Conditions: Locally Advanced Solid Tumor
Keywords: antibody drug conjugate (ADC)
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 44
Healthy volunteers: no

Brief summary:
The purpose of this study is to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of OBI-999 as monotherapy, and to characterize the safety and preliminary clinical activity profile of the RP2D of OBI-999 in patients with advanced solid tumors.

Detailed description:

Arms:
arm 1: Part A: Five cohorts at escalating dose levels 0.4, 0.8, 1.2, 1.6 and 2.0 mg/kg (capping calculations at a maximum at 100 kg) of OBI-999 liquid form via IV infusion to establish maximum tolerated dose (MTD) and Recommended phase 2 dose (RP2D). arm 2: Part B: Five cohorts of patients at RP2D of OBI-999 liquid form, as determined from Part A, via IV infusion.

Interventions: intervention 1: OBI-999 intervention 2: OBI-999
Intervention descriptions: intervention 1: For the dose-escalation phase, OBI-999 will be administered on Day 1 of each 21-day cycle, for up to 35 cycles. intervention 2: For the dose-expansion phase, OBI-999 will be administered on Day 1 of each 21-day cycle, for up to 35 cycles.

Protocol document:
Prot_000.pdf: 
 
OBI Pharma, Inc. 
Room W1907, 19F, #3, YuanQu St. 
Nankang Software Park, Nangang District,  
Taipei  11503, Taiwan 
 
OBI Pharma USA, Inc. 
6020 Cornerstone Court W, Suite 200 
San Diego, CA92121, USA  
 
 
 
This document contains confidential information of OBI Pharma, Inc. Nothing herein is to be disclosed 
in any way without the prior express written permission of OBI Pharma, Inc. 
 
CLINICAL RESEARCH PROTOCOL 
STUDY DRUG: 
OBI-999 (a humanized Globo H monoclonal 
antibody drug conjugate) 
STUDY NUMBER: 
OBI-999-001 
PROTOCOL TITLE: 
A Phase 1/2, Open-Label, Dose-Escalation 
and Cohort-Expansion Study Evaluating the 
Safety, Pharmacokinetics, and Therapeutic 
Activity of OBI-999 in Patients With 
Advanced Solid Tumors 
TRIAL REGISTRATION NUMBERS: 
 
ClinicalTrials.gov:  
NTC04084366 
US FDA IND Number: 
143960 
SPONSOR: 
OBI Pharma, Inc. 
Room W1907, 19F, #3, YuanQu St. 
Nankang Software Park, Nangang District, 
Taipei City 115, Taiwan, R.O.C. 
VERSION NUMBER: 
Version 7.0 
 
 
 
 
 
CONFIDENTIAL 






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OBI-999 
 
 
PROTOCOL OBI-999-001 
A PHASE 1/2, OPEN-LABEL, DOSE-ESCALATION AND COHORT-EXPANSION 
STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, AND 
THERAPEUTIC ACTIVITY OF OBI-999 IN PATIENTS WITH ADVANCED 
SOLID TUMORS 
 
CONFIDENTIALITY AND INVESTIGATOR STATEMENT 
The information contained in this protocol and all other information relevant to OBI-999-011 
are the confidential and proprietary information of OBI Pharma, Inc., and except as may be 
required by federal, state or local laws or regulation, may not be disclosed to others without 
prior written permission of OBI Pharma, Inc. 
I have read the protocol, including all appendices, and I agree that it contains all of the 
necessary information for me and my staff to conduct this study as described. I will conduct 
this study as outlined herein, in accordance with the in the Declaration of Helsinki, Federal 
Code of Regulations for Good Clinical Practices and International Conference on 
Harmonization guidelines and all applicable regulatory requirements. I 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 any 
amendments, and access to all information provided by OBI Pharma, Inc. or specified 
designees. I will discuss the material with them to ensure that they are fully informed about 
OBI-999 and the study. 
Investigator’s Signature 
 Date 
 
 
 
  
Name (printed) 
 Site 


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1 Synopsis 
Title of Study: 
A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion 
Study Evaluating the Safety, Pharmacokinetics, and Therapeutic 
Activity of OBI-999 in Patients with Advanced Solid Tumors. 
Protocol 
Number: 
OBI-999-001 
Phase of 
Development: 
1/2 
Rationale: 
Globo H is a hexasaccharide glycosphingolipid located endogenously 
on the outer membrane of epithelial cells and was first identified in 
breast cancer cells.  Globo H was found to be overexpressed on the 
cell surface of several epithelial cancers such as breast, pancreatic, 
ovarian, endometrial, gastric, lung, and prostate cancers.  Globo H has 
been associated with tumor stem cells, as a potent inducer of 
angiogenesis and immune suppressor through Notch signaling, 
rendering it a target for cancer therapy.  
OBI-999 is an antibody drug conjugate (ADC) composed of a human 
recombinant immunoglobulin G (IgG) monoclonal antibody that 
selectively and specifically binds to Globo H, attached by a linker to 
the antimitotic agent monomethyl auristatin E (MMAE).  The 
mechanism of action of OBI-999 is based on tumor-selective delivery 
of MMAE to Globo H-expressing tumors with subsequent tumor cell 
death. 
Preclinical studies demonstrated that OBI-999 antibody binds 
specifically to Globo H antigen, and antitumor efficacy was noted in 
preclinical breast, gastric, pancreatic, and lung cancer tumor xenograft 
models. 
Study Purpose: 
This is a 2-part study: Part A (Dose-Escalation) is designed to 
establish the maximum tolerated dose (MTD) and Recommended 
Phase 2 dose (RP2D) of OBI-999 as monotherapy.  Part B 
(Cohort-Expansion) is intended to further characterize the safety and 
preliminary clinical activity profile of the RP2D of OBI-999 in 
patients with advanced solid tumors.  
Objectives: 
The primary objectives are:  
• To determine the safety and tolerability of OBI-999 when 
administered intravenously (IV) to patients with advanced 
solid tumors.  
• To determine the MTD and RP2D of OBI-999. 
The secondary objectives are:  
• To evaluate the preliminary clinical activity profile of OBI-999 
(objective response rate [ORR], clinical benefit rate [CBR], 
duration of response [DOR], and progression-free survival 
[PFS]). 


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• To evaluate the immunogenicity of OBI-999 (anti-drug 
antibodies [ADAs]). 
• To determine the serum pharmacokinetics (PK) of OBI-999 
and its active metabolite MMAE. 
The exploratory objective is:  
• To explore potential predictive biomarkers of OBI-999 
activity. 
Study Design: 
This is a Phase 1/2, open-label, dose-escalation, and cohort-expansion 
study of OBI-999, an ADC-targeting Globo H in patients with 
advanced solid tumors. 
Part A – Dose-Escalation:   
Up to 30 eligible patients with advanced solid tumors will be enrolled 
in Part A.  No Globo H expression testing will be required for 
inclusion. 
Five cohorts of escalating dose levels of 0.4, 0.8, 1.2, 1.6, and 
2.0 mg/kg (capping calculations at a maximum of 100 kg) OBI-999 
were planned to be enrolled and assessed using a 3+3 design to 
identify the MTD and RP2D.  The RP2D of OBI-999 was determined 
to be 1.2 mg/kg (capping calculations at a maximum of 100 kg) 
administered on Day 1 of each 21-day cycle. 
Three patients were enrolled at the lowest dose level.  If none of the 
3 patients experienced a dose-limiting toxicity (DLT) in the first 
21-day cycle, the next cohort of 3 patients was enrolled at the next 
higher dose level.  If 1 of 3 patients in the initial dose cohort 
experienced a DLT, that cohort was expanded to 6 patients.  If only 1 
of these 6 patients had a DLT, the next cohort of 3 patients was 
enrolled at the next higher dose level.  If 2 or more patients of the 
3-6 patients in a cohort experienced a DLT, dose-escalation ceased, 
and the lower dose level was designated as the MTD, where no more 
than 1 of 6 patients experienced at DLT.  New patients were enrolled 
at the previous lower (tolerated) dose level until that cohort had 
6 patients.  This lower dose level was considered the MTD if ≤1 in 
6 patients had a DLT.   
A patient who withdraws from the study within the DLT evaluation 
period for reasons other than drug related adverse events (AEs) will be 
replaced.  
Escalation to higher OBI-999 dose cohorts is not permitted during the 
study.  After a DLT is experienced by a patient, dose interruption, 
modifications, or dose delays may apply, as per Investigator 
judgement. 
Patients will continue to receive treatment with OBI-999 until disease 
progression, unacceptable toxicity, consent withdrawal, or for up to 
35 cycles (approximately 2 years), whichever occurs first. 
 


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Part B – Expansion Cohort:   
Up to 57 additional patients with advanced solid tumors that have high 
Globo H expression (defined as an H-score ≥ 100 using a validated 
immunohistochemistry [IHC] assay) will be enrolled in Part B using a 
Simon’s two-stage cohort expansion design.  Part B will be conducted 
to obtain additional safety data, characterize the PK profile of 
OBI-999, and obtain a preliminary assessment of the clinical activity 
of OBI-999 in Globo H expressing advanced solid tumors.   
Patients enrolled in Part B will receive the RP2D dose of 1.2 mg/kg 
(capping calculations at a maximum of 100 kg) OBI-999 on Day 1 of 
each 21-day cycle.  
The following 3 cohorts of patients who have high expression of 
Globo H by a qualified laboratory assessment (Globo H H-score  100 
using a validated IHC assay) will be enrolled in Part B.  
• Cohort 1:  Pancreatic cancer 
• Cohort 2:  Colorectal cancer 
• Cohort 3: Basket (any solid tumor type other than those 
included in Cohorts 1 and 2) 
Patients will continue to receive treatment with OBI-999 until disease 
progression, unacceptable toxicity, consent withdrawal, or for up to 
35 cycles (approximately 2 years), whichever occurs first.   
Selection of 
Patients – 
Inclusion 
Criteria: 
Inclusion Criteria:  
Patients must meet all of the following criteria in order to be included 
in the study (for both Parts A and B unless specified otherwise): 
1. Male or female patients, 18 years of age or older at the time of 
consent. 
2. Provide written informed consent prior to performing any 
study-related procedure. 
3. Histologically or cytologically confirmed patients with 
advanced solid tumors. 
4. Patients must have been treated with established 
standard-of-care therapy, or physicians have determined that 
such established therapy is not sufficiently efficacious, or 
patients have declined to receive standard-of-care therapy. In 
the latter case, the informed consent must state the effective 
therapies the patient is declining.  
5. Measurable disease (i.e., at least one measurable lesion per 
Response Evaluation Criteria in Solid Tumors version 1.1 
[RECIST 1.1]).  
6. Eastern Cooperative Oncology Group (ECOG) performance 
status of 0 or 1.  
7. Adequate organ function defined as: 
a. Hepatic: 


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i. 
Serum alanine aminotransferase (ALT) 
≤3 × upper limit of normal (ULN), ≤5 × ULN in 
the presence of liver metastases 
ii. 
Serum aspartate aminotransferase (AST) 
≤3 × ULN, ≤5 × ULN in presence of liver 
metastases 
iii. 
Serum bilirubin 1.5 × ULN (unless due to 
Gilbert’s syndrome or hemolysis) 
b. Renal: 
i. 
Creatinine clearance >50 mL/minute using 
Cockcroft Gault equation 
c. Hematologic: 
i. 
Absolute neutrophil count ≥1,500/µL 
ii. 
Platelets ≥100,000/µL 
iii. 
Hemoglobin ≥8 g/dL 
8. Patient is willing and able to comply with all protocol-required 
assessments, visits, and procedures, including pretreatment 
tumor biopsy.  Archival tumor biopsies are acceptable at 
baseline.  
9. Females of childbearing potential must have negative serum 
pregnancy test prior to starting study therapy, and agree to use 
a reliable form of contraceptive during the study treatment 
period and for at least 120 days following the last dose of 
study drug.   
Patient not of childbearing potential (i.e., permanently 
sterilized, postmenopausal) can be included in study.  
Postmenopausal is defined as 12 months with no menses 
without an alternative medical cause. 
Male patients must agree to use an adequate method of 
contraception during the study treatment period and for at least 
120 days following the last dose of study drug. 
10. Cannot be breast feeding. 
11. Patients with human immunodeficiency virus (HIV) infection 
are eligible if CD4+ T-cell counts ≥ 350 cells/μL; patients on 
anti-retroviral therapy (ART) should be on an established dose 
for at least 4 weeks and have an HIV viral load less than 
400 copies/mL prior to enrollment. 
12. Patients with serological evidence of chronic hepatitis B virus 
(HBV) infection are eligible if they have an HBV viral load 
below the limit of quantification with or without concurrent 
viral suppressive therapy. 
13. Patients with a history of hepatitis C virus (HCV) infection 
should have completed curative antiviral treatment and have a 
viral load below the limit of quantification. 


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14. Patients in Part B (Cohort-Expansion) – must have documented 
Globo H H-score ≥ 100 from a qualified laboratory IHC assay in one 
of the following tumor types to be enrolled in the respective cohort: 
• Cohort 1:  Pancreatic cancer 
o Histopathologically confirmed patients with 
metastatic adenocarcinoma of the pancreas. 
• Cohort 2:  Colorectal cancer 
o Histopathologically confirmed patients with 
metastatic colorectal adenocarcinoma.  
• Cohort 3:  Basket (any solid tumor type other than those 
included in Cohorts 1 and 2). 
o Histologically or cytologically confirmed patients with 
advanced solid tumors. 
Selection of 
Patients – 
Exclusion 
Criteria: 
Exclusion Criteria:  
Patients meeting any of the following criteria are ineligible to 
participate in this study: 
1. Less than 3 weeks from prior cytotoxic chemotherapy or radiation 
therapy; and less than 5 half-lives or 3 weeks, whichever is shorter, 
from prior biologic therapies, prior to the first dose of OBI-999. 
2. Has undergone a major surgical procedure (as defined by the 
Investigator) or significant traumatic injury within 28 days prior to 
the first dose of OBI-999. 
3. Sensory or motor neuropathy of Grade 2 or greater. 
4. Patients with a history of solid organ transplant. 
5. Unresolved toxicities from prior anticancer therapy, defined as 
having not resolved to Grade 0 or 1 (using National Cancer Institute 
Common Terminology Criteria for Adverse Events [NCI CTCAE] 
version 5.0), except for alopecia and laboratory values listed in the 
inclusion criteria. 
6. Receipt of any prior therapy targeting Globo H. 
7. Known hypersensitivity to OBI-999 or its excipients. 
8. Has known untreated central nervous system (CNS) metastases.  
Patients with treated brain metastases are eligible if there is no 
evidence of progression for at least 4 weeks after CNS-directed 
treatment, as ascertained by clinical examination and brain imaging 
(magnetic resonance imaging [MRI] or computed tomography [CT]) 
during the screening period.  
9. Has significant clinical cardiac abnormality (e.g., clinical heart 
failure or unstable angina). 
10. Any medical co-morbidity that is life-threatening or, in the opinion 
of the Investigator, renders the patient unsuitable for participation in 
a clinical trial due to possible noncompliance, would place the 


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patient at an unacceptable risk and/or potential to affect 
interpretation of results of the study. 
11. Is receiving any concurrent prohibited medication as listed in 
Section 8.6.3. 
Planned Sample 
Size: 
Up to 30 patients will be enrolled in the 3+3 dose-escalation portion of 
the study (Part A).   
The cohort-expansion portion of the study (Part B) will enroll up to 
57 patients based on Simon’s two-stage design.  The first stage will 
recruit up to 9 patients in each of three cohorts.  If at least 1 objective 
response is observed, a second stage recruitment will occur with up to 
10 additional patients enrolled into that cohort, for a total of up to 
19 patients per cohort.  If at least 4 objective responses are observed in 
the 19 patients, then OBI-999 will be considered worthy of further 
evaluation in that indication.  Patients will be followed up to the 
24-week scheduled response assessment for the purposes of counting 
objective responses for Simon’s two-stage design success criteria.  
This design is based on a level of low interest for a treatment with an 
ORR of 10% versus a level of high interest for a treatment with an 
ORR of 25%.  The sample size is based on a one-sided alpha of 0.12 
and 72% power.  The two-stage design limits the number of patients 
treated for a treatment with low levels of activity. 
Dose/ Route/ 
Regimen for 
Investigational 
Therapy: 
OBI-999 is an anti-Globo H ADC.  OBI-999 drug product (in final 
concentration 5 mg/mL) will be supplied by OBI Pharma Inc. 
OBI-999 will be administered as a 60±10-minute IV infusion on 
Day 1 of each 21-day cycle.  The infusion duration for Cycles 3 and 
beyond may be reduced, at the Investigator’s discretion, to 30 minutes 
if the infusions in the first 2 cycles are well tolerated. 
• For Part A, OBI-999 was planned to be given at doses of 0.4, 
0.8, 1.2, 1.6, and 2.0 mg/kg (capping calculations at a 
maximum of 100 kg) until the MTD and RP2D were 
determined.  
• For Part B, OBI-999 will be given at the RP2D of 1.2 mg/kg 
(capping calculations at a maximum of 100 kg).  
Reference 
Therapy: 
None 
Treatment 
Duration: 
The study will include a screening period (up to 28 days), a treatment 
period, and a follow-up period.   
Patients will continue to receive treatment with OBI-999 until disease 
progression, unacceptable toxicity, consent withdrawal, or for up to 
35 cycles (approximately 2 years), whichever occurs first.   
The safety follow-up visit will be conducted 28 days after the last dose 
of study treatment for both parts of the study. 


