/toxicity, consent withdrawal or death.  
After discontinuation of study treatment, all patients will be followed for 
survival and disease-specific therapies of the clinician’s choice will be 
administered.  Follow-up visits will be scheduled every 3 weeks for 
9 weeks, thereafter every 9 weeks until the end of the study. 
The study will be completed 36 weeks after the last patient has received 
their 1st treatment with SCB01A. 
 
Dose Limiting Toxicity (DLT) definition (in run-in phase) 
 
All toxicities will be classified according to the National Cancer 
Institute (NCI) Common Terminology Criteria for AEs (CTCAE) 
version 4.03.  DLT will be defined as the occurrence of any of the 
following criteria unless there is definitive alternative evidence that 
administration of SCB01A did not cause the specific toxicity: 
1. Grade 4 neutropenia exceeding 5 days duration; 
2. Grade 4 thrombocytopenia; 
3. Grade 4 anemia; 
4. Grade 3 or greater neutropenia with complications (e.g., fever, 
infection, etc.); 
5. Grade 3 or greater thrombocytopenia with complications (e.g., 
bleeding); 
6. Grade 3 or greater non-hematological AEs including Grade 3 
unmanageable nausea and vomiting that persist for 3 or more 
days after drug administration.  Grade 3 fatigue lasting for 
≤1 week is not considered as a DLT; 
7. Grade 3 or greater prolonged QTc interval; 
8. Grade 3 or greater neurotoxicity; 
9. Delayed treatment is exceeding 14 days duration due to drug-


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related toxicity. 
 
Safety Monitoring Committee (SRC) 
 
The SRC, composed of the principle investigators at each 
participating site, an independent medical monitor (physician 
experienced in oncology studies), and medical and safety 
representatives of the Sponsor, will be responsible for making 
decisions regarding dose escalation, determining the recommended 
dose, and starting enrollment of cohort expansions. Serial 
assessments of PK results also may be taken into account for the 
determination of the MTD and Optimal Dose.   
Safety Monitoring Committee will meet after completion of Each 
Cohort in the Run-in Phase and after the completion of Phase II stage 
1.  
 
MTD Definition  
The MTD is defined as the dose immediately preceding the dose level 
at which DLTs are observed in 2 or more patients.  
Number of 
Planned 
Patients: 
Up to 64 patients will be enrolled, consisting up to 30 patients in the run-
in phase; 7 to 10 patients at Stage 1 of Phase II at the ‘Optimal Dose’ 
and 21 patients in Stage 2 of Phase II.  During the run-in phase, any 
patients who do not complete the 3 cycles of study treatment, and do not 
experience a DLT, will be replaced, while no patients will be replaced 
during Phase II. 
Diagnosis and 
main criteria for 
enrolment: 
Inclusion Criteria: 
1. Aged ≥20 years; 
2. Signed informed consent obtained prior to initiation of any 
study-specific procedures and treatment;  
3. Histological or cytological confirmed squamous cell carcinoma 
of head and neck; 
4. Patients with non-resectable, unfeasible radiotherapy, recurrent 
or metastatic head and neck squamous cell carcinoma, after 
previous treatment with a platinum agent; 
5. At least one measurable tumor lesion  toas defined by RECIST 
version 1.1 as assessed by the investigator (local radiological 
image assessment); 
6. Eastern Cooperative Oncology Group (ECOG) Performance 
Status  (PS) 0-2;  
7. Life expectancy of 12 weeks or longer; 
8. Patients must have radiological measurable or clinically 
evaluable disease.  Physical examination and radiographic 
studies have to be performed within 28 days of enrolment; 
9. Concurrent local therapy is not allowed, but concurrent 
palliative radiation therapy to non-measurable sites of disease 
such as painful bone metastasis is permitted; 
10. All eligible patients of childbearing potential have to use 


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effective contraception; that is, double barrier contraceptive 
methods; 
11. Documented progressive disease within past 6 months; 
12. Adequate bone marrow reserve, cardiac, renal and liver 
function: 
 
a. Absolute neutrophil count (ANC) > 1.5 x 109/L; 
b. White blood cell (WBC) > 3 x 109/L  
c. Platelet count > 75 x 109/L;  
d. Hemoglobin > 9 g/dL (> 5.6 mmol/l); 
e. Prothrombin time (PT)/international normalized ratio 
(INR) ≤1.5 x upper limit of normal (ULN)  
f. Creatinine clearance (Cockcroft & Gault formula) >50 
mL/min;  
g. Alanine aminotransferase (ALT, SGPT) and aspartate  
                         aminotransferase (AST, SGOT) and Alkaline 
                         Phosphatase (ALP) < 3 x ULN.     
h. Serum albumin ≥ 3 g/dL;  
i. 
INR ≤ 1.5 x ULN  
j. 
Total Bilirubin  ≤ 1.5 x ULN 
 
Exclusion Criteria: 
1. Known primary CNS malignancy or CNS involvement (except 
for brain metastases that have been treated and are stable and 
patient is off steroids);  
2. Systemic cancer therapy, Chemotherapy, radiation therapy, 
major surgery or investigational agents less than 4 weeks prior 
to study drug treatment; 
3. History of malignancy other than head and neck cancer.  Second 
primary head and neck tumors are excluded with the exception 
of early stage non-melanoma skin cancer or carcinoma in situ of 
cervix; 
4. Ultrasound or radiological evidence of liver cirrhosis; 
5. Severe pulmonary obstructive or restrictive disease; 
6. Uncontrolled inflammatory disease (autoimmune or infectious); 
7. Clinically significant cardiac disease (NYHA class > 2); 
8. Other serious illness or medial conditions, such as active 
infection, 
unresolved 
bowel 
obstruction, 
or 
psychiatric 
disorders;  
9. Known HIV positivity;  
10. Participation in another clinical trial or treatment with any 
investigational drug within 30 days prior to study entry;  
11. QTc > 450 msec; 
12. Pregnant or breast-feeding patients, and men and women of 
child-bearing potential not using effective contraception while 
on study treatment;Known hypersensitivity to any component of 
SCB01A; 


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13. History of exposure to SCB01A or its analogues; 
14.  History of active or significant neurological disorder or 
psychiatric disorder that would prohibit the understanding and 
giving of informed consent, or would interfere with the clinical 
and radiological evaluation of central nervous system during the 
trial; 
15. Any other reason the investigator deems the patient to be 
unsuitable for the study 
Duration of 
Treatment: 
Patients will receive the recommended dose of monotherapy of SCB01A 
for 9 weeks (3wk*3 cycles) or until disease progression, intolerable 
toxicity, consent withdrawal or death, whichever occurs first. 
Endpoints: 
Primary endpoint: 
 
DCR, defined as; complete response (CR) + partial response (PR) + 
stable disease (SD) at Week 9, according to RECIST v1.1 criteria 
Secondary endpoints: 
 
PFS 
 
OS rate at 36 weeks after first treatment with SCB01A 
 
Safety:  The safety endpoints used to achieve the secondary 
objectives of this study are: 
o Hematology, clinical chemistry, coagulation factors and 
urinalysis laboratory data changes  
o AE/SAE incidence 
o Physical examination results changes 
o Vital sign changes 
o Electrocardiogram (ECG) (including PR, QRS, QT, QTc, 
and RR intervals) results 
 
Health outcomes assessment using patient-reported EORTC 
QLQ-C30 and H&N35 questionnaires. 
Criteria for 
Evaluation: 
Efficacy measurements: 
Tumor Measurement: 
Tumor response will be assessed by using computerized tomography 
(CT) or MRI scans according to RECIST v1.1 at baseline, and every 
3 cycles prior to the next cycle until progression of the disease.  For 
patients who meet DC criteria after the first 3 cycles of study treatment, 
additional radiological tumor assessments will be performed at Week 12. 
Scans must include brain, chest, abdomen, and pelvis.  The imaging 
technique used at baseline should be used throughout the study.  
Patients will be considered evaluable for DCR in this study if they fulfill 
the criteria for evaluation according to RECIST v1.1, i.e., those patients 
who undergo a baseline disease assessment within 4 weeks of treatment 
initiation, and who undergo at least 1 disease assessment on the study. 
 
 
DCR is defined as the percentage of patients who have achieved CR, 
PR and SD at a particular time point after first treatment, according 


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to RECIST v1.1. 
 
PFS is defined as the time from the start of treatment up to the date 
of first progression based on RECIST v1.1, second primary 
malignancy or death from any cause, whichever occurs first.  
 
OS rate is defined as the percentage of patients who are still alive at 
a particular time point after first treatment with SCB01A  
Survival data will be collected throughout the active treatment phase and 
during the 36 weeks follow-up period.  Survival follow-up after patient 
discontinuation of treatment will be conducted every 3 weeks during the 
first 9 weeks, thereafter every 9 weeks until the end of the study to 
assess for survival.  Survival rate will only be assessed in patients with 
measurable disease at baseline. 
 
Dose Limiting Toxicity (DLT) (only in run-in phase) 
 
All toxicities will be classified according to the National Cancer 
Institute (NCI) Common Terminology Criteria for AEs (CTCAE) 
version 4.03.  DLT will be defined as the occurrence of any of the 
following criteria unless there is definitive alternative evidence that 
administration of SCB01A did not cause the specific toxicity: 
1. Grade 4 neutropenia exceeding 5 days’ duration; 
2. Grade 4 thrombocytopenia; 
3. Grade 4 anemia; 
4. Grade 3 or greater neutropenia with complications (e.g., 
fever, infection, etc.); 
5. Grade 3 or greater thrombocytopenia with complications 
(e.g., bleeding); 
6. Grade 3 or greater non-hematological AEs including 
Grade 3 unmanageable nausea and vomiting that persist 
for 3 or more days after drug administration.  Grade 3 
fatigue lasting for ≤1 week is not considered as a DLT; 
7. Grade 3 or greater prolonged QTc interval; 
8. Grade 3 or greater neurotoxicity; 
9. Delayed treatment exceeding 14 days duration due to 
drug-related toxicity. 
Safety measurements: 
 
Incidence and intensity of AEs evaluated using the CTCAE 
version 4.03 
 
Incidence and intensity of clinically significant abnormal laboratory 
values evaluated using the CTCAE version 4.03 
 
Percentage of patients experiencing dose modifications including 
delays or omissions or discontinuation of study medication 
 
Physical examination findings 
 
Vital signs measurements 
 
ECG (including PR, QRS, QT, QTc and RR intervals) findings 


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PK measurements: 
 
PK will be performed on patients enrolled in the run-in phase. 
PK blood samples will be taken immediately pre-infusion then at 2, 
3, 4, 6, 10, 21 and 24 hours after the start of infusion on Days 1 and 
8 of Cycles 1, 2 and 3 (time window at each sample collected: ±5 
min). 
Bioanalytical measurements: 
Exploratory research will be performed to analyze relevant biomarkers 
and the correlation with clinical outcome. 
 
Biomarkers analysis will be performed on patients enrolled in the 
run-in phase including circulating endothelial cells (CEC), vascular 
endothelial growth factor (VEGF) and circulating endothelial 
progenitor (CEP) cells 
 
Tumor micro vessel density and blood flow by dynamic 
contrast-enhanced MRI (DCE-MRI) will be performed in patients 
with identified sites which be selected by the sponsor at both 
baseline and 6 hours after the infusion of the drug on C1D1 
 
Human Papillomavirus (HPV) status (expression of p16 by 
immunohistochemistry [IHC]) at baseline for all patients. The 
sample could be collected from the previously adapted tissue. 
Health outcomes measurements: 
The following health outcomes assessments will be completed by 
patients: 
 
EORTC QLQ-C30, version 3; 
 
EORTC QLQ-H&N35 
Health outcomes assessments will be performed at screening and before 
study drug administrated, except C1D1. 
Statistical 
Methods: 
Populations for Analysis 
Patients will be categorized into the following populations for analysis: 
 
FAS: The FAS consists of all patients enrolled in the run-in phase 
who either completed at least 3 cycles of study treatment or 
experience a DLT, and all patients enrolled in the continuation phase 
(Phase II).  
 
Per-protocol (PP) population: The PP population will consist of all 
patients who completed at least 3 cycles of study treatment regimen 
defined for Phase II, have measurable baseline disease and, at least, 
one post-baseline RECIST assessment (PD, SD, PR or CR).  Patients 
with a major protocol deviation or AE, deemed by the Medical 
Monitor to have an impact on the study endpoints, will be excluded 
from the PP population. 
 
Safety population:  The safety population will consist of all patients 
who received, at least, one dose of SCB01A, and have at least one 
post-dose safety evaluation. 
 
PK population: The PK population will consist of all patients who 
received, at least, one dose of SCB01A with sufficient post-dose 
bio-samples collected for PK profile characterization (run-in phase 


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Page 29 of 82 
only). 
Details of any other populations for analysis will be described in the 
statistical analysis plan (SAP). 
 
Statistical Analysis 
Assumption of sample size calculation: 
 
Study design: Simon’s optimal two stage design1,2 
 
Type I error (one-sided): 10% 
 
Power: 80% 
 
Response probability of null hypothesis (P0): 0.10 
 
Response probability of SCB01A (P1): 0.25 
 
According to these hypotheses, up to 64 patients need to be recruited 
into the study (including patients from the run-in phase).  At least 
6 patients are required to achieve CR, PR or SD at the end of the 9th 
week after first treatment with SCB01A for the study to meet its primary 
objective.  The trial will be discontinued if DC is observed in one or 
none patients after the Stage 1Disease Controls Review. 
 
Stopping rule: stopped early for futility if less than 2/13 (including 0 or 
1 of 13 patients) show DCR in Stage 1 of Phase II with no further 
investigation of the drug if less than 6/34 achieve DCR by the end of 
Stage 2 of Phase II. 
 
Both according to FAS and PP approaches (all enrolled patients who 
meet the eligibility criteria and do not present major deviations during 
the study) will be included in the analyses.  The conclusion will be 
summarized according to analyses of PP population. Inferential analysis 
results will be expressed as point estimates and their 95% confidence 
intervals (CIs).  To be consistent with the sample size calculation, the 
90% CI will also be presented.  Analyses will be carried out using SAS® 
Software, version 9.3 or higher (SAS Institute, Cary, North Carolina, 
USA). 
All time-to-event endpoints, including OS time and PFS, will be 
reported in days (median with 95% CI and range) and calculated using 
Kaplan-Meier methods.  Patients who have not progressed or who have 
died at the time of the analysis will be censored at the last disease 
assessment date. 
 
PK Evaluations 
The blood samples will be assayed for SCB01A and PK parameters (area 
under the plasma concentration-time curve from time zero to time t 
[AUC0-t], area under the plasma concentration-time curve from time zero 
to infinite time [AUC0-inf], and maximum plasma concentration [Cmax], 
clearance [CL], volume of distribution [Vd], half-life [t1/2], elimination 


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Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
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Page 30 of 82 
constant [Kel], mean residence time [MRT] and time to maximum 
concentration [Tmax]) will be determined and presented graphically and 
descriptively (as appropriate). 
 
A detailed SAP will be finalized prior to final database lock.  Any 
significant changes to the analyses described in this protocol will be 
highlighted in the SAP and the Clinical Study Report. 
Duration of the 
Study 
The planned duration of the entire study is approximately 30 months 
with an enrolment period of 12 months.  
End of Study 
The study will be completed 36 weeks after the last patient receiving 1st 
treatment with SCB01A 
 
 


SynCore Biotechnology Co. Ltd. 
 
 
 
 
 
 
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       Version 3.0: 25 Jul 2016 
 
 
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Page 31 of 82 
Table 1: 
Study Schedule, Run-in phase (Dose 1, 0a, 1a, 2, 2a, 3, 3a, and 4 SCB01A) 
Study Visit1 
Screening 
C1D1 
C1D8 
C1D15 
C2D1 
C2D8 
C2D15 
C3D1 
C3D8 
C3D15 
C4D1-
CXD14 
C4D8-
CXD84 
EOT/ 
Early 
With-
drawal2 
Follow-
Up 
(Phone 
Call)3 
Un-
sche-
duled 
Study Days 
- 28 to -1 
1 (±0) 
8 (±1) 
15 (±2) 
22 (±1) 
29 (±1) 
36 (±2) 
43 (±1) 
50 (±1) 
57 (±2) 
64 (±1) 
71 (±1) 
NA 
NA 
NA 
Activities 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Eligibility Criteria 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical 
Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
BSA Calculation 
  
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
  
  
  
ECOG Performance 
Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
Adverse Events 
Review5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG6 
X 
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
X 
  
X16 
Radiological Image 
Assessements7 
X 
  
  
  
  
  
  
 
  
  
X 
  
X 
  
X16 
Safety Laboratory 
X 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X16 
Urinalysis 
X 
X8 
  
  
X 
  
  
X 
  
  
X 
  
X 
  
X16 
Serum Pregnancy 
Test9 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Coagulation 
  
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X16 
HPV 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Study Drug 
Administration 
  
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
  
  
  
EORTC 
Questionnaires10 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
PK11 
  
X 
X 
  
X 
X 
  
X 
X 
  
  
  
  
  
  
Biomarker12 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  


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Study Visit1 
Screening 
C1D1 
C1D8 
C1D15 
C2D1 
C2D8 
C2D15 
C3D1 
C3D8 
C3D15 
C4D1-
CXD14 
C4D8-
CXD84 
EOT/ 
Early 
With-
drawal2 
Follow-
Up 
(Phone 
Call)3 
Un-
sche-
duled 
Study Days 
- 28 to -1 
1 (±0) 
8 (±1) 
15 (±2) 
22 (±1) 
29 (±1) 
36 (±2) 
43 (±1) 
50 (±1) 
57 (±2) 
64 (±1) 
71 (±1) 
NA 
NA 
NA 
Activities 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
DCE-MRI13 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Survival Status14 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Cancer Therapy15 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Nerve Conduction 
Velocity 17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Patients may continue treatment beyond 3 cycles (9 weeks) of SCB01A treatment per investigator discretion if they are experiencing clinical benefit, until the study is terminated. 
2 EOT visit should be conducted 21 ± 2 days after the last infusion. Early withdrawal visit should be conducted within 21 days after the patient received the last dose of study treatment. 
3 Follow-up visits will be performed after the patient completes EOT visit or early withdrawal visit. Follow-up visits will be scheduled every 3 weeks for 9 weeks, thereafter every 9 weeks until 
the end of the study.  These visits can be conducted by phone. 
4 Starting from cycle 4, there will be no study visit on Day 15. 
5All AEs including SAEs must be reported from the time of informed consent signed and must continue to be followed for 28 days after last administration of study treatment. 
6 ECG will be performed prior to study drug administration, within 1 hour following study drug administration, 2 hours after study drug administration, immediately after the 3 hour infusion, 
4 hours after study drug administration, and 24 hours after administration of the study drug. Starting from Cycle 4, the ECG will be obtained at every treatment cycle within 1 hour following 
study drug administration and at EOT/early withdrawal visit (time window: ±5 min). 
7Tumor assessments should be performed at baseline, and every 3 cycles prior to next cycle until progression of disease.  For patients who meet DC criteria after the first 3 cycles of study 
treatment, additional radiological tumor assessments should be perfor med at Week 12.  Any additional assessment can be arranged when clinically indicated.  
8 Test results within 7 days prior to Cycle 1, Day 1 (C1D1) are acceptable. Only items not performed or obtained within 7 days prior to C1D1 should be tested. 
9 Serum pregnancy test for women of childbearing potential must be performed ≤ 14 day prior to first dose. 
10 Quality of Life questionnaires (EORTC QLQ-C30 and H&N35) should be performed at Screening and all clinic visits (before study drug administered, where applicable, except at C1D1). 
11 PK blood samples will be taken immediately pre-infusion then at 2, 3, 4, 6, 10, 21 and 24 hours after start of infusion on Day 1 and Day 8 of Cycles 1, 2 and 3 (time window: ±5 min). 
12 Blood Sample for VEGF and CEC will be taken immediately pre-infusion then at 6, 10 and 24 hours after start of infusion on C1D1 and C3D15. Blood Samples for CEP will be taken 
immediately pre-infusion and C3D15. 
13 Tumor microvessel density and blood flow by DCE-MRI at both baseline (-28 to -1 Day) and 6 hours (+/- 1hour) after the infusion of the drug on C1D1. 
14 Follow-up for survival status will performed via telephone call if the site is unable to confirm via chart review or clinical visit. 
15Cancer therapies evaluated at the Follow-Up visit or phone call include anti-cancer medications, cancer-related radiotherapy and cancer-related surgery/procedures since last contact. 
16 To be performed when necessary at the patient’s request or per Investigator decision.  
17 To be performed for all patients at baseline and then during the trial only if grade 2 or above neurological symptoms experienced by the patient after receiving treatment with SCB01A.Refer 
section 5.9 for further details.  
 