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Criteria for 
Evaluation: 
Safety: 
Safety assessments will include incidence and severity of AEs and 
serious adverse events (SAEs), clinical laboratory tests (hematology, 
serum chemistry, coagulation, and urinalysis), vital sign 
measurements, electrocardiograms (ECGs), ophthalmology, and 
physical examination. Physical examinations will include a targeted 
assessment for signs and symptoms of peripheral neuropathy.  Safety 
assessments will be performed at screening and throughout the study.  
DLTs (Part A only): 
A DLT is defined as the occurrence of any of the following events, 
within the first cycle of treatment that is considered to be at least 
possibly related to OBI-999.   
• Grade 4 neutropenia lasting more than 7 days. 
• Febrile neutropenia. 
• Grade 4 thrombocytopenia. 
• Grade 3 thrombocytopenia with ≥Grade 2 bleeding requiring 
platelet transfusions. 
• ≥Grade 3 fatigue, nausea and vomiting or diarrhea that does 
not resolve to Grade 1 or Baseline within 72 hours despite 
optimal supportive care. 
• Grade 4 gastrointestinal toxicity. 
• Any other Grade 3 or Grade 4 non-hematological toxicity 
(except Grade 3 fatigue, nausea, vomiting, or diarrhea lasting 
<24 hours with optimal therapy, Grade 3 non-hematologic 
laboratory abnormalities that resolve to Grade 1 or Baseline 
within 14 days).  
All AEs unless they are determined to be not related to study drug will 
be taken into consideration in determining DLTs.  NCI CTCAE 
version 5.0 will be the basis for the descriptive terminology and 
grading of AEs.  The period for DLT observation is 21 days from the 
start of first dose of OBI-999 (i.e., Day 1).  
Immunogenicity: 
Samples for evaluation of ADAs will be collected prior to infusion on 
Day 1 of Cycles 1-8, Cycle 12 and every 4 cycles thereafter.  A single 
sample will be collected at the end of study or end of treatment visit.  
Pharmacokinetics:  
Samples for the evaluation of serum concentration of OBI-999 total 
antibody, ADC, and free MMAE will be collected as follows: 
Part A of the study: 
• Day 1 of Cycles 1 and 2 – prior to infusion, and 30 minutes, 
2 hours, 4 hours, 8 hours after the end of infusion. 


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• Days 2, 4, 8, 11 and 15 of Cycles 1 and 2 (ie, 24, 72, 168, 240 
and 336 hours after the end of infusion). 
• Day 1 of Cycle 3 and Cycle 4 – prior to infusion and 
30 minutes after the end of infusion. 
• Day 8 of Cycle 3 and Cycle 4 – 168 hours after the end of 
infusion. 
• Day 1 of Cycles 5-8, 12 and every 4 cycles – prior to infusion 
and 30 minutes after the end of infusion. 
• End of treatment visit – single sample. 
 
Part B of the study: 
• Day 1 of Cycles 1 and 2 – prior to infusion, and 30 minutes 
and 6 hours after the end of infusion.  
• Days 2 and 4 of Cycles 1 and 2 (ie, 24 and 72 hours after the 
end of infusion, this intensive PK sampling will be collected 
from first 5 patients in each cohort). 
• Day 8 and 15 of Cycles 1 and 2 (ie, 168 and 336 hours after 
the end of infusion). 
• Day 1 of Cycle 3, Cycle 4, Cycle 8, and every 4 cycles - prior 
to infusion and 30 minutes after the end of infusion. 
• End of treatment visit – single sample. 
Pharmacokinetic parameters will be calculated using a 
non-compartmental method from the PK samples collected during 
Cycles 1 and 2 and will include but will not be limited to maximum 
serum concentration (Cmax), area under the concentration curve 
(AUC), elimination half-life (t1/2), clearance (Cl), time to reach 
maximum concentration (Tmax), and volume of distribution (Vd).   
Preliminary Clinical Activity Profile:  
Tumor response will be evaluated by the Investigator using 
RECIST 1.1.  Tumor status assessment will be performed pretreatment 
(up to 28 days prior to dosing).  During the study, tumor response will 
be assessed every 6 weeks for the first 3 months and then every 
9 weeks until discontinuation of study treatment, disease progression, 
death, or initiation of further systemic cancer therapy, including 
radiation therapy, whichever occurs earlier.  
Study Endpoints: 
Part A – Dose-Escalation: 
Primary endpoints:   
• AEs/SAEs and laboratory abnormalities as graded by 
NCI CTCAE version 5.0. 
• DLTs with OBI-999. 
• MTD and RP2D of OBI-999. 
 


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Secondary endpoint: 
• PK parameters of OBI-999 and its active metabolite MMAE. 
Exploratory endpoint: 
• Potential predictive biomarkers for OBI-999 activity such as 
expression of Globo H and other tumor-associated glycans or 
tumor molecular phenotypes. 
 
Part B – Expansion Cohort: 
Primary endpoints:   
• Percentage of patients with objective rsponse, clinical benefit, 
DOR, and PFS according to RECIST 1.1.  
• Percentage of patients with ADAs in blood. 
Secondary endpoints: 
• AEs/SAEs and laboratory abnormalities as graded by 
NCI CTCAE version 5.0. 
• PK parameters of OBI-999 and its active metabolite MMAE. 
Exploratory endpoint: 
• Potential predictive biomarkers for OBI-999 activity such as 
expression of Globo H and other tumor-associated glycans or 
tumor molecular phenotypes. 
Statistical 
Methods and 
Planned 
Analyses: 
Analyses will be conducted by dose level in Part A and by cancer type 
in Part B.  Descriptive summaries for categorical variables will 
include counts and percentages.  Descriptive summaries for 
continuous variables will include means, medians, standard 
deviations, minimum and maximum values.  Descriptive summaries of 
time to event data will include medians and confidence intervals.  
Graphical summaries of the data may be presented.  All data will be 
listed for all patients.   
Further details of the analysis, including the handling of missing data, 
transformations, other data handling procedures, and analytical 
methodology will be provided in the Statistical Analysis Plan (SAP).  
Additional exploratory analyses of the data will be conducted as 
deemed appropriate. 
Analyses of safety data will be performed on all enrolled patients who 
receive at least 1 dose of study drug. Analyses of preliminary clinical 
activity will require at least one follow-up tumor assessment scan. 
 
Safety Analyses 
Adverse events will be coded according to Medical Dictionary for 
Regulatory Activities (MedDRA) version 21.0 or higher and assessed 
for severity using NCI CTCAE version 5.0.  Adverse events will be 
summarized by system organ class and preferred term and presented in 


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decreasing order of incidence.  Dose-limiting toxicities will also be 
summarized by dose and cohort. 
Vital signs, ECG data, ophthalmology, hematology, serum chemistry, 
coagulation, and urinalysis parameters from baseline and during study 
will be examined.  Treatment-emergent changes in key laboratory 
parameters will be identified.  Clinical laboratory data will be 
summarized for each time point that specimens are collected.  
Changes from baseline for select clinical laboratory analytes may also 
be explored as specified in the SAP. 
 
Pharmacokinetic Analyses 
Pharmacokinetic parameters will be calculated using a 
non-compartmental method from the PK samples collected during 
Cycles 1 and 2 and will include, but is not limited to Cmax, AUC, t1/2, 
Cl, Tmax, and Vd.   
To describe the dependency on dose, scatter plots of Cmax and AUC 
versus dose will be provided.  Summary statistics will be tabulated for 
the trough concentration (Cmin) and peak concentrations (end of 
infusion) by dose and study day.   
Pharmacometric methods may also be applied to further investigate 
OBI-999 and MMAE exposure (e.g., accumulation of OBI-999, 
presence of dose- or time-dependent OBI-999 PK behavior, 
verification of influential factors on OBI-999 PK). 
 
Clinical Activity Analyses 
Objective response rate (ORR) is defined as the percentage of patients 
with confirmed partial response (PR) or complete response (CR) 
according to RECIST 1.1.  The CBR is defined as the percentage of 
patients with confirmed CR, PR, or stable disease.  The DOR is 
defined as time from the date of reported confirmed PR or CR to the 
date of progression will be summarized descriptively using time-
oriented summary statistics.  Additionally, a listing of DOR for those 
patients experiencing response will be provided.  The PFS is defined 
as the time from first dose of study drug until radiographically 
determined disease progression or death due to any cause, whichever 
event occurs first.  Patients who are still alive or who have no 
progressive disease reported at analysis will be censored at their last 
evaluable tumor assessment.   
Kaplan-Meier estimates and 95% confidence intervals will be 
presented for time to event endpoints such as PFS if sufficient 
numbers of events to calculate meaningful statistics are observed. 


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2 
Table of Contents 
1 
Synopsis ............................................................................................................................... 5 
2 
Table of Contents .............................................................................................................. 15 
2.1 
In-Text Tables ........................................................................................................ 18 
2.2 
List of Figures ........................................................................................................ 18 
3 
List of Abbreviations ......................................................................................................... 19 
4 
Introduction ....................................................................................................................... 22 
4.1 
Globo H as Tumor-Associated Carbohydrate Antigen .......................................... 22 
4.2 
Background on OBI-999 ........................................................................................ 24 
4.3 
Nonclinical Studies ................................................................................................ 24 
4.3.1 
In Vivo Efficacy .................................................................................... 24 
4.3.2 
Tumor Targeting ................................................................................... 26 
4.3.3 
Pharmacokinetics .................................................................................. 26 
4.3.4 
Safety Pharmacology ............................................................................ 26 
4.3.5 
Toxicology ............................................................................................ 26 
4.4 
Clinical Risks/Benefits of OBI-999 ....................................................................... 28 
4.5 
Rationale ................................................................................................................ 28 
4.5.1 
Rationale for Selection of Study Population ......................................... 28 
4.5.2 
Rationale for Dose Selection ................................................................. 29 
5 
Study Objectives and Endpoints ........................................................................................ 30 
5.1 
Study Objectives .................................................................................................... 30 
5.1.1 
Primary Objectives ................................................................................ 30 
5.1.2 
Secondary Objectives ............................................................................ 30 
5.1.3 
Exploratory Objectives .......................................................................... 30 
5.2 
Study Endpoints ..................................................................................................... 31 
5.2.1 
Part A – Dose Escalation ....................................................................... 31 
5.2.2 
Part B – Expansion Cohort .................................................................... 31 
6 
Investigational Plan ........................................................................................................... 31 
6.1 
Description of Overall Study Design and Plan ...................................................... 31 
6.1.1 
Part A – Dose-Escalation ...................................................................... 32 
6.1.2 
Part B – Cohort-Expansion ................................................................... 33 
6.1.3 
Duration of Study .................................................................................. 33 
6.2 
Definition of Dose-Limiting Toxicities (Part A only) ........................................... 34 
6.3 
Discussion of Study Design ................................................................................... 34 
7 
Selection and Withdrawal of Patients ................................................................................ 34 
7.1 
Inclusion and Exclusion Criteria ........................................................................... 34 
7.1.1 
Inclusion Criteria ................................................................................... 34 
7.1.2 
Exclusion Criteria .................................................................................. 36 


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7.2 
Treatment Discontinuation and Withdrawal of Patients ........................................ 37 
7.3 
Follow-Up for Drug Discontinuation/Patient Withdrawal from Study ................. 37 
8 
Treatments ......................................................................................................................... 38 
8.1 
Details of Study Treatment .................................................................................... 38 
8.1.1 
Packaging and Labeling ........................................................................ 38 
8.1.2 
Storage ................................................................................................... 38 
8.2 
Treatment Regimen ............................................................................................... 38 
8.2.1 
OBI-999 Doses ...................................................................................... 38 
8.2.2 
OBI-999 Administration ....................................................................... 38 
8.2.3 
Prophylactic Measures .......................................................................... 39 
8.3 
Dose Modifications and Toxicity Management .................................................... 39 
8.3.1 
Infusion Reactions ................................................................................. 40 
8.3.2 
Peripheral Neuropathy .......................................................................... 41 
8.4 
Study Treatment Assignment ................................................................................ 41 
8.5 
Treatment Accountability and Compliance ........................................................... 41 
8.6 
Prior and Concomitant Illnesses and Medications ................................................. 42 
8.6.1 
Prior and Concomitant Illnesses ............................................................ 42 
8.6.2 
Prior and Concomitant Medications ...................................................... 42 
8.6.3 
Prohibited Medications ......................................................................... 42 
9 
Study Procedures ............................................................................................................... 43 
9.1 
Patient Informed Consent ...................................................................................... 43 
9.2 
Procedures by Study Period ................................................................................... 43 
10 Clinical Activity Profile Assessments ............................................................................... 49 
11 Pharmacokinetics ............................................................................................................... 49 
11.1 
Pharmacokinetic Sampling .................................................................................... 49 
11.2 
Pharmacokinetic Analytical Methodology ............................................................ 49 
12 Safety Assessments ........................................................................................................... 50 
12.1 
Vital Signs ............................................................................................................. 50 
12.2 
Physical Examination ............................................................................................ 50 
12.3 
Electrocardiogram .................................................................................................. 50 
12.4 
Laboratory Assessments ........................................................................................ 51 
12.5 
Adverse Events ...................................................................................................... 53 
12.5.1 
Adverse Events ...................................................................................... 53 
12.5.2 
Serious Adverse Events ......................................................................... 54 
12.5.3 
Serious Adverse Event Reporting ......................................................... 55 
12.5.4 
Pregnancy .............................................................................................. 55 
12.5.5 
Overdose ............................................................................................... 56 
12.6 
ECOG Performance Status .................................................................................... 56 


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12.7 
Immunogenicity ..................................................................................................... 56 
13 Exploratory Analyses ........................................................................................................ 57 
13.1 
Tumor Tissue Samples .......................................................................................... 57 
14 Statistical Analysis ............................................................................................................ 57 
14.1 
Determination of Sample Size ............................................................................... 58 
14.2 
Analysis of Populations ......................................................................................... 58 
14.3 
Clinical Activity Analysis ...................................................................................... 58 
14.4 
Pharmacokinetic Analysis ..................................................................................... 59 
14.5 
Safety Analysis ...................................................................................................... 59 
14.6 
Safety Review Committee ..................................................................................... 60 
14.7 
Interim Analysis ..................................................................................................... 60 
15 Study Management ............................................................................................................ 60 
15.1 
Approval and Consent ........................................................................................... 60 
15.1.1 
Regulatory Guidelines ........................................................................... 60 
15.1.2 
Institutional Review Board/Independent Ethics Committee ................. 60 
15.1.3 
Informed Consent .................................................................................. 60 
15.2 
Data Handling ........................................................................................................ 61 
15.3 
Source Documents ................................................................................................. 61 
15.4 
Record Retention ................................................................................................... 61 
15.5 
Monitoring ............................................................................................................. 62 
15.6 
Quality Control and Quality Assurance ................................................................. 62 
15.7 
Protocol Amendment and Protocol Deviation ....................................................... 62 
15.7.1 
Protocol Amendment ............................................................................ 62 
15.7.2 
Protocol Deviations ............................................................................... 62 
15.8 
Ethical Considerations ........................................................................................... 63 
15.9 
Financing and Insurance ........................................................................................ 63 
15.10 Publication Policy and Disclosure of Data ............................................................ 64 
16 References ......................................................................................................................... 65 
17 Appendices ........................................................................................................................ 68 
17.1 
Appendix 1:  Drug Preparation Instruction for OBI-999 ....................................... 68 
17.2 
Appendix 2:  Examples of Strong Inducers or Inhibitors of CYP3A .................... 70 
17.3 
Appendix 3:  Examples of Clinical Inhibitors of P-Glycoprotein ......................... 71 
 
 
 


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2.1 
In-Text Tables 
Table 4-1 
Pharmacokinetic Summary – Part A of OBI-999-001 .......................... 30 
Table 8-1 
OBI-999 Dose Modifications for Toxicity ............................................ 39 
Table 8-2 
Therapeutic Antiemetic and Anti-Diarrheal Recommendations ........... 40 
Table 9-1 
Schedule of Assessments ...................................................................... 44 
Table 9-2 
Part A - Pharmacokinetic and ADA Sampling Schedule ...................... 47 
Table 9-3 
Part B - Pharmacokinetic and ADA Sampling Schedule ...................... 48 
Table 12-1 
Laboratory Assessments ........................................................................ 52 
Table 12-2 
Classification of Adverse Events by Intensity (NCI CTCAE Grade) ... 53 
Table 12-3 
Classification of Adverse Events by Relationship to Study Drug ........ 54 
Table 12-4 
ECOG Performance Status .................................................................... 56 
2.2 
List of Figures 
Figure 4-1 
Globo H H-score in Various Tumor Tissues ......................................... 23 
Figure 4-2 
Effect of OBI-999, OBI-888, OBI-910-101 and MMAE on Tumor 
Growth in Nude Mice Inoculated with NCI-N87 Human Gastric 
Cancer Cells .......................................................................................... 25 
Figure 4-3 
Effect of OBI-999 on Tumor Growth in Nude Mice Inoculated with 
HPAC Human Pancreatic Cancer Cells ................................................ 25 
 


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3 
List of Abbreviations 
Abbreviation 
Definition 
ADA 
anti-drug antibody 
ADC 
antibody drug conjugate 
AE 
adverse event 
ALT (SGPT) 
alanine aminotransferase (serum glutamic pyruvic transaminase) 
AST (SGOT) 
aspartate aminotransferase (serum glutamic oxaloacetic 
transaminase) 
ADA 
anti-drug antibody 
ART 
anti-retroviral therapy 
AUC 
area under the concentration curve  
CBR 
clinical benefit rate 
CDX 
cell line derived xenograft 
Cl 
clearance 
CFR 
Code of Federal Regulations 
Cmax 
maximum serum concentration 
Cmin 
trough concentration 
CNS 
central nervous system 
CR 
complete response 
CRO 
Contract Research Organization 
CT 
computed tomography 
DCF 
Data Clarification Form 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DP 
drug product 
DS 
drug substance 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
ELISA 
enzyme-linked immunosorbent assay 
FACS 
fluorescence-activated cell sorting 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GMP 
Good Manufacturing Practice 
GLP 
Good Laboratory Practice 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 


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Abbreviation 
Definition 
ADA 
anti-drug antibody 
HED 
human equivalent dose 
HEENT 
head, eyes, ears, nose, throat 
HIPAA 
Health Insurance Portability Accountability Act 
HIV 
human immunodeficiency virus 
HNSTD 
highest non-severely toxic dose 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IHC 
immunohistochemistry 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMAE 
monomethyl auristatin E 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NOAEL 
no observed adverse effect level 
ORR 
objective response rate 
PDX 
patient-derived xenograft 
PFS 
progression-free survival 
PK 
pharmacokinetics 
PR 
partial response 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RP2D 
Recommended Phase 2 Dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SD 
Sprague Dawley  
SPECT 
single-photon emission computed tomography 
SRC 
Safety Review Committee 
t1/2 
elimination half-life 
TAb 
total antibody 


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Abbreviation 
Definition 
ADA 
anti-drug antibody 
TACA 
tumor-associated carbohydrate antigen 
TEAE 
treatment-emergent adverse event 
TGI 
tumor growth inhibition 
Tmax 
time to reach maximum concentration 
ULN 
upper limit of normal 
Vd 
volume of distribution 
WHO 
World Health Organization 


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4 
Introduction 
4.1 
Globo H as Tumor-Associated Carbohydrate Antigen 
Globo H is a neutral hexasaccharide (Fucα1→2Ga1β1→3GalNAcβ1→3Ga1α1→4Ga1β1→ 
4G1cβ1) glycosphingolipid that was originally isolated from the human breast cancer cell line 
MCF-7 (Menard, et al., 1983; Bremer, et al. 1984).  Its overexpression has been seen on a variety 
of epithelial cell tumors such as colon, ovarian, gastric, pancreatic, endometrial, lung, prostate, 
and breast cancers using monoclonal antibodies (mAbs), MBrl (immunoglobulin M [lgM]) 
(Menard, et al., 1983; Bremer, et al. 1984; Canevari, et al., 1983) and VK-9 (immunoglobulin 
G [IgG] 3) (Ragupathi, et al., 1999).  Globo H is considered to be a tumor-associated 
carbohydrate antigen (TACA).  Figure 4-1 shows the prevalence of Globo H expression in 
various cancer types from tumor specimens and tumor tissue microarray using a validated 
immunohistochemical (IHC) assay with an H-score cut-off of 100 (i.e., H-score ≥ 100) (Globo 
H IHC Pan-Tumor Validation Summary and Globo H IHC Pan Tumor Expanded Precision 
Validation Summary, as well as in-house preliminary data). 