 


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Page 33 of 82 
Table 2: 
Study Schedule, Phase II, Stage 1 and Stage 2, Optimal dose SCB01A 
Study Visit1 
Screening 
C1D1 
C1D8 
C1D15 
C2D1 
C2D8 
C2D15 
C3D1 
C3D8 
C3D15 
C4D1-
CXD14 
C4D8-
CXD84 
EOT/ 
Early 
With-
drawal2 
Follow-
Up 
(Phone 
Call)3 
Un-
sche-
duled 
Study Days 
- 28 to -1 
1 (±0) 
8 (±1) 
15 (±2) 
22 (±1) 
29 (±1) 
36 (±2) 
43 (±1) 
50 (±1) 
57 (±2) 
64 (±1) 
71 (±1) 
NA 
NA 
NA 
Activities 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Informed Consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical History 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Eligibility Criteria 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
Physical 
Examination 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
BSA Calculation 
  
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
  
  
  
ECOG Performance 
Status 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X 
Adverse Events 
Review5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-Lead ECG6 
X 
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
X 
  
X15 
Radiological Image 
Assessements7 
X 
  
  
  
  
  
  
 
  
  
X 
  
X 
  
X15 
Safety Laboratory 
X 
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X15 
Urinalysis 
X 
X8 
  
  
X 
  
  
X 
  
  
X 
  
X 
  
X15 
Serum Pregnancy 
Test9 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Coagulation 
  
X8 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
X15 
HPV 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Study Drug 
Administration 
  
X 
X 
  
X 
X 
  
X 
X 
  
X 
X 
  
  
  
EORTC 
Questionnaires10 
X 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
Biomarker11 
  
X 
  
  
  
  
  
  
  
X 
  
  
  
  
  
DCE-MRI12 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  


SynCore Biotechnology Co. Ltd. 
 
 
 
 
 
 
          Protocol No: SCB01A-21 
 
 
 
 
 
 
 
       Version 3.0: 25 Jul 2016 
 
 
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Page 34 of 82 
Study Visit1 
Screening 
C1D1 
C1D8 
C1D15 
C2D1 
C2D8 
C2D15 
C3D1 
C3D8 
C3D15 
C4D1-
CXD14 
C4D8-
CXD84 
EOT/ 
Early 
With-
drawal2 
Follow-
Up 
(Phone 
Call)3 
Un-
sche-
duled 
Study Days 
- 28 to -1 
1 (±0) 
8 (±1) 
15 (±2) 
22 (±1) 
29 (±1) 
36 (±2) 
43 (±1) 
50 (±1) 
57 (±2) 
64 (±1) 
71 (±1) 
NA 
NA 
NA 
Activities 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Survival Status13 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Cancer Therapy14 
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Nerve Conduction 
Velocity 16 
X16 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Patients may continue treatment beyond 3 cycles (9 weeks) of SCB01A treatment per investigator discretion if they are experiencing clinical benefit, until the study is terminated. 
2 EOT visit should be conducted 21 ± 2 days after the last infusion. Early withdrawal visit should be conducted within 21 days after the patient received the last dose of study treatment. 
3 Follow-up visits will be performed after the patient completes EOT visit or early withdrawal visit. Follow-up visits will be scheduled every 3 weeks for 9 weeks, thereafter every 9 weeks until 
the end of the study.  These visits can be conducted by phone. 
4 Starting from cycle 4, there will be no study visit on Day 15. 
5All AEs including SAEs must be reported from the time of informed consent signed and must continue to be followed for 28 days after last administration of study treatment. 
6 ECG will be performed prior to study drug administration, within 1 hour following study drug administration, 2 hours after study drug administration, immediately after the 3 hour infusion, 
4 hours after study drug administration, and 24 hours after administration of the study drug. Starting from Cycle 4, the ECG will be obtained at every treatment cycle within 1 hour following 
study drug administration and at EOT/early withdrawal visit (time window: ±5 min). 
7Tumor assessments should be performed at baseline, and every 3 cycles prior to next cycle until progression of disease.  For patients who meet DC criteria after the first 3 cycles of study 
treatment, additional radiological tumor assessments should be perfor med at Week 12.  Any additional assessment can be arranged when clinically indicated.  
8 Test results within 7 days prior to Cycle 1, Day 1 (C1D1) are acceptable. Only items not performed or obtained within 7 days prior to C1D1 should be tested. 
9 Serum pregnancy test for women of childbearing potential must be performed ≤ 14 day prior to first dose. 
10 Quality of Life questionnaires (EORTC QLQ-C30 and H&N35) should be performed at Screening and all clinic visits (before study drug administered, where applicable, except at C1D1). 
11 Blood Sample for VEGF and CEC will be taken immediately pre-infusion then at 6, 10 and 24 hours after start of infusion on C1D1 and C3D15. Blood Samples for CEP will be taken 
immediately pre-infusion and C3D15. 
12 Tumor microvessel density and blood flow by DCE-MRI at both baseline (-28 to -1 Day) and 6 hours (+/- 1hour) after the infusion of the drug on C1D1. 
13 Follow-up for survival status will performed via telephone call if the site is unable to confirm via chart review or clinical visit. 
14Cancer therapies evaluated at the Follow-Up visit or phone call include anti-cancer medications, cancer-related radiotherapy and cancer-related surgery/procedures since last contact. 
15 To be performed when necessary at the patient’s request or per Investigator decision.  
16 To be performed for all patients at baseline and then during the trial only if grade 2 or above neurological symptoms experienced by the patient after receiving treatment with SCB01A.Refer 
section 5.9 for further details.  
 


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Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 35 of 82 
 
 
1. 
Introduction 
1.1. 
Background 
Vascular disrupting agents (VDAs) are designed to disrupt the already abnormal 
vasculature that supports tumors by targeting their already dysmorphic endothelial 
cells.  VDAs induce rapid and selective shutdown of the tumor blood supply resulting 
in tumor death while leaving the blood supply in normal tissues relatively intact3,4.  
The largest group of VDAs is the tubulin-binding combretastatins.  Combretastatin 
A4 phosphate (CA4P) is a small organic molecule found in the bark of the African 
bush willow tree (Combretum caffrum)3 .  Endothelial cells have been shown to be 
particularly sensitive to the effects of CA4P compared with various other cell types 
and several preclinical studies have demonstrated selective in vitro activity of CA4P 
against proliferating endothelial cells3. 
 
SCB01A is a novel heterocyclic combretastatin A-4 (CA-4) analogue that binds to the 
colchicines-binding site of the ß-subunit of tubulin thereby inhibiting polymerization 
and effectively preventing mitosis in a manner similar to that seen with other “spindle 
poisons”, e.g., vincristine, vinblastine and vinorelbine, which are in use as cancer 
chemotherapeutic agents.  Because SCB01A has VDAs property, SynCore plans to 
develop SCB01A as a treatment for a variety of oncologic indications such as 
non-small cell lung cancer, breast cancer, head and neck cancer, acute lymphoblastic 
leukemia, nephroblastoma and testicular cancer. 
 
Compounds that interfere with the cell cycle by interfering with normal biology of 
tubulin are prominent anti-cancer agents because they can inhibit the proliferation of 
tumor cell lines derived from various organs.  Tubulin-containing structures are 
important for diverse cellular functions, including chromosome segregation during 
cell division, intracellular transport, development and maintenance of cell shape, cell 
motility, and possibly distribution of molecules on cell membranes.  The drugs that 
interact with tubulin are heterogeneous in chemical structure.  However, a common 
characteristic of these agents is that while binding to tubulin, they cause its 
precipitation and sequestration to interrupt many important biologic functions that 
depend on the microtubular class of subcellular organelles.  One class of 
well-characterized and clinically used antimitotic drugs is those of natural origin, 
including the taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine, vinblastine, 
vinorelbine) and podophyllotoxins.  These agents either inhibit the polymerization of 
tubulin (vinca alkaloids) or prevent the disassembly of microtubules (taxanes). 
 
SCB01A has been studied extensively since 2005 to evaluate its pharmacokinetic (PK) 
profile, metabolism, in vitro genotoxicity and acute and sub-acute toxicity.  SCB01A 
binds to colchicine binding sites of tubulin much more strongly than colchicines, and 
as with other antimicrotubule inhibitors, it arrests the cells on the G2/M phase in a 
time- and concentration-dependent manner, subsequently leading to cell apoptosis.  
Additional studies indicate that the effect of SCB01A on cell-cycle arrest is associated 
with an increase in cyclin B1 levels and a mobility shift of Cdc2 and Cdc25C.  The 
changes in Cdc2 and Cdc25C coincide with the appearance of phosphoepitopes 
recognized by a marker of mitosis, MPM-2.  Furthermore, phosphorylated forms of 


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Page 36 of 82 
Bcl-2, perturbed membrane mitochondrial potential, and activation of the caspase 3 
cascade may be involved in SCB01A-induced apoptosis. 
1.2. 
Rationale for the Study 
The research data available to date indicate that SCB01A is a promising anti-cancer 
agent with vascular disrupting activity that has potential for treatment of various 
malignancies, particularly for patients with drug resistance to existing therapies.  The 
drug has been trialed in human patients in dose-escalation phase I study, and 
maximum tolerated dose (MTD) is 24 mg/m2 (each cycle consists of one intravenous 
[i.v.] administration of SCB01A via a central line every 3 weeks).  In the phase I 
study, partial response (PR) (shrinkage of tumor size to 50%) was observed in cycle 9 
(3 mg/m2) of one patient with right buccal squamous cell carcinoma, and disease 
stabilization lasted for 14 cycles.  Summary from current clinical findings note a total 
of 19/33 (57.6%) patients had stable disease (SD) for at least 2 cycles.  s. Extended 
disease stabilizations were especially observed for 23 cycles in one patient with 
cholangiocarcinoma (4 mg/m2) and 15 cycles in one patient with rectal cancer 
(3 mg/m2) respectively, suggested that the most prominent SD patients remain in low 
dose (less than 6.5 mg/m2). 
 
A pre-clinical study demonstrated that SCB01A inhibited Detroit562 head and neck 
cell line proliferation.  The inhibition concentration of 50% (IC50) was 41 nM which 
is identical to the IC50 of paclitaxel in our study.  SCB01A was able to inhibit 
microtubule polymerization significantly under the concentration from 200 nM to 800 
nM in 6 hours culture in vitro.  Also, PK evidences suggested low dose SCB01A was 
following the one-compartment model, implying that 200 nM plasma concentrations 
will be enough to inhibit tumor growth.  A pre-clinical study of SCB01A showed that the 
concentration at which tubulin inhibition occurred was 200 nM.  Pharmacokinetic (PK) 
results demonstrated that average serum concentration of SCB01A reached 1000 nM at 
24 mg/m2 suggesting that the current dose is safe and beyond its probable efficacious 
concentration..  From pre-clinical toxicology study, the five days repeated doses of 
SCB01A showed no major toxicity in rat and dog models.  These results support the 
treatment schedule for consecutive 5-days treatment every 3 weeks according to the 
International Conference on Harmonization (ICH) S9.  The administration of 
SCB01A on Days 1 and 8 of a 3-week cycle applied in this Phase II study is below the 
maximum safety regimen suggested by regulatory guideline. 
 
 
Two phase I clinical studies were performed “A Phase 1 Dose Escalation Study of 
SCB01A in Subjects with Advanced Solid Tumors Who Have Failed Standard 
Therapy” and “Long-Term Compassionate Use Study for Continued Administration 
of SCB01A in Subjects Who Completed Treatment With SCB01A in the Previous 
Protocol #SCB01A-01” respectively. The phase I study demonstrated that SCB01A 
has encouraging safety and efficacy and support for further Phase II study. 33 subjects 
were enrolled in the study and 31 subjects completed the main treatment. Among the 
31 subjects, 11 of them completed the extension treatment of SCB01A. Up to date, 5 
subjects, two in main and extension period respectively, experienced 7 SUSAR events.  
(Including gastric ulcer bleeding, thrombocytopenia, cough, radiation recall dermatitis 
and thromboembolic event, Muscle weakness lower limb and Sepsis).  In addition, 5 
dose limiting toxicities and 61 adverse reactions were reported in this study.  
 


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Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
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Page 37 of 82 
The aim of this Phase II study with SCB01A is to determine the effect of SCB01A in 
patients with squamous cell carcinoma of head and neck who have failed previous 
platinum based therapies. 
 
 
2. 
Study Objectives 
2.1. 
Run-In Phase: 
            Primary Objective 
To determine the optimal dose for 3 cycles of i.v. administration of SCB01A on   
Days 1 and 8   of each cycle in a 3-week cycle. 
 
           Secondary Objective: 
To evaluate the safety and toxicity for 3 cycles of i.v. administration of SCB01A on 
Days 1 and 8 of each cycle in a 3-week cycle 
  
2.2. 
Phase II: 
            Primary Objective: 
To assess the disease control rate (DCR) at the end of the 9th week (3 cycles, each 
cycle consists of 21 days) after treatment with SCB01A, according to the Response 
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 
           Secondary Objectives 
The secondary objectives of the study are listed below: 
 To assess the overall survival rate at 36 weeks after treatment of SCB01A in 
patients with recurrent or metastatic squamous cell head and neck cancer who 
have previously been treated with platinum therapy. 
 To assess the progression-free survival (PFS) 
 To determine the recommended dose regimen of SCB01A for further investigation 
in different settings of head and neck squamous cell cancer. 
 To assess the safety and toxicity profile of study treatment. 
 To assess the PK profile of SCB01A of patients in the run-in phase. 
 To assess health outcomes using patient-reported European Organization for 
Research and Treatment of Cancer Quality of Life Questionnaires (EORTC 
QLQ-C30) and EORTC QLQ H&N35 questionnaires. 
 To assess biomarkers relevant to the efficacy and mechanism of action of 
SCB01A. 
 To explore the possible association between biomarkers and clinical outcomes. 
 


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3. 
Investigational Plan 
 
3.1. 
Description of Overall Study Design and Plan 
This study is a single arm, open-label, Phase II trial.  There will be two phases in this 
study, the run-in phase and the continuation phase (Phase II).  Phase II will consist of 
2 stages. 
 
Run-in Phase 
 
During the run-in phase, three patients will be enrolled and will receive 3 cycles of i.v. 
administration of SCB01A at a dose of 3.25 mg/m2 on Days 1 and 8 of each cycle in a 
3-week cycle (Dose 1).  If one of the three patients experienced a Dose Limiting 
(DLT) during the first 3 cycles, an additional three patients will be enrolled at the 
same dose level (Dose 1). If ≤ 1of subjects experienced DLT at the given dose level, 
the dose of the subsequent cohort will be increased to the next level, then this process 
will continue until ≥ 2/3 or 2/6 of subjects experience DLT at certain dose level or the 
maximum dose( Dose 4)  in this protocol, 24 mg/ m2 is reached. 
 
Rules for dose escalation for the run-in phase of the study are listed as following: 
 
1. If 0/3 subjects have a DLT, escalate to the next higher dose level with a cohort 
of three subjects, unless the maximum dose to be tested in this study, i.e. 24 
mg/m2 (Dose 4). If 0/3 subjects have DLT in a cohort of 24 mg/m2 (Dose 4), 
the 24 mg/m2 (Dose 4) will be determined as the Optimal Dose. 
2. If 1/3 subjects have DLT(s), enrol three more subjects at the same dose level: 
a) If the dose for the cohort is less than 24 mg/m2 (Dose 4) and 1/6 subjects have 
DLT(s), escalate to the next higher dose level; 
b) If the dose for the cohort is higher than 3.5mg/m2 (Dose 1) and > 1/6 subjects 
have a DLT, de-escalate to the next dose level (0a, 1a, 2a or 3a) with 3 
subjects .  
c) If >1 out of 6 subjects in the next lower dose (0a, 1a, 2a or 3a ) have DLT(s), 
then the previous dose will be defined as the MTD. 
d) If ≤ 1 out of 6 subjects in the next lower dose (0a, 1a, 2a or 3a) have DLT(s), 
then that dose will be defined as the Optimal Dose. 
3. If the dose for the cohort is 24 mg/m2 (Dose 4) and 1≤/6 subjects have a DLT, 
then the dose level of 24 mg/m2 (Dose 4) will be determined as the Optimal 
Dose. 
 
 
Patients enrolled in the run-in phase must either complete 3 cycles of study treatment 
or experience a DLT to be included in the Full Analysis Set (FAS) for statistical 
analyses.  During the run-in phase, patients who do not complete the 3 cycles of study 
treatment, and do not experience a DLT, will be replaced. 
 
 


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Phase II (The continuation phase) 
 
After the Optimal Dose was determined in the run-in phase, a total number of 
13 patients (including patients received Optimal Dose in the run-in phase) will be 
enrolled for stage 1 to receive 3 cycles of i.v. administration of SCB01A at Optimal 
Dose. 
A safety committee review will be performed after stage 1 with the patients who 
completed 3 cycles of SCB01A treatment at the Optimal Dose. If more than two 
disease controls (DCs) are observed, another 21 patients will be enrolled into Stage 2 
at the same dose level. 
No patients will be replaced in the continuation phase (Phase II). 
 
 
Figure 2: 
Schematic Study Design 
All patients will be treated until occurrence of progressive disease, intolerable adverse 
events (AEs)/toxicity, consent withdrawal or death.  After discontinuation of study 
treatment, all patients will be followed for survival and disease-specific therapies of 
the clinician’s choice.  Follow-up visits will be scheduled every 3 weeks for 9 weeks, 
thereafter every 9 weeks until the end of the study. 
 
The study will be terminated 36 weeks after the last patient has received their 1st 
treatment with SCB01A. 
 
Safety monitoring committee: 
A safety monitoring committee will be established to: 
 Evaluate all AEs, and safety laboratory data for the run-in phase; 


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 Decide on the recommended dose regimen of SCB01A for Phase II. 
 
The schedule of assessments for the run-in phase and Phase II, stages 1 and 2 is 
shown in detail in Table 1 and Table 2, respectively.  The results of protocol specific 
assessments and procedures will be recorded in the source documents for the patients 
and on the appropriate page of the electronic case report form (eCRF).  The different 
study days are described below. 
 
3.2. 
 Run-In Phase 
3.2.1 
Screening Evaluations  
 
The following procedures/assessments will be performed during the screening visit, 
which will be performed within 28 days prior to Day 1 of Cycle 1: 
 Written informed consent 
 Review of inclusion and exclusion criteria 
 Initial history and pre-existing conditions 
 Human Papillomavirus (HPV) status 
 Historic illnesses 
 Physical examination 
 Vital signs 
 Eastern Cooperative Oncology Group (ECOG) performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Tumor measurement 
 Radiological imaging according to RECIST 
 Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) 
 Urinalysis 
 EORTC QLQ-C30 and H&N35 
 Laboratory tests (hematology, clinical chemistry and serum pregnancy test) 
 Nerve Conduction Velocity (within 30 days before C1D1 for all subjects.) 
 
 
 


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3.2.2 
Cycle 1, Day 1 (C1D1)  
The following procedures/assessments will be performed: 
 Review of inclusion and exclusion criteria 
 Physical examination 
 Vital signs 
 Calculation of body surface area (BSA) 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Urinalysis* 
 Laboratory tests (hematology*, clinical chemistry* and coagulation) 
 Study treatment infusion 
 PK sampling 
 Collection of blood samples for biomarkers (vascular endothelial growth factor 
[VEGF], circulating endothelial cells [CEC] and circulating endothelial progenitor 
[CEP] cells). 
 DCE-MRI 
*Test results within 7 days are acceptable, only items not performed for screening within 7 days before this 
visit need to be tested again. 
 Study Drug Administration 
 
3.2.3 
Cycle 1, Day 8 (C1D8) ±1 day 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 Calculation of BSA 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 Study treatment infusion 
 EORTC QLQ-C30 and H&N35 
 PK sampling 
 Study Drug Administration 
 
 
 


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3.2.4 
Cycle 1, Day 15 (C1D15) ±2 days 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 ECOG performance status 
 AEs 
 Concomitant medication 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 EORTC QLQ-C30 and H&N35 
 
3.2.5 
Cycle 2, Day 1 (C2D1) ±1 day 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 Calculation of BSA 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Urinalysis 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 Study treatment infusion 
 EORTC QLQ-C30 and H&N35 
 PK sampling 
 Study Drug Administration 
 
3.2.6 
Cycle 2, Day 8 (C2D8) ±1 day 
The assessments on Day 8 of Cycle 2 is identical to Cycle 1, Day 8 (see Section 3.2.3 
above) 
 
3.2.7 
Cycle 2, Day 15 (C2D15) ±2 days 
The assessments on Day 15 of Cycle 2 is identical to Cycle 1, Day 15 (see 
Section 3.2.4 above) 
 
3.2.8 
Cycle 3, Day 1 (C3D1) ±1 day 
The assessments on Day 1 of Cycle 3 are identical to Cycle 2, Day 1 (see 
Section 3.2.5 above). 
 


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3.2.9 
Cycle 3, Day 8 (C3D8) ±1 day 
The assessments on Day 8 of Cycle 3 is identical to Cycle 1, Day 8 and Cycle 2, 
Day 8 (see Section 3.2.3 above) 
 
3.2.10 
Cycle 3, Day 15 (C3D15) ±2 days 
The assessments on Day 15 of Cycle 3 is identical to Cycle 1, Day 15 and Cycle 2, 
Day 15 (see Section 3.2.4 above) and also includes collection of blood samples for 
biomarkers (VEGF, CEC and CEP) 
 
3.2.11 
3.2.11 Cycle 4, Days 1 and 8 (C4D1 and C4D8) 
Patients may continue with treatment of SCB01A at the same dose per investigator 
discretion if the patient is experiencing clinical benefit, until the study is terminated.  
The assessments on Days 1 and 8 will continue to be the same as for Cycle 2, Day 1 
and Day 8 (see Sections 3.2.5 ) with the exception that no PK sampling will be 
performed. 
 
Tumor assessment should be performed at baseline, and at the end of every 3 cycles 
which needs to be arranged within 5 days prior to the next cycle. 
 
3.3. 
Phase II 
During Phase II, Optimal Dose will be administered depending on the decision made 
by the safety committee.  The Optimal Dose decided by safety committee, will be 
infused on Days 1 and 8 of each 3-week cycle as for the run-in phase. There will be 
no PK assessments to be performed in this phase. 
3.3.1 Screening Evaluations 
The screening procedures/assessments will be performed within 28 days prior to 
Day 1 of Cycle 1 and are identical to the screening assessments performed before the 
run-in phase (see Section 0.1). 
 