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Figure 4-1 
Globo H H-score in Various Tumor Tissues 
 
Gray line: H-score cut-off; Red bar: median H-score 
* Tumor samples without cancer subtype information  
Note: Globo H H-score was determined using a validated immunohistochemistry assay. 


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In normal tissues, Globo H is weakly expressed in apical epithelial cells of lumen border, a site 
which is generally inaccessible to the immune system.  Globo H ceramide sheds from tumor 
cells and may act as an immune checkpoint molecule to facilitate the escape of cancer cells 
from immune surveillance, thereby inhibiting the activation of immune cells (Tsai, et al., 2013).  
Incorporation of Globo H ceramide by endothelial cells results in enhanced angiogenic activity 
to promote tumor growth (Cheng, et al., 2014).  
4.2 
Background on OBI-999 
OBI-999, an antibody drug conjugate (ADC), is composed of a humanized monoclonal IgG1 
antibody conjugated with monomethyl auristatin E (MMAE, vedotin), targeting Globo H for 
the treatment of Globo-H over-expressing cancers.  The naked anti-Globo H antibody named 
OBI-888 is an investigational new drug (IND# 136961) currently in Phase 1 clinical trial.  
MMAE is an ultrapotent antimitotic agent that causes cell cycle arrest by inhibiting the 
polymerization of tubulin (Francisco et al., 2003; Doronina et al., 2003).  The Thiobridge™ 
conjugate vcPAB linker connecting MMAE to the mAb is stable in extracellular fluid.  The 
binding affinity and specificity of OBI-999 to Globo H have been demonstrated by 
enzyme-linked immunosorbent assay (ELISA) and fluorescence-activated cell sorting (FACS).  
Upon binding to Globo H, OBI-999 is internalized into the cell and delivered to lysosomes 
where the linker is cleaved by cathepsin, releasing the antimitotic MMAE.  These evidences 
support that OBI-999 exhibits tumor-killing activity via internalization and lysosome 
dependent, protease mediated cytotoxicity of MMAE. 
4.3 
Nonclinical Studies 
4.3.1 
In Vivo Efficacy 
OBI-999 showed potent and long lasting anti-tumor efficacy, with tumor growth inhibition 
(TGI) ranging between 85–118% in multiple cell line derived xenograft (CDX) models, 
including MCF7 breast cancer, NCI-N87 gastric cancer, NCI-H526 small cell lung cancer, and 
HPAC pancreatic cancer, as well as the LU-01-0266 non-small cell lung cancer patient-derived 
xenograft (PDX) model.  Globo H expression levels in the CDX and PDX models were 
approximately 57-99% and 27%, respectively.  Most importantly, in the NCI-N87 gastric cancer 
CDX model, 1 day after implanting 2.5 x 106 cells, OBI-999 was administered at doses of 1, 3, 
or 10 mg/kg once weekly for 4 weeks; the percent TGI reached 83%, 97% and 97% on Day 53 
(about 1 month after the last injection) (Figure 4-2).  In the HPAC pancreatic cancer CDX 
model, on Day 7 after implanting 3 x 106 cells, OBI-999 was administered at a dose of 1, 3, and 
10 mg/kg once weekly for 4 weeks; the maximum percent TGI was 104% on Day 36 post-
treatment (Figure 4-3).  OBI-999 was well tolerated and no significant changes in body weight 
were observed over the course of the study compared with the vehicle group.  No overt toxicities 
were observed during the study period.  Additional details are provided in the [OBI-999 
Investigators’ Brochure]. 




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4.3.2 
Tumor Targeting 
OBI-999’s tumor targeting ability has been demonstrated by biodistribution and single-photon 
emission computed tomography (SPECT) imaging in NCI-N87 xenograft mice.  At 168 hours 
post-injection, the tumor/muscle ratio reached 16.25, indicating that OBI-999 targeted and 
accumulated in Globo H expressing tumors.  At one-hour post-injection, OBI-999 accumulated 
mostly in blood-rich organs, including lung, liver, spleen, and kidney.  The concentration of 
OBI-999 in these organs gradually decreased with blood clearance.  The biodistribution pattern 
in organs was similar between normal mice and tumor-bearing mice.  Although a certain amount 
of 111In-DTPA-labeled OBI-999 were observed in the female genital system, no specific 
binding was found in tissue-cross-reactivity of the parental antibody, OBI-888, in humans.   
Good laboratory practice (GLP) tissue-cross-reactivity studies of OBI-888 were conducted on 
human and monkey tissues to determine the potential cross-reactivity of OBI-888 with human 
cryosections and cynomolgus monkey tissues.  OBI-888-specific staining was most frequently 
observed in the luminal epithelium, which is consistent with the Globo H expression pattern in 
tissues.  The above studies support the tumor targeting ability of OBI-999. 
4.3.3 
Pharmacokinetics 
The pharmacokinetics (PK) of OBI-999 were evaluated in normal and tumor bearing mice, rats 
and monkeys following intravenous (IV) administration of OBI-999.  Serum samples were 
analyzed for total antibody (TAb), intact ADC (OBI-999) and free MMAE.  In these species, 
exposure of OBI-999 increased with dose proportionally.  No sex difference was observed 
across the dose ranges.  No accumulation was observed following the repeated dosing of 
OBI-999.  Total antibody exposure was similar to those of OBI-999.  Limited systemic exposure 
of free MMAE was observed, indicating that OBI-999 was stable in serum after administration 
to animals.  In vitro serum stability revealed that free MMAE levels produced from OBI-999 in 
human serum was very limited, and the payload-antibody conjugation of OBI-999 is shown to 
be stable in human serum. 
4.3.4 
Safety Pharmacology 
Evaluation of the cardiovascular system (blood pressure and electrocardiogram), respiratory 
function (respiration rates and pulse oximetry) and central nervous system (CNS) effects 
(neurological examination) were incorporated into the 3-week repeated dose study in 
cynomolgus monkeys.  No adverse events were observed at doses up to 10 mg/kg.  OBI-999 
was well-tolerated in monkeys with no undesired pharmacological effects on cardiovascular, 
respiratory, and CNS functions. 
4.3.5 
Toxicology 
Single-dose and multiple-dose GLP toxicology studies were carried out in Sprague Dawley 
(SD) rats and Cynomolgus monkeys.  Both species are considered relevant species due to a 
Globo H expression pattern similar to humans. 
Sprague Dawley rats were administered single doses of 0, 3, 10, or 30 mg/kg OBI-999 by slow 
IV injection (5 to 10 minutes/animal) at a volume of 10 mL/kg.  Animals were observed for 
14 treatment-free days and sacrificed on Day 15.  A single dose of OBI-999 caused effects on 
hematopoietic and male reproductive system in SD rats.  Hematologic changes included 
decreased red blood cell parameters responded by increased reticulocyte counts and splenic 


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extramedullary hematopoiesis at 30 mg/kg in both sexes, suggesting potential toxicity on bone 
marrow.  Male rats administered 10 or 30 mg/kg showed decreased testis size and weights that 
correlate with microscopic degenerative findings.  Exposure of OBI-999 increased with dose 
proportionally.  No gender difference was observed across the dose range.  Total antibody 
exposure was generally greater than exposures to conjugated antibody.  Systemic exposure to 
free MMAE was limited.  The no observed adverse effect level (NOAEL) was considered to be 
3 mg/kg. 
Sprague Dawley rats were administered 0, 3, 10, or 30 mg/kg OBI-999 (N = 10/sex/group for 
main study) once every 3 weeks for 3 weeks (2 total doses) by slow bolus infusion followed by 
a 3-week recovery period. OBI-999-related reversible effects on body weight, body weight gain, 
food consumption, and ophthalmology were observed in animals administered 30 mg/kg.  
Hematologic effects were identified in males administered 30 mg/kg and females administered 
≥10 mg/kg and generally reversed after 3 weeks of recovery.  These effects were likely 
associated with bone marrow suppression at the terminal sacrifice and a physiologic 
hematopoietic response at the recovery sacrifice.  OBI-999-related effects on male reproductive 
system including degeneration/atrophy of the seminiferous tubules, testis, and prostate, and 
hypospermia in the epididymis were observed at level ≥10 mg/kg/dose.  OBI-999-related effects 
on clinical chemistry results were identified in animals administered 30 mg/kg/dose.  These 
effects including higher cholesterol and triglycerides, lower albumin, and higher aspartate 
aminotransferase (AST) and alanine aminotransferase (ALT), were small in magnitude and 
generally reversible.  The NOAEL in SD rats was 3 mg/kg/dose. 
Cynomolgus monkeys were administered single doses of 0, 10, or 30 mg/kg OBI-999 
(N = 1/sex/group) by slow bolus IV injection at a volume of 6 mL/kg.  Animals were observed 
for 14 treatment-free days to assess the reversibility, persistence, or delayed occurrence of 
effects.  OBI-999-related mortality was observed in the male and female monkey on Day 6 at 
the level of 30 mg/kg.  All other animals survived to scheduled sacrifice.  Hematologic effects 
in animals administered 10 mg/kg were maximal on Day 10 with improvement on Day 15, 
suggesting reversibility.  The highest non-severely toxic dose (HNSTD) was 10 mg/kg due to 
the marked severity of hematologic findings and the lack of evidence of lethality or 
life-threatening toxicities in animals administered 10 mg/kg. 
Cynomolgus monkeys were administered vehicle control article (OBI Formulation Buffer) or 
2, 5, or 10 mg/kg/dose OBI-999 (N = 3/sex/group for main study) once every 3 weeks via IV 
infusion followed by a 3-week recovery period.  OBI-999-related decreases in body weight and 
food consumption were observed for animals administered 10 mg/kg/dose.  These findings 
showed evidence of reversibility during the recovery period.  OBI-999-related bone marrow 
suppression was dose-dependent and reversible during the recovery period.  OBI-999 related 
non-adverse microscopic findings included decreased lymphocytes and/or increased 
lymphocyte apoptosis of the thymus in animals administered ≥2 mg/kg/dose; decreased myeloid 
cellularity of the bone marrow in animals administered ≥5 mg/kg/dose.  Thus, the HNSTD was 
10 mg/kg/dose.  This dose level corresponded to mean peak concentration (Cmax) and area under 
the concentration time curve (AUC) values of 210 μg/mL and 9730 μg x hr/mL, respectively, 
in males and 217 μg/mL and 9680 μg x hr/mL, respectively, in females on Day 1 of the dosing 
phase. 
Additional details are provided in the [OBI-999 Investigators’ Brochure]. 


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4.4 
Clinical Risks/Benefits of OBI-999  
OBI-999 is an ADC composed of a humanized monoclonal IgG1 antibody conjugated with 
MMAE.  Toxicities may include myelosuppression and neuropathy as these side effects have 
been observed with other ADCs based on the MMAE molecule.  A complete discussion of 
guidance for the investigator is provided in the OBI-999 Investigator Brochure. 
The risk-to-benefit ratio for this study is considered acceptable based upon the patient 
population, the available limited treatment options for patients with advanced solid tumors, the 
toxicology results and activity data observed in the preclinical safety studies, and the results of 
the Dose Escalation Phase of this study. 
As of 02 June 2020, 13 out of 15 patients enrolled in Part A had an investigator driven tumor 
response assessment. The best overall response per Response Evaluation Criteria in Solid 
Tumors version 1.1 (RECIST 1.1) criteria was stable disease, which was observed in 5 patients, 
including 1 patient from Cohort 1 (0.4 mg/kg with rectal cancer), 2 patients from Cohort 2 (0.8 
mg/kg; 1 with pancreatic cancer and 1 with esophageal cancer), and 2 patients from Cohort 3 
(1.2 mg/kg; 1 with head and neck cancer and 1 with cancer of the appendix).  However, due to 
the limited sample size in Part A (Dose-Escalation), a relationship between Globo H expression 
level and depth of clinical activity at the Recommended Phase 2 Dose (RP2D) has yet to be 
established in this patient population.  This relationship will be further evaluated in Part B of 
the study at the RP2D of 1.2 mg/kg. 
4.5 
Rationale 
Globo H is a hexasaccharide glycosphingolipid located endogenously on the outer membrane 
of epithelial cells and was first identified in breast cancer cells.  Globo H was found to be 
overexpressed on the cell surface of several epithelial cancers such as breast, pancreatic, 
ovarian, endometrial, gastric, lung, and prostate cancers.  Globo H has been associated with 
tumor stem cells, as a potent inducer of angiogenesis and immune suppressor through Notch 
signaling, rendering it a target for cancer therapy (Cheng, et al., 2014).  
This is a 2-part study: Part A (Dose-Escalation) is designed to establish the maximum tolerated 
dose (MTD) of OBI-999 as monotherapy.  Part B (Cohort-Expansion) is intended to further 
characterize the safety and preliminary clinical activity profile of the MTD dose of OBI-999 in 
patients with advanced solid tumors. 
4.5.1 
Rationale for Selection of Study Population 
The target population enrolled in Part A includes patients with advanced solid tumors refractory 
to at least one line of systemic therapy or intolerable with standard therapy or for which no 
standard treatment is available, regardless of Globo H status. The RP2D has been established 
based on dose limiting toxicities (DLTs), with consideration of the overall toxicities and 
available PK data from the dose-escalation phase of the study. 
Part B is being initiated to obtain additional safety data, and assess the preliminary clinical 
activity profile of OBI-999 in patients with advanced solid tumors that have evidence of Globo 
H overexpression using a validated immunohistochemistry assay, and hence a potentially 
enhanced likelihood of seeing objective responses.  In addition to any cancer type with a Globo 
H H-score ≥ 100, gastrointestinal tumor types with reasonable frequencies of Globo H 
overexpression, based on available tissue microarray samples, were selected for evaluation, 
including pancreatic and colorectal cancer.  


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4.5.2 
Rationale for Dose Selection 
4.5.2.1 
Selection of Doses for Dose Escalation (Part A) 
The dose levels for Part A resulted from calculations based on data from preclinical studies and 
knowledge of the DLTs and recommended doses for other MMAE-based ADCs.  The first-in-
human starting dose was determined by using 1/6th the human equivalent dose (HED) of the 
HNSTD observed in non-human primates.  The HNSTD in cynomolgus monkeys was 10 
mg/kg, equivalent to a HED of 3.24 mg/kg.  One sixth of this is equal to 0.54 mg/kg.  To be 
conservative, an additional safety margin was applied and the initial dose chosen for this study 
was 0.4 mg/kg administered on Day 1 of every 21-day cycle.   
Based on FDA feedback (Pre-Investigational New Drug Application #143960 Meeting Request 
Written Responses, dated 12 June 2019), the dose levels of OBI-999 that were to be evaluated 
in Part A (0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg [capping calculations at a maximum of 100 kg]) 
were similar to the dose ranges used by other MMAE-bearing ADCs.   
4.5.2.2 
Selection of the Recommended Phase 2 Dose 
As of 02 June 2021, the Dose-Escalation Phase of this study was completed after enrolling a 
total of 15 patients with diverse solid tumors, including 3 patients each for Cohorts 1, 2, and 4 
(0.4, 0.8 and 1.6 mg/kg), and 6 patients for Cohort 3 (1.2 mg/kg). Patients were treated with 
OBI-999 on Day 1 of a 21-day cycle. 
All 3 patients in Cohort 4 (1.6 mg/kg) developed Grade 4 neutropenia, with details as follows: 
• Patient U01-016 had Grade 4 neutropenia (preferred term neutropenia) that was 
serious and met DLT criteria (lasting greater than 7 days). 
• Patient U01-018 had Grade 4 neutropenia (preferred term neutropenia) which was 
serious, required hospitalization, and was accompanied by Grade 4 acute kidney 
injury, Grade 4 respiratory distress, Grade 4 hypocalcemia, and Grade 4 multi-organ 
failure. All of these events were considered related to study therapy. The patient was 
discontinued due to clinical progression of the disease. 
• Patient U01-017 had Grade 4 neutropenia (preferred term neutropenia) which was 
serious and required hospitalization. 
All 3 events of Grade 4 neutropenia were considered likely related to OBI-999, with 1 event 
meeting the DLT criteria (Patient U01-016).  Based on these findings, the 1.6 mg/kg dose level 
was considered to have exceeded the MTD. 
Based on the design of the Dose-Escalation Phase, 3 additional patients (total of 6 patients) 
were enrolled at the next lower dose level (Cohort 3; 1.2 mg/kg) to confirm the MTD and 
establish the RP2D.  In Cohort 3 (1.2 mg/kg), no events of Grade 4 neutropenia were observed, 
none of the 6 patients had a DLT, and administration of 1.2 mg/kg OBI-999 was generally well 
tolerated.   
Pharmacokinetic results revealed that OBI-999 exhibited nonlinear clearance at doses lower 
than 1.2 mg/kg.  The exposure of the active metabolite, MMAE, was extremely high at a dose 
of 1.6 mg/kg and generally comparable at doses less than or equal to 1.2 mg/kg (Table 4-1).  