3.3.2 Cycle 1, Day 1 (C1D1) (Optimal Dose)) 
The following assessments will be performed: 
 Review of inclusion and exclusion criteria 
 Physical examination 
 Vital signs 
 Calculation of BSA 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Urinalysis* 
 Laboratory tests (hematology*, clinical chemistry* and coagulation) 


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 Study treatment infusion 
 DCE-MRI 
*Test results within 7 days are acceptable, only items not performed for screening within 7 days before this visit 
need to be tested again. 
 Study Drug Administration 
3.3.3 Cycle 1, Day 8 (C1D8) ±1 day (Optimal Dose) 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 Calculation of BSA 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 Study treatment infusion 
 EORTC QLQ-C30 and H&N35 
 Nerve Conduction Velocity 
 Study Drug Administration 
3.3.4 Cycle 1, Day 15 (C1D15) ±2 days (Optimal Dose) 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 ECOG performance status 
 AEs 
 Concomitant medication 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 EORTC QLQ-C30 and H&N35 
 
3.3.5 Cycle 2, Day 1 (C2D1) ±1 day (Optimal Dose) 
The following assessments will be performed: 
 Physical examination 
 Vital signs 
 Calculation of BSA 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Urinalysis 


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 Laboratory tests (hematology, clinical chemistry and coagulation) 
 Study treatment infusion 
 EORTC QLQ-C30 and H&N35 
 Study Drug Administration 
3.3.6 Cycle 2, Day 8 (C2D8) ±1 day (Optimal Dose)  
The assessments on Day 8 of Cycle 2 is identical to Cycle 1, Day 8 (see Section 3.3.3 
above) 
3.3.7 Cycle 2, Day 15 (C2D15) ±2 days ( Optimal Dose) 
The assessments on Day 15 of Cycle 2 is identical to Cycle 1, Day 15 (see 
Section 3.3.4 above) 
 
3.3.8 Cycles >2, Day 1 ±1 day (Optimal Dose) 
The assessments on Day 1 of Cycles >2 are identical to Cycle 2, Day 1 of Phase II 
(see Section 3.3.5 above) ). 
 
3.3.9 Cycles >2, Day 8 ±1 day ( Optimal Dose) 
The assessments on Day 8 of Cycles >2 are identical to Cycle 1, Day 8 of Phase II 
(see Section 3.3.3 above). 
 
3.3.10 Cycles >2, Day 15 ±2 days ( Optimal Dose) 
The assessments on Day 15 of Cycle 2 is identical to Cycle 1, Day 15 (see 
Section 3.3.4 above) 
 
3.4. 
End of Treatment (EOT) Evaluation/Early Withdrawal 
EOT visit should be conducted 21 ± 2 days after the last infusion.  Early withdrawal 
visit should be conducted within 21 days after the patient receives the last dose of 
study treatment. 
 
The following assessments will be performed at the EOT/early withdrawal visit: 
 Physical examination 
 Vital signs 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG 
 Tumor assessment (radiological imaging) 
 Urinalysis 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
 EORTC QLQ-C30 and H&N35 
 


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3.5. 
Follow-up 
After discontinuation of study treatment, all patients will be followed for survival and 
disease-specific therapies of the clinician’s choice will be administered.  The data will 
be collected and can be done by telephone.  Follow-up visits will be scheduled every 
3 weeks for 9 weeks, thereafter every 9 until the end of the study.   
 
3.6. 
Unscheduled Visit 
The following assessments will be performed during an unscheduled visit: 
 Physical examination 
 Vital signs 
 ECOG performance status 
 AEs 
 Concomitant medication 
 12-lead ECG*  
 Tumor assessment (radiological imaging)* 
 Urinalysis* 
 Laboratory tests (hematology, clinical chemistry and coagulation) 
**To be performed when necessary at the patient’s request or per Investigator decision. 
 
3.7. 
Study Design, Including the Choice of Control Groups 
There is no control group in this Phase II study.  The rationale for the study is 
discussed in Section 1.2. 
 
 
3.8. 
Selection of Study Population 
3.8.1. Inclusion Criteria: 
1. Aged ≥20 years; 
2. Signed informed consent obtained prior to initiation of any study-specific 
procedures and treatment;  
3. Histological or cytological confirmed squamous cell carcinoma of head and 
neck; 
4. Patients with non-resectable, unfeasible radiotherapy, recurrent or metastatic 
head and neck squamous cell carcinoma, after previous treatment with 
platinum agent; 
5. At least one measurable tumor lesion as defined by RECIST version 1.1 as 
assessed by the investigator (local radiological image assessment); 
6. Eastern Cooperative Oncology Group (ECOG) Performance Status  (PS) 0-2;  
7. Life expectancy of 12 weeks or longer; 
8. Patients must have radiological measurable or clinically evaluable disease.  
Physical examination and radiographic studies have to be performed within 28 
days of enrolment; 
9. Concurrent local therapy is not allowed, but concurrent palliative radiation 


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therapy to non-measurable sites of disease such as painful bone metastasis is 
permitted; 
10. All eligible patients of childbearing potential have to use effective 
contraception; that is, double barrier contraceptive methods; 
11. Documented progressive disease within past 6 months; 
12. Adequate bone marrow reserve, cardiac, renal and liver function: 
 
a. Absolute neutrophil count (ANC) > 1.5 x 109/L; 
b. White blood cell (WBC) > 3 x 109/L  
c. Platelet count > 75 x 109/L;  
d. Hemoglobin > 9 g/dL ( > 5.6 mmol/l); 
e. Prothrombin time (PT)/international normalized ratio (INR) ≤1.5 x 
upper limit of normal (ULN)  
f. Creatinine clearance (Cockcroft & Gault formula) >50 mL/min;  
g. Alanine aminotransferase (ALT, SGPT) and aspartate  
                         aminotransferase (AST, SGOT) and Alkaline 
                         Phosphatase (ALP) < 3 x ULN.     
h. Serum albumin ≥ 3 g/dL;  
i. INR ≤ 1.5 x ULN  
j. Total Bilirubin  ≤ 1.5 x ULN 
 
 
3.8.2. Exclusion Criteria: 
1. Known primary CNS malignancy or CNS involvement (except for brain 
metastases that have been treated and are stable and patient is off steroids);  
2. Chemotherapy, radiation therapy, major surgery or investigational agents less 
than 4 weeks prior to study drug treatment; 
3. History of malignancy other than head and neck cancer.  Second primary head 
and neck tumors are excluded with the exception of early stage non-melanoma 
skin cancer or carcinoma in situ of cervix; 
4. Ultrasound or radiological evidence of liver cirrhosis; 
5. Severe pulmonary obstructive or restrictive disease; 
6. Uncontrolled inflammatory disease (autoimmune or infectious); 
7. Clinically significant cardiac disease (NYHA class > 2); 
8. Other serious illness or medial conditions, such as active infection, unresolved 
bowel obstruction, or psychiatric disorders;  
9. Known HIV positivity;  
10. Participation in another clinical trial or treatment with any investigational drug 
within 30 days prior to study entry;  
11. QTc > 450 msec; 
12. Pregnant or breast-feeding patients, and men and women of child-bearing 
potential not using effective contraception while on study treatment;Known 
hypersensitivity to any component of SCB01A; 
13. History of exposure to SCB01A or its analogues; 
14. History of active or significant neurological disorder or psychiatric disorder 
that would prohibit the understanding and giving of informed consent, or 


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would interfere with the clinical and radiological evaluation of central nervous 
system during the trial; 
15. Any other reason the investigator deems the patient to be unsuitable for the 
study. 
3.9. 
Removal of Patients from Treatment or Assessment 
3.9.1. Early Discontinuation of the Study 
The study may be discontinued at the sole discretion of the Sponsor for any reason, 
including medical or ethical reasons affecting the continued performance of the study, 
or difficulties in the recruitment of patients. 
 
The study may also be discontinued based on evidence of either substantial efficacy, 
or likely failure to meet the primary objective. 
 
3.9.2. Early Discontinuation of Individual Patients 
The investigator may remove a patient from study treatment at his/her discretion for 
any of the following reasons: 
 Disease progression  
 Intolerable AE(s) or failure to tolerate the study treatment 
 Patient decides to discontinue study therapy 
 Any medically appropriate reason or significant protocol violation, in the opinion 
of the investigator 
 Lost follow-up 
 
Patients may decide to discontinue study treatment for any reason.  Patients who elect 
to discontinue study treatment should be encouraged to continue in the study so that 
follow-up information on disease progression and survival status may be obtained.  
However, patients may elect to withdraw consent and decline further participation in 
the trial. 
 
All patients will be followed until disease progression, withdrawal of consent, 
intolerable AEs/toxicity, death, loss to follow-up or the end of the study. 
 
The investigator must determine the primary reason for a patient’s discontinuation of 
study treatment and record this information on the eCRF.  Patients who are 
prematurely withdrawn from study treatment are not eligible to re-initiate study 
treatment on this protocol at a later date. 
4. 
Treatments 
4.1. 
Identity of Investigational Product (IP) 
SCB01A (a novel heterocyclic CA-4 analogue) is composed of absolute EtOH, PEG 
300, and Solutol®.  The average molecular weight is about 300 and conforms to the 
requirements of the European Pharmacopoeia monograph.  Dehydrated alcohol 
contains > 99.2% by weight, corresponding to > 99.5% by volume at 15.56oC of 
C2H5OH and conforms to the requirements of the US Pharmacopoeia monograph. 
 


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SCB01A is a water insoluble, white to slightly yellow solid.  At room temperature, 
the water solubility of SCB01A is 0.9 μg/ml.  Formulated SCB01A is a sterile, clean, 
colorless to slightly yellow viscous solution. 
 
4.2. 
Study Drug Packaging and Labeling 
The study drug is packaged in glass vials with a rubber stopper and flip-off seal 
labeled with the study protocol number, contents, directions for use, storage directions, 
clinical trial statement, and sponsor name. 
 
4.3. 
Study Drug Storage Conditions 
Formulated SCB01A can be stored at temperatures < 30 oC.  Although direct data on 
its photosensitivity is unavailable, the avoidance of light is recommended. 
 
4.4. 
Study Drug Dose Preparation and Administration 
The study drug, SCB01A is packaged as 10 mg/ml in 5 ml/vials.  The injection 
volume of SCB01A should be calculated based on the BSA of the subject. (See 
section 5.1.3). The study drug will be diluted in normal saline solution before infusion.  
An equal volume of normal saline will be drawn out from a 250 ml normal saline 
container before adding the SCB01A injection solution.  The total volume of study 
drug diluted solution will be equal to 250 ml.  The study drug should be administered 
over a period of 3 hours by i.v. infusion through a central line in order to avoid 
potential extravasation and tissue necrosis. For further details, please refer to the IMP 
Manual. 
 
4.5. 
Study Drug Accountability 
Drug Accountability records will be maintained by the study sites.  All used and 
partially used supplies of SCB01A will be destroyed by the study site in accordance 
with institutional policies after accountability performed by the monitor.  The site will 
maintain detailed documentation of the number and identification of vials, which are 
used and destroyed, and copies of these documents will be provided to the sponsor or 
Clinical Research Organization (CRO).  Disposition of all unused boxes of study drug 
will be carried out according to instructions provided by the sponsor or CRO at the 
end of the study and after a final drug accountability assessment is performed by the 
monitor. 
 
4.6. 
Method of Assigning Patients to Treatment Groups 
There is no randomization to be done.  All patients will receive the study drug, and 
the dose is dependent upon the phases of the study to which the patient is enrolled.  
Patients will be assigned to Dose 1 initially when they enter the run-in phase of the 
study.  Dose selection for the Phase II will be based on the occurrence of DLTs during 
the run-in phase and the decision made by the safety committee. 
 
4.7. 
Selection of Doses in the Study 


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Doses were selected based on pre-clinical data and data obtained from an ongoing 
Phase I study as described in Section 1.2. 
 
4.8. 
Selection and Timing of Dose for each Patient 
The selection and timing of dose for each patient is described in Section 3.1.  
 
Patients entered into the run-in phase will be allocated to Dose 1 to Dose 4.  Dose 
selection for Phase II will be based on the occurrence of DTLs during the run-in phase 
and the decision made by safety committee on the Optimal Dose for the Phase II (see 
Section 3.1). 
 
Dose 1: 
one i.v. administration of 3.25 mg/m2 SCB01A on Days 1 and 8 of a 
3-week cycle; or 
Dose 0a: 
one i.v. administration of 5 mg/m2 SCB01A on Day 1 and Day 8 of a 
3-week cycle. 
Dose 1a: 
one i.v. administration of 10 mg/m2 SCB01A on Day 1 and Day 8 of a 
3-week cycle. 
Dose 2: 
one i.v. administration of 12 mg/m2 SCB01A on Days 1 and 8 of a 
3-week cycle; or 
Dose 2a: 
one i.v. administration of 15 mg/m2 SCB01A on Day 1 and Day 8 of a  
                        3-week cycle      
Dose 3: 
one i.v. administration of 18 mg/m2 SCB01A on Days 1 and 8 of a 
3-week cycle; or 
Dose 3a: 
one i.v. administration of 21 mg/m2 SCB01A on Day 1 and Day 8 of a  
                        3-week cycle 
Dose 4: 
one i.v. administration of 24 mg/m2 SCB01A on Days 1 and 8 of a 
3-week cycle; or 
4.9. 
Dose Adjustment and Toxicity Management 
There is no dose adjustment envisaged in this study.  Where a study treatment-related 
Grade 3 or 4 AE occurs, the study treatment will be placed on hold until the event is 
resolved to grade ≤ 1 or returns to baseline before resuming the study drug.  If the 
Grade 3 or 4 event does not resolve or return to baseline within 14 days or return to 
grade 3 or 4 toxicity after resuming, treatment with the study drug will cease.  
However the patient should be followed-up for survival analysis until the end of the 
study. 
 
4.10. Blinding 
This is an open-labelled study.  Therefore blinding procedures are not applicable. 
 
4.11. Prior and Concomitant Therapy 
Concomitant medication is defined as any prescription or over-the-counter 
preparation, including vitamins, dietary supplements, and oral herbal preparations. 
 


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All medications that are taken by, or being administered to, the patient at the time of 
the Screening Visit, within 30 days prior to the Screening Visit, and for the duration 
of the study will be recorded in the eCRF. 
 
For each medication the following will be documented: 
 Medication/treatment name (generic name). 
 
Dose, unit, and frequency of dosing (total daily dose). 
 Route of administration 
 Indication for use 
 The start date 
 The stop date (if medication/therapy is not ongoing) 
 
4.12. Prohibited Medications 
Patients will be infused with their study treatment at the clinical site by trained 
personnel and the infusion start and end times will be recorded in source documents 
and in the eCRF 
 
1. Any study participant that has had any investigational drug, chemotherapy, 
targeting agent(s), biology therapy, immunotherapy, herbal medicine or hormonal 
therapy administered within 4 weeks before the date of the first study treatment 
should be excluded from enrolment until at least 4 weeks have passed. 
2. Concomitant administrations of compounds that inhibit CYP1A2 or CYP2D6 are 
prohibited for 3 weeks prior to study drug infusions and throughout the study.  
Excluded concomitant medications of CYP1A2 and CYP2D6 inhibitors include 
(except antibiotics whenever they are clinically indicated): fluvoxamine, 
ciprofloxacin, 
cimetidine, 
bupropion, 
cinacalcet, 
fluoxetine, 
paroxetine, 
quinidine1, duloxetine, sertraline, terbinafine and amiodarone. 
3. Therapy with anticoagulants, antiplatelet treatments (e.g. warfarin, heparins) are 
not allowed during the study 
 
4.13. Treatment Compliance 
Patients will be infused with their study treatment at the clinical site by trained 
personnel and the infusion start and end times will be recorded in source documents 
and in the eCRF. 
 
5. 
Study Assessments and Procedures 
5.1. 
Safety Procedures and Assessments 
5.1.1. Medical History 
Medical history will be assessed at screening and will include the following: 
1. Histological or cytological confirmed metastatic squamous cell carcinoma in 
head and neck. 


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2. At least one measurable tumor lesion according to RECIST version 1.1 as 
assessed by the investigator (local radiological image assessment). 
3. Details of the prior therapy that failed or intolerable to platinum agent and also 
not amenable to further surgical or radiation therapy due to disease progression or 
toxicity. 
4. Smoking status (current smoker or past history of smoking). 
5. Betel nut consumption status or history. 
6. Additionally, all relevant medical histories, medical conditions, or symptoms 
experienced during 30 days prior to screening are to be recorded, using the body 
system categories outlined below.  For each history, the specific medical 
terminology for the disease/disorder/condition, the date of diagnosis, and the 
history status (resolved or ongoing) will be documented. 
 
Cardiovascular 
 
 
Lymphatic 
Respiratory 
 
 
Hematologic 
Gastrointestinal  
 
Immunologic 
Renal 
 
 
 
Dermatologic 
Hepatic 
 
 
 
Psychiatric 
Neurological 
 
 
Genitourinary 
Endocrine  
 
 
Other 
 
5.1.2. Physical Examination 
A complete physical examination will be performed at baseline and each clinic visit 
prior to drug administration, if applicable and the EOT/Early Withdrawal visit to 
include a review of all systems.  Each body system will be classified as being either 
normal or abnormal, with abnormalities for each body system noted.  Subsequent 
physical examinations will identify changes from the baseline examination with both 
positive and negative changes being noted.  The physical examination will include 
routine examinations for the following: 
 
Height (cm) (only performed at baseline) 
 
Weight (kg) at each visit before a study treatment infusion 
 
Abnormalities of the extremities 
 
Heart/cardiovascular abnormalities 
 
Musculoskeletal abnormalities 
 
Dermatologic abnormalities 
 
Neurologic abnormalities 
 
Any other body system, for which an abnormality is noted and which, in the opinion 
of the Investigator, is relevant to the safety of the participant or could impact safety or 
efficacy results for the study patient; i.e., the abnormality is clinically significant. 
 
5.1.3. BSA Calculation 
BSA will be calculated on dosing days, using the formula below5: 
 
BSA (m2) = [Height (cm) x Body Weight (kg)/3600]½ 
 
The total dose (mg) will be calculated as: Total Dose 1/Dose 2 (mg/m2) x BSA (m2) 


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5.1.4. Vital Signs 
Vital signs will be obtained at baseline, clinic visits prior to study drug administration, 
if applicable and at the EOT/Early Withdrawal visit. 
 
Vital signs will include heart rate, blood pressure, respiratory rate, and body 
temperature.  Respiratory rate, heart rate and blood pressure (systolic/diastolic) will 
be obtained after the patient has been at rest for at least 5 minutes in a sitting position. 
 
If vital sign measurements coincide with a blood sample, the vital signs will be taken 
prior to obtaining the blood sample. 
 
Body temperature will be taken and recorded in degrees Centigrade. 
 
5.2. 
ECOG Performance Status 
The ECOG performance status will be documented at baseline and at all clinic visits. 
 
Table 3: 
ECOG Performance Status Scale6 
Grade 
Descriptions 
0 
Normal activity.  Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Symptoms, but ambulatory.  Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (e.g., 
light housework, office work). 
2 
In bed < 50% of the time.  Ambulatory and capable of all self-care, but 
unable to carry out any work activities.  Up and about more than 50% of 
waking hours. 
3 
In bed > 50% of the time.  Capable of only limited self-care, confined to bed 
or chair more than 50% of waking hours. 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
Dead. 
 
 
5.3. 
12-lead ECG 
During the run-in phase, the 12-lead ECG will be obtained prior to study drug 
administration, within 1 hour following study drug administration, 2 hours after study 
drug administration, immediately after the 3 hour infusion, 4 hours after study drug 
administration, and 24 hours after administration of the drug.  After cycle 4, the ECG 
will be obtained at every treatment cycle within 1 hour following study drug 
administration, and EOT/early withdrawal visit (time window: ±5 min). 
 


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During Phase II (stage 1 and 2), the 12-lead ECG will be obtained at every treatment 
cycle within 1 hour following study drug administration and at EOT/Early 
Withdrawal visit. 
 
The allowed time window for each ECG assessment is ±5 min.  ECGs will be 
obtained whenever deemed necessary at the investigator’s discretion.  The following 
ECG measurements will be recorded in the patient’s source documents and on the 
appropriate page(s) of the eCRF: 
 
QRS interval 
 
PR interval 
 
QT interval 
 
QTc interval 
 
RR interval 
 
Investigator’s interpretation of the ECG results (NOTE: for all abnormalities, 
the nature of the abnormality will be noted and the Investigator will comment 
regarding the clinical significance of the abnormality). 
 
5.4. 
DCE-MRI 
Tumor micro vessel density and blood flow by DCE-MRI for the patients with 
identified sites at both baseline and 6 hours after the 1st infusion of the drug in C1D1. 
 
5.5. 
Safety Laboratory Assessments 
The local laboratory for the study site will be used and all procedures will be 
performed following the standard operating procedure (SOP) of the local laboratory. 
 
Hematology and clinical chemistry blood samples will be obtained at screening, all 
clinic visits and the EOT/Early Withdrawal visit.  Coagulation will be determined at 
all clinic visits (excluding screening).  During the run-in phase minimum of 19 
samples (180 ml) will be take. The number of sample might differ based on actual 
number of cycles completed and if there are any unscheduled visits done.  
 
Urinalysis will be determined at Screening and Day 1 of each cycle prior to study 
treatment administration. 
 