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Based on these findings, 1.2 mg/kg administered on Day 1 of a 21-day cycle was selected as 
the RP2D.  This dose allows for effective dose reduction in Part B (Expansion Cohort) in the 
event that unacceptable toxicities are observed at the RP2D. 
Table 4-1 
Pharmacokinetic Summary – Part A of OBI-999-001 
MMAE 
OBI-999 
Cohort 
Dose 
Tmax 
Cmax 
AUC 
T1/2 
Cmax 
AUC 
Cl 
T1/2 
Vd 
(mg/kg) 
(d) 
(ng/mL) 
(ng*d/mL) 
(d) 
(μg/mL) 
(μg*d/mL) 
(L/day) 
(d) 
(L) 
1 
0.4 
0.79 
2.7 
12.5 
2.66 
5.9 
6 
5.3 
1.8 
8.2 
2 
0.8 
0.38 
3.9 
16.5 
3.51 
11.3 
15.8 
4.2 
3.9 
8 
3 
1.2* 
0.59 
3.9 
16.6 
2.96 
20.6 
29.9 
2.8 
3.6 
6.8 
4 
1.6 
2.79 
7.6 
53.6 
3.09 
33.7 
60.4 
2.6 
2 
5.7 
*data calculated from 5 subjects dosing at 1.2 mg/kg. 
5 
Study Objectives and Endpoints 
5.1 
Study Objectives 
5.1.1 
Primary Objectives 
The primary objectives are:  
• To determine the safety and tolerability of OBI-999 when administered IV to patients 
with advanced solid tumors. 
• To determine the MTD and RP2D of OBI-999. 
5.1.2 
Secondary Objectives 
The secondary objectives are:  
• To evaluate the preliminary clinical activity profile of OBI-999 (objective response 
rate [ORR], clinical benefit rate [CBR], duration of response [DOR], and 
progression-free survival [PFS]). 
• To evaluate the immunogenicity of OBI-999 (anti-drug antibodies [ADAs]). 
• To determine the serum PK of OBI-999 and its active metabolite MMAE. 
5.1.3 
Exploratory Objectives 
The exploratory objective is:  
• To explore potential predictive biomarkers of OBI-999 activity. 


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5.2 
Study Endpoints 
5.2.1 
Part A – Dose Escalation 
5.2.1.1 
Primary Endpoints 
• Adverse events (AEs)/serious adverse events (SAEs) and laboratory abnormalities as 
graded by National Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI CTCAE) version 5.0. 
• DLTs with OBI-999.  
• MTD and RP2D of OBI-999. 
5.2.1.2 
Secondary Endpoint 
• PK parameters of OBI-999 and its active metabolite MMAE. 
5.2.1.3 
Exploratory Endpoint 
• Potential predictive biomarkers for OBI-999 activity such as expression of Globo H 
and other tumor-associated glycans or tumor molecular phenotypes. 
5.2.2 
Part B – Expansion Cohort 
5.2.2.1 
Primary Endpoints 
• Percentage of patients with objective response, clinical benefit, DOR and PFS 
according to RECIST 1.1. 
• Percentage of patients with ADAs in blood. 
5.2.2.2 
Secondary Endpoints 
• AEs/SAEs and laboratory abnormalities as graded by NCI CTCAE version 5.0. 
• PK parameters of OBI-999 and its active metabolite MMAE. 
5.2.2.3 
Exploratory Endpoints  
• Potential predictive biomarkers for OBI-999 activity such as expression of Globo H 
and other tumor-associated glycans or tumor molecular phenotypes. 
6 
Investigational Plan 
6.1 
Description of Overall Study Design and Plan 
This is a Phase 1/2, open-label, dose-escalation, and cohort-expansion study of OBI-999, an 
ADC-targeting Globo H in patients with advanced solid tumors.  
This is a 2-part study.  Part A (Dose-Escalation) is designed to establish the MTD and RP2D of 
OBI-999 as monotherapy.  Part B (Cohort-Expansion) is intended to further characterize the 
safety and preliminary clinical activity profile of the RP2D of OBI-999 in patients with 
advanced solid tumors. 


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Safety Review Committee (SRC) meetings were conducted throughout Part A of the study. The 
SRC reviewed the safety data (AEs and laboratory toxicities) of each lower level dose cohort 
before proceeding to the next dose level during Part A.  At the end of Part A, the SRC reviewed 
the safety and PK data to confirm the MTD and establish the RP2D before start of Part B, as 
specified in a separate charter.  
During Part B, the SRC will continue to monitor the severity and frequency of acute and 
cumulative toxicities at regular intervals, e.g., every 3 months, to ensure acceptable tolerability 
of the selected RP2D and of the effectiveness of dose modification rules. 
6.1.1 
Part A – Dose-Escalation 
Up to 30 eligible patients with advanced solid tumors will be enrolled in Part A.  No Globo H 
expression testing will be required for inclusion. 
Five cohorts of escalating dose levels of 0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg (capping calculations 
at a maximum of 100 kg) OBI-999 were planned to be enrolled and assessed using a 3+3 design 
to identify the MTD and RP2D.  The RP2D of OBI-999 was determined to be 1.2 mg/kg 
(capping administered dose to a maximum of 120 mg for 100 kg) administered on Day 1 of 
each 21-day cycle.  
Three patients were enrolled at the lowest dose level.  If none of the 3 patients experienced a 
DLT in the first 21-day cycle, the next cohort of 3 patients was enrolled at the next higher dose 
level.  If 1 of 3 patients in the initial dose cohort experienced a DLT, that cohort was expanded 
to 6 patients.  If only 1 of these 6 patients had a DLT, the next cohort of 3 patients was enrolled 
at the next higher dose level.  If 2 or more patients of the 3-6 patients in a cohort experienced a 
DLT, dose-escalation ceased, and the lower dose level was designated the MTD, where no more 
than 1 of 6 patients experienced at DLT.  New patients were enrolled at the previous lower 
(tolerated) dose level until that cohort had 6 patients.  This lower dose level was considered the 
MTD if ≤1 in 6 patients had a DLT.   
A patient who withdraws from the study within the DLT evaluation period for reasons other 
than drug-related AE will be replaced.  
Escalation to higher OBI-999 dose cohorts is not permitted during the study.  After a DLT is 
experienced by a patient, dose interruption, modifications, or dose delays may apply, as per 
Investigator judgement (refer protocol Section 8.3). 
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs 
first.   
6.1.1.1 
Stopping Rules 
The Sponsor, Investigator (following consultation with the Sponsor), or regulatory officials 
(regulatory agency or an Institutional Review Board [IRB]/ Independent Ethics Committee 
[IEC]) have the right to prematurely discontinue or suspend the study or investigational site at 
their discretion, at any time; if study and/or site conditions warrant. This action may be taken 
after appropriate consultation among the Sponsor, Investigator, and clinical monitor. The 
reasons for such action may include, but are not limited to the following: 
• Safety concerns, such as more than one third of the patients within a dose cohort have 
one of the following: 


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o ≥ Grade 3 systemic infusion reactions (despite pre-medication),  
o Grade 4 DLTs (Refer to Section 6.2), or  
o Related SAEs (Refer to Section 8.2.3 & Section 8.3.1.1) 
• The Investigator does not comply with the protocol, Good Clinical Practice (GCP), 
and/or any contract between the Investigator and Sponsor, including Contract Research 
Organizations (CROs) and subsidiaries thereof 
In the circumstance of such an event, the Sponsor reserves the right to halt and review this study 
and will discuss with the Investigator (including the reasons for taking such action) about dose 
modification, amendment to protocol, or study stopping. Final decision about continuing, 
termination or any other change in the study would remain with the Sponsor. 
6.1.2 
Part B – Cohort-Expansion 
Up to 57 additional patients with advanced solid tumors that have high Globo H expression 
(defined as an H-score ≥ 100 using a validated IHC assay) will be enrolled in Part B using a 
Simon’s two-stage cohort expansion design.  Part B will be conducted to obtain additional 
safety data, characterize the PK profile of OBI-999, and obtain a preliminary assessment of the 
clinical activity profile of OBI-999 in Globo H expressing advanced solid tumors.  
Patients enrolled in Part B will receive the RP2D dose of 1.2 mg/kg (capping calculations at a 
maximum of 100 kg) OBI-999 on Day 1 of each 21-day cycle.  
The following 3 cohorts of patients who have high expression of Globo H by a qualified 
laboratory assessment (Globo H H-score ≥ 100 using a validated IHC assay) will be enrolled in 
Part B.  
• Cohort 1:  Pancreatic cancer 
• Cohort 2:  Colorectal cancer 
• Cohort 3:  Basket (any solid tumor type other than those included in Cohorts 1 and 2) 
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs 
first.   
6.1.3 
Duration of Study 
The study (Parts A and B) will include a screening period (up to 28 days), a treatment period, 
and a follow-up period.   
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs 
first.  Patients will be followed up to the 24-week scheduled response assessment for the 
purposes of counting objective responses for Simon’s two-stage design success criteria. 
The safety follow-up visit will be conducted 28 days after the last dose of study treatment. 


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6.2 
Definition of Dose-Limiting Toxicities (Part A only) 
A DLT is defined as the occurrence of any of the following events, within the first cycle of 
treatment that is considered to be at least possibly related to OBI-999: 
• Grade 4 neutropenia lasting more than 7 days. 
• Febrile neutropenia. 
• Grade 4 thrombocytopenia. 
• Grade 3 thrombocytopenia with ≥ Grade 2 bleeding requiring platelet transfusions. 
• Grade 3 fatigue, nausea and vomiting or diarrhea that does not resolve to Grade 1 or 
Baseline within 72 hours despite optimal supportive care. 
• Any Grade 4 gastrointestinal (GI) toxicity. 
• Any other Grade 3 or Grade 4 non-hematological toxicity (except Grade 3 fatigue, 
nausea, vomiting, or diarrhea lasting <24 hours with optimal therapy, Grade 3 
non-hematologic laboratory abnormalities that resolve to Grade 1 or Baseline within 
14 days). 
All AEs unless they are determined to be not related to study drug will be taken into 
consideration in determining DLTs.  NCI CTCAE version 5.0 will be the basis for the 
descriptive terminology and grading of AEs.  The period for DLT observation is 21 days from 
the start of first dose of OBI-999 (i.e., Day 1).   
6.3 
Discussion of Study Design 
This study will be undertaken in patients with advanced cancer that has progressed on prior 
therapy.  In this setting, patients will be seeking to alleviate symptoms of their fatal disease and 
prolong life through exposure to a novel agent.  
Patient safety, and a favorable risk/benefit balance, will be carefully monitored throughout and 
after treatment.  Additionally, attention will be taken to enroll only patients who are felt to be 
in sufficient condition to undertake this clinical trial, as defined by adequate performance status, 
suitable baseline organ function, and the Investigator’s determination that there are no 
significant comorbid conditions which present undue risk.  Nevertheless, unexpected toxicity 
of the investigational drug may occur, and all patients will have informed consent prior to 
treatment. 
7 
Selection and Withdrawal of Patients 
7.1 
Inclusion and Exclusion Criteria 
7.1.1 
Inclusion Criteria 
Patients must meet all of the following criteria in order to be included in the study (for both 
Parts A and B unless specified otherwise): 
1. Male or female patients, 18 years of age or older at the time of consent. 
2. Provide written informed consent prior to performing any study-related procedure. 
3. Histologically or cytologically confirmed patients with advanced solid tumors. 


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4. Patients must have been treated with established standard-of-care therapy, or physicians 
have determined that such established therapy is not sufficiently efficacious, or patients 
have declined to receive standard-of-care therapy. In the latter case, the informed 
consent must state the effective therapies the patient is declining. 
5. Measurable disease (i.e., at least one measurable lesion per RECIST 1.1) 
(Eisenhauer, et al., 2009). 
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 
(Oken, et al., 1982).  
7. Adequate organ function defined as: 
a. Hepatic: 
i. Serum ALT ≤3 × upper limit of normal (ULN), ≤5 × ULN in the presence of 
liver metastases 
ii. Serum AST ≤3 × ULN, ≤5 × ULN in presence of liver metastases 
iii. Serum bilirubin 1.5 × ULN (unless due to Gilbert’s syndrome or hemolysis) 
b. Renal: 
i. Creatinine clearance >50 mL/minute using Cockcroft Gault equation 
c. Hematologic: 
i. Absolute neutrophil count ≥1,500/µL 
ii. Platelets ≥100,000/µL 
iii. Hemoglobin ≥8 g/dL  
8. Patient is willing and able to comply with all protocol-required assessments, visits, and 
procedures, including a pretreatment tumor biopsy.  Archival tumor biopsies are 
acceptable at baseline.  
9. Females of childbearing potential must have negative serum pregnancy test prior to 
starting study therapy, and agree to use a reliable form of contraceptive during the study 
treatment period and for at least 120 days following the last dose of study drug.   
Patient not of childbearing potential (i.e., permanently sterilized, postmenopausal) can 
be included in study.  Postmenopausal is defined as 12 months with no menses without 
an alternative medical cause.  
Male patients must agree to use an adequate method of contraception during the study 
treatment period and for at least 120 days following the last dose of study drug. 
10. Cannot be breast feeding. 
11. Patients with human immunodeficiency virus (HIV) infection are eligible if CD4+ 
T-cell counts  350 cells/L; patients on antiretroviral therapy (ART) should be on an 
established dose for at least 4 weeks and have an HIV viral load less than 400 copies/mL 
prior to enrollment. 
12. Patients with serological evidence of chronic hepatitis B virus (HBV) infection are 
eligible if they have an HBV viral load below the limit of quantification with or without 
concurrent viral suppressive therapy. 
13. Patients with a history of hepatitis C virus (HCV) infection should have completed 
curative antiviral treatment and have a viral load below the limit of quantification.  


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14. Patients in Part B (Cohort-Expansion) must have documented Globo H H-score ≥ 100 
from a qualified laboratory IHC assay in one of the following tumor types to be enrolled 
in the respective cohort: 
• Cohort 1:  Pancreatic cancer 
o Histopathologically confirmed patients with metastatic adenocarcinoma of the 
pancreas. 
• Cohort 2:  Colorectal cancer 
o Histopathologically confirmed patients with metastatic colorectal 
adenocarcinoma.  
• Cohort 3:  Basket (any solid tumor type other than those included in Cohorts 1 and 
2) 
o Histologically or cytologically confirmed patients with advanced solid tumors. 
7.1.2 
Exclusion Criteria 
Patients meeting any of the following criteria are ineligible to participate in this study: 
1. Less than 3 weeks from prior cytotoxic chemotherapy or radiation therapy; and less than 
5 half-lives or 3 weeks, whichever is shorter, from prior biologic therapies, prior to the 
first dose of OBI-999. 
2. Has undergone a major surgical procedure (as defined by the Investigator) or significant 
traumatic injury within 28 days prior to the first dose of OBI-999. 
3. Sensory or motor neuropathy of Grade 2 or greater. 
4. Patients with a history of solid organ transplant. 
5. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to 
Grade 0 or 1 (using NCI CTCAE version 5.0), except for alopecia and laboratory values 
listed in the inclusion criteria. 
6. Receipt of any prior therapy targeting Globo H. 
7. Known hypersensitivity to OBI-999 or its excipients. 
8. Has known untreated central nervous system metastases.  Patients with treated brain 
metastases are eligible if there is no evidence of progression for at least 4 weeks after 
CNS-directed treatment, as ascertained by clinical examination and brain imaging 
(magnetic resonance imaging [MRI] or computed tomography [CT]) during the 
screening period.  
9. Has significant clinical cardiac abnormality (e.g., clinical heart failure or unstable 
angina).  
10. Any medical co-morbidity that is life-threatening or, in the opinion of the Investigator, 
renders the patient unsuitable for participation in a clinical trial due to possible 
noncompliance, would place the patient at an unacceptable risk and/or potential to affect 
interpretation of results of the study. 
11. Is receiving any concurrent prohibited medication as listed in Section 8.6.3. 


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7.2 
Treatment Discontinuation and Withdrawal of Patients 
A patient who withdraws from the study within the DLT evaluation period for reasons other 
than drug related AE will be replaced.  
A patient may voluntarily withdraw or be withdrawn from the study treatment at any time for 
reasons including, but not limited to, the following: 
• Progressive disease. 
• Grade 4 infusion reactions and OBI-999-related toxicity.  
• Dose reductions required on more than 2 occasions for toxicity related to OBI-999.  
• Treatment interruption for more than 2 consecutive doses for related or unrelated 
reasons. 
• Patient withdrawal of consent:  At any time, a patient's participation in the study may 
be terminated at his/her request or on the basis of the Investigator’s clinical judgment.   
• Inter-current illness:  A condition, injury, or disease unrelated to the primary diagnosis 
that becomes apparent during treatment and necessitated the patient's termination from 
the study. 
• General or specific changes in the patient's condition that renders him/her ineligible 
for further treatment according to the inclusion/exclusion criteria. 
• Protocol deviation:  The patient’s findings or conduct fail to meet the protocol entry 
criteria or fail to adhere to the protocol requirements (e.g., drug noncompliance, failure 
to return for defined number of visits) such that the Sponsor and the Investigator agree 
that the deviation necessitates premature termination from the study. 
• Lost to follow-up:  The patient stops coming for visits, and study personnel are unable 
to contact the patient. 
7.3 
Follow-Up for Drug Discontinuation/Patient Withdrawal from 
Study 
If a patient discontinues study treatment and is withdrawn from the study for any reason, the 
study site must immediately notify the Sponsor. The date and the reason for study treatment 
discontinuation / study withdrawal must be recorded on the electronic case report form (eCRF).  
Patients who withdraw prematurely are to attend an early termination visit, if possible, and 
complete all assessments. 
In the event that a patient discontinues prematurely from the study due to a treatment-emergent 
adverse event (TEAE) or serious TEAE, the TEAE or serious TEAE will be followed until it 
resolves (returns to normal or baseline values) or stabilizes, or until it is judged by the 
Investigator to be no longer clinically significant.   
Once a patient is withdrawn from the study, the patient may not re-enter the study. 