The parameters assessed are detailed below: 
 
Hematology 
WBC with differential, red blood cell (RBC), hematocrit (Hct), Hb, mean corpuscular 
volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin 
concentration (MCHC), platelet count 
 
Clinical Chemistry 
Blood urea nitrogen (BUN), Creatinine, AST, ALT, ALP, Total Bilirubin, Albumin, 
Calcium, Glucose, Uric Acid, Potassium, Total creatine kinase (Ck) (if total Ck is 
above the ULN for the laboratory, Troponin-T or Troponin-I will be determined), 
gamma-glutamyl transferase (GGT).  Total cholesterol, high-density lipoprotein 


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(HDL), low-density lipoprotein (LDL), triglycerides (TG), amylase and lipase will be 
tested at the Screening Visit. 
 
Coagulation 
PT, INR 
 
Urinalysis 
Specific gravity, pH, protein, glucose, leucocytes, erythrocyte, nitrite, ketone, 
urobilinogen, bilirubin and sediment including RBC, WBC, Hyaline, Cast, CAOX, 
Crystal, AMOR and mucus. 
 
Pregnancy test 
A serum beta-HCG test for women of childbearing potential will be performed ≤ 14 days 
prior to the first dose of study treatment. 
 
 
 
 
 
5.6. 
Bioanalytical Assessments  
PK Procedures 
 
PK will be performed on patients enrolled in the run-in phase. 
PK blood samples will be taken immediately pre-infusion then at 2, 3, 4, 6, 10, 21 and 
24 hours after start of infusion on Days 1 and 8 of Cycles 1, 2 and 3 (time window at 
each sample collected: ±5 min).  Sixteen (16) samples (10 mL) per cycle will be taken 
(480 mL during 3 cycles of the run-in phase).  Also see Section 6.4 for more detail. 
 
Biomarkers 
 
Blood samples (10 mL) will be collected for biomarkers analysis on patients enrolled 
in the run-in phase; including CEC, VEGF and CEP cells. 
 
Blood samples for biomarkers will be taken immediately pre-infusion then at 6, 10 
and 24 hours after start of infusion on Day 1 of Cycle 1 and one sample during the 
clinic visit on Day 15 of Cycle 3 (5 samples per cycle).  VEGF and CEC will be 
analyzed for all time points that samples were taken and CEP will be analyzed only 
from pre-infusion sample and the Day 15 Cycle 3 sample. 
 
5.7. 
EORTC QLQ-C30 
Patients will complete the questionnaire at Screening and before study drug 
administered, except C1D1. 
 
The questionnaire consists of 65 questions that help determine the health outcome of 
the patients. 
 
5.8. 
EORTC QLQ H&N35 


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Patients will complete the questionnaire at Screening and before study drug 
administered, except C1D1. 
 
5.9. 
Nerve Conduction Velocity 
Patients will undergo testing for the nerve conduction velocity at the following time 
points based on neurological symptoms: 
 
a. Baseline: within 30 days before C1D1 for all subjects. 
b. Within 7-30 days, since the onset for grade 2 or above neurological symptom 
after receiving treatment of SCB01A; 
c. Within 90-120 days, since the consent withdraw or received the last treatment 
of SCB01A, after the onset for grade 2 or above neurological symptom after 
receiving treatment of SCB01A;  
The test results of nerve conduction velocity will not lead to modification of treatment 
schedule (i.e. Investigators do not have to wait for the test report to make decision 
regarding subsequent treatment continuation or modification) unless the symptom is 
deemed as clinical significant. 
 
5.10. Appropriateness of Measurements 
The measurements used in this in study are considered appropriate for the indication 
studied.  Disease response is a common tool used in cancer trials to study the 
effectiveness of the study drug.  Safety and tolerability of the study drug will be 
reported during the trial. 
 
6. 
Safety and Efficacy Variables 
6.1. 
Efficacy Measurements 
Tumor response will be assessed by using computerized tomography (CT) or MRI 
scans according to RECIST v1.1 at baseline, and every 3 cycles prior to next cycle 
until progression of disease.  For patients who meet DC criteria after the first 3 cycles 
of study treatment, additional radiological tumor assessments should be performed at 
Week 12.  Any additional assessments can be arranged when clinically indicated. 
 
Scans must include brain, chest, abdomen, and pelvis.  The imaging technique used at 
baseline should be used throughout the study. 
 
Survival data will be collected throughout the active treatment phase and during the 
follow-up period.  Survival follow-up after patient discontinuation of treatment will 
be conducted every 3 weeks during the first 9 weeks, thereafter every 9 weeks until 
the end of the study.  Survival rate will only be assessed in patients with measurable 
disease at baseline. 
 
6.2. 
Dose Limiting Toxicity (DLT) 
All toxicities will be classified according to the NCI Common Terminology Criteria 
for AEs (CTCAE) version 4.03. 
 


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DLT will be defined as the occurrence of any of the following criteria during the 
run-in phase, unless there is definitive alternative evidence that administration of 
SCB01A did not cause the specific toxicity: 
 
Grade 4 neutropenia exceeding 5 days’ duration 
 
Grade 4 thrombocytopenia 
 
Grade 4 anemia 
 
Grade 3 or greater neutropenia with complications (e.g., fever, infection etc.) 
 
Grade 3 or greater thrombocytopenia with complications (e.g., bleeding) 
 
Grade 3 or greater non-hematological AEs including Grade 3 unmanageable 
nausea and vomiting that persist for 3 or more days after drug administration.  
Grade 3 fatigue lasting for ≤1 week is not considered as a DLT 
 
Grade 3 or greater prolonged QTc interval 
 
Grade 3 or greater neurotoxicity 
 
Delayed treatment exceeding 14 days duration due to drug-related toxicity. 
 
6.3. 
Safety Measurements 
The following safety assessments will be done during the study: 
 
Incidence and intensity of AEs evaluated using the CTCAE version 4.03 
 
Incidence and intensity of clinically significant abnormal laboratory values 
evaluated using the CTCAE version 4.03 
 
Percentage of patients experiencing dose adjustments, including delays or 
discontinuation of study medication 
 
Physical examination findings 
 
Vital signs measurements 
 
ECG (including PR, QRS, QT, QTc and RR intervals) findings 
 
6.4. 
Pharmacokinetic Measurements 
PK will be performed on patients enrolled in the run-in phase. 
 PK blood samples will be taken immediately pre-infusion then at 2, 3, 4, 6, 10, 21 
and 24 hours after start of infusion on Days 1 and 8 of Cycles 1, 2 and 3 (time 
window at each sample collected: ±5 min). 
 Blood samples will be collected, using 10 mL sodium heparin Vacutainer® tubes. 
The tube will be gently inverted to ensure adequate mixing of the blood sample 
and anticoagulant.  Samples will be placed on ice until separation and must be 
centrifuged within 20 minutes of collection.  A precise record of blood sample 
collection times must be maintained on the appropriate source document. 
 Plasma samples will be analyzed via a validated high performance liquid 
chromatography/tandem mass spectrometry (HPLC/MS-MS) method for SCB01A. 
 
6.5. 
Bioanalytical Measurements 


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Exploratory research will be performed to analyze relevant biomarkers and the 
correlation with clinical outcome. 
 Biomarkers analysis will be performed on patients enrolled in the run-in phase, 
including CEC, VEGF and CEP cells) 
 Tumor micro vessel density and blood flow by DCE-MRI will be performed in the 
patients with identified sites at both baseline and at 6 hours after the infusion of 
the drug on C1D1 
 HPV status (expression of p16 by immunohistochemistry [IHC]) at baseline for all 
patients 
 
6.6. 
Health outcomes measurements 
The following health outcomes assessments will be completed by patients (see 
Section 11.3 [Appendix 4]): 
 EORTC QLQ-C30), version 3; 
 EORTC QLQ-H&N35 
 
Health outcomes assessments will be performed at screening and all clinic visits 
(before study drug administered, where applicable, except at C1D1) 
 
7. 
Adverse Events Definitions and Reporting 
7.1. 
Adverse Events  
An AE is any untoward medical occurrence that occurs in a patient or clinical 
investigation patient administered a pharmaceutical product, and which does not 
necessarily have to have a causal relationship with this treatment.  An AE can 
therefore be any unfavorable and unintended sign (including abnormal laboratory 
finding), symptom, or disease temporally associated with the use of an IP, whether or 
not considered related to the medicinal product (definition per ICH E2A and E6 R1). 
 
All AEs, regardless of seriousness, severity, or presumed relationship to study therapy, 
must be recorded using medical terminology on the AE eCRF page.  Whenever 
possible, diagnoses should be given when signs and symptoms are due to a common 
etiology (e.g., cough, runny nose, sneezing, sore throat, and head congestion should 
be reported as “upper respiratory infection”).  All measures required for AE 
management must be recorded in the source document and reported according to 
Sponsor instructions. 
 
For all AEs, the Investigator must pursue and obtain information adequate to both 
determine the outcome of the AE and to assess whether it meets the criteria for 
classification as an SAE (see Section on SAEs) requiring immediate notification to 
the Sponsor or its designated representative.  For all AEs, sufficient information 
should be obtained by the Investigator to determine the causality of the AE. 
 
Interventions for pre-treatment conditions (e.g., elective cosmetic surgery) or medical 
procedures that were planned before study enrolment are not considered AE. 


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7.1.1. Intensity Assessment 
The severity of the AE will be graded according to the NCI Common Terminology 
Criteria for AEs (CTCAE) Grading Scale Version 4.03 (Publish Date: May 28, 2009, 
http://ctep.cancer.gov/reporting/ctc.html). 
 
The maximum severity (intensity) of the AE will be categorized by the Investigator as 
follows: 
 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated 
Grade 2 
Moderate; minimal, local or non-invasive intervention indicated; 
limiting age-appropriate instrumental activities of daily living 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated 
Grade 5 
Death related to AE 
 
For AEs not covered by NCI CTCAE, the severity will be characterized as “mild,” 
“moderate,” or “severe” according to the following definitions: 
 
 Mild events are usually transient and do not interfere with the patient’s daily 
activities 
 Moderate events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities 
 Severe events interrupt the patient’s usual daily activities. 
 
When changes in the intensity of an AE occur more frequently than once a day, the 
maximum intensity for the experience should be noted. If the intensity category 
changes over a number of days, then those changes should be recorded separately 
(with distinct onset dates). All AEs, due to any cause that occurs during the 
investigation, whether or not related to the study drug, should be reported to the 
Safety Coordinator. 
 
7.1.2. Causality Assessment 
 Unrelated: The AE is clearly related to other causes such as participant’s clinical 
state, environmental factors, or other therapies administered. 
 Unlikely to be related: The AE does not follow a reasonable temporal sequence 
from study drug administration; could readily have been produced by other causes 
such as the participant’s clinical state, environmental factors, or other therapies 
administered; does not follow a known response pattern to the study drug.  
 Possibly related: The AE follows a reasonable temporal sequence from study 
drug administration; follows a known response pattern to the study drug; could 


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readily have been produced by other causes such as the participant’s clinical state, 
environmental factors, or other therapies administered.  
 Probably related: The AE follows a reasonable temporal sequence from study 
drug administration; follows a known response pattern to the study drug; cannot 
be reasonably explained by other factors such as the participant’s clinical state, 
environmental factors, or other therapies administered; improvement upon 
cessation of test drug.  
 Definitely related: The AE follows a reasonable temporal sequence from study 
drug administration; follows a known response pattern to the study drug; cannot 
be reasonably explained by other factors such as the participant’s clinical state, 
environmental factors, or other therapies administered; improvement upon 
cessation of test drug or reappears upon repeat exposure (if rechallenge occurs). 
 
7.2. 
Adverse Event Reporting 
All AEs occurring during the study (from the time of informed consent obtained until 
28 days after the last dose of study treatment) observed by the Investigator or reported 
by the patient (whether or not attributed to study drug), will be reported on the eCRF.  
Clinically significant AEs considered related or non-related to the IP by the 
Investigator or the Sponsor will be followed until resolved or considered stable by the 
Investigator.  The following information must be provided:  description; dates of 
onset and resolution; severity; assessment of relatedness to IP, other suspect drug, or 
device; and action taken.  The investigator may be asked to provide follow-up 
information. 
 
All AEs, serious or not, that result in the patient’s permanent withdrawal of IP or from 
the study will be discussed between the investigator and medical monitor.  The eCRF 
for EOT/Early Withdrawal Visit should be completed including reason of withdrawal. 
 
It will be the investigator’s clinical judgment whether or not an AE is of sufficient 
severity to require the patient’s removal from study treatment.  A patient may also 
voluntarily withdraw from study treatment due to what he or she perceives as an 
intolerable AE.  If either of these occurs, the patient must undergo EOT assessment 
and be given appropriate care under medical supervision until symptoms cease or the 
condition becomes stable. 
 
7.3. 
Serious Adverse Events (SAEs) 
An SAE is defined as any untoward medical occurrence that at any dose (ICH E2A and 
E6 R1):  
 Results in death.  
 Is life-threatening.  
 This means that the patient is at risk of death at the time of the event; it does not 
mean that the event hypothetically might have caused death if it were more severe.  
 Requires inpatient hospitalization or prolongation of existing hospitalization.  
 Results in persistent or significant disability or incapacity.  


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 Is a congenital anomaly or birth defect.  
 
Other important medical events that may not be immediately life-threatening or result 
in death or hospitalization, based upon appropriate medical judgment, are considered 
SAEs if they are thought to jeopardize the patient and/or require medical or surgical 
intervention to prevent one of the outcomes defining a SAE. 
 
Since SAEs are critically important for the identification of significant safety 
problems, it is important to take into account both the Investigator’s and the sponsor’s 
assessment.  If either the sponsor or investigator believes that the event is serious, the 
event must be considered serious and evaluated by the Sponsor for expedited 
reporting. 
 
All SAEs must be reported to the sponsor or sponsor designee immediately after the 
Investigator becomes aware of the event, along with a determination as to whether it 
is associated with the IP or any other study procedure. 
 
Disease progression should not be recorded as an AE or SAE term; instead, signs and 
symptoms of clinical sequelae resulting from disease progression will be reported if 
they fulfil the SAE definition.  
 
7.4. 
Serious Adverse Event Reporting 
All SAEs, irrespective of relationship to IP, must be reported within 24 hours of the 
Investigator knowledge of the event to the Sponsor or CRO. In particular, if the SAE 
is fatal or life-threatening, notification to the Sponsor must be made immediately, 
irrespective of the extent of available AE information. This timeframe also applies to 
follow-up information on previously forwarded SAE reports as well as to the initial 
and follow-up reporting of exposure during pregnancy and exposure via breast 
feeding cases. 
 
Relevant medical records should be provided to the Sponsor or CRO as soon as they 
become available; autopsy reports should be provided for deaths if available.  Should 
an Investigator be made aware of an SAE occurring any time after the reporting 
period, it must be promptly reported.  
 
All SAEs that have not resolved by the end of the study, or that have not resolved 
upon discontinuation of the patient's participation in the study, must be followed until 
any of the following occurs:  
 The event resolves.  
 The event stabilizes.  
 The event returns to baseline, if a baseline value/status is available.  
 The event can be attributed to agents other than the IP or to factors unrelated to 
study conduct.  
 It becomes unlikely that any additional information can be obtained (patient or 
health care practitioner refusal to provide additional information, lost to follow-up 
after demonstration of due diligence with follow-up efforts).  
 


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7.5. 
Pregnancies 
All initial reports of pregnancy must be reported to the Sponsor within 24 hours of the 
Investigator knowledge of the event using the appropriate pregnancy form.  
 
For IP, an exposure during pregnancy occurs if:  
 A female becomes, or is found to be, pregnant either while receiving or having 
been directly exposed (e.g., environmental exposure) to the IP, or the female 
becomes, or is found to be, pregnant after discontinuing and/or being directly 
exposed to the IP (maternal exposure) for 28 days after last dose of or exposure to 
IP.  
 A male partner of a pregnant female has been exposed to the IP, either due to 
treatment or environmental exposure, within 3 months prior to the time of 
conception and/or is exposed during his partner’s pregnancy (paternal exposure).  
 
If any study patient or study patient’s partner becomes or is found to be pregnant 
during the study patient’s treatment with the IP or exposure as defined above, the 
Investigator must submit this information on a Pregnancy form to the Sponsor (or its 
designated representative).  In addition, the Investigator must submit information 
regarding environmental exposure to an IP in a pregnant woman (e.g., a patient 
reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) using the Pregnancy form.  This must be done irrespective of whether an 
AE has occurred and within 24 hours of awareness of the pregnancy.  The information 
submitted should include the anticipated date of delivery (see following information 
related to induced termination of pregnancy). 
 
Follow-up is conducted to obtain pregnancy outcome information on all exposure 
during pregnancy reports with an unknown outcome.  The Investigator will follow the 
pregnancy until completion or until pregnancy termination (e.g., induced abortion) 
and then notify the Sponsor or its designated representative of the outcome as a 
follow-up to the initial Pregnancy form.  In the case of a live birth, the structural 
integrity of the neonate can be assessed at the time of birth.  In the event of a 
termination, the reason(s) for termination should be specified and, if clinically 
possible, the structural integrity of the terminated fetus should be assessed by gross 
visual inspection (unless pre-procedure test findings are conclusive for a congenital 
anomaly and the findings are reported).  
 
If the outcome of the pregnancy meets the criteria for immediate classification as an 
SAE (e.g., ectopic pregnancy, spontaneous abortion, intrauterine fetal demise, 
neonatal death, or congenital anomaly [including that in a live born, a terminated fetus, 
an intrauterine fetal demise, or a neonatal death]), the Investigator should follow the 
procedures for reporting SAEs.  
 
Additional information about pregnancy outcomes that are classified as SAEs follows:  
 “Spontaneous abortion” includes miscarriage and abortion.  
 All neonatal deaths that occur within 1 month of birth should be reported, without 
regard to causality, as SAEs.  In addition, infant deaths after 1 month should be 
reported as SAEs when the Investigator assesses the neonatal death as related to 
exposure to IP.  


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Additional information regarding the exposure during pregnancy may be requested by 
the Investigator.  Follow-up information regarding the outcome of the pregnancy and 
any postnatal sequelae in the infant will be required.  
8. 
Statistical Methods and Determination of Sample Size 
8.1. 
Statistical and Analytical Plans 
A brief description is given of the planned analysis methodology.  Detailed 
descriptions of the statistical analysis methods and data conventions will be provided 
as a separate document; i.e., the Statistical Analysis Plan (SAP).  The SAP may also 
include additional exploratory analyses not explicitly mentioned in the following 
sections.  A detailed SAP will be finalized prior to final databased lock.  Any 
significant changes to the analyses described in this protocol will be highlighted in the 
SAP and the Clinical Study Report. 
 
8.2. 
Determination of Sample Size 
Assumption of sample size calculation: 
 Study design: Simon’s optimal two stage design1,2 
 Type I error (one-sided): 10% 
 Power: 80% 
 Response probability of null hypothesis (P0): 0.10 
 Response probability of SCB01A (P1): 0.25 
 
According to these hypotheses, up to 58 patients need to be recruited into the study 
(including patients from the run-in phase).  At least 6 patients are required to achieve 
complete response (CR), PR or SD at the end of the 9th week after first treatment with 
SCB01A for the study to meet its primary objective.  The trial will be discontinued if 
DC is observed in two or fewer patients after the Stage 1 interim analysis review. 
 
8.3. 
Populations for Analysis 
Patients will be categorized into the following populations for analysis: 
 
FAS: The FAS consists of all patients enrolled in the run-in phase who either 
completed at least 3 cycles of study treatment or experience a DLT, and all patients 
enrolled in the continuation phase (Phase II). 
 
Per-protocol (PP) population: The PP population will consist of all patients who 
completed at least 3 cycles of study treatment regimen defined for Phase II, have 
measurable baseline disease and at least one post-baseline RECIST assessment (PD, 
SD, PR or CR).  Patients with a major protocol violation, or AE, deemed by the 
Medical Monitor to have an impact on the study endpoints will be excluded from the 
PP population. 
 


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Safety population:  The safety population will consist of all patients who received at 
least one dose of SCB01A, and have at least one post-dose safety evaluation. 
 
PK population: The PK population will consist of all patients who received at least 
one dose of SCB01A with sufficient post-dose bio-samples collected for PK profile 
characterization. 
 
Details of any other populations for analysis will be described in the SAP. 
 
8.4. 
Safety Analysis 
Safety profile will be evaluated by the following endpoints. 
 Hematology, clinical chemistry, coagulation factors and urinalysis laboratory data 
changes  
 AE incidence/SAE incidence 
 Physical examination result changes 
 Vital sign changes 
 Electrocardiogram (ECG) (including PR, QRS, QT, QTc, and RR intervals) 
results 
 
All safety endpoint data will be listed and summarized for each dose and day within 
cycle using descriptive statistics.  The change from baseline data for the safety 
endpoints will also be summarized using descriptive statistics. 
 
Number and percentage of patients experiencing at least one DLT or AE will be 
tabulated by dose.  Further details regarding any DLTs or AEs experienced will be 
provided in data listings.  All recorded AEs will be listed and tabulated by system 
organ class and preferred term using the Medical Dictionary for Regulatory Activities 
(MedDRA) and by dose level.  The incidence of Treatment Emergent AEs (TEAEs) 
during the study period will be tabulated by dose group, body system, and preferred 
term.  TEAEs are those events that occur or worsen on or after first dose of IP and up 
to 28 days after the last dose.  TEAEs are AEs with onset dates on or after the first 
dosing date.  Those with missing onset dates will be included as treatment emergent.  
Number and percentage of patients who withdrew/stopped dosing will be tabulated.  
Number and percentage of patients who missed 1 or more doses (1 dose, 2 doses, etc.) 
in any cycle will be tabulated by cycle. 
 