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8 
Treatments 
8.1 
Details of Study Treatment 
OBI-999 is an ADC composed of a Globo H-targeting humanized IgG1 mAb (OBI-888; 
IND #136,961), which is covalently linked to MMAE by a cathepsin B protease cleavable 
linker.  Globo H is a TACA. 
OBI-999 drug product (DP) liquid is packaged in a single-use 10 mL transparent borosilicate 
type 1 glass vial for IV infusion.  Each vial of OBI-999 DP liquid contains 5 mL of 5 mg/mL 
OBI-999 drug substance (DS) in a pH 6.0 solution formulated with 25 mM sodium citrate, 
150 mM Arginine, and 0.02 % (w/v) Polysorbate 80.  OBI-999 DP is diluted to the appropriate 
concentration in 0.9 % sodium chloride or 5% glucose prior to administration by IV infusion. 
All study drug will be supplied by OBI Pharma Inc., and must remain under adequate security 
and proper storage conditions.  Do not use study drug after the expiration date, which is 
imprinted on the drug container. 
The OBI-999 DP should be administered to the study subjects within 4 hours of reconstitution 
at room temperature. Overall storage of the DP material should not exceed 8 hours at room 
temperature. Refer to Appendix 1 for details of dispensing, volume needed, mixing and 
reconstitution of OBI-999. 
8.1.1 
Packaging and Labeling 
OBI-999 drug product will be packaged in carton boxes.  Each box will contain ten OBI-999 
vials.  The labels on each kit will meet the applicable regulatory requirements for each country. 
OBI-999 will be packaged and labeled according to current Good Manufacturing Practices 
(GMP) guidelines.  Details of the packaging and labeling are provided in the Pharmacy Manual.  
8.1.2 
Storage 
OBI-999 drug product must be stored at a temperature of 2 to 8°C.   
8.2 
Treatment Regimen 
8.2.1 
OBI-999 Doses 
For Part A (Dose-Escalation), OBI-999 was planned to be given at doses of 0.4, 0.8, 1.2, 1.6, 
and 2.0 mg/kg (capping calculations at a maximum of 100 kg) using a 3+3 design to identify 
the MTD and RP2D. 
For Part B (Cohort-Expansion), OBI-999 will be given at the RP2D of 1.2 mg/kg (capping 
administered dose to a maximum of 120 mg for 100 kg).  
8.2.2 
OBI-999 Administration 
OBI-999 investigational drug solution (OBI-999 drug product mixed with saline/glucose 
infusion solution) will be administered on Day 1 of each 21-day cycle by the site staff.  The 
infusion should be given for a duration of approximately 60 minutes (± 10 minutes), for the 
initial 2 cycles (Cycle 1 and Cycle 2).  The infusion duration for Cycles 3 and beyond may be 
reduced, at the Investigator’s discretion, to 30 minutes if no infusion related AEs occur during 
the first 2 cycles. 


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Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, 
or for up to 35 cycles (approximately 2 years), whichever occurs first.  
8.2.3 
Prophylactic Measures 
Approximately 30 to 60 minutes prior to OBI-999 administration, all patients should receive 
prophylactic treatment for infusion reactions.  Prophylactic treatments include acetaminophen 
orally and diphenhydramine (or equivalent) orally or IV (recommended doses are: 
acetaminophen 650 mg, diphenhydramine 50 mg).  If an alternative premedication regimen is 
thought to be required, Sponsor approval should be sought.  
For patients who experience an infusion reaction despite initial premedication, additional 
prophylactic treatment may be added prior to subsequent doses, including an H2 blocker such 
as ranitidine, and/or corticosteroids.   
Prophylactic treatment for infusion reactions may be withheld at the Investigator’s discretion if 
no infusion reactions were observed with the first cycle of treatment.  Additional details are 
provided in Section 8.3.1.1. 
8.3 
Dose Modifications and Toxicity Management 
Escalation to a higher OBI-999 dose cohort is not permitted during the study.  
Dose modifications for hematologic toxicity, non-hematologic toxicity, and infusion reactions 
should be independently assessed at each visit.  Recommendations for dose modifications for 
toxicity are provided in Table 8-1. 
Table 8-1 
OBI-999 Dose Modifications for Toxicity 
Toxicity 
Hold Dose 
% of Full Dose after 
Recovery to Grade 0-1 
Grade 1 
Do not hold dose 
100 
Grade 2 
Hold dose until resolution to Grade 0 or 1 
75 
Grade 3 
Hold dose until resolution to Grade 0 or 1 
75 
Grade 4 
Treatment should be discontinued 
Not applicable 
Once the dose has been reduced for toxicity and found to be well tolerated, re-escalation may 
be permitted at the Investigator’s discretion.  If a patient requires dose reductions on more than 
2 occasions for toxicity related to OBI-999, the patient should discontinue from the study. 
All reasons for treatment modifications should be fully explained.  
The study drug dose which is not administered within the permitted window period of ±3 days, 
must be skipped, and the next dose will be administered as per protocol schedule. Any skipped 
dose due to safety reason and if medically justified, for OBI-999 treatment related or unrelated 
reasons, will not be captured as a protocol deviation for this study.  
Treatment interruption for more than 2 consecutive doses for related or unrelated reasons may 
necessitate discontinuation of study treatment. 
Treatment interruption for intercurrent non-treatment related AEs will be at the Investigator’s 
discretion and based on the well-being of the patient.  All reasons for treatment interruption and 


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delays should be fully explained.  Treatment for hematologic and non-hematologic toxicity may 
be implemented as clinically indicated according to institutional guidelines.  Refer Table 8-2 
for therapeutic antiemetic and anti-diarrheal recommendations. 
Table 8-2 
Therapeutic Antiemetic and Anti-Diarrheal Recommendations 
Diarrhea and Abdominal Cramping 
Nausea, Vomiting, or Anorexia 
Dicyclomine: Recommended when the predominant 
issue is cramping or abdominal pain 
1st line: 5HT3-inhibitors 
Diphenoxylate/Atropine 
or/and 
Loperamide 
2nd-line: Dexamethasone, ideally in 
combination with a 5HT3-inhibitor. Short 
term use can be very effective 
Other agents: anti-histamines; 
benzodiazepines; proton pump inhibitors; 
dopamine antagonists; cannabinoids 
Hyoscine: Anti spasmodic agents helpful for 
abdominal cramping 
 
Budesonide (Entocort EC): Corticosteroid with 
limited systemic absorption; 9 mg once daily for up 
to 8-12 weeks 
 
8.3.1 
Infusion Reactions 
Signs/symptoms of infusion reactions may include: allergic reaction/hypersensitivity (including 
drug fever); arthralgia (joint pain); bronchospasm; cough; dizziness; dyspnea (shortness of 
breath); fatigue (asthenia, lethargy, malaise); headache; hypertension; hypotension; myalgia 
(muscle pain); nausea; pruritic/itching; rash/ desquamation; rigors/chills; sweating 
(diaphoresis); tachycardia; tumor pain (onset or exacerbation of tumor pain due to treatment); 
urticaria (hives, welts, wheals); and vomiting. 
In the event of an infusion reaction, additional serum/plasma samples may be drawn at the time 
of the event to evaluate drug concentration and ADA, as well as to assess levels of cytokines 
and/or other markers of inflammation. 
8.3.1.1 
Management of Infusion Reactions 
As stated in Section 8.2.3 all patients will receive prophylaxis prior to the first dose of treatment. 
If no infusion reactions occur with prophylactic treatments, these may be withheld for 
subsequent doses at the Investigator’s discretion. Prophylactic treatment as described in 
Section 8.2.3 should be resumed for all future doses if subsequent dosing without prophylaxis 
is associated with infusion reactions. 
In the event of an infusion reaction, the OBI-999 infusion should be interrupted and medical 
therapy administered according to institutional standard of care.  
Patients who experience a Grade 1 or Grade 2 infusion reaction may resume the infusion of 
drug at a reduced infusion rate (30% to 50% slower than initial rate) on the same day following 
appropriate medical management, as long as this falls within the 4-hour drug administration 
window (see Section 8.1 and Appendix 1).  If the 4-hour window from product reconstitution 
is exceeded, new drug may be prepared to administer the remainder of the planned dose. 


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Patients who experience a Grade 3 infusion reaction may be retreated at the discretion of the 
Investigator at the next scheduled treatment.  Such patients should receive additional 
premedication that may include an acetaminophen, an antihistamine, or a corticosteroid. 
Patients should be followed for at least 4 hours and until resolution of the infusion reaction. In 
person or telephonic follow up the next day should also be arranged to ensure there are no 
recurrent symptoms. Patients should also be instructed to contact study personnel if symptoms 
recur at later time points.  
OBI-999 should be permanently discontinued in patients who experience a life-threatening 
(Grade 4) infusion reaction. 
8.3.2 
Peripheral Neuropathy 
Signs/symptoms of peripheral neuropathy may include: hypoesthesia, hyperesthesia, 
paresthesia, discomfort, a burning sensation, neuropathic pain, or weakness. 
If peripheral neuropathy is observed, additional serum/plasma samples may be drawn at the 
time of the event to evaluate drug concentration and ADA, as well as to assess levels of 
cytokines and/or other markers of inflammation. 
Peripheral neuropathy is a known adverse event from MMAE-based ADCs and can be expected 
to occur with OBI-999. Therefore, specific assessment for signs and symptoms of peripheral 
neuropathy should be performed at each physical exam. Patients who develop peripheral 
neuropathy should be followed until resolution in order to define the time to resolution of the 
neuropathy. 
Additionally, non-symptomatic patients will continue to be monitored for possible signs and 
symptoms of peripheral neuropathy as part of the Safety Follow-Up period. 
8.3.2.1 
Management of Peripheral Neuropathy 
For new or worsening Grade 2 or 3 peripheral neuropathy, OBI-999 dosing should be held until 
neuropathy improves to Grade 1 or baseline.  OBI-999 dosing may be restarted at a reduced 
dose (75% of the full dose; see Table 8-1).   
For Grade 4 peripheral neuropathy, OBI-999 should be permanently discontinued.  
8.4 
Study Treatment Assignment 
During Part A, patients were assigned to a dose level in the order of study entry. 
During Part B, all patients will receive a dose level of 1.2 mg/kg (capping administered dose to 
a maximum of 120 mg for 100 kg) of OBI-999.  
8.5 
Treatment Accountability and Compliance 
All drug supplies will be provided by the Sponsor.  Administration of study drug will be 
supervised by study personnel to ensure compliance.  


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8.6 
Prior and Concomitant Illnesses and Medications 
8.6.1 
Prior and Concomitant Illnesses 
Investigators should document all prior significant illnesses that the patient has experienced 
prior to screening.  Additional illnesses present at the time when informed consent is given and 
up to the time of first dosing are to be regarded as concomitant illnesses.  Illnesses first occurring 
or detected during the study and/or worsening of a concomitant illness during the study are to 
be documented as AEs on the eCRF. 
8.6.2 
Prior and Concomitant Medications 
All medications and other treatments taken by the patient prior to the start of the study at 
screening and treatments initiated during the study, must be recorded on the eCRF.  The entry 
must include the dose, regimen, route, indication, and dates of use. 
After the baseline visit, medication to treat minor illness(es) are generally permitted, including: 
• Use of localized palliative radiation for pre-existing lesions to control pain, at the 
discretion of the physician. 
• Corticosteroids use: topical, inhaled, ophthalmologic, intra-articular, or intranasal 
corticosteroids; systemic steroids at physiologic doses not to exceed 10 mg/day of 
prednisone or equivalent.  For management of side effects including nausea or infusion 
reactions, intermittent prophylactic or therapeutic use of glucocorticoids is allowed at 
doses required for medical therapy administered according to institutional standard of 
care and at the Investigator’s discretion. 
8.6.3 Prohibited Medications 
If there is a clinical indication for the use of one of the following prohibited medications, then 
discontinuation from the study drug may be required. 
• Anti-neoplastic therapy, whether approved or experimental, including but are not 
limited to: chemotherapy, immunotherapy, surgery, radiotherapy are not allowed with 
OBI-999.  NOTE:  Use of localized palliative radiation for pre-existing lesions to 
control pain may be allowed at the discretion of the physician. 
• Immunosuppressive therapy (e.g., cyclosporine, rapamycin, tacrolimus, 
cyclophosphamide, methotrexate, etc.). 
• Systemic steroids of >10 mg/day prednisone or equivalent  
• Any other concurrent investigational therapy, regardless of indication. 
• Strong inhibitors or inducers of CYP3A (see Appendix 2) 
• Clinical inhibitors of P-glycoprotein (see Appendix 3) 


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9 
Study Procedures 
Table 9-1 outlines the timing of procedures, and assessments to be performed throughout the 
study.   
Table 9-2 and Table 9-3 outline the PK and ADA Sampling Schedules in Part A and Part B, 
respectively. 
9.1 
Patient Informed Consent 
Prior to performing any study-related procedures, the Investigator (or his/her designated staff 
member) will obtain written informed consent from the patient. A separate biospecimen consent 
(pre-screening) for Globo H testing may be utilized in order to ensure that eligibility criterion 
is met for Part B patients prior to consenting the subject for the remaining eligibility-related 
procedures. This two-step consent process may streamline the screening process, ensuring 
timely availability of the Globo H result and avoiding having the patient consent for the 
remaining procedures until he/she is confirmed to have the requisite Globo H expression for 
study entry.  
9.2 
Procedures by Study Period 
Assessments and study procedures are to be performed as outlined in the Schedule of 
Assessments, Table 9-1.  The PK and ADA Sampling Schedules are provided in Table 9-2 
(Part A) and Table 9-3 (Part B).  
The Investigator may at his/her discretion arrange for a patient to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or an AE considered by the 
Investigator to be possibly related to the use of study drug.  The unscheduled visit page on the 
eCRF must be completed.  Additional visits to follow-up positive ADA may happen after end 
of study (Table 9-1).  
 




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EoS Visit is the safety follow-up visit, conducted 28±7 days after the last OBI-999 dose.  ET Visit lab assessments will be conducted for patients 
discontinuing study treatment, if last available tests are before 2 weeks.  
*The - 1 day window (1 day prior) for C1D1 is for safety laboratory assessments.  Blood can be drawn 1 day prior to initiation of study drug infusion on 
C1D1.  Safety laboratory results should be available and reviewed by the Investigator prior to the OBI-999 administration. 
Footnotes:  
a. Informed consent to be obtained before any other study procedures are performed. 
b. Medical history, including previous cancer therapies, cancer history, and past and ongoing concomitant illnesses which are relevant to the 
disease under study. 
c. A complete physical examination is required at screening and end of study/early termination. Directed physical examinations may be limited to 
problem focused review of symptoms and major organ systems. This should include an assessment for signs and symptoms of peripheral 
neuropathy as this is a known adverse event associated with MMAE-based ADCs and may be expected to occur with OBI-999. 
d. Height to be obtained at screening only. 
e. Vital signs include temperature, blood pressure and pulse. Temperature measurement will be obtained as clinically indicated. 
f. 
Performed by ophthalmologist as follows: 
• 
Part A - At screening, every 2 cycles for the first 6 months (C2, C4, C6, C8), then every 3 cycles thereafter (C11, C14 and so on), and 
the end of study/early termination visit.  
• 
Part B – At screening and at the discretion of the Investigator during the course of the study. 
g. ECOG performance status: at screening, D1 of each cycle, and end of study/early termination 
h. 12-lead ECG with assessment of QTcF: at screening, Cycle 1 Day 1, Cycle 1 Day 3 (48 2 hours after the end of the Cycle 1 Day 1 OBI-999 
infusion) and EoS/ET. The ECG testing on C1D4 could be tested 24 hours before but no later than C1D4. 
i. 
Pregnancy testing should be performed in females of childbearing potential only. A serum pregnancy test is required during screening. A urine 
or serum pregnancy test is acceptable end of study or early termination 
j. 
Tumor biopsy samples are mandatory at screening visit. Fresh (preferred) tissue or archival tissue is acceptable. A minimum of 5 slides are 
required for the central laboratory Globo H assay for determination of eligibility in Part B. Up to 10 unstained additional slides should be 
provided, depending on availability, for the protocol defined exploratory studies. 
k. Hematology and Serum chemistry (Laboratory Assessments: Table 12-1). Blood draw is prior to OBI-999 infusion. For C2D1 and each cycle 
after, laboratory assessments may be drawn 72 hours in an advance of infusion. 
Hematology: hematocrit, hemoglobin, erythrocyte count, white blood count, absolute counts of leukocytes, neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, and platelet count.  
Serum chemistry: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, phosphorus, magnesium, total 
protein, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, lactate dehydrogenase, total 
bilirubin, and uric acid. Creatinine clearance will be calculated by Cockcroft Gault equation at screen visit, week 1 and EoS/ET.  


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l. 
Coagulation, and Urinalysis (Laboratory Assessments: Table 12-1). Blood draw and urine collection is prior to OBI-999 infusion. Only 
urinalysis will be collected at Day 1 of Cycles 2-35. 
Coagulation: prothrombin time, activated partial thromboplastin time, and international normalized ratio.  
Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, nitrite, leukocyte esterase as assessed by dipstick. A 
microscopic urinalysis (only if needed) evaluating white blood cells, red blood cells, epithelial cells, bacteria, cast and crystals 
m. OBI-999 is given on Day 1 of each 21-day cycle until DLT, disease progression, unacceptable toxicity, or withdrawal of consent, whichever 
occurs earlier. 
n. Pharmacokinetic: (for analysis of serum concentration of OBI-999 total antibody, ADC and free MMAE). Detailed sampling schedule in Table 
9-2 (Part A) and Table 9-3 (Part B). 
o. Immunogenicity studies (ADA) - ADA samples will be collected. Detailed sampling schedule in Table 9-2 (Part A) and Table 9-3 (Part B). For 
patients with persistent antibodies at end of study, an additional ADA sample will be collected at 4 months after the end of study visit. 
p. Radiology (CT or MRI scan) evaluations of tumor response: Performed during screening and during the study every 6 weeks for the first 
3 months, and then every 9 weeks until discontinuation of study treatment, disease progression, death, or initiation of further systemic cancer 
therapy, including radiation therapy, whichever occurs earlier. CT or MRI scan will be performed within 1 week prior to the start of the next 
cycle. Unscheduled scan can be performed anytime, if needed to confirm disease progression. Radiology assessment for early 
termination/end of study, should ONLY be performed if ≥9 weeks have passed from the previous scheduled CT/MRI scan. Same assessment 
method and same technique should be used on each patient while on study.  






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10 
Clinical Activity Profile Assessments 
Radiology (CT or MRI scan) evaluations (±7 days) of tumor response are to be performed 
during screening within 28 days prior to Cycle 1 Day 1 (first dose of study medication), and 
thereafter during the study every 6 weeks for the first 3 months and then every 9 weeks until 
discontinuation of study treatment, disease progression, death, or initiation of further systemic 
cancer therapy, including radiation therapy.  Radiology assessment for end of study follow-up 
and early termination should be performed unless the patient already has radiographic 
confirmation of progressive disease ≤ 9 weeks prior to permanent discontinuation of study drug.  
The same assessment method and the same technique should be used on each patient while on 
study. 
An end-of-treatment radiology assessment should be performed unless the patient already has 
radiographic confirmation of progressive disease ≤ 9 weeks prior to permanent discontinuation 
of study drug.  The same assessment method and the same technique should be used on each 
patient while on study. 
Overall tumor response and progression will be evaluated by the Investigator according to 
RECIST 1.1.  
11 
Pharmacokinetics 
11.1 
Pharmacokinetic Sampling 
Blood samples for PK analysis of OBI-999 levels will be collected at the time points indicated 
in the Pharmacokinetic and ADA Sampling Schedules (see Table 9-2 [Part A] and Table 9-3 
[Part B]).  The actual date and time of each blood sample collection will be recorded.  The 
timing of PK samples may be altered and/or PK samples may be obtained at additional time 
points to ensure thorough PK monitoring. 
Details of PK blood sample collection, processing, storage, and shipping procedures are 
provided in a separate laboratory manual.  
11.2 
Pharmacokinetic Analytical Methodology 
The concentrations of OBI-999 total antibody, ADC, and MMAE will be determined from the 
serum samples using a validated analytical method.  Details of the method validation and 
sample analysis will be included with the final clinical study report.  
Pharmacokinetic parameters will be calculated using a non-compartmental method from the PK 
samples collected during Cycles 1 and 2 and will include but will not be limited to Cmax, AUC, 
elimination half-life (t1/2), clearance (Cl), time to reach maximum concentration (Tmax), and 
volume of distribution (Vd).   
Pharmacokinetic methods may also be applied to further investigate OBI-999 exposure 
(e.g., accumulation of OBI-999, presence of dose- or time-dependent OBI-999 PK behavior, 
verification of influential factors on OBI-999 PK). 


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12 
Safety Assessments 
Safety assessments (vital signs, physical examinations, electrocardiogram [ECG] recording, 
AEs, ECOG, ophthalmology, clinical laboratory results [routine hematology, serum chemistry, 
coagulation, and urinalysis], and immunogenicity [ADAs]) are to be performed at 
protocol-specified visits, as specified in the Schedule of Assessments, Table 9-1. 
12.1 
Vital Signs 
Vital signs (body temperature, heart rate, systolic, and diastolic blood pressure measurements) 
will be evaluated at the visits indicated in the Schedule of Assessments (Table 9-1).  All vital 
signs will be measured after the patient has been resting for at least 5 minutes.  Blood pressure 
measurements are to be taken in the same arm for the duration of the study.  Temperature 
measurement will be obtained as clinically indicated.  
Body weight (without shoes) will be recorded whenever vital signs are recorded, and height 
(without shoes) will be recorded at screening only. 
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur.  Out-of-range blood pressure, respiratory rate or heart rate measurements will be repeated 
at the Investigator’s discretion.  Any confirmed, clinically significant vital sign measurements 
must be recorded as AEs. 
12.2 
Physical Examination 
A complete physical examination (head, eyes, ears, nose, throat [HEENT], heart, lungs, 
abdomen, skin, cervical and axillary lymph nodes, neurological, and musculoskeletal systems) 
will be performed at screening and early termination.  Medical history will be recorded at 
screening, including smoking history, if applicable. 
A limited physical examination to verify continued patient eligibility and to follow up any 
change in medical history will be performed at the visits indicated in the Schedule of 
Assessments (Table 9-1).  Symptom-driven limited physical examinations will be performed as 
clinically indicated at any study visit.  All changes not present at baseline or described in the 
past medical history and identified as clinically noteworthy must be recorded as AEs.   
Physical examinations should include an assessment for signs and symptoms of peripheral 
neuropathy as this is a known adverse event associated with MMAE-based ADCs and may be 
expected to occur with OBI-999. 
As potential retinal and corneal findings were observed at the highest dose in the rat multiple 
dose toxicology study, ophthalmology examinations will be conducted as indicated in the 
Schedule of Assessments (Table 9-1) to document any treatment-emergent changes. 
Medical history will include previous cancer therapies, cancer history, and past and ongoing 
concomitant illnesses.  
12.3 
Electrocardiogram 
A 12-lead resting ECG will be obtained at the visits indicated in the Schedule of Assessments 
(Table 9-1). 


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At screening, the Investigator will examine the ECG traces for signs of cardiac disease that 
could exclude the patient from the study.  An assessment of normal or abnormal will be recorded 
and if the ECG is considered abnormal, the abnormality will be documented on the eCRF.  
ECGs will be repeated if clinically significant abnormalities are observed or artifacts are 
present. 
Additionally, a 12-lead resting ECG will be obtained in order to assess QTcF on Cycle 1 Day 1 
prior to study drug infusion and on Cycle 1 Day 3 (48 ± 2 hours after the end of the study drug 
infusion on Day 1).  If the QTcF increases above the upper limit of normal or if it increases on 
Day 3 more than 10 msec greater than at baseline, then repeat ECG testing for QTcF assessment 
should be performed prior to and 48 ± 2 hours after then next OBI-999 dose. 
12.4 
Laboratory Assessments 
Laboratory assessment samples (Table 12-1) are to be obtained at designated visits as detailed 
in the Schedule of Assessments (Table 9-1). 


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Table 12-1 
Laboratory Assessments 
Hematology 
Serum chemistry 
Urine analysis (dipstick) 
• Hemoglobin (Hb) 
• Hematocrit 
• Mean corpuscular 
hemoglobin (MCH) 
• Mean corpuscular 
hemoglobin concentration 
(MCHC) 
• Mean corpuscular volume 
(MCV) 
• Platelet count 
• Red blood cell (RBC) count 
• White blood cell (WBC) 
count with differential  
• Albumin 
• Alanine aminotransferase 
(ALT) 
• Alkaline phosphatase (ALP) 
• Aspartate aminotransferase 
(AST) 
• Blood urea nitrogen (BUN) or 
Urea 
• Bicarbonate 
• Creatinine 
• Creatine kinase 
• Electrolytes (Na, K, Cl, Ca, P, 
Mg) 
• Glucose 
• Lactate dehydrogenase (LDH) 
• Total bilirubin 
• Total protein 
• Uric acid 
• Appearance 
• Blood 
• pH 
• Protein 
• Glucose 
• Ketones 
• Nitrite 
• Leukocyte esterase 
• Specific gravity 
• Urine human chorionic 
gonadotropin (HCG) 
(pre-menopausal females 
only)  
• Urobilinogen 
• Bilirubin 
• Microscopic, as needed 
Coagulation 
Pregnancy test 
 
• Prothrombin time (PT) 
• International Normalized 
Ratio (INR) 
• Activated partial 
thromboplastin time (aPTT) 
To be performed on all female 
patients of child-bearing 
potential at the screening visit 
and early termination visit. 
 
Routine safety laboratory testing will be performed at the local laboratory following the 
laboratory’s guidelines.  Pharmacokinetic samples, ADAs, and biomarkers will be analyzed at 
a central laboratory facility.  Urine samples will be analyzed by dipstick, and a microscopic 
analysis will be performed if the results of dipstick indicate abnormalities to be further 
investigated.  All laboratory reports must be reviewed, signed, and dated by the Investigator 
and/or Sub-investigator.  The signature and date can be wet ink or electronic.  Any laboratory 
test results considered by the Investigator to be clinically significant should be considered an 
AE (clinically significant AEs include those that require an intervention).  Clinically significant 
abnormal values occurring during the study will be followed until repeat test results return to 
normal, stabilize, or are no longer clinically significant.  


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12.5 
Adverse Events 
12.5.1 
Adverse Events 
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
period or worsens during the study, regardless of the suspected cause of the event.  All medical 
and psychiatric conditions (except those related to the indication under study) present at 
screening will be documented in the medical history eCRF.  Changes in these conditions and 
new symptoms, physical signs, syndromes, or diseases should be noted on the AE eCRF during 
the rest of the study.  Clinically significant laboratory abnormalities should also be recorded as 
AEs.  Surgical procedures that were planned before the patient enrolled in the study are not 
considered AEs if the conditions were known before study inclusion; the medical condition 
should be reported in the patient’s medical history. 
Patients will be instructed to report AEs at each study visit.  All AEs are to be followed until 
resolution or until a stable clinical endpoint is reached. 
Each AE is to be documented on the eCRF with reference to date of onset, duration, incidence, 
severity, relationship to study drug, action taken with study drug, treatment of event, and 
outcome.  Furthermore, each AE is to be classified as being serious or non-serious.  Changes in 
AEs and resolution dates are to be documented on the eCRF. 
For the purpose of this study, treatment emergent AEs will be collected starting from the time 
the patient receives the first dose of study drug (from Cycle 1 Day 1) until 28 days after the last 
dose of study drug.  Follow-up of the AE, even after the date of therapy discontinuation, is 
required if the AE persists until the event resolves or stabilizes at a level acceptable to the 
Investigator. 
Specific guidelines for classifying AEs by intensity (Grade) and relationship to study drug are 
given in Table 12-2 and Table 12-3.  The severity of AEs will be graded according to the 
NCI CTCAE version 5.0 (Grades 1 to 5). 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the event should be noted.   
Table 12-2 
Classification of Adverse Events by Intensity (NCI CTCAE Grade) 
Mild (Grade 1): An event that is easily tolerated by the patient, causing minimal discomfort, and 
not interfering with everyday activities. 
Moderate (Grade 2): An event that is sufficiently discomforting to interfere with normal everyday 
activities. 
Severe (Grade 3): An event that prevents normal everyday activities. 
Life-threatening (Grade 4) 
Death (Grade 5) 


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Table 12-3 
Classification of Adverse Events by Relationship to Study Drug 
Unrelated:  This category applies to those AEs that are clearly and incontrovertibly due to 
extraneous causes (disease, environment, etc.). 
Unlikely:  This category applies to those AEs that are judged to be unrelated to the test drug, but for 
which no extraneous cause may be found.  An AE may be considered unlikely to be related to study 
drug if or when it meets 2 of the following criteria:  (1) it does not follow a reasonable temporal 
sequence from administration of the test drug; (2) it could readily have been produced by the 
patient’s clinical state, environmental or toxic factors, or other modes of therapy administered to the 
patient; (3) it does not follow a known pattern of response to the test drug; or (4) it does not 
reappear or worsen when the drug is re-administered. 
Possibly:  This category applies to those AEs for which a connection with the test drug 
administration appears unlikely but cannot be ruled out with certainty.  An AE may be considered 
possibly related if or when it meets 2 of the following criteria: (1) it follows a reasonable temporal 
sequence from administration of the drug; (2) it could not readily have been produced by the 
patient’s clinical state, environmental or toxic factors, or other modes of therapy administered to the 
patient; or (3) it follows a known pattern of response to the test drug. 
Probably:  This category applies to those AEs that the Investigator feels with a high degree of 
certainty are related to the test drug.  An AE may be considered probably related if or when it meets 
3 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not be reasonably explained by the known characteristics of the patient’s clinical 
state, environmental or toxic factors, or other modes of therapy administered to the patient; (3) it 
disappears or decreases on cessation or reduction in dose (note that there are exceptions when an AE 
does not disappear upon discontinuation of the drug, yet drug-relatedness clearly exists; for 
example, as in bone marrow depression, fixed drug eruptions, or tardive dyskinesia); or (4) it 
follows a known pattern of response to the test drug. 
Definitely:  This category applies to those AEs that the Investigator feels are incontrovertibly 
related to test drug.  An AE may be assigned an attribution of definitely related if or when it meets 
all of the following criteria: (1) it follows a reasonable temporal sequence from administration of the 
drug; (2) it could not be reasonably explained by the known characteristics of the patient’s clinical 
state, environmental or toxic factors, or other modes of therapy administered to the patient; (3) it 
disappears or decreases on cessation or reduction in dose and recurs with re-exposure to drug (if 
re-challenge occurs); and (4) it follows a known pattern of response to the test drug. 
12.5.2 
Serious Adverse Events 
An AE is considered “serious” if in the view of either the Investigator or Sponsor, it meets one 
or more of the following criteria:  
• Is fatal 
• Is life-threatening 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant incapacity or substantial disruption of the ability 
to conduct normal life functions 


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• Is a congenital anomaly/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 the Investigator believes that an event is serious, 
the event must be considered serious and evaluated by the Sponsor for expedited reporting. 
12.5.3 
Serious Adverse Event Reporting 
An SAE occurring during the study from the first dose of study treatment (Cycle 1 Day 1) to 
within 28 days of stopping the treatment must be reported to the contracted CRO and will be 
communicated to the Sponsor.  Any such SAE due to any cause, whether or not related to the 
study drug, must be reported within 24 hours of occurrence or when the Investigator first 
becomes aware of the event.  The Investigator must enter all SAE information into the electronic 
data capture (EDC) (preferred method), electronic mail (SAE Report Form), dedicated fax line 
or telephone line (emergency), to the Sponsor/contracted CRO. 
If the Investigator contacts the contracted CRO by telephone, then a written report must follow 
within 24 hours and is to include a full description of the event and sequelae in the format 
detailed in the SAE reporting form. 
The event must also be recorded on the standard AE eCRF.  Preliminary reports of SAEs must 
be followed by detailed descriptions later on, including clear and anonymized photocopies of 
hospital case reports, consultant reports, autopsy reports, and other documents when requested 
and applicable.  SAE reports must be made whether or not the Investigator considers the event 
to be related to the investigational drug. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded.  Clinical, laboratory, and diagnostic measures should be employed as needed in order 
to determine the etiology of the problem.  The Investigator must report all additional follow-up 
evaluations to the contracted CRO within 10 calendar days.  All SAEs will be followed until 
the Investigator and Sponsor agree the event is satisfactorily resolved or returns to the baseline 
condition. 
Any SAE that is not resolved by the end of the study or upon discontinuation of the patient’s 
participation in the study is to be followed until it either resolves, stabilizes, returns to baseline 
values (if a baseline value is available), or is shown to not be attributable to the study drug or 
procedures. 
12.5.4 
Pregnancy 
Female patients of child-bearing potential must have a negative pregnancy test at the screening 
(serum) and the end of study/early termination visit (serum / urine).  Following administration 
of study drug (from Cycle 1 Day 1 until 28 days after the last dose), any known cases of 
pregnancy in female patients will be reported until the patient completes or withdraws from the 
study.  The pregnancy will be reported immediately by phone and by faxing/emailing a 


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completed Pregnancy Report to the Sponsor (or designee) within 24 hours of knowledge of the 
event.  The pregnancy will not be processed as an SAE; however, pregnancies should be 
considered important medical events and should be reported on the pregnancy report form/SAE 
form within 24 hours of the first learning of the event for further processing.  The pregnancy 
will be categorized as a non-serious AE in the safety database for tracking purposes. The 
Investigator will follow the patient until completion of the pregnancy and must assess the 
outcome in the shortest possible time but not more than 30 days after completion of the 
pregnancy.  The Investigator should notify the Sponsor (or designee) of the pregnancy outcome 
by submitting a follow-up Pregnancy Report.  If the outcome of the pregnancy meets the criteria 
for immediate classification of an SAE (e.g., spontaneous or therapeutic abortion [any 
congenital anomaly detected in an aborted fetus is to be documented], stillbirth, neonatal death, 
or congenital anomaly), the Investigator will report the event by phone and by faxing a 
completed SAE form to the Sponsor (or designee) within 24 hours of knowledge of the event 
and the SAE reporting process will be followed.  
12.5.5 
Overdose 
The Investigator must immediately notify the Sponsor of any occurrence of overdose with study 
drug. 
12.6 
ECOG Performance Status 
ECOG performance status will be evaluated at the visits indicated in the Schedule of 
Assessments (Table 9-1).  A summary of ECOG performance status is provided in Table 12-4.  
Table 12-4 
ECOG Performance Status 
Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
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 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
12.7 
Immunogenicity 
Safety assessment will also include evaluation of immunogenicity (i.e., ADAs).  
Immunogenicity assessments will be performed on Day 1 of Cycles 1-8, Cycle 12 and every 
4 cycles thereafter, as well as end of study or early termination visit (Table 9-1).   