Serious AEs, Grade 3 and above AEs, AEs related to study treatment, and AEs 
causing discontinuation will be tabulated.  AEs for individual patients will be listed, 
along with information regarding onset, duration, severity, and relationship to study 
treatment. 
 
Vital signs, physical examination, ECG, and clinical laboratory test results will be 
listed and summarized by dose group, cycle and day within cycle as applicable and 
may be presented graphically.  Any significant or outside normal range limits value 
for vital signs, physical examination, ECG, or clinical laboratory results will be listed 
 


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8.5. 
Efficacy Analysis 
The primary efficacy analysis will be performed to assess the DCR and secondary 
efficacy analysis will be performed to assess the PFS and overall survival rate. 
 
Patients will be considered evaluable for DCR in this study if they fulfill the criteria 
for evaluation according to RECIST v1.1, i.e., those patients who undergo a baseline 
disease assessment within 4 weeks of treatment initiation, and who undergo at least 
1 disease assessment on-study: 
 DCR is defined as the percentage of patients who have achieved CR, PR and SD 
at a particular time point after first treatment, according to RECIST v1.1. 
 PFS is defined as the time from the start of treatment up to the date of first 
progression based on RECIST v1.1, second primary malignancy or death from 
any cause, whichever occurs first.  
 Overall survival rate is defined as the percentage of patients who are still alive at 
36 weeks after first treatment with SCB01A.  
 
Inferential analysis results will be expressed as point estimates and their 95% CIs.  To 
be consistent with the sample size calculation, the 90% CI will also be presented for 
the primary endpoint.  Analyses will be carried out using SAS® Software, version 9.3 
or higher (SAS Institute, Cary, North Carolina, USA). 
 
All time-to-event endpoints, including overall survival time and PFS, will be reported 
in days (median with 95% CI and range) and calculated using Kaplan-Meier methods.  
Patients who have not progressed or who have died at the time of the analysis will be 
censored at the last disease assessment date. 
 
The study will be stopped early for futility if less than three DCRs are observed 
following the completion of the first stage of Phase II.  In addition, no further 
investigation of the drug will be pursued if less than 6 patients achieve DCR by the 
end of Stage 2 of Phase II. 
 
8.6. 
PK Analysis 
The blood samples will be assayed for SCB01A and PK parameters (area under the 
plasma concentration-time curve from time zero to time t [AUC0-t], area under the 
plasma concentration-time curve from time zero to infinite time [AUC0-inf], and 
maximum plasma concentration [Cmax], clearance [CL], volume of distribution [Vd], 
half-life [t1/2], elimination constant [Kel], mean residence time [MRT] and time to 
maximum concentration [Tmax]) will be determined and presented graphically and 
descriptively (as appropriate). 
 
8.7. 
Health Outcomes Assessments 
Health outcomes assessment using EORTC QLQ C30 and H&N35 questionnaires and 
will be completed by patients at time points specified in Table 1 and Table 2.  
Questionnaire data will be listed and summarized by dose group, cycle and day within 
cycle as applicable and may be presented graphically. 
 


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8.8. 
Interim Analysis 
An interim statistical analysis will be performed following the completion of stage 1, 
Phase II.  If more than two DCs are observed, an additional 21 patients will be 
enrolled into Stage 2 at the same dose level.  The study will be stopped early for 
futility if less than 3 DCRs are observed following the completion of the first stage of 
Phase II with no further investigation of the drug if less than 6/34 achieve DCR by the end of 
Stage 2 of Phase II. 
 
 
9. 
Study Management 
9.1. 
Regulatory Guidelines 
The study will be performed in accordance with US Investigational New Drug (IND) 
regulations (21 Code of Federal Regulations [CFR] 56) or local national laws (as 
applicable), the guidelines of ICH, and the guidelines of the declaration of Helsinki 
adopted by the 18th World Medical Assembly in Helsinki, Finland in 1964 and 
amended by subsequent assemblies in Tokyo, Japan in 1975; Venice, Italy in 1983; 
Hong Kong in 1989; Somerset West, South Africa in 1996, and in Edinburgh, 
Scotland in 2000; notes of clarification were added in 2002 and 2004 (see 
Section 11.2 [Appendix 2]). 
 
9.2. 
Ethics 
9.2.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
Before implementing this study, the protocol, the proposed patient informed consent 
forms (ICFs) and other information for the patients, must be reviewed by a properly 
constituted committee(s) responsible for approving clinical studies.  The IRB/IEC 
written, signed approval letter/form must contain approval of the designated 
investigator, the protocol (identifying protocol title, date and version number), and of 
the patient ICF (date, version). 
 
Any change or addition to the protocol can only be made in a written protocol 
amendment that must be approved by the Sponsor and the IRB/IEC. 
 
9.2.2. Ethical Conduct of the Study 
The study will be conducted in accordance with the approved study protocol and 
SOPs of the Sponsor or CRO that meet the guidelines provided by the ICH E6 for 
GCP in clinical studies. 
 
9.3. 
Patient Information and Consent 
The investigator must fully inform the patient of all pertinent aspects of the trial 
including the written information approved by the IRB/IEC. 
 
Prior to the start of screening, the written ICF must be signed and personally dated by 
the patient and by the investigator who conducted the informed consent discussion.  


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One copy of the written information and signed consent form must be given to each 
patient and one copy must be retained in the investigator's study records. 
 
9.4. 
Confidentiality and Disclosure 
Data on patients collected on eCRFs during the trial will be documented in an 
anonymous fashion and the patient will only be identified by the patient number, and 
by his/her initials if also required.  If, as an exception, it is necessary for safety or 
regulatory reasons to identify the patient, all parties are bound to keep this 
information confidential. 
 
The investigator will guarantee that all persons involved will respect the 
confidentiality of any information concerning the trial patients.  All parties involved 
in the study will maintain strict confidentiality to assure that neither the person nor the 
family privacy of a patient participating in the trial is violated.  Likewise, the 
appropriate measures shall be taken to prevent access of non-authorized persons to the 
trial data. 
 
All information provided to the investigator by the Sponsor, or their designee, will be 
kept strictly confidential.  No disclosure shall be made except in accordance with a 
right of publication granted to the investigator. 
 
No information about this study or its progress will be provided to anyone not 
involved in the study other than the Sponsor, or its authorized representatives, or in 
confidence to the IRB, or similar committee, except if required by law. 
 
9.5. 
Indemnification 
The sponsor’s indemnification of the investigator and institution during the conduct of 
this study is addressed in a letter of indemnification provided as a separate document.  
Other indemnification or insurance will be provided as required under local 
regulations. 
 
9.6. 
Discontinuation of the Study by the Sponsor 
The sponsor reserves the right to discontinue the study at this site or at multiple sites 
for safety or administrative reasons at any time.  In particular, a site that does not 
recruit at a reasonable rate may be discontinued.  Should the study be terminated 
and/or the site closed for whatever reason, all documentation and study medication 
pertaining to the study must be returned to the Sponsor or its representative. 
 
9.7. 
Study Documentation 
By signing a copy of Form FDA 1572 or other country-specific regulatory forms, the 
Principal Investigator acknowledges that he/she has received a copy of the 
Investigator’s Brochure (IB) on the IP and assures the Sponsor that he/she will 
comply with the protocol and the provisions stated in Form FDA 1572 and other 
country-specific forms.  No changes in this protocol can be made without the 
Sponsor’s written approval. 
 


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The Investigator will supply the Sponsor with the following documents: 
 Original, signed Form FDA 1572 and other country-specific forms 
 Curricula vitae for all Investigators listed on Form FDA 1572 and other forms 
 Copy of Principal Investigator’s medical licensure/medical registration number 
 Signed protocol signature page 
 List of IRB/IEC members and their occupations/affiliations or multiple assurance 
number 
 Letter indicating IRB/IEC approval to conduct the protocol 
 Copy of IRB/IEC-approved ICF 
 
The Sponsor will supply the Investigator with the following documents: 
 Clinical study protocol 
 IB 
 Sample ICF 
 CRFs/instruction manual 
 Laboratory certification records and reference ranges, if applicable 
 Insurance certificate 
 
9.8. 
Data Handling and Record Retention 
9.8.1. Source Documents 
Source documents are considered to be all information in original records and 
certified copies of original records of clinical findings, observations, data, or other 
activities in a clinical study necessary for the reconstruction and evaluation of the 
study. 
 
9.8.2. Recording and Collection of Data 
All source documents and eCRFs will be completed as soon as possible after the 
patient’s visit.  Corrections to data on the source will be documented.  The 
investigator will review eCRFs to indicate that, to his/her knowledge, they are 
complete and accurate.  Designated source documents will be signed and dated by the 
appropriate study personnel.  The investigator must agree to complete and maintain 
source documents and eCRFs for each patient participating in the study. 
 
9.8.3. Clinical Data Management 
The sponsor and/or designated CRO will be responsible for the processing and quality 
control of the data.  Data management will be carried out as described in the sponsor’s 
or CRO’s SOPs for clinical studies. 
 
The handling of data, including data quality control, will comply with regulatory 
guidelines (e.g., ICH GCP, and local regulations where applicable) and the sponsor’s 
or the CRO’s SOPs as well as provisions of the study-specific Data Management Plan. 
 


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9.8.4. Archiving 
The investigator must make original study data (paper or electronic) accessible to the 
study monitor, other authorized sponsor representatives, and regulatory agency 
inspectors (eg, US FDA) upon request.  A file for each patient must be maintained 
that includes the signed ICF and copies of all source documentation related to that 
patient.  The investigator must ensure the reliability and availability of source 
documents from which the information on the eCRF was derived. 
 
Patient identity information recorded will be maintained for at least 15 years on the 
patient confidentiality log or longer if required by local regulations. 
 
Investigators must maintain all study documentation for at least 2 years following the 
approval of the drug, or until 2 years after the investigational drug program is 
discontinued, or longer if required by local regulations.  Study documentation 
includes all essential documents as defined in ICH E6 Guidelines for GCP.  The 
sponsor or designee will notify the investigator when any records may be discarded, 
but investigators must comply with local regulations. 
 
9.9. 
Monitoring 
The study will be monitored to ensure that the study is conducted and documented 
properly according to the protocol, GCP, and all applicable regulatory requirements.  
 
On-site visits will be made at appropriate times during the period of the study.  
Monitors must have direct access to source documentation in order to check the 
consistency of the data recorded in the eCRFs. 
 
The investigator will make available source documents, medical records, and source 
data necessary to complete eCRFs to the monitor.  In addition, the investigator will 
work closely with the monitor and, as needed, provide them appropriate evidence that 
the conduct of the study is being done in accordance with applicable regulations and 
GCP guidelines. 
 
9.10. Protocol Amendments, other Changes in Study Conduct 
9.10.1. Protocol Amendments 
Any changes to the study protocol will be addressed in a Protocol Amendment which 
will receive IEC approval before implementation thereof. 
 
9.10.2. Other Changes in Study Conduct 
Any other changes to the study conduct or statistical analyses will be described in the 
clinical study report. 
 
9.11. Quality Control and Quality Assurance 
The sponsor or its designee will perform the quality assurance and quality control 
activities of this study; however, responsibility for the accuracy, completeness, and 


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reliability of the study data presented to the sponsor lies with the investigator 
generating the data. 
 
Audits may be conducted at the discretion of the sponsor as part of the 
implementation of quality assurance to ensure that the study is being conducted in 
compliance with the protocol, SOPs, GCP, and all applicable regulatory requirements.  
Audits will be independent of and separate from the routine monitoring and quality 
control functions.  If such an audit occurs, the investigator must agree to allow access 
to required patient records.  By signing this protocol, the Investigator grants 
permission to personnel from the sponsor, its representatives, and appropriate 
regulatory authorities for on-site monitoring of all appropriate study documentation, 
as well as on-site review of the procedures employed in eCRF generation, where 
clinically appropriate. 
 
9.12. Publication Policy 
An ICH-compliant integrated clinical and statistical report will be prepared upon 
completion of the study and data analysis.  The results of the study will be published 
in a relevant peer- reviewed journal, with authorship status and ranking designated 
according to the acknowledged contributions of participating investigators, 
institutions and the Sponsor.  No publications will be allowed without the agreement 
of the Sponsor. 
 


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10. References 
 
1 Simon R, 1989. Optimal Two-Stage Designs for Phase II Clinical Trials. Controlled 
Clinical Trials. 10: 1-10. 
2 Jung SH et al., 2004. Admissible two-stage designs for phase II cancer clinical trials, 
Statistics in Medicine 23:561-569. 
3 Cooney, MM., Heeckeren, W., Shyam, B., et al. Drug Insight: Vascular disrupting 
agents and angiogenesis-novel approaches for drug delivery. Nat Rev Clin Oncology.  
2006; 3: 682-692. 
4 Tozer, GM., Kanthou, C., & Baguley, BC. Disrupting tumor blood vessels. Nat Rev 
Cancer. 2005; 5(6): 423-435. 
5  Mosteller RD. "Simplified calculation of body-surface area". N Engl J Med 1987; 
317:1098.  PMID 3657876. 
6  Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. Am J Clin Oncol1982;5:649-655 


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11. Appendices 
11.1. Appendix 1 – Reference List of Known Inhibitors of CYP1A2 and 
CYP2D6 Inhibitors 
1A2 
2D6 
Strong 
fluvoxamine 
ciprofloxacin 
 
Weak  
cimetidine 
 
Others 
amiodarone 
efavirenz 
fluoroquinolones 
fluvoxamine 
furafylline1 
interferon 
methoxsalen 
mibefradil 
ticlopidine 
Strong 
bupropion 
cinacalcet 
fluoxetine 
paroxetine 
quinidine 
 
Moderate 
duloxetine 
sertraline 
terbinafine 
 
Weak 
amiodarone 
cimetidine 
 
Others 
celecoxib 
chlorpheniramine 
chlorpromazine 
citalopram 
clemastine 
clomipramine 
cocaine 
diphenhydramine 
doxepin 
doxorubicin 
escitalopram 
halofantrine 
haloperidol 
histamine H1 receptor antagonists 
hydroxyzine 
levomepromazine 
methadone 
metoclopramide 
mibefradil 
midodrine 
moclobemide 
perphenazine 
ranitidine 
reduced-haloperidol 
ritonavir 
ticlopidine 
tripelennamine 


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A Strong inhibitor is one that causes a > 5-fold increase in the plasma AUC values or more 
than 80% decrease in clearance. 
A Moderate inhibitor is one that causes a > 2-fold increase in the plasma AUC values or 
50-80% decrease in clearance. 
A Weak inhibitor is one that causes a > 1.25-fold but < 2-fold increase in the plasma AUC 
values or 20-50% decrease in clearance. 
URL: http://medicine.iupui.edu/clinpharm/ddis/main-table/ 


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11.2. Appendix 2 – Declaration of Helsinki 
 
WORLD MEDICAL ASSOCIATION (WMA) DECLARATION OF HELSINKI 
Ethical Principles for Research Involving Human Patients 
Adopted by the 18th WMA General Assembly, Helsinki, Finland, June 1964 and amended by the 29th 
WMA General Assembly, Tokyo, Japan, October 1975; the 35th WMA General Assembly, Venice, 
Italy, October 1983; the 41st WMA General Assembly, Hong Kong, September 1989; the 48th WMA 
General Assembly, Somerset West, Republic of South Africa, October 1996; and the 52nd WMA 
General Assembly, Edinburgh, Scotland, October 2000. A note of clarification on Paragraph 29 was 
added by the 54th WMA General Assembly, Washington, 2002; and a note of clarification on 
Paragraph 30 was added by the 56th WMA General Assembly, Tokyo, 2004. 
 
A. INTRODUCTION 
1. 
The World Medical Association has developed the Declaration of Helsinki as a statement 
of ethical principles to provide guidance to physicians and other participants in medical 
research involving human patients. Medical research involving human patients includes 
research on identifiable human material or identifiable data. 
2. 
It is the duty of the physician to promote and safeguard the health of the people. The 
physician's knowledge and conscience are dedicated to the fulfilment of this duty. 
3. 
The Declaration of Geneva of the World Medical Association binds the physician with 
the words, "The health of my patient will be my first consideration," and the 
International Code of Medical Ethics Declares that, "A physician shall act only in the 
patient's interest when providing medical care which might have the effect of weakening 
the physical and mental condition of the patient."  
4. 
Medical progress is based on research which ultimately must rest in part on 
experimentation involving human patients. 
5. 
In medical research on human patients, considerations related to the well-being of the 
human patient should take precedence over the interests of science and society. 
6. 
The primary purpose of medical research involving human patients is to improve 
prophylactic, diagnostic and therapeutic procedures and the understanding of the 
etiology and pathogenesis of disease. Even the best proven prophylactic, diagnostic, and 
therapeutic methods must continuously be challenged through research for their 
effectiveness, efficiency, accessibility and quality.  
7. 
In current medical practice and in medical research, most prophylactic, diagnostic and 
therapeutic procedures involve risks and burdens.  
8. 
Medical research is patient to ethical standards that promote respect for all human beings 
and protect their health and rights.  Some research populations are vulnerable and need 


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special protection. The particular needs of the economically and medically 
disadvantaged must be recognized. Special attention is also required for those who 
cannot give or refuse consent for themselves, for those who may be patient to giving 
consent under duress, for those who will not benefit personally from the research and for 
those for whom the research is combined with care.  
9. 
Research Investigators should be aware of the ethical, legal and regulatory requirements 
for research on human patients in their own countries as well as applicable international 
requirements. No national ethical, legal or regulatory requirement should be allowed to 
reduce or eliminate any of the protections for human patients set forth in this Declaration. 
B. BASIC PRINCIPLES FOR ALL MEDICAL RESEARCH 
10. It is the duty of the physician in medical research to protect the life, health, privacy, and 
dignity of the human patient.  
11. Medical research involving human patients must conform to generally accepted scientific 
principles, be based on a thorough knowledge of the scientific literature, other relevant 
sources of information, and on adequate laboratory and, where appropriate, animal 
experimentation. 
12. Appropriate caution must be exercised in the conduct of research which may affect the 
environment, and the welfare of animals used for research must be respected. 
13. The design and performance of each experimental procedure involving human patients 
should be clearly formulated in an experimental protocol. This protocol should be 
submitted for consideration, comment, guidance, and where appropriate, approval to a 
specially appointed ethical review committee, which must be independent of the 
Investigator, the Sponsor or any other kind of undue influence. This independent 
committee should be in conformity with the laws and regulations of the country in which 
the research experiment is performed. The committee has the right to monitor ongoing 
trials. The researcher has the obligation to provide monitoring information to the 
committee, especially any serious adverse events. The researcher should also submit to 
the committee, for review, information regarding funding, Sponsors, institutional 
affiliations, other potential conflicts of interest and incentives for patients.  
14. The research protocol should always contain a statement of the ethical considerations 
involved and should indicate that there is compliance with the principles enunciated in 
this Declaration.  
15. Medical research involving human patients should be conducted only by scientifically 
qualified persons and under the supervision of a clinically competent medical person. 
The responsibility for the human patient must always rest with a medically qualified 
person and never rest on the patient of the research, even though the patient has given 


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consent. 
16. Every medical research project involving human patients should be preceded by careful 
assessment of predictable risks and burdens in comparison with foreseeable benefits to 
the patient or to others. This does not preclude the participation of healthy volunteers in 
medical research. The design of all studies should be publicly available. 
17. Physicians should abstain from engaging in research projects involving human patients 
unless they are confident that the risks involved have been adequately assessed and can 
be satisfactorily managed. Physicians should cease any investigation if the risks are 
found to outweigh the potential benefits or if there is conclusive proof of positive and 
beneficial results. 
18. Medical research involving human patients should only be conducted if the importance 
of the objective outweighs the inherent risks and burdens to the patient. This is especially 
important when the human patients are healthy volunteers.  
19. Medical research is only justified if there is a reasonable likelihood that the populations 
in which the research is carried out stand to benefit from the results of the research.  
20. The patients must be volunteers and informed participants in the research project. 
21. The right of research patients to safeguard their integrity must always be respected. 
Every precaution should be taken to respect the privacy of the patient, the confidentiality 
of the patient's information and to minimize the impact of the study on the patient's 
physical and mental integrity and on the personality of the patient. 
22. In any research on human beings, each potential patient must be adequately informed of 
the aims, methods, sources of funding, any possible conflicts of interest, institutional 
affiliations of the researcher, the anticipated benefits and potential risks of the study and 
the discomfort it may entail. The patient should be informed of the right to abstain from 
participation in the study or to withdraw consent to participate at any time without 
reprisal. After ensuring that the patient has understood the information, the physician 
should then obtain the patient's freely-given informed consent, preferably in writing. If 
the consent cannot be obtained in writing, the non-written consent must be formally 
documented and witnessed.  
23. When obtaining informed consent for the research project the physician should be 
particularly cautious if the patient is in a dependent relationship with the physician or 
may consent under duress. In that case the informed consent should be obtained by a 
well-informed physician who is not engaged in the investigation and who is completely 
independent of this relationship.  
24. For a research patient who is legally incompetent, physically or mentally incapable of 
giving consent or is a legally incompetent minor, the Investigator must obtain informed 


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consent from the legally authorized representative in accordance with applicable law. 
These groups should not be included in research unless the research is necessary to 
promote the health of the population represented and this research cannot instead be 
performed on legally competent persons.  
25. When a patient deemed legally incompetent, such as a minor child, is able to give assent 
to decisions about participation in research, the Investigator must obtain that assent in 
addition to the consent of the legally authorized representative. 
26. Research on individuals from whom it is not possible to obtain consent, including proxy 
or advance consent, should be done only if the physical/mental condition that prevents 
obtaining informed consent is a necessary characteristic of the research population. The 
specific reasons for involving research patients with a condition that renders them unable 
to give informed consent should be stated in the experimental protocol for consideration 
and approval of the review committee. The protocol should state that consent to remain 
in the research should be obtained as soon as possible from the individual or a legally 
authorized surrogate. 
27. Both authors and publishers have ethical obligations. In publication of the results of 
research, the Investigators are obliged to preserve the accuracy of the results. Negative as 
well as positive results should be published or otherwise publicly available. Sources of 
funding, institutional affiliations and any possible conflicts of interest should be declared 
in the publication. Reports of experimentation not in accordance with the principles laid 
down in this Declaration should not be accepted for publication.  
C. ADDITIONAL PRINCIPLES FOR MEDICAL RESEARCH COMBINED WITH 
MEDICAL CARE  
28.  The physician may combine medical research with medical care, only to the extent that 
the research is justified by its potential prophylactic, diagnostic or therapeutic value. 
When medical research is combined with medical care, additional standards apply to 
protect the patients who are research patients. 
29. The benefits, risks, burdens and effectiveness of a new method should be tested against 
those of the best current prophylactic, diagnostic, and therapeutic methods. This does not 
exclude the use of placebo, or no treatment, in studies where no proven prophylactic, 
diagnostic or therapeutic method exists.1 
30. At the conclusion of the study, every patient entered into the study should be assured of 
access to the best proven prophylactic, diagnostic and therapeutic methods identified by 
the study.2 
31. The physician should fully inform the patient which aspects of the care are related to the 
research. The refusal of a patient to participate in a study must never interfere with the 


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patient-physician relationship. 
32. In the treatment of a patient, where proven prophylactic, diagnostic and therapeutic 
methods do not exist or have been ineffective, the physician, with informed consent from 
the patient, must be free to use unproven or new prophylactic, diagnostic and therapeutic 
measures, if in the physician's judgment it offers hope of saving life, re-establishing 
health or alleviating suffering. Where possible, these measures should be made the object 
of research, designed to evaluate their safety and efficacy. In all cases, new information 
should be recorded and, where appropriate, published. The other relevant guidelines of 
this Declaration should be followed. 
1 Note of clarification on Paragraph 29 of the WMA Declaration of Helsinki:  The WMA hereby 
reaffirms its position that extreme care must be taken in making use of a placebo-controlled trial 
and that in general this methodology should only be used in the absence of existing proven 
therapy. However, a placebo-controlled trial may be ethically acceptable, even if proven therapy 
is available, under the following circumstances:  where for compelling and scientifically sound 
methodological reasons, its use is necessary to determine the efficacy or safety of a prophylactic, 
diagnostic, or therapeutic method; or where a prophylactic, diagnostic, or therapeutic method is 
being investigated for a minor condition, and the patients who receive placebo will not be patient 
to any additional risk or serious or irreversible harm. All other provisions of the Declaration of 
Helsinki must be adhered to, especially the need for appropriate ethical and scientific review. 
2 Note of clarification on Paragraph 30 of the WMA Declaration of Helsinki:  The WMA hereby 
reaffirms its position that it is necessary during the study planning process to identify post-trial 
access by study participants to prophylactic, diagnostic, and therapeutic procedures identified as 
beneficial in the study or access to other appropriate care. Post-trial access arrangements or other 
care must be described in the study protocol so the ethical review committee may consider such 
arrangements during its review. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11.3. Appendix 3– Questionnaires EORTC QLQ C30 and QLQ H&N35 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 79 of 82 
EORTC QLQ C30 
 
 
 
 
 
 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 80 of 82 
 
 
QLQ H&N35 
 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 81 of 82 
 
 
 
 
 
 
 
 


SynCore Biotechnology Co. Ltd. 
 
Protocol No: SCB01A-21 
 
 
Version 3.0: 25-Jul-2016 
 
 
Confidential 
 
Page 82 of 82 
 

SAP_001.pdf: 
Protocol Number: SCB01A-21 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
Page 1 of 39 
STATISTICAL ANALYSIS PLAN 
AN OPEN-LABEL, PHASE II STUDY TO EVALUATE SCB01A IN 
PATIENTS WITH RECURRENT OR METASTATIC SQUAMOUS CELL HEAD 
AND NECK CANCER WHO HAVE RECEIVED PLATINUM-BASED 
TREATMENT 
Protocol No.: SCB01A-21 
Product Code: SCB01A 
PREPARED FOR:  SynCore Biotechnology Co., Ltd. 
No. 84 Chung-Shan Rd., 
Chung-Shan Village, 
Tung-Shan Shine, ILan, 
Taiwan, R.O.C. 
PREPARED BY:  Novotech (Australia) Pty Ltd 
Level 3, 235 Pyrmont Street 
Pyrmont, NSW, 2009  
Australia 
VERSION/STATUS: Final Version 1.2 
VERSION DATE: 27Oct2017 
AUTHOR: Jian Wu 


Protocol Number: SCB01A-21 
 
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Page 2 of 39 
SAP APPROVAL 
 
By my signature, I confirm that this SAP has been approved for use on the SCB01A-21 study: 
 
Name 
Title / Company 
Signature 
Date and Time 
Meng-Hsiung 
Chang 
Project Manager / 
SynCore Biotechnology 
Co., Ltd 
 
 
 
 
 


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Table of Contents 
 
1. Introduction ................................................................................................................ 5 
2. Project Overview ........................................................................................................ 6 
2.1. Description of Overall Study Design and Plan ................................................................ 6 
2.2. Objectives ....................................................................................................................... 7 
2.3. Study Endpoints .............................................................................................................. 8 
2.4. Sample Size ..................................................................................................................... 9 
2.5. Randomization and Assignment of Subjects to Treatment Groups ............................... 9 
3. Statistical Considerations ......................................................................................... 10 
4. Analysis Populations ................................................................................................ 11 
5. Subject Disposition ................................................................................................... 12 
6. Protocol Deviations .................................................................................................. 13 
7. Demographic and Baseline Information .................................................................. 14 
7.1. Demographics ............................................................................................................... 14 
7.2. Medical history and cancer history .............................................................................. 14 
7.3. Inclusion/Exclusion Criteria .......................................................................................... 14 
7.4. Serum Pregnancy Test .................................................................................................. 14 
7.5. Human Papillomavirus (HPV) Status ............................................................................ 14 
7.6. Nerve Conduction Velocity ........................................................................................... 14 
8. Study Drug Administration ....................................................................................... 15 
9. Safety ....................................................................................................................... 16 
9.1. Adverse Events ............................................................................................................. 16 
9.2. Concomitant medication .............................................................................................. 17 
9.3. Laboratory .................................................................................................................... 17 
9.3.1. Laboratory Parameters ........................................................................................................ 17 
9.3.2. Biostatistical methods.......................................................................................................... 19 
9.4. Vital Signs ..................................................................................................................... 19 
9.4.1. Vital Sign Parameters ........................................................................................................... 19 
9.4.2. Biostatistical methods.......................................................................................................... 19 
9.5. Physical examination .................................................................................................... 19 
9.5.1. Body Systems Assessed ....................................................................................................... 19 
9.5.2. Biostatistical methods.......................................................................................................... 20 
9.6. 12-lead ECG .................................................................................................................. 20 
9.6.1. ECG Parameters ................................................................................................................... 20 
9.6.2. Biostatistical methods.......................................................................................................... 20 
10. Efficacy ................................................................................................................... 21 
10.1. Tumor Response and Disease Control Rate ............................................................... 21 
10.2. Progression-free Survival and Overall Survival........................................................... 21 


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11. Health Outcome and ECOG-PS ............................................................................... 22 
11.1. EORTC QLQ-C30 .......................................................................................................... 22 
11.2. EORTC QLQ-H&N35 .................................................................................................... 24 
11.3. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ..................... 25 
12. Pharmacokinetics (PK) ........................................................................................... 26 
12.1. Definition of variables ................................................................................................ 26 
12.2. Biostatistical methods ................................................................................................ 26 
13. Bioanalytical Measurement ................................................................................... 28 
14. Handling of Missing Data ....................................................................................... 29 
15. Changes to the Planned Analysis ........................................................................... 30 
16. Interim and Final Analysis ...................................................................................... 31 
16.1. Interim Analyses ......................................................................................................... 31 
16.2. Final Analysis (End of Study) ....................................................................................... 31 
17. Software ................................................................................................................. 32 
18. Tables ..................................................................................................................... 33 
19. Listings ................................................................................................................... 35 
20. Figures .................................................................................................................... 37 
21. References .............................................................................................................. 39 
 
 
 
 
 


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1.Introduction 
The following Statistical Analysis Plan (SAP) provides the outline for the statistical analysis of 
the data from SCB01A-21 study. This SAP is based on the study protocol version 3.0 (dated 
on 25Jul2016). 
 
The planned analyses identified in this SAP may be included in clinical study reports (CSRs), 
regulatory submissions, or future manuscripts. Also, post hoc analyses not necessarily 
identified in this SAP may be performed to further examine study data.  Any post hoc, or 
unplanned, exploratory analyses performed will be clearly identified as such in the final CSR. 
 
Note: This study was designed to have two phases, namely run-in phase I (dose escalation 
phase) and phase II. This study was terminated early in run-in phase I, with eight (8) subjects 
screened and five (5) subjects enrolled. There was no recruitment for phase II. In light of the 
small number of subjects enrolled in this study, the SAP will focus on safety data analysis. 
Efficacy data will be conducted only if there are enough subjects/events, as appropriate, for the 
analysis methods.  
 
 
 


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2.Project Overview 
2.1.Description of Overall Study Design and Plan 
This is an open-label, phase II study to evaluate SCB01A in patients with recurrent or 
metastatic squamous cell head and neck cancer, who have received platinum-based treatment. 
This study was designed with two phases: one run-in phase I (dose escalation phase) and one 
continuation phase (phase II). 
Run-in Phase I (Dose Escalation Phase) 
The run-in phase I was to determine the optimal dose for SCB01A to be used in phase II. In 
the phase I, dose-escalation was involved, in which successive cohorts of three subjects would 
receive escalating doses of SCB01A until 24 mg/m2. Dose escalation assessment would be 
based on tolerability observed during 3 cycles of treatment. An Optimal Dose would be agreed 
upon. 
Dose level was initiated at 3.25 mg/m2 (Dose 1) in the first cohort, and could be escalated to 
12 mg/m2 (Dose 2), 18 mg/m2 (Dose 3) and 24 mg/m2 (Dose 4) by an up and down approach. 
Briefly, at each dose level, if 1 of the three subjects experienced a dose limiting toxicity (DLT) 
during the first 3 cycles of SCB01A treatment, an additional three subjects will be enrolled at 
the same dose level. If 0/6 or 1/6 i.e ≤1 of subjects experienced DLT at the given dose level, 
the dose of the subsequent cohort would be increased to the next level, then this process would 
continue until >1/6 of subjects experienced DLT at certain dose level or the maximum dose in 
this protocol, 24 mg/m2 (Dose 4) was reached. This process could continue at a reduced dose 
level, if >1/6 of subjects experienced DLT at a higher dose level. The reduced dose levels 
potentially to be tested were specified in the protocol as 10 mg/ m2 (Dose 1a), 5 mg/m2 (Dose 
0a), 15 mg/m2 (Dose 2a), and 21mg/m2 (Dose 3a). 
When the study was terminated in run-in phase I, subjects were recruited only for cohorts of 
3.25 mg/m2 (Dose 1) and 12 mg/m2 (Dose 2). 
Phase II  
In the phase II of the study additional subjects would be enrolled to evaluate the Optimal Dose 
as established by review of the safety committee. 
The phase II followed a Simon’s optimal two-stage design to test the disease control rate 
(including complete response, partial response and stable disease) in subjects treated with 
SCB01A was at least 25% (alternative hypothesis). In the first stage of phase II, a total of 13 
subjects would be enrolled at the optimal dose level, including those already enrolled at the 
optimal dose level from Run-in Phase I. If 1 or fewer patient was observed with disease control 
response in the stage 1 of phase II, then the study would be stopped for futility, with disease 
control rate concluded to be less than or equal to 10% (null hypothesis). Otherwise, the phase 
II would enter into its stage 2, in which an additional 21 subjects would be enrolled at the optimal 
dose level. If 6 or more subjects were observed with disease control response out of the 34 
subjects enrolled (13 + 21) in the stage 2, the disease control rate in subjects treated with 
SCB01A would be concluded to be at least 25%. Otherwise, the disease control rate in subjects 
treated with SCB01A would be concluded to be less than or equal to 10%, and further 
investigation of the investigational treatment was not warranted.      


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The study was terminated without any recruitment for phase II. 
Subjects would receive the recommended dose of mono-therapy of SCB01A for 9 weeks (3 
weeks*3 cycles) or until disease progression, intolerable toxicity, consent withdrawal or death, 
whichever occurs first. DLT and safety would be followed in each phase of study. 
Pharmacokinetic (PK) would be performed on subjects enrolled in the run-in phase, with PK 
blood samples taken immediately pre-infusion then at 2, 3, 4, 6, 10, 21 and 24 hours after the 
start of infusion on Days 1 and 8 of Cycles 1, 2 and 3. Bioanalytical measurements and health 
outcome data (EORTC QLQ-C30 and EORTC QLQ-H&N35) were to be collected. Tumor 
response would be assessed by using computerized tomography (CT) or MRI scans according 
to RECIST v1.1 at baseline, and every 3 cycles prior to the next cycle until progression of the 
disease. 
 
 
2.2.Objectives  
Run-in Phase I (Dose Escalation Phase) 
 
Primary objective: 
• 
To determine the optimal dose for 3 cycles of i.v. administration of SCB01A on Days 1 
and 8 of each cycle in a 3-week cycle 
 
Secondary Objective: 
• 
To evaluate the safety and toxicity for 3 cycles of i.v. administration of SCB01A on Days 
1 and 8 of each cycle in a 3-week cycle 
• 
To assess the PK profile of SCB01A of subjects in the run-in phase. 
 
 
Phase II  
 
Primary Objective: 
• 
To assess the disease control rate (DCR) at the end of the 9th week (3 cycles, each 
cycle consists of 21 days) after treatment with SCB01A, according to the Response 
Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 
 
Secondary Objectives: 
• 
To assess the overall survival (OS) rate at 36 weeks after first treatment with SCB01A 
in subjects with recurrent or metastatic squamous cell head and neck cancer who have 
previously been treated with platinum therapy. 


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• 
To assess the progression-free survival (PFS) 
• 
To assess health outcomes using patient-reported European Organization for Research 
and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and 
EORTC QLQ H&N35 questionnaires. 
• 
To assess biomarkers relevant to the efficacy and mechanism of action of SCB01A. 
• 
To explore the possible association between biomarkers and clinical outcomes 
 
 
2.3.Study Endpoints  
Safety 
 
• 
Hematology, clinical chemistry, coagulation factors and urinalysis laboratory data 
changes 
• 
AE/SAE incidence 
• 
Physical examination results changes 
• 
Vital sign changes 
• 
Electrocardiogram (ECG) (including PR, QRS, QT, QTc, and RR intervals) results 
 
Efficacy 
• 
Disease Control Rate (DCR) is defined as the percentage of subjects who have 
achieved complete response (CR), partial response (PR) and stable disease (SD) at 
Week 9 after first treatment, according to RECIST v1.1. 
• 
Progression-free Survival (PFS) is defined as the time from the start of treatment up to 
the date of first progression based on RECIST v1.1, second primary malignancy or 
death from any cause, whichever occurs first. 
• 
Overall survival (OS) rate at Week 36 is defined as the percentage of subjects who are 
still alive at 36 weeks after first treatment with SCB01A. 
• 
Health outcomes assessment using patient-reported EORTC QLQ-C30 and QLQ-
H&N35 questionnaires. 
 
Health outcomes assessment 
• 
EORTC QLQ-C30 
• 
EORTC QLQ-H&N35 
 
Pharmacokinetic 
 
PK concentration: 
• 
Plasma concentration of SCB01A at the sampling time 
 
PK parameters: 
• 
AUC0-t: area under the plasma concentration-time curve from time zero to time t 
• 
AUC0-inf: plasma concentration-time curve from time zero to infinite time 
• 
Cmax: maximum plasma concentration 
• 
Tmax: maximum concentration 
• 
CL: clearance 
• 
Vd: volume of distribution 


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• 
t1/2: half-life 
• 
Kel: elimination constant 
• 
MRT: mean residence time 
 
Bioanalytical measurement 
 
• 
Circulating endothelial cells (CEC), vascular endothelial growth factor (VEGF) and 
circulating endothelial progenitor (CEP) cells 
 
• 
Tumor micro vessel density and blood flow by dynamic contrast-enhanced MRI (DCE-
MRI) at baseline and 6 hours after the infusion of the drug on C1D1 
 
• 
Human Papillomavirus (HPV) status (expression of p16 by immunohistochemistry 
[IHC]) at baseline 
 
 
2.4.Sample Size 
Run-in Phase I (Dose Escalation Phase) 
 
No formal statistical calculation of sample size was conducted for run-in phase I (dose 
escalation phase). This was a standard 3 + 3 up/down dose escalation design. The sample 
size was empirical. The small numbers per cohort in this phase were not intended for statistical 
hypotheses. Only five (5) subjects were recruited in run-in phase I when the trial was 
terminated. 
 
Phase II  
 
The sample size in phase II was based on Simon’s optimal two-stage design to test that the 
disease control rate in subjects treated with SCB01A was less than or equal to 10% (null 
hypothesis), or at least 25% (alternative hypothesis), with a significance level of 0.10 (one-
sided) and power of 80%. As mentioned above, in stage 1 of phase II, 13 subjects would be 
needed, and 21 subjects would be needed in stage 2 of phase II, with a total of 34 subjects (13 
+ 21) needed in phase II. There was no recruitment for phase II. 
 
2.5.Randomization and Assignment of Subjects to Treatment Groups 
This is an open label study, and no randomization is applicable. 
 
 
 
 
 


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3.Statistical Considerations 
 
Data will be handled and processed according to the sponsor’s representative (Novotech 
(Australia) Pty Ltd) Standard Operating Procedures (SOPs), which are written based on the 
principles of Good Clinical Practice (GCP). 
 
All data collected on the eCRFs will be presented in the data listings and will be listed and 
sorted by subject number and visit, where applicable. All summaries will present the data by 
SCB01A dose level (cohort) and overall (total enrolled subjects), as applicable. Patient data 
will be separated via cohort and presented for enrolled subjects. 
 
Unless otherwise stated, the following statistical approaches will be taken: 
• 
Continuous variables: Descriptive statistics will include the number of non-missing 
values (N), mean, standard deviation (SD), median, minimum, maximum.  
• 
Categorical variables: Descriptive statistics will include frequency counts and 
percentages per category. Percentages will be rounded to one decimal place, with the 
denominator being the number of subjects in the relevant population with non-missing 
data, unless otherwise specified.  
• 
Imputation: No missing data will be imputed generally.  
• 
Pharmacokinetic (PK) data: For PK data  the arithmetic mean, standard deviation (SD), 
median, minimum, maximum, geometric mean and coefficient of variation (CV%) values 
will  be presented. 
• 
Confidence intervals (CIs): CIs will be two-sided and will use 95% confidence levels 
unless specified otherwise. 
• 
Baseline: Baseline values will be defined as the last non-missing observation for each 
subject prior to the dosing of study medication (i.e. start of infusion on Cycle 1, Day 1). 
• 
Repeat assessments: Repeat assessments will be included in summary presentations 
(Tables). Only the original values will be used in summary presentations.  All repeat 
assessments captured in the Electronic Data Capture (EDC) system will be presented 
in the data listings. 
 
Continuous variables will be reported to the same precision as the source data. Derived 
variables will be reported using the same precision to the value(s) from which they were 
derived. For the reporting of descriptive statistics, the mean (95% CI) and median will be 
reported to 1 decimal place more than the source data; the minimum, and the maximum values 
will be presented to the same precision as the source data; and standard deviation will be 
reported to 2 decimal places more than the source data. Rounding is not allowed in the middle 
of the calculation. It only takes place at the last step to report the final result. Post-dose time 
points/visits will be calculated relative to start time of infusion on Day 1.  Study day will be 
defined as assessment day minus dosing day +1. 
Analysis will conducted for run-in phase I only. The dose levels (cohorts) will be referred to in 
the text, tables and listings as follows,  
• 
3.25 mg/m2 (Dose 1)  
• 
12 mg/m2 (Dose 2)  
• 
Total    
 


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4.Analysis Populations 
 
The protocol pre-specified the analysis populations of Full Analysis Set, Per-protocol, Safety 
and PK. However, this study was terminated early with only five (5) subjects enrolled, thus the 
analysis populations were modified accordingly as follows.  
 
Furthermore, any additional analysis populations not identified in the SAP will be identified in 
the final CSR as post hoc analyses. This may include the addition of additional study 
populations or subgroups of interest.  
 
• 
Full Analysis Set (FAS): The FAS consists of all subjects enrolled in the run-in phase. 
This population will be used for the listing and summary of efficacy, health outcome, and 
bioanalytical measurement data. 
 
• 
Safety population: The safety population will consist of all subjects who received at least 
one dose of SCB01A. All safety, treatment exposure, demographic and baseline 
characteristic data will be listed and summarized using the Safety Population 
 
• 
PK population: The PK population will consist of all subjects who received at least one 
dose of SCB01A with sufficient post-dose bio-samples collected for PK profile 
characterization. PK analysis will be conducted using the PK Population. 
 
 


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5.Subject Disposition 
All subjects who provide informed consent and are enrolled will be accounted for in this 
study. Subject disposition will be summarized using the Safety Population. 
 