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If a patient is found to be ADA-positive at the end-of-study, the persistence of the ADA will be 
evaluated by collecting one more sample, 4 months later after the last study visit.  The serum 
from each time point will test for anti-OBI-999 antibody concentration by a validated assay. 
13 
Exploratory Analyses 
13.1 
Tumor Tissue Samples 
Tumor tissue biopsy or tissue samples will be collected at time of screening in both Part A and 
Part B of the study.  Fresh (preferred) or archival tissue that is less than 10 years old is 
acceptable.  Tumor tissue samples with fewer than 100 tumor cells will be deemed not evaluable.  
A fine needle aspirate, frozen sample, plastic embedded sample, bone, bone marrow, cell block, 
clot, cytologic specimen, decalcified sample, or formalin fixed sample that was frozen at any 
point prior to fixation will not be accepted.  All attempts should be made to obtain fresh biopsy 
specimens.  However, if historical sample is available, they should be retained along with 
histology/pathology report, if possible.  All fresh biopsy specimens or historical samples should 
be sent to the qualified laboratory for testing.  A minimum of 5 slides are required for the central 
laboratory Globo H assay for determination of eligibility for Part B.  Up to 10 unstained 
additional slides should be provided, depending on availability, for testing tumor associated 
biomarkers as well as conducting a bridging study for the future companion diagnostic test. 
The mandated baseline slides are to be used for Globo H testing by IHC to define the level and 
extent of Globo H expression, as this is the target of OBI-999.  The 5 slides required for patients 
in Part B are part of the eligibility assessments, as all patients in Part B of the study must have 
a Globo H H-score of  100 to be eligible for study entry. 
An analysis will be performed to determine whether there is a potential correlation between 
baseline tumor Globo H expression as assessed by IHC H-score and response to OBI-999 
treatment, as assessed by change from baseline in the sum of diameters of measurable lesions 
and by RECIST response. 
Apart from the mandatory Globo H assessments, up to 10 additional slides have been requested, 
if available, to identify potential predictive biomarkers for OBI-999 activity such as assessment 
of expression of additional tumor-associated glycans which may be pathologically associated 
with Globo H overexpression (e.g., SSEA-3 and SSEA-4) or molecular phenotypes of tumors 
which may be associated with aberrant Globo H expression.  
14 
Statistical Analysis 
The Statistical Analysis Plan (SAP) will be prepared after the protocol is approved.  This 
document will provide further details on the definitions of analysis populations, variables, and  
methodology in order to address all study objectives.  The SAP will serve as a complement to 
the protocol and supersedes it in case of differences. 
The statistical evaluation will be performed using the SAS® Version 9.4 or higher (SAS 
Institute, Cary, NC).   
Analyses will be conducted by dose level in Part A and by cancer type in Part B.  Descriptive 
summaries for categorical variables will include counts and percentages.  Descriptive 


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summaries for continuous variables will include means, medians, standard deviations, 
minimum, and maximum values. Categorical ordinal variables will be presented as a 
combination of class frequencies and percentages, together with mean and standard deviations 
of the ordinal scores.  Descriptive summaries of time to event data will include medians and 
confidence intervals.  Graphical summaries of the data may be presented.  All data will be listed 
for all patients.   
Further details of the analysis, including the handling of missing data, transformations, other 
data handling procedures, and analytical methodology will be provided in the SAP.  Additional 
exploratory analyses of the data will be conducted as deemed appropriate. 
14.1 
Determination of Sample Size 
This is a 2-part study: Part A (Dose-Escalation) and Part B (Cohort-Expansion).   
Up to 30 patients were to have been enrolled in the 3+3 dose-escalation portion of the study 
(Part A).   
The cohort-expansion portion of the study (Part B) will enroll up to 57 patients based on 
Simon’s two-stage design.  The first stage will recruit up to 9 patients in each of three cohorts.  
If at least 1 objective response is observed, a second stage recruitment will occur with up to 
10 additional patients enrolled into that cohort, for a total of up to 19 patients per cohort.  If at 
least 4 objective responses are observed in the 19 patients, then OBI-999 will be considered 
worthy of further evaluation in that indication.  Patients will be followed up to the 24-week 
scheduled response assessment for the purposes of counting objective responses for Simon’s 
two-stage design success criteria. This design is based on a level of low interest for a treatment 
with an ORR of 10% versus a level of high interest for a treatment with an ORR of 25%.  The 
sample size is based on a one-sided alpha of 0.12 and 72% power.  The two-stage design limits 
the number of patients treated for a treatment with low levels of activity. 
14.2 
Analysis of Populations 
The safety population to be analyzed will include all enrolled patients who receive at least 
1 dose of study drug.  The population used for analysis of clinical activity will be all enrolled 
patients who received at least one dose of study drug and had at least one follow-up tumor 
assessment scan.  
14.3 
Clinical Activity Analysis 
ORR is defined as the percentage of patients with confirmed partial response (PR) or complete 
response (CR) based on tumor assessment as determined by RECIST 1.1.  A confirmed 
response will be defined as two or more consecutive assessments separated by at least 3 weeks.  
Patients who discontinue due to toxicity or clinical progression prior to post-baseline tumor 
assessments will be considered as non-responders and retained in the denominator.  
CBR is defined as the percentage of patients with confirmed CR, PR, or stable disease. A 
confirmed response will be defined as two or more consecutive assessments separated by at 
least 3 weeks.  Patients who discontinue prior to post-baseline tumor assessments will be 
considered as non-responders and retained in the denominator.   


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DOR is defined as time from date of reported confirmed PR or CR to the date of progression, 
and will be summarized descriptively using time-oriented summary statistics.  Additionally, a 
listing of DOR for those patients experiencing response will be provided. 
PFS is defined as the time from first dose of study drug until radiographically determined 
disease progression or death due to any cause, whichever occurs first.  Patients who are still 
alive or who have no progressive disease reported at analysis, will be censored at their last 
evaluable tumor assessment.   
Kaplan Meier estimates and 95% confidence intervals will be presented for time-to-event 
endpoints such as PFS, if sufficient numbers of events to calculate meaningful statistics are 
observed. 
14.4 
Pharmacokinetic Analysis 
Pharmacokinetic parameters will be calculated using a non-compartmental method from the PK 
samples collected during Cycles 1 and 2 and will include, but is not limited to Cmax, AUC, t1/2, 
Cl, Tmax, and Vd.   
To describe the dependency on dose, scatter plots of Cmax and AUC versus dose will be 
provided.  Summary statistics will be tabulated for the trough concentration (Cmin) and peak 
concentrations (end of infusion) by dose and study day.   
Pharmacometric methods may also be applied to further investigate OBI-999 and MMAE 
exposure (e.g., accumulation of OBI-999, presence of dose- or time-dependent OBI-999 PK 
behavior, verification of influential factors on OBI-999 PK). 
14.5 
Safety Analysis 
Adverse events will be coded according to Medical Dictionary for Regulatory Activities 
(MedDRA) version 21.0 or higher and assessed for severity using NCI CTCAE version 5.0.  
Adverse events will be summarized by system organ class and preferred term and presented in 
decreasing order of incidence.  Dose-limiting toxicities will also be summarized by dose and 
cohort.  The incidence of TEAEs (events with onset dates on or after the start of the study drug) 
will be included in incidence tables.  Events with missing onset dates will be included as 
treatment-emergent.  If a patient experiences more than 1 occurrence of the same AE, the 
occurrence with the greatest severity and the closest association with the study drug will be used 
in the summary tables.  Serious adverse events and AEs causing discontinuation will be 
tabulated.  All AEs will be listed by patient, along with information regarding onset, duration, 
relationship and severity to study drug, action taken with study drug, treatment of event, and 
outcome. 
Vital signs, ECG data, ophthalmology, hematology, serum chemistry, coagulation, and 
urinalysis parameters from baseline and during study will be examined.  Treatment-emergent 
changes in key laboratory parameters will be identified.  Clinical laboratory data will be 
summarized for each time point that specimens are collected.  Changes from baseline, for select 
clinical laboratory analytes may also be explored as specified in the SAP. 
Summary tables will be provided for concomitant medications initiated prior to study 
enrollment or during the study period. 


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14.6 
Safety Review Committee 
The SRC for this study will be comprised of the clinical lead, medical monitor, and the 
Investigator(s) or designee.  The SRC will act in an advisory capacity to monitor patient safety 
and efficacy during the trial and its activities will be defined in a separate SRC charter. 
This SRC convened after each cohort completed the first cycle of treatment during Part A 
(Dose-Escalation), to review safety data (AEs and laboratory toxicities) and to determine 
whether DLTs occurred.   
The RP2D for Part B (Cohort-Expansion) was determined by the SRC based on both the 
frequency of DLTs observed during Cycle 1 according to the 3+3 design, and also by the 
frequency and severity of cumulative toxicities such as peripheral neuropathy.  The SRC will 
continue to monitor the severity and frequency of acute and cumulative toxicities at regular 
intervals, i.e., every 3 months, to ensure acceptable tolerability of the selected RP2D and of the 
effectiveness of dose modification rules. The SRC will receive updated tabulations of 
recruitment, adverse events, SAEs, clinical laboratory events, and dose modifications which 
will serve as the basis for their assessments. 
14.7 
Interim Analysis 
There will not be a formal interim analysis; however, a description of the Dose Escalation 
Phase and the selection of the RP2D may be written up for the purposes of a manuscript. 
15 
Study Management 
15.1 
Approval and Consent 
15.1.1 
Regulatory Guidelines 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, Subpart D, of 
Title 21 of the Code of Federal Regulations (CFR), and in compliance with GCP guidelines. 
15.1.2 
Institutional Review Board/Independent Ethics Committee 
Conduct of the study must be approved by an appropriately constituted IRB/ IEC.  Approval is 
required for the study protocol, Investigator’s Brochure (IB), protocol amendments, informed 
consent forms (ICFs), and patient information sheets.   
15.1.3 
Informed Consent 
For each study patient, written informed consent will be obtained prior to any protocol-related 
activities.  As part of this procedure, the Principal Investigator or one of his/her associates must 
explain orally and in writing the nature, duration, and purpose of the study, and the action of 
the drug in such a manner that the patient is aware of the potential risks, inconveniences, or 
adverse effects that may occur.  The patient should be informed that he/she may withdraw from 
the study at any time, and the patient will receive all information that is required by local 
regulations and International Conference on Harmonization (ICH) guidelines.  The Principal 


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Investigator will provide the Sponsor or its representative with a copy of the IRB/IEC-approved 
ICF prior to the start of the study. 
15.2 
Data Handling 
Any data to be recorded directly on the eCRFs (to be considered as source data) will be 
identified at the start of the study.  Data reported on the eCRF that are derived from source 
documents should be consistent with the source documents, or the discrepancies must be 
explained. 
Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List.  AEs will be coded using the MedDRA terminology.  
Clinical data will be entered on eCRFs for transmission to the Sponsor.  Data on eCRFs 
transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site, unless the study site makes direct data entry to the 
databases for which no other original or source documentation is maintained.  In such cases, the 
study site should document which eCRFs are patient to direct data entry and should have in 
place procedures to obtain and retain copies of the information submitted by direct data entry.  
All study forms and records transmitted to the Sponsor must carry only coded identifiers such 
that personally identifying information is not transmitted.  The primary method of data 
transmittal is via the secure, internet-based EDC system.  Access to the EDC system is available 
to authorized users via the study’s Internet web site, where an assigned username and password 
are required for access. 
Any changes made to data after collection will be made through the use of Data Clarification 
Forms (DCF).  The eCRFs will be considered complete when all missing and/or incorrect data 
have been resolved. 
15.3 
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. 
15.4 
Record Retention 
Study records and source documents must be preserved for at least 2 years after the completion 
or discontinuation of/withdrawal from the study or 2 years after the last approval of a marketing 
application in an ICH region, whichever is the longer time period. 
The Investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of patient health information, including, but not limited to, 
the Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 [HIPAA] Privacy Regulation).  The 
Investigator shall ensure that study patients authorize the use and disclosure of protected health 
information in accordance with HIPAA Privacy Regulation and in a form satisfactory to the 
Sponsor. 


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15.5 
Monitoring 
The study will be monitored to ensure that it is conducted and documented properly according 
to the protocol, GCP, and all applicable regulatory requirements.  
On-site monitoring visits will be made at appropriate times during the study.  Clinical monitors 
must have direct access to source documentation in order to check the completeness, clarity, 
and consistency of the data recorded in the eCRFs for each patient.   
The Investigator will make available to the clinical monitor source documents and medical 
records necessary to complete eCRFs.  In addition, the Investigator will work closely with the 
clinical 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.  
15.6 
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 reliability of the study 
data presented to the Sponsor lies with the Investigator generating the data. 
The Sponsor will arrange audits as part of the implementation of quality assurance to ensure 
that the study is being conducted in compliance with the protocol, Standard Operating 
Procedures, GCP, and all applicable regulatory requirements.  Audits will be independent of 
and separate from the routine monitoring and quality control functions.  Quality assurance 
procedures will be performed at study sites and during data management to assure that safety 
and preliminary clinical activity profile data are adequate and well documented.  
15.7 
Protocol Amendment and Protocol Deviation  
15.7.1 
Protocol Amendment 
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no impact 
on the safety of patients or the conduct of the study will be classed as administrative 
amendments and will be submitted to the IRB/IEC for information only.  The Sponsor will 
ensure that acknowledgement is received and filed.  Amendments that are classed as substantial 
amendments must be submitted to the appropriate Regulatory Authorities and the IRBs/IECs 
for approval. 
15.7.2 
Protocol Deviations 
Should a protocol deviation occur, the Sponsor must be informed as soon as possible.  Protocol 
deviations and/or violations and the reasons for which they occurred will be included in the 
clinical study report.  Reporting of protocol deviations to the IRB/IEC and in accordance with 
applicable Regulatory Authority requirements is an Investigator responsibility. 


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15.8 
Ethical Considerations 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, Subpart D, of 
Title 21 of the CFR, and in compliance with GCP guidelines. 
IRBs/IECs will review and approve this protocol and the ICF.  All patients are required to give 
written informed consent prior to participation in the study.   
15.9 
Financing and Insurance 
Prior to the study commencing, the Sponsor (or its designee) and the Investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study.  This agreement 
will be documented in a financial agreement that will be signed by the Investigator (or the 
institution signatory) and the Sponsor (or its designee).  
The Investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice.  The Sponsor will provide insurance coverage for the clinical study as 
required by national regulations. 


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15.10 
Publication Policy and Disclosure of Data  
Both the use of data and the publication policy are detailed within the clinical study agreement.  
Intellectual property rights (and related matters) generated by the Investigator and others 
performing the clinical study will be patient to the terms of a clinical study agreement that will 
be agreed between the Institution and the Sponsor or their designee.  With respect to such rights, 
the Sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by Investigators and others performing the clinical study 
described in this protocol, patient to the terms of any such agreement.  In order to facilitate such 
ownership, Investigators will be required to assign all such inventions either to their Institution 
or directly to the Sponsor or its designee, as will be set forth in the clinical study agreement. 


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16 
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[Palanca-Wessels MC, Czuczman M, Salles G, et al. (2015)]. Safety and activity of the 
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[Petrylak DP, Heath EI, Sonpavde G, et al. (2016)]. Anti-tumor activity, safety and 
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[Ragupathi G, Slovin SF, Adluri S, et al. (1999)]. A Fully Synthetic Globo H Carbohydrate 
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17 
Appendices 
17.1 
Appendix 1:  Drug Preparation Instruction for OBI-999 
1. OBI-999 
• 
Dosage intravenous infusion: according to clinical protocol Section 8.2.   
• 
Part A include dose levels of 0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg (capping calculations at a 
maximum of 100 kg).  
• 
Part B will include the Recommended Phase 2 dose of 1.2 mg/kg (capping calculations at a 
maximum of 100 kg). 
2. Storage Condition:   
• 
OBI-999 vials are to be stored at 2-8oC.   
3. Investigational Drugs: 
• 
OBI-999 fill concentration and volume: 5 mg/mL, 5 mL in 10 mL transparent borosilicate 
type 1 glass vial. 
Contents:  5 mg/mL OBI-999 in 25 mM sodium citrate, 150 mM Arginine, pH 6.0, 0.02% 
Polysorbate 80. 
At time of treatment, calculate the volume of OBI-999 DP needed according to the treatment dosage.  
Withdraw the volume from OBI-999 DP vial by using a sterile syringe and add the volume into an 
infusion bag containing 500 mL 0.9% saline or 5% glucose.  Mix infusion bag by gently inverting 
the bag 4~5 times.  Do not shake the infusion bag vigorously.  After reconstitution, administer via 
intravenous infusion within 60±10 minutes. 
The combined OBI-999 and infusion solution, 0.9% normal saline or 5% glucose.  The administration 
of the drug must be completed within four hours after reconstitution to minimize potential microbial 
growth.  If administration is not possible within four hours from reconstitution, the combined product 
should be destroyed according to the institutional pharmacy Standard Operating Procedure and 
documented in the drug accountability records. 
The OBI-999 Drug Product (DP) should be administered to the study subjects within 4 hours of 
reconstitution at room temperature. Overall storage of the DP material should not exceed 8 hours at 
room temperature. 




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17.2 
Appendix 2:  Examples of Strong Inducers or Inhibitors of CYP3A 
Strong Inhibitor of CYP3A 
Strong Inducer of CYP3A 
boceprevir 
clarithromycin 
cobicistat 
conivaptan 
danoprevir and ritonavir 
diltiazem 
elvitegravir and ritonavir 
grapefruit juicea 
idelalisib 
indinavir and ritonavir 
itraconazole 
ketoconazole 
lopinavir and ritonavir 
nefazodone 
nelfinavir 
paritaprevir, ritonavir, and (ombitasvir and/or 
dasabuvir) 
posaconazole 
ritonavir 
saquinavir and ritonavir 
telaprevir 
tipranavir and ritonavir 
troleandomycin 
voriconazole 
carbamazepine 
enzalutamide 
mitotane 
phenytoin 
rifampin 
St. John’s wortb 
a.  The effect of grapefruit juice varies widely among brands and is concentration-, dose-, and 
preparation-dependent. Studies have shown that it can be classified as a “strong CYP3A inhibitor” 
when a certain preparation was used (e.g., high dose, double strength) or as a “moderate CYP3A 
inhibitor” when another preparation was used (e.g., low dose, single strength). 
b.  The effect of St. John’s wort varies widely and is preparation-dependent 
Source: Table 3-2 and Table 3-3 of https://www.fda.gov/drugs/drug-interactions-labeling/drug-
development-and-drug-interactions-table-substrates-inhibitors-and-inducers 


OBI Pharma, Inc. 
Confidential 
Page 71 
Protocol OBI-999-001, V 7.0, 21 Jul 2021 
OBI-999 
 
 
17.3 
Appendix 3:  Examples of Clinical Inhibitors of P-Glycoprotein 
Inhibitor of P-Glycoprotein 
amiodarone 
carvedilol 
clarithromycin 
dronedarone 
itraconazole 
lapatinib 
lopinavir and ritonavir 
propafenone 
quinidine 
ranolazine 
ritonavir 
saquinavir and ritonavir 
telaprevir 
tipranavir and ritonavir 
verapamil 
Source: Table 5-2 of https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers#table5-2 

SAP_001.pdf: 


Statistical Analysis Plan: OBI-999-001 
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Version: 2.0 
 
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CONFIDENTAL 
Page 2 of 62 
1. 
DOCUMENT HISTORY 
VERSION HISTORY 
Version # 
Version Date 
Final 1.0 
21-APR-2023 
Final 2.0 
12-JUL-2024 
REVISION HISTORY 
Version # 
Chapter 
Revision Summary 
Reason(s) for Revision 
2.0 
Throughout the 
document 
Editorial changes and 
updates to reflect an 
abbreviated CSR (aCSR). 
On 10Nov2023 Sponsor stated 
they stop the OBI-999-001 
study and elected to generate 
an aCSR. 
 