By-subject data listings for subject disposition will be generated, including informed consent 
date, phase, completion status, date completed, date discontinued and reason for 
discontinuation from the study, if applicable. 
 
The number of subjects enrolled, as well as the number and percentage of subjects completing 
the study, and withdrawn from the study will be presented by dose levels and overall. The 
reason for discontinuation will also be summarized for all subjects who do not complete the 
study. 
 
 
 


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6.Protocol Deviations 
In case protocol deviations are reported, protocol deviations will be presented for each subject 
in the by-subject data listings.  
 
Prior to database lock, all protocol deviations will be reviewed by medical monitors and 
assigned a category (see below). 
 
A protocol deviation is defined as any intentional or unintentional change to, or noncompliance 
with, the approved protocol procedures or requirements. Deviations may result from the action 
or inaction of the patient, investigator, or site staff. All deviations will be tracked and should be 
reported to (Institutional Review Board) IRBs in accordance with their reporting policy. 
Examples of deviations include, but are not limited to:  
• 
Failure to adhere to study exclusion and inclusion criteria; 
• 
Failure to comply with dispensing or dosing requirements; 
• 
Use of medications, food, drink, herbal remedies, or supplements that are specifically 
prohibited in the protocol; 
• 
Missed or out-of-window visits; 
• 
Drug dosing not administered within the time frame specified in the protocol; 
• 
Failure to adhere to test requirements, including vital signs, laboratory tests, physical 
examinations, blood draws, medical history, etc. – either tests not done, incorrect tests 
done, or not done within the time frame specified in the protocol; 
• 
Procedural deviations such as incorrect storage of study drug, failure to update the ICF 
when new risks become known, failure to obtain IRB/EC approvals for the protocol and 
ICF revisions. 
 
 
 


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7.Demographic and Baseline Information 
Demographic and baseline body measurements will be summarized using the Safety 
Population. 
 
7.1.Demographics 
Demographic data, including age, gender, race, ethnicity, weight, height, BMI, smoking status, 
number of years discontinued smoking, number of years smoked, and number of smokes per 
day will be summarized by dose level (cohort) and overall. A by-subject data listing for 
demographic characteristics will be generated. 
 
7.2.Medical history and cancer history 
Past medical history will be coded using the Medical Dictionary for Regulatory Activities, 
MedDRA® Version 19.1 or above. Medical history data, including the MedDRA codes, will be 
presented in the by-subject data listings. 
 
Cancer history including date of initial diagnosis, type of cancer diagnosis, date for diagnosis 
of recurrent, differentiate grading of tumor, date for diagnosis of metastasis, and metastatic 
sites will be listed for each subject. Betel nut use status will be listed.  
 
7.3.Inclusion/Exclusion Criteria 
Inclusion/exclusion eligibility criteria information, including any criteria not met, will be listed for 
each subject. 
 
7.4.Serum Pregnancy Test 
A serum beta-HCG test for women of childbearing potential will be performed ≤ 14 days prior 
to the first dose of study treatment. Child-bearing potential (yes/no), and pregnancy test dates 
and results will be included in the by-subject data listings.  
 
7.5.Human Papillomavirus (HPV) Status  
Data for Human Papillomavirus (HPV) status at screening will be listed for each subject.  
 
7.6.Nerve Conduction Velocity   
Nerve conduction velocity would be performed for all patients at baseline and then during the 
trial only if grade 2 or above neurological symptoms experienced by the patient after receiving 
treatment with SCB01A. Baseline nerve conduction velocity will be summarized by NCI grade 
and the data will be listed as well. 


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8.Study Drug Administration 
Study drug administration results will be presented using the Safety Population. Study drug is 
the administration of SCB01A. The dosing was scheduled as 3 cycles of I.V. administration of 
SCB01A on Days 1 and 8 of each cycle in a 3-week cycle.  
 
A by-subject data listing will be generated for study drug administration. This listing will include 
date, start time, end time of administration, dose on schedule/delay (including reason for delay 
and days of delay), dose level, and actual dose given for SCB01A.    
 
Dose delay, days of delay, dose omission will be summarised by dose level (cohort) and overall 
and by treatment cycle/day. Dose omission is defined as the missed dosing for a scheduled 
treatment cycle/day before early withdrawal or end of treatment. Study drug discontinuation 
and reason for premature study drug discontinuation will be summarised as well. Date and 
reason of early study drug discontinuation will be listed as well.   
 
Body surface area (BSA) was calculated for dosing purpose, BSA will be summarised 
descriptively and listed for each subject.  
 
 
 
 


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9.Safety  
Statistical methods for the safety analyses will be primarily descriptive in nature. Each dose 
level (cohort) will be summarized separately. No formal statistical comparisons of SCB01A 
dose levels will be made. 
 
Safety endpoints include in the analysis are AEs, concomitant medications, clinical laboratory 
assessments (hematology, clinical chemistry, coagulation, and urinalysis), vital signs, physical 
examination, and 12-lead ECG. Safety endpoints will be analyzed using the Safety Population. 
 
9.1.Adverse Events 
Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA®, Version 19.1 or higher), and data will be summarized by System Organ Class 
(SOC) and Preferred Term (PT). The number and percent of subjects reporting each AE will 
be summarized for each dose level (cohort) and overall. A subject with two or more AEs within 
the same level of summarization (i.e., SOC or PT) will be counted only once in that level using 
the most severe (i.e., highest severity/grade) event or most related (for the relationship to study 
drug table). Percentages will be based on the number of subjects in the Safety Population 
within each dose level (cohort). The number of AEs reported will also be presented.  
 
Treatment-emergent AEs (TEAEs) are defined as pre-treatment existing conditions that worsen 
after study drug administration, or events that occur during the course of the study during or 
after administration of study drug. Only TEAEs will be included in the AE summary tables which 
will present data by dose level (cohort). The cohorts to be included in each table are listed in 
section 3. In the case of a missing AE start date or stop date, the most conservative approach 
will be followed to classify AE into TEAE. 
 
An overall summary of AEs will be produced including the number of TEAEs; the number and 
% of subjects reporting at least one: TEAE, serious TEAE, Dose Limiting Toxicity (DLT), grade 
3 or higher TEAE, TEAE related to study treatment (possibly, probably, or definitely related), 
serious TEAE related to study treatment, grade 3 or higher TEAE related to the study drug, 
TEAEs by maximum severity and TEAEs by maximum relationship. 
 
Additional AE tables will be generated as follows: 
• 
TEAEs by SOC and PT 
• 
Study Medication Related TEAEs by SOC and PT 
• 
TEAEs by (Maximum) Severity 
• 
TEAEs by (Maximum) Relationship to Study Medication 
• 
Grade 3 or Higher TEAE by SOC and PT 
• 
Treatment Emergent SAEs 
• 
Study Medication Related SAEs by SOC and PT 
• 
Dose Limiting Toxicity (DLT) by SOC and PT 
• 
TEAEs Leading to Study Medication Permanently Discontinued 
• 
TEAEs Leading to Study Medication Interrupted 
• 
TEAEs Leading to Death 
• 
Duration from Last Dosing to the Start of TEAE (days of each TEAE since its immediate 
last dosing) 
 


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A by-subject AE data listing, including verbatim term, MedDRA SOC and PT, severity, outcome 
and relationship to study treatment, will be provided. A separate listing will be generated for 
SAEs. 
 
9.2.Concomitant medication 
Concomitant medications will be coded using World Health Organization Drug Dictionary 
(WHO-DD, September 2016 or higher). Concomitant medications are medications taken at 
least once after the start of first study-drug administration. Medications stopped prior to the day 
of the start of first study-drug administration will not be considered concomitant medication. 
The prior medication will not be summarized, but they will be listed along with concomitant 
medications. Only concomitant medications will be summarized.  
 
Individual data listings will be presented for each subject and summarized by WHO-DD 
Anatomical Therapeutic Chemical (ATC) anatomical group, and preferred term using frequency 
counts and percentages. Subjects who take the same medication more than once will be 
counted only once for that preferred term.   
 
Follow-up visits were scheduled after end of treatment or early withdrawal visit with regards to 
cancer radiation therapy, cancer systemic therapy, or cancer surgery. These treatments, if any, 
will be listed separately.   
 
9.3.Laboratory 
9.3.1.Laboratory Parameters 
 
Hematology Parameters 
• 
WBC 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
• 
Red blood cell (RBC) 
• 
Hematocrit (Hct) 
• 
Hemoglobin  
• 
Mean corpuscular volume (MCV) 
• 
Mean corpuscular hemoglobin (MCH) 
• 
Mean corpuscular haemoglobin concentration (MCHC),  
• 
Platelet count 
 
 


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Chemistry Parameters 
• 
Blood urea nitrogen (BUN) 
• 
Creatinine 
• 
AST 
• 
ALT 
• 
ALP 
• 
Total Bilirubin 
• 
Albumin 
• 
Calcium  
• 
Glucose  
• 
Uric Acid  
• 
Potassium  
• 
Total creatine kinase (Ck) (if total Ck is above the ULN for the laboratory, Troponin-T 
or Troponin-I will be determined) 
• 
Gamma-glutamyl transferase (GGT) 
• 
Total cholesterol 
• 
High-density lipoprotein (HDL)  
• 
Low-density lipoprotein (LDL) 
• 
Triglycerides (TG)  
• 
Amylase 
• 
Lipase 
 
Coagulation Parameters 
• 
Prothrombin Time  
• 
INR  
  
Urinalysis Parameters 
• 
Specific gravity 
• 
pH 
• 
Protein 
• 
Glucose 
• 
Leucocytes  
• 
Erythrocyte  
• 
Nitrite 
• 
Ketone body 
• 
Urobilinogen 
• 
Bilirubin  
• 
RBC 
• 
WBC 
• 
Hyaline 
• 
Cast 
• 
CAOX 
• 
Crystal 
• 
AMOR  
• 
Mucus 
 
 


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9.3.2.Biostatistical methods 
All hematology, chemistry and coagulation parameters will be summarized using descriptive 
statistics for each dose level (cohort) for all time points assessed, including change from 
baseline (last pre-dose value) for all post-dose assessments. All continuous parameters will be 
summarized using the units reported from the laboratory.  
 
Urinalysis will be summarised as categorical data by using frequency and percentage, as 
appropriate, except for specific gravity and pH which will be treated as continuous data. 
 
Subjects with abnormal laboratory values will be summarized for each laboratory parameter by 
study visit and by dose cohort. The frequency counts and percentages of subjects with 
laboratory value out of reference range (low/high) and their clinical significance (if any data) 
will be summarized. Shift tables from Cycle 1, Day 1 (pre-dose) to all follow-up visits will also 
be generated for each chemistry laboratory parameter with values of Within Normal Limits 
(WNL), High, and Low used for the shift categories.  
 
All laboratory data will be included in the by-subject data listings. Laboratory values will be 
compared to normal range of the single local laboratory and values that fall outside of the 
normal ranges will be flagged as: H (High) and L (Low) in the data listings. 
 
9.4.Vital Signs 
9.4.1.Vital Sign Parameters  
• 
Heart Rate (beats/min) 
• 
Systolic Blood Pressure (SBP) (mmHg) 
• 
Diastolic Blood Pressure (DBP) (mmHg) 
• 
Respiratory rate (breaths/minute) 
• 
Body Temperature (°C) 
9.4.2.Biostatistical methods 
All vital sign parameters will be summarized using descriptive statistics for each dose level 
and overall for all time points assessed, including change from baseline (last pre-dose 
value) for all post-dose assessments. Pre-dosing vital sign on Cycle1, Day 1 will be used 
as baseline data. If the baseline value is missing, then the data from Screening will be used 
as baseline data. 
 
 
9.5.Physical examination 
9.5.1.Body Systems Assessed 
• 
General Appearance 
• 
Dermatologic 
• 
HEENT (Head, Eyes, Ears, Nose and Throat) 
• 
Respiratory 
• 
Cardiovascular  
• 
Musculoskeletal  
• 
Gastrointestinal 


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• 
Abdomen/Pelvic 
• 
Neurological 
• 
Other 
 
For abnormal result of physical examination: 
• 
Abnormal NCS (Not Clinically Significant) 
• 
Abnormal CS (Clinically Significant) 
 
9.5.2.Biostatistical methods 
Physical examination will be summarized by study visit and treatment cohort. The frequency 
counts and percentages of subjects with different physical examination results and their clinical 
significance (for abnormal) will be summarized. 
 
By-subject data listings will be generated for the physical examination data, including the 
Investigator assessment of clinical significance for abnormal findings, for all time points 
assessed.  
 
9.6.12-lead ECG 
9.6.1.ECG Parameters  
• 
Ventricular Rate (beats/min) 
• 
PR interval (msec) 
• 
QRS duration (msec) 
• 
QT interval (msec) 
• 
QTc interval (msec) 
• 
RR interval (msec) 
• 
Overall interpretation of 12-lead ECG: 
o Normal 
o Abnormal NCS (Not Clinically Significant) 
o Abnormal CS (Clinically Significant) 
9.6.2.Biostatistical methods 
Descriptive statistics will be calculated for ventricular rate, PR interval, QRS duration, QT 
interval, QTc interval, and RR interval, including change from baseline (last pre-dose value on 
Cycle 1, Day 1) for each dose level (cohort) for all time points assessed. If triplicate ECG 
parameters are available, the average of the triplicate ECG parameters will be used. 
Unscheduled visits will be excluded from summary tables. However, the findings from the 
unscheduled will be listed. 
 
In addition, the overall interpretation of 12-lead ECG results will be classified using frequency 
counts and percentages for the categories of Normal, Abnormal - Not Clinically Significant 
(NCS) and Abnormal - Clinically Significant (CS) for each treatment group for all time points 
assessed. 
 
All ECG data will be presented in the by-subject data listings. 


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10.Efficacy  
Statistical methods for the efficacy analyses will be primarily descriptive in nature, due to small 
number of subjects enrolled. Each dose level (cohort) and overall group will be summarized 
separately. No formal statistical comparisons of SCB01A dose levels will be made. 
 
Efficacy endpoints include in the analysis are DCR, PFS, and OS. Efficacy endpoints will be 
analyzed using the Full Analysis Set. For PFS and OS, if there is no event reported 
(progression or death), their survival functions can not be estimated. Thus, only simple 
descriptive statistics will be provided. 
 
When confidence interval (CI) is estimated, both 90% CI and 95% CI will be provided for DCR. 
For other endpoints, only 95% CI will be provided. 
 
10.1.Tumor Response and Disease Control Rate 
Tumor assessments were made based upon the RECIST criteria (Response Evaluation 
Criteria in Solid Tumors version 1.1). Tumor assessments were scheduled at baseline, and 
every 3 cycles prior to next cycle until progression of disease. For this analysis purpose, tumor 
response evaluation at Week 9 (Cycle 4, Day 1) or end of treatment/early termination will be 
pooled and used as the best overall response from start of dosing up to Week 9.   
 
For the analysis of tumor response, a summary table presenting the number and proportion of 
responders (DC) and non-responders (non-DC) in each dose level, together with the two-sided 
90% and 95% confidence intervals for response rates will be produced. The proportion and the 
corresponding 90% and 95% confidence interval for each of the response categories (CR, PR, 
SD, PD, and unevaluable) by dose level will also be presented. The confidence interval will be 
based on Pearson-Clopper exact CI. 
 
The details of target lesions, non-target lesion, and new lesions (if any) will be listed for each 
subject.  
 
10.2.Progression-free Survival and Overall Survival 
Progression-free Survival (PFS) is defined as the time from the start of treatment up to the 
date of first progression based on RECIST v1.1, second primary malignancy or death from 
any cause, whichever occurs first. Patients without progression or death will be censored at 
the last disease assessment date.  
 
Overall survival (OS) is defined as the time from the start of treatment up to the date of death, 
regardless of causes. Patients without death will be censored at the last follow up date.   
  
The analysis of PFS and OS is based on the survivor function, which is the probability to survive 
or, more generally, to stay event-free beyond a certain point in time. The survival function is 
estimated by the Kaplan-Meier method. The survival function will be summarized for 25th 
percentile, median, and 75th percentile and their 95% confidence intervals. For OS, survival 
rate at Week 36 will be reported, based on the survival function, if this estimate is available. 
The plot of Kaplan-Meier estimates for the dose levels will be presented. If there is no event 
reported (progression or death), only simple descriptive statistics will be provided. 
 
 


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11.Health Outcome and ECOG-PS 
Statistical methods for the health outcome analyses will be primarily descriptive in nature. Each 
dose level (cohort) will be summarized separately. No formal statistical comparisons of 
SCB01A dose levels will be made.  
 
Patients would complete the EORTC QLQ-C30 and QLQ-H&N35 questionnaires at screening 
and before study drug administered, except Cycle 1, Day1. The questionnaire consists of 65 
questions that help determine the health outcome of the patients. Health outcome endpoints 
will be analyzed using the Full Analysis Set.  
  
Analysis of Eastern Cooperative Oncology Group Performance Status (ECOG-PS) will be 
provided as well. 
 
11.1.EORTC QLQ-C30 
The EORTC quality of life questionnaire (QLQ) is an integrated system for assessing the 
health-related quality of life (QoL) of cancer patients participating in international cancer trials. 
The QLQ-C30 (version 3.0, 30 questions) is composed of both multi-item scales and single-
item measures. According to the EORTC QLQ-C30 scoring manual, these questions are 
grouped into five functional scales, three symptom scales, a global health status/QoL scale and 
six single items. The 30 questions of the QLQ-C30 are numbered 1 to 30 and the grouping is 
summarized as follows. 
Grouping of the EORTC QLQ-C30 Questionnaire 
Description of Sub-scores 
Number of 
Questions 
Question Number 
in CRF 
Range* 
Global Health Status/QoL 
 
 
 
Global health status/QoL 
2 
29, 30 
6 
Functional Scales 
 
 
3 
Physical functioning 
5 
1 to 5 
3 
Role functioning 
2 
6, 7 
3 
Emotional functioning 
4 
21 to 24 
3 
Cognitive functioning 
2 
20, 25 
3 
Social functioning 
2 
26, 27 
3 
Symptom Scales /Items 
 
 
 
Fatigue 
3 
10, 12, 18 
3 
Nausea and Vomiting 
2 
14, 15 
3 
Pain 
2 
9, 19 
3 
Dyspnoea 
1 
8 
3 
Insomnia 
1 
11 
3 
Appetite loss 
1 
13 
3 
Constipation 
1 
16 
3 
Diarrhoea 
1 
17 
3 
Financial difficulties 
1 
28 
3 
* Difference between the highest and the lowest possible answer to a question 
 
The computation of the scores for each scale based on the questions assigned to it will be 
completed in several steps and will follow the scoring procedure given in the manual.  The 
individual steps are briefly outlined below. 


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Calculation of the Raw Score 
A Raw Score (RS) is calculated by averaging the answers given for all items I1, I2, …, In included 
in a scale according to the formula 
 
 
 
 
RS = (I1 + I2 + …, In) / n 
where Ii is the answer to the question I (i=1,…,n) and n denotes the total number of questions 
in the scale to be analyzed. 
As an example, the RS for the functional scale “Physical Functioning” is calculated by adding 
up all the answers a patient gives to questions 1 to 5 and subsequently dividing the result by 
5. The RS for the functional scale “Role Functioning” is similarly obtained be averaging the two 
scores the patient selects for questions 6 and 7. 
Standardization 
As specified in the manual, the Raw Scores are subsequently standardized for each of the 
functional scales, symptom scales /items and global health status/QoL to a value between 0 
and 100. For all functional scales of the QLQ-C30 the linear transformation applied is 
 
 
 
 
 


100
1
1










range
RS
S
. 
 
 
 
 
For the symptom scales/items and the global health status formulae/QoL the linear 
transformation is 
 
 
 
 



100
1



range
RS
S
. 
 
 
 
 
The range is the difference between the possible maximum and minimum response a patient 
can select for each scale. 
Handling of Missing Values 
The psychometrically validated method according to the EORTC manual will be used to handle 
cases where some questions belonging to a symptom scale, functional scale or global health 
status are not answered. If at least half of the items from the scale have been answered, the 
missing items are imputed and will have values equal to the average of those items which are 
present for that respondent. Otherwise, the raw score of the scale is set to missing. 
Interpretation 
The scores S computed according to formulae above have the following interpretation: 
• 
a high score for a functional scale represents a high / healthy level of functioning 
• 
a high score for the global health status/QoL represents a high QoL 
• 
a high score for a symptom scale/item represents a high level of symptomatology / 
problems 
 
 


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Biostatistical methods 
The assessment of EORTC QLQ-C30 conducted at screening is regarded as the baseline 
assessment, as it is taken prior to dosing. Quality of life data will be summarised descriptively. 
Global health status/QoL, each functional scale, and each symptom scale/item 
will be summarized using descriptive statistics for each dose level for all time points assessed, 
including change from baseline for all post-dose assessments. Plots of mean values and 95% 
confidence intervals by dose level over time will be provided for each scale or item.    
 
11.2.EORTC QLQ-H&N35 
The QLQ-H&N35 is used among a wide range of patients with head & neck cancer, varying in 
disease stage and treatment modality. There are 35 questions assessing symptoms and side 
effects of treatment, social function and body image/sexuality. The questions are grouped into 
seven multi-item scales that assess pain, swallowing, senses (taste and smell), speech, social 
eating, social contact and sexuality. There are also eleven single items. The 35 questions of 
the QLQ-STO22 are numbered 31 to 65 and the grouping is summarized as follows. 
Grouping of the EORTC QLQ-H&N35 Questionnaire 
Description of Sub-scores 
Number of 
Questions 
Question Number 
in CRF 
Range* 
Symptom Scales / Items 
 
 
 
Pain 
4  
31, 32, 33, 34 
3 
Swallowing 
4 
35, 36, 37, 38 
3 
Senses problems 
2 
43, 44 
3 
Speech problems 
3 
46, 53, 54 
3 
Trouble with social eating 
4 
49, 50, 51, 52 
3 
Trouble with social contact 
5 
48, 55, 56, 57, 58 
3 
Less sexuality 
2 
59, 60 
3 
Teeth 
1 
39 
3 
Opening mouth 
1 
40  
3 
Dry mouth 
1 
41 
3 
Sticky saliva 
1 
42 
3 
Coughing 
1 
45 
3 
Felt ill 
1 
47 
3 
Pain killers 
1 
61 
1 
Nutritional supplements 
1 
62 
1 
Feeding tube 
1 
63 
1 
Weight loss 
1 
64 
1 
Weight gain 
1 
65 
1 
* Difference between the highest and the lowest possible answer to a question 
 
The principle for scoring the scales is the same as for the EORTC QLQ-C30 questionnaire 
symptom scales/items, as described above. 
• 
Estimate the average of the items that contribute to the scale to obtain the Raw Score 
• 
Use a linear transformation to standardize the raw score, so that scores range from 0 to 
100; a high score represents a higher (“worse”) level of symptoms  
 
 
Biostatistical Methods 


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The assessment of EORTC QLQ-H&N35 conducted at screening is regarded as the baseline 
assessment, as it is taken prior to dosing. Quality of life data will be summarised descriptively. 
Each symptom scale/item will be summarized using descriptive statistics for each dose level 
for all time points assessed, including change from baseline for all post-dose assessments. 
Plots of mean values and 95% confidence intervals by dose level over time will be provided for 
each scale or item.    
 
11.3.Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 
ECOG-PS will be treated as continuous data, and will be summarised descriptively for each 
dose level for all time points assessed, including change from baseline for all post-dose 
assessments. ECOG-PS will be listed for all subjects. 
 
 


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12.Pharmacokinetics (PK) 
PK analyses will be conducted with the PK Population. PK analysis of SCB01A plasma 
concentration-time data will be performed using validated PK software (Phoenix WinNonlin 
version 6.3 or higher), by a standard non-compartmental model. The actual plasma sampling 
times from the CRF database, i.e., the elapsed time of the blood sampling time from the dosing 
time, will be used for PK analysis. The PK blood samples would be taken immediately pre-
infusion then at 2, 3, 4, 6, 10, 21 and 24 hours after the start of infusion on Days 1 and 8 of 
Cycles 1, 2 and 3 
 
12.1.Definition of variables 
Whenever possible, the PK parameters listed below will be calculated for each subject based 
on the plasma concentrations of SCB01A according to the model independent approach. 
 
SCB01A Plasma, Day 1 and Day 8 of each Cycle 
AUC0-t 
The area under the plasma concentration-time curve, from time 0 
(time of dosing) to the last time point with measurable analyte 
concentration, calculated by the log-linear trapezoidal method.  
AUC0-inf 
The area under the plasma concentration-time curve from time 0 
extrapolated to infinity. AUC0-inf is calculated as the sum of AUC0-t 
plus the ratio of the last measurable plasma concentration to the 
elimination rate constant (λz). 
Cmax 
Maximum observed concentration. 
Tmax 
The first time when Cmax is observed 
CL 
Apparent clearance calculated as Dose/AUC0-inf. 
Vd 
Apparent total volume of distribution at the terminal phase, 
calculated as Dose/(Kel × AUC0-inf). 
t½ 
Apparent terminal elimination half-life of medication, calculated as 
0.693/λz. 
Kel: 
The apparent first-order terminal elimination rate constant, 
calculated by linear least-squares regression analysis the terminal 
log-linear phase of the plasma concentration vs. time curves using 
at least 3 time points. 
MRT 
mean residence time 
 
12.2.Biostatistical methods 
SCB01A plasma concentrations will be listed by subject, dose level, and nominal (scheduled) 
sampling time. SCB01A concentrations will be summarized by dose level and nominal 
sampling time for the PK Analysis Population. Plasma concentrations that are below the limit 
of quantitation (BLQ) will be set to 0 for calculation of summary statistics for concentration data 
at each time point, except geometric statistics (geometric mean and geometric CV%). For the 


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Page 27 of 39 
calculation of the geometric statistics they will be treated as equal to the Lower Limit of 
Quantification (LLQ). Missing values will be omitted from the calculation of descriptive statistics. 
 
The actual blood sampling dates and times relative to dosing time will be listed by study group 
(dose level), subject and nominal sampling time, with time deviation calculated, for all subjects 
with available plasma concentration data, including subjects excluded from the PK Analysis 
Population. 
 
Figures of individual plasma concentration vs. actual time profiles for SCB01A will be produced 
on both linear and semi-log scales for the PK Analysis Population. Mean and median plasma 
blood concentration vs. nominal time curves for all dose levels in the PK Analysis Population 
will be plotted together on both linear and semi-log scales for SCB01A.  
 
Pharmacokinetic parameters for each dose level will be calculated from the concentrations of 
SCB01A measured in pre-dose and post-dose plasma samples. Actual collection time will be 
used in the calculation of plasma PK parameters. For the calculation of the PK parameters, all 
plasma concentrations that are BLQ prior to the first measurable concentration will be set to 
zero. The BLQ values that are between measurable concentrations will be set to missing. The 
BLQ values that occur at the end of the profile (after the last quantifiable concentration) will be 
set to missing and will not be used for the estimation of parameter values.  
 
For each dose level, descriptive statistics will be provided for the PK parameters. Summary 
tabulations will display the number of observations, mean, SD, CV%, median, minimum and 
maximum. Geometric means and geometric CV% will be calculated for AUCs and Cmax. PK 
parameters will be displayed by dose levels. AUC0-t, AUC0-inf, and Cmax will also be presented 
in scatter plots by treatment. 
 
 


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13.Bioanalytical Measurement 
Exploratory research would be performed to analyze relevant biomarkers. 
• 
Biomarkers analysis would be performed on patients enrolled in the run-in phase 
including circulating endothelial cells (CEC), vascular endothelial growth factor (VEGF) 
and circulating endothelial progenitor (CEP) cells 
• 
Tumor micro vessel density and blood flow by dynamic contrast-enhanced MRI (DCE-
MRI) will be performed in patients with identified sites which be selected by the sponsor 
at both baseline and 6 hours after the infusion of the drug on Cycle 1, Day 1. Analysis of 
DCE-MRI data might not be covered by this SAP.  
 
Depending on the availability of biomarker data (CEC, VEGF and CEP), these data will be 
summarised descriptively by dose level and overall. These data will be listed as well for all 
subjects. 
 


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14.Handling of Missing Data 
Missing values will not be imputed. 
 
 
 


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15.Changes to the Planned Analysis 
 
Any changes to the analyses outlined in the approved SAP will be detailed in the Clinical 
Study Report (CSR). 
 
 


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16.Interim and Final Analysis 
 
16.1.Interim Analyses 
An interim statistical analysis was planned following the completion of stage 1, Phase II. 
However, this study was terminated in run-in phase I. 
 
16.2.Final Analysis (End of Study) 
The final end of study analysis, post the data base lock, will be based on the final version of 
the SAP. 
 
 
 


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17.Software 
The following software will be used to perform the statistical analyses: SAS® Version 9.2 or 
higher (SAS Institute, Cary, North Carolina, USA) 
 
 
 
 


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18.Tables 
No. 
Title 
Analysis 
Population 
Table to be 
Generated 
 
Disposition and Baseline Data 
 
 
14.1.1.1 
Summary of Disposition and Analysis Populations 
Safety 
Y 
14.1.1.2 
Summary of Demographics 
Safety 
Y 
14.1.1.3 
Summary of Baseline Never Conduction Velocity by 
NCI Grade 
Safety 
 
 
Efficacy 
 
 
14.2.1.1 
Summary of Tumor Response and Disease Control 
Rate 
FAS 
Y 
14.2.1.2 
Summary of Progression-free Survival 
FAS 
Y 
14.2.1.3 
Summary of Overall Survival 
FAS 
Y 
 
Health Outcome 
 
 
14.2.2.1 
Summary of EORTC QLQ-C30 (Version 3.0) Over 
Time 
FAS 
Y 
14.2.2.2 
Summary of EORTC QLQ-H&N35 Over Time 
FAS 
Y 
14.2.2.3 
Summary of Eastern Cooperative Oncology Group 
Performance Status (ECOG-PS) 
FAS 
 
 
PK 
 
 
14.2.3.1 
Summary of Plasma Concentrations of SCB01A by 
Dose Level 
PK 
Y 
14.2.3.2 
Summary of Plasma Pharmacokinetic Parameters of 
SCB01A by Dose Level and Treatment Cycle/Day 
PK 
Y 
 
Biomarker 
 
 
14.2.4.1 
Summary of Biomarker Data (if available) 
FAS 
 
 
Study Treatment 
 
 
14.3.1.1 
Summary of Dose Delay, Dose Omission and Early 
Study Drug Discontinuation 
Safety 
 
14.3.1.2 
Summary of Body Surface Area (BSA, m2) 
Safety 
 
 
Adverse Events 
 
 
14.3.2.1 
Overall Summary of Treatment Emergent Adverse 
Events 
Safety 
Y 
14.3.2.2 
Summary of Treatment Emergent Adverse Events by 
SOC (System Organ Class) and PT (Preferred Term) 
Safety 
Y 
14.3.2.3 
Summary of Related Treatment Emergent Adverse 
Events by SOC (System Organ Class) and PT 
(Preferred Term) 
Safety 
Y 
14.3.2.4 
Summary of Treatment Emergent Adverse Events by 
Maximum Severity 
Safety 
 
14.3.2.5 
Summary of Treatment Emergent Adverse Events by 
Maximum Relationship to Study Medication 
Safety 
 
14.3.2.6 
Summary of Grade 3 or Higher Treatment Emergent 
Adverse Events by SOC (System Organ Class) and PT 
(Preferred Term) 
Safety 
 
14.3.2.7 
Summary of Treatment Emergent Serious Adverse 
Events by SOC (System Organ Class) and PT 
(Preferred Term) 
Safety 
Y 
14.3.2.8 
Summary of Related Treatment Emergent Serious 
Adverse Events by SOC (System Organ Class) and PT 
(Preferred Term) 
Safety 
 
14.3.2.9 
Summary of Dose Limiting Toxicity (DLT) by SOC 
(System Organ Class) and PT (Preferred Term) 
Safety 
Y 


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No. 
Title 
Analysis 
Population 
Table to be 
Generated 
14.3.2.10 
Summary of Treatment Emergent Adverse Events 
Leading to Study Medication Permanently 
Discontinued 
Safety 
 
14.3.2.11 
Summary of Treatment Emergent Adverse Events 
Leading to Study Medication Interrupted 
Safety 
 
14.3.2.12 
Summary of Treatment Emergent Adverse Events 
Leading to Death 
Safety 
 
14.3.2.13 
Summary of Duration from Last Dosing to the Start of 
Treatment Emergent Adverse Events 
Safety 
Y 
 
Concomitant Medications 
 
 
14.3.3.1 
Summary of Concomitant Medications 
Safety 
Y 
 
Laboratory 
 
 
14.3.4.1 
Laboratory - Hematology: Summary and Change from 
Baseline 
Safety 
Y 
14.3.4.2 
Laboratory - Chemistry: Summary and Change from 
Baseline 
Safety 
Y 
14.3.4.3 
Laboratory - Coagulation: Summary and Change from 
Baseline 
Safety 
Y 
14.3.4.4 
Laboratory - Urinalysis: Summary and Clinical 
Significance 
Safety 
Y 
14.3.4.5 
Laboratory - Hematology: Out of Range and Clinical 
Significance 
Safety 
Y 
14.3.4.6 
Laboratory - Chemistry: Out of Range and Clinical 
Significance 
Safety 
Y 
14.3.4.7 
Laboratory - Coagulation: Out of Range and Clinical 
Significance 
Safety 
Y 
14.3.4.8 
Laboratory – Hematology: Shift Table 
Safety 
 
14.3.4.9 
Laboratory - Chemistry: Shift Table 
Safety 
 
14.3.4.10 
Laboratory - Coagulation: Shift Table 
Safety 
 
 
Vital Signs 
 
 
14.3.5.1 
Summary of Vital Signs 
Safety 
Y 
 
Physical Examination 
 
 
14.3.6.1 
Summary of Physical Examination 
Safety 
 
 
ECG 
 
 
14.3.7.1 
Summary of ECG Values 
Safety 
Y 
14.3.7.2 
Summary of ECG Findings 
Safety 
Y 
Due to limitation of available data, only those tables marked as ‘Y’ will be generated.  
 
 


Protocol Number: SCB01A-21 
 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
 
Page 35 of 39 
19.Listings 
No. 
Title 
Analysis 
Population 
Listing to be 
Generated 
 
Disposition and Baseline Data 
 
 
16.2.1.1 
Listing of Enrolment, Informed Consent and 
Disposition 
Safety 
Y 
16.2.2.1 
Listing of Protocol Deviations 
Safety 
 
16.2.3.1 
Listing of Analysis Populations 
Safety 
Y 
16.2.4.1 
Listing of Demographics 
Safety 
Y 
16.2.4.2 
Listing of Medical History 
Safety 
Y 
16.2.4.3 
Listing of Cancer History 
Safety 
Y 
16.2.4.4 
Listing of Betel Nut Use Status 
Safety 
Y 
16.2.4.5 
Listing of Inclusion/Exclusions Criteria 
Safety 
Y 
16.2.4.6 
Listing of Serum Pregnancy Test – Females Only 
Safety 
 
16.2.4.7 
Listing of Human Papillomavirus (HPV) Status 
Safety 
 
16.2.4.8 
Listing of Never Conduction Velocity 
Safety 
 
 
Study Treatment 
 
 
16.2.5.1 
Listing of Study Drug Administration 
Safety 
Y 
16.2.5.2 
Listing of Early Study Drug Discontinuation 
Safety 
Y 
16.2.5.3 
Listing of Body Surface Area (BSA) 
Safety 
 
 
Concomitant Medications 
 
 
16.2.5.4 
Listing of Concomitant and Prior Medications 
Safety 
Y 
16.2.5.5 
Listing of Cancer-Radiation Therapy 
Safety 
Y 
16.2.5.6 
Listing of Cancer-Systemic Therapy 
Safety 
Y 
16.2.5.7 
Listing of Cancer-Surgery 
Safety 
Y 
 
Efficacy 
 
 
16.2.6.1 
Listing of Target Lesions 
FAS 
Y 
16.2.6.2 
Listing of Non-Target Lesions 
FAS 
Y 
16.2.6.3 
Listing of Tumor Response Evaluation (Based on 
RECIST) 
FAS 
Y 
16.2.6.4 
Listing of Survival Status 
FAS 
Y 
16.2.6.5 
Listing of EORTC QLQ-C30 
FAS 
Y 
16.2.6.6 
Listing of EORTC QLQ-H&N35 
FAS 
Y 
16.2.6.7 
Listing of Eastern Cooperative Oncology Group 
Performance Status (ECOG-PS) 
FAS 
Y 
 
PK 
 
 
16.2.6.8 
Listing of Individual SCB01A Plasma 
Concentration Data 
PK 
Y 
16.2.6.9 
Listing of Individual SCB01A Plasma 
Pharmacokinetic Parameters by Treatment 
Cycle/Day 
PK 
Y 
 
Biomarker 
 
 
16.2.6.10 
Listing of Biomarker Data (if available) 
FAS 
 
 
Adverse Events 
 
 
16.2.7.1 
Listing of Adverse Events 
Safety 
Y 
16.2.7.2 
Listing of Serious Adverse Events 
Safety 
Y 
16.2.7.3 
Listing of Dose Limiting Toxicity (DLT)   
Safety 
 
16.2.7.4 
Listing of Adverse Events Leading to Study 
Medication Permanently Discontinued or 
Interrupted 
Safety 
 
 
Laboratory 
 
 
16.2.8.1 
Listing of Haematology 
Safety 
Y 


Protocol Number: SCB01A-21 
 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
 
Page 36 of 39 
No. 
Title 
Analysis 
Population 
Listing to be 
Generated 
16.2.8.2 
Listing of Biochemistry  
Safety 
Y 
16.2.8.3 
Listing of Coagulation 
Safety 
Y 
16.2.8.4 
Listing of Urinalysis 
Safety 
Y 
 
Vital Signs 
 
 
16.2.9.1 
Listing of Vital Signs 
Safety 
Y 
 
Physical Examination 
 
 
16.2.10.1 
Listing of Physical Examination 
Safety 
Y 
 
ECG 
 
 
16.2.11.1 
Listing of ECG Values and Findings 
Safety 
Y 
Due to limitation of available data, only those listings marked as ‘Y’ will be generated.  
 
 


Protocol Number: SCB01A-21 
 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
 
Page 37 of 39 
20.Figures 
No. 
Title 
Analysis 
Population 
Figures to be 
Generated 
 
Efficacy 
 
 
14.2.1.1 
Kaplan-Meier Curve of Progression-free Survival 
FAS 
Y 
14.2.1.2 
Kaplan-Meier Curve of Overall Survival 
FAS 
Y 
 
Health Outcome 
 
 
14.2.2.1a Plot of Mean Global Health Status Score/QoL with 
95% Confidence Interval Over Time (EORTC QLQ-
C30) 
FAS 
Y 
14.2.2.1b Plot of Mean Physical Functioning Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1c 
Plot of Mean Role Functioning Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1d Plot of Mean Emotional Functioning Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1e Plot of Mean Cognitive Functioning Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1f 
Plot of Mean Social Functioning Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1g Plot of Mean Fatigue Score with 95% Confidence 
Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1h Plot of Mean Nausea and Vomiting Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1i 
Plot of Mean Pain Score with 95% Confidence Interval 
Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1j 
Plot of Mean Dyspnoea Score with 95% Confidence 
Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1k 
Plot of Mean Insomnia Score with 95% Confidence 
Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1l 
Plot of Mean Appetite Loss Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1
m 
Plot of Mean Constipation Score with 95% Confidence 
Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1n Plot of Mean Diarrhoea Score with 95% Confidence 
Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.1o Plot of Mean Financial Difficulties Score with 95% 
Confidence Interval Over Time (EORTC QLQ-C30) 
FAS 
 
14.2.2.2a Plot of Mean Pain Score with 95% Confidence Interval 
Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2b Plot of Mean Swallowing Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2c 
Plot of Mean Senses Problems Score with 95% 
Confidence Interval Over Time (EORTC QLQ- H&N35) 
FAS 
 
14.2.2.2d Plot of Mean Speech Problems Score with 95% 
Confidence Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2e Plot of Mean Trouble with Social Eating Score with 
95% Confidence Interval Over Time (EORTC QLQ-
H&N35) 
FAS 
 
14.2.2.2f 
Plot of Mean Trouble with Social Contact Score with 
95% Confidence Interval Over Time (EORTC QLQ-
H&N35) 
FAS 
 


Protocol Number: SCB01A-21 
 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
 
Page 38 of 39 
No. 
Title 
Analysis 
Population 
Figures to be 
Generated 
14.2.2.2g Plot of Mean Less Sexuality Score with 95% 
Confidence Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2h Plot of Mean Teeth Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2i 
Plot of Mean Opening Mouth Score with 95% 
Confidence Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2j 
Plot of Mean Dry Mouth Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2k 
Plot of Mean Sticky Saliva Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2l 
Plot of Mean Coughing Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2
m 
Plot of Mean Felt Ill Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2n Plot of Mean Pain Killers Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2o Plot of Mean Nutritional Supplements Score with 95% 
Confidence Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2p Plot of Mean Feeding Tube Score with 95% 
Confidence Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2q Plot of Mean Weight Loss Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
14.2.2.2r 
Plot of Mean Weight Gain Score with 95% Confidence 
Interval Over Time (EORTC QLQ-H&N35) 
FAS 
 
 
PK 
 
 
14.2.3.1a Mean (+SD) Plasma Concentrations of SCB01A Over 
Time by Dose Level (Linear Scale) 
PK 
 
14.2.3.1b Mean (+SD) Plasma Concentrations of SCB01A Over 
Time by Dose Level (Semilogarithmic Scale) 
PK 
Y 
14.2.3.2a Median Plasma Concentrations of SCB01A Over Time 
by Dose Level (Linear Scale) 
PK 
 
14.2.3.2b Median Plasma Concentrations of SCB01A Over Time 
by Dose Level (Semilogarithmic Scale) 
PK 
 
14.2.3.3a Individual Plasma Concentrations of SCB01A Over 
Time (Linear Scale) 
PK 
 
14.2.3.3b Individual Plasma Concentrations of SCB01A Over 
Time (Semilogarithmic Scale) 
PK 
Y 
14.2.3.4a Scatterplot of Individual and Mean Plasma AUC0-t of 
SCB01A versus Dose Level by Treatment Cycle/Day 
PK 
 
14.2.3.4b Scatterplot of Individual and Mean Plasma AUC0-inf of 
SCB01A versus Dose Level by Treatment Cycle/Day 
PK 
 
14.2.3.4c 
Scatterplot of Individual and Mean Plasma Cmax of 
SCB01A versus Dose Level by Treatment Cycle/Day 
PK 
 
Due to limitation of available data, only those figures marked as ‘Y’ will be generated.  
 


Protocol Number: SCB01A-21 
 
27 Oct 2017 
Document status: Final SAP Version 1.2 
Novotech - Strictly Confidential 
 
Page 39 of 39 
21.References 
1) 
SCB01A-21 Clinical Study Protocol, Version 3.0, 25Jul2016