3.0 
Sentence added about aCSR. To clarify the scope of the TFLs 
that will be generated. 
 
5.4 
Sentence 
“The 
description 
above represents the initial 
interim 
analysis 
planning 
based on the protocol. In 
reality at the end of the first 
stage of Part B, four patients 
did not have a RECIST post-
baseline assessment and so it 
has been decided to replace 
them to have enough data to 
perform the go/no-go analysis. 
2 'replacement' patients have 
been 
enrolled 
in 
the 
pancreatic 
cohort, 
while 
searching for 2 'replacement' 
patients 
in 
the 
colorectal 
cohort was in progress. On 
10th November 2023, Sponsor 
stated they stop the study and 
elected to generate an aCSR 
and 
so 
formal 
go/no-go 
analysis never happened.” 
added. 
To clarify about the go/no-go 
analysis. 
 
8.0 
Sentence “Analysis endpoints 
are listed as per protocol. 
Only those endpoints marked 
with * will be analyzed in 
aCSR as per sponsor 
To clarify responsibilities 


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decision. Exploratory 
analyses will be conducted by 
OBI Translational Biology (or 
their designee) and may be 
included in the aCSR” added. 
 
8.1—8.3 
Added asterisks to show 
which endpoints will be 
analyzed. 
The aCSR will not include all 
endpoints planned in the 
protocol. 
 
10.7 
Sentence “Only those 
analyses marked with * will 
be analyzed in aCSR as per 
sponsor decision.“ added. 
The aCSR will not include all 
endpoints planned in the 
protocol. 
 
10.7.1 
Sentences “Only Those AEs 
marked with * will be 
analyzed in the aCSR as per 
sponsor decision.”. 
The aCSR will not include all 
adverse events planned in the 
SAP version 1.0. 
 
10.7.1 
Added asterisks to show 
which adverse events will be 
analyzed and listed.  
The aCSR will not include all 
adverse events planned in the 
SAP version 1.0. 
 
10.7.1 
Added asterisks to show 
which analyses will be 
conducted. 
The aCSR will not include all 
endpoints planned in the 
protocol. 
 
11 
Sentence added about aCSR. To clarify the scope of the TFLs 
that will be generated. 


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APPROVAL SIGNATURES 
STUDY TITLE: A Phase 1/2, Open-Label, Dose-Escalation and Cohort-Expansion 
Study Evaluating the Safety, Pharmacokinetics, and Therapeutic Activity of OBI-999 in 
Patients With Advanced Solid Tumors 
PROTOCOL NUMBER: OBI-999-001 (V 7.0, 21-July-2021) 
SAP Final 2.0, 12-JUL-2024 
 
 
Author: 
 
Signature: 
................................................................ 
Date: ...................... 
 
Peer-reviewer 
 
Signature: 
........... .................................................... 
Date: ...................... 
 
 
Project Manager: 
 
Signature: 
................................................................ 
Date: ...................... 
 
 
OBI Pharma 
SVP Biostatistics: 
 
Signature: 
................................................................ 
Date: ...................... 
 
 
 
 


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TABLE OF CONTENTS 
1. 
DOCUMENT HISTORY .................................................................................................................................... 2 
2. 
LIST OF ABBREVIATIONS .............................................................................................................................. 7 
3. 
INTRODUCTION ............................................................................................................................................. 9 
4. 
STUDY OBJECTIVES ...................................................................................................................................... 9 
4.1 
Primary Objectives ....................................................................................................................................... 9 
4.2 
Secondary Objectives .................................................................................................................................. 9 
4.3 
Exploratory Objective ................................................................................................................................... 9 
5. 
STUDY DESCRIPTION .................................................................................................................................... 9 
5.1 
Study Design ............................................................................................................................................... 9 
5.1.1 
Part A – Dose-Escalation ............................................................................ 9 
5.1.2 
Stopping Rules ......................................................................................... 10 
5.1.3 
Part B-Cohort-Expansion .......................................................................... 11 
5.1.4 
Study Duration .......................................................................................... 11 
5.2 
Study Treatment ........................................................................................................................................ 11 
5.3 
Safety Review Committee ........................................................................................................................... 11 
5.4 
Interim Analysis ......................................................................................................................................... 12 
6. 
RANDOMIZATION AND BLINDING ................................................................................................................ 12 
7. 
SAMPLE SIZE AND POWER CALCULATION .................................................................................................. 13 
8. 
ANALYSIS ENDPOINTS ................................................................................................................................ 13 
8.1 
Primary endpoints: ..................................................................................................................................... 13 
8.2 
Secondary endpoints: ................................................................................................................................. 13 
8.3 
Exploratory endpoints: ................................................................................................................................ 13 
9. 
ANALYSIS POPULATIONS ............................................................................................................................ 14 
10. 
ANALYTICAL PLAN AND STATISTICAL METHODS ........................................................................................ 14 
10.1 
General Conventions and Statistical Considerations ..................................................................................... 14 
10.2 
Definition of Baseline, Study Visits, and Visit Windows ................................................................................. 15 
10.3 
Handling of Missing Data ............................................................................................................................ 15 
10.4 
Patient Disposition ..................................................................................................................................... 15 
10.5 
Protocol Deviations .................................................................................................................................... 16 
10.6 
Patient Characteristics ................................................................................................................................ 16 
10.6.1 
Baseline and Demographic Characteristics ............................................... 16 
10.6.2 
Medical History and Current Medical Conditions ....................................... 17 
10.6.3 
Prior and Concomitant Medications .......................................................... 17 
10.6.4 
Cancer history........................................................................................... 18 
10.6.5 
Other Medical History ............................................................................... 18 
10.6.6 
Prior Cancer Surgeries ............................................................................. 18 
10.6.7 
Prior Cancer Radiotherapy........................................................................ 18 
10.6.8 
Prior Cancer Medication Therapy.............................................................. 18 
10.6.9 
Smoking History ........................................................................................ 18 
10.7 
Analysis of Study Endpoints ........................................................................................................................ 19 
10.7.1 
Primary Endpoints .................................................................................... 19 
10.7.2 
Secondary Endpoints ................................................................................ 24 
10.7.3 
Exploratory Endpoints ............................................................................... 24 
10.8 
Safety Endpoints ........................................................................................................................................ 24 
10.8.1 
Exposure to Study Treatment and Treatment Compliance ........................ 25 
10.8.2 
Laboratory Data ........................................................................................ 25 


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10.8.3 
Vital Signs ................................................................................................. 26 
10.8.4 
Electrocardiogram ..................................................................................... 26 
10.8.5 
Other Safety Parameters .......................................................................... 27 
11. 
DEVIATIONS FROM ANALYSIS AS DESCRIBED IN THE PROTOCOL .............................................................. 27 
12. 
PROGRAMMING SPECIFICATIONS ............................................................................................................... 28 
13. 
LIST OF TABLES, LISTINGS, AND FIGURES .................................................................................................. 29 
14. 
REFERENCES .............................................................................................................................................. 29 
15. 
APPENDIX I. SCHEDULE OF ASSESSMENTS ................................................................................................ 30 
16. 
APPENDIX II IMPUTATION RULES FOR MISSING DATES ............................................................................... 37 
17. 
APPENDIX III PHARMACOKINETIC ANALYSIS PLAN ..................................................................................... 39 
Pharmacokinetic Analysis Plan Signature Page ....................................................................................................... 40 
Modification History ................................................................................................................................................ 41 
Table of Contents .................................................................................................................................................. 42 
1. 
Introduction................................................................................................................................................ 44 
2. 
CLINICAL STUDY METHODS .................................................................................................................... 44 
2.1. 
Analysis Groups ......................................................................................................................................... 44 
2.2. 
Dose Administration ................................................................................................................................... 44 
2.3. 
PK Sampling Schedule ............................................................................................................................... 44 
2.4. 
Analytical Methods ..................................................................................................................................... 45 
3. 
PHARMACOKINETIC AN ALYSIS METHODS ............................................................................................. 45 
3.1. 
Analysis Population and Handling of Missing Time Points ............................................................................. 45 
3.2. 
Demographic and Baseline Characteristics .................................................................................................. 45 
3.3. 
Dosing and Pharmacokinetic Sampling Summary ........................................................................................ 46 
3.4. 
Definition and Estimation of Individual NCA PK Parameters .......................................................................... 46 
3.5. 
Descriptive Statistics .................................................................................................................................. 49 
4. 
LISTING OF PROPOSED TABLES, FIGURES, AND LISTINGS ................................................................... 49 
 


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2. 
LIST OF ABBREVIATIONS 
Abbreviation  
Definition  
aCSR 
abbreviated Clinical Study Report 
ADAs  
anti-drug antibodies  
ADC 
antibody-drug conjugate 
AE  
adverse event  
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body mass index 
BOR 
Best overall response 
CBR  
clinical benefit rate  
CI 
Confidence interval 
CR  
complete response  
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CV 
Coefficient of variation 
DLT  
dose-limiting toxicity  
DOR  
duration of response  
ECG  
electrocardiogram  
ECOG  
Eastern Cooperative Oncology Group  
eCRF  
Electronic Case Report Form  
GCP 
Good Clinical Practice 
IEC 
Independent Ethics Committee 
IHC 
immunohistochemistry 
IRB 
Institutional Review Board 
IV  
intravenous(ly)  
MedDRA  
Medical Dictionary for Regulatory Activities  
MMAE 
Monomethyl auristatin E 
MTD  
maximum tolerated dose  
NCI CTCAE  
National Cancer Institute Common Terminology Criteria for Adverse 
Events  
NE 
Not evaluable 
ORR  
objective response rate  
PCSA 
Potentially clinically significant abnormality 
PD  
pharmacodynamic / progressive disease (depending on context) 
PFS  
progression-free survival  
PK  
pharmacokinetics  
PR  
partial response  
PT 
Preferred Term 
RECIST  
Response Evaluation Criteria in Solid Tumors  
RP2D  
recommended phase 2 dose  
SAE  
serious adverse event  
SAP  
Statistical Analysis Plan  
SD 
Stable disease / standard deviation (depending on context) 
SOC 
System Organ Class 
SRC 
Safety review committee 
TEAE  
treatment-emergent adverse event  


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WHO-DD 
World Health Organization Drug Dictionary 


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3. 
INTRODUCTION 
This Statistical Analysis Plan (SAP) covers the statistical analysis and reporting for the protocol 
OBI-999-001 final version 7.0 (dated 21 July 2021), and electronic case report form (eCRF) 
production of 13 December 2021. 
On 10 November 2023, Sponsor stated they stop the OBI-999-001 study and elected to generate 
an abbreviated Clinical Study Report (aCSR). 
4. 
STUDY OBJECTIVES 
4.1 
PRIMARY OBJECTIVES 
The primary objectives are: 
x 
To determine the safety and tolerability of OBI-999 when administered intravenously (IV) 
to patients with advanced solid tumors. 
x 
To determine the maximum tolerated dose (MTD) and recommended phase 2 dose 
(RP2D) of OBI-999. 
4.2 
SECONDARY OBJECTIVES 
The secondary objectives are: 
x 
To evaluate the preliminary clinical activity profile of OBI-999 (objective response rate 
[ORR], clinical benefit rate [CBR], duration of response [DOR], and progression-free 
survival [PFS]). 
x 
To evaluate the immunogenicity of OBI-999 (anti-drug antibodies [ADAs]). 
x 
To determine the serum pharmacokinetics (PK) of OBI-999 and its active metabolite 
monomethyl auristatin E (MMAE). 
4.3 
EXPLORATORY OBJECTIVE 
The exploratory objective is: 
x 
To explore potential predictive biomarkers of OBI-999 activity. 
5. 
STUDY DESCRIPTION 
5.1 
STUDY DESIGN 
This is a Phase 1/2, open-label, dose-escalation, and cohort-expansion study of OBI-999, an 
antibody-drug conjugate (ADC)-targeting Globo H in patients with advanced solid tumors. 
This is a 2-part study. Part A (Dose-Escalation) is designed to establish the MTD and RP2D of 
OBI-999 as monotherapy. Part B (Cohort-Expansion) is intended to further characterize the safety 
and preliminary clinical activity profile of the RP2D of OBI-999 in patients with advanced solid 
tumors. 
5.1.1 PART A – DOSE-ESCALATION 
Twenty-two patients with advanced solid tumors were enrolled in Part A. No Globo H expression 
testing was required for inclusion. 


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Five cohorts of escalating dose levels of 0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg (capping calculations at 
a maximum of 100 kg) OBI-999 were planned to be enrolled and assessed using a 3+3 design to 
identify the MTD and RP2D. The RP2D of OBI-999 was determined to be 1.2 mg/kg (capping 
administered dose to a maximum of 120 mg for 100 kg) administered on Day 1 of each 21-day 
cycle. 
Three patients were enrolled at the lowest dose level. If none of the 3 patients experienced a 
dose-limiting toxicity (DLT) in the first 21-day cycle, the next cohort of 3 patients was enrolled at 
the next higher dose level. If 1 of 3 patients in the initial dose cohort experienced a DLT, that 
cohort was expanded to 6 patients. If only 1 of these 6 patients had a DLT, the next cohort of 3 
patients was enrolled at the next higher dose level. If 2 or more patients of the 3-6 patients in a 
cohort experienced a DLT, dose-escalation ceased, and the lower dose level was designated the 
MTD, where no more than 1 of 6 patients experienced at DLT. New patients were enrolled at the 
previous lower (tolerated) dose level until that cohort had 6 patients. This lower dose level was 
considered the MTD if ≤ 1 in 6 patients had a DLT. 
A patient who withdraws from the study within the DLT evaluation period for reasons other than 
drug-related adverse event (AE) were replaced.  
Escalation to higher OBI-999 dose cohorts is not permitted during the study. After a DLT is 
experienced by a patient, dose interruption, modifications, or dose delays may apply, as per 
Investigator judgement (refer protocol Section 8.3). 
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs first. 
5.1.2 STOPPING RULES 
The Sponsor, Investigator (following consultation with the Sponsor), or regulatory officials 
(regulatory agency or an Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) 
have the right to prematurely discontinue or suspend the study or investigational site at their 
discretion, at any time, if study and/or site conditions warrant. This action may be taken after 
appropriate consultation among the Sponsor, Investigator, and clinical monitor. The reasons for 
such action may include, but are not limited to the following: 
x 
Safety concerns, such as more than one third of the patients within a dose cohort have 
one of the following: 
o ≥ Grade 3 systemic infusion reactions (despite pre-medication), 
o Grade 4 DLTs (Refer to Protocol Section 6.2), or  
o Related serious adverse events (SAEs) (Refer to Protocol Section 8.2.3 & 8.3.1.1) 
x 
The Investigator does not comply with the protocol, Good Clinical Practice (GCP), and/or 
any contract between the Investigator and Sponsor, including Contract Research 
Organizations (CROs) and subsidiaries thereof. 
In the circumstance of such an event, the Sponsor reserves the right to halt and review this study 
and will discuss with the Investigator (including the reasons for taking such action) about dose 
modification, amendment to protocol, or study stopping. Final decision about continuing, 
termination or any other change in the study would remain with the Sponsor. 


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5.1.3 PART B-COHORT-EXPANSION 
Up to 57 additional patients with advanced solid tumors that have high Globo H expression 
(defined as an H-score ≥ 100 using a validated immunohistochemistry [IHC] assay) will be enrolled 
in Part B using a Simon’s two-stage cohort expansion design. Part B will be conducted to obtain 
additional safety data, characterize the PK profile of OBI-999, and obtain a preliminary 
assessment of the clinical activity profile of OBI-999 in Globo H expressing advanced solid tumors. 
Patients enrolled in Part B will receive the RP2D dose of 1.2 mg/kg (capping calculations at a 
maximum of 100 kg) OBI-999 on Day 1 of each 21-day cycle. 
The following 3 cohorts of patients who have high expression of Globo H by a qualified laboratory 
assessment (Globo H H-score ≥ 100 using a validated IHC assay) will be enrolled in Part B. 
x 
Cohort 1: Pancreatic cancer 
x 
Cohort 2: Colorectal cancer 
x 
Cohort 3: Basket (any solid tumor types other than those included in Cohorts 1 and 2) 
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs first. 
5.1.4 STUDY DURATION 
The study (Parts A and B) will include a screening period (up to 28 days), a treatment period, and 
a follow-up period. 
Patients will continue to receive treatment with OBI-999 until disease progression, unacceptable 
toxicity, consent withdrawal, or for up to 35 cycles (approximately 2 years), whichever occurs first. 
Patients will be followed up to the 24-week scheduled response assessment for the purposes of 
counting objective responses for Simon’s two-stage design success criteria. 
The safety follow-up visit will be conducted 28 days after the last dose of study treatment. 
5.2 
STUDY TREATMENT 
For Part A (Dose-Escalation), OBI-999 was planned to be given at doses of 0.4, 0.8, 1.2, 1.6, and 
2.0 mg/kg (capping calculations at a maximum of 100 kg) using a 3+3 design to identify the MTD 
and RP2D. 
For Part B (Cohort-Expansion), OBI-999 will be given at the RP2D of 1.2 mg/kg (capping 
administered dose to a maximum of 120 mg for 100 kg). 
OBI-999 investigational drug solution (OBI-999 drug product mixed with saline/glucose infusion 
solution) will be administered on Day 1 of each 21-day cycle by the site staff. The infusion should 
be given for a duration of approximately 60 minutes (± 10 minutes), for the initial 2 cycles (Cycle 
1 and Cycle 2). The infusion duration for Cycles 3 and beyond may be reduced, at the 
Investigator’s discretion, to 30 minutes if no infusion related AEs occur during the first 2 cycles. 
Treatment will continue until disease progression, unacceptable toxicity, consent withdrawal, or 
for up to 35 cycles (approximately 2 years), whichever occurs first. 
5.3 
SAFETY REVIEW COMMITTEE 
The safety review committee (SRC) for this study will be comprised of the clinical lead, medical 
monitor, and the Investigator(s) or designee. The SRC will act in an advisory capacity to monitor 


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patient safety and efficacy during the trial and its activities will be defined in a separate SRC 
charter. 
This SRC convened after each cohort completed the first cycle of treatment during Part A (Dose-
Escalation), to review safety data (AEs and laboratory toxicities) and to determine whether DLTs 
occurred. 
The RP2D for Part B (Cohort-Expansion) was determined by the SRC based on both the 
frequency of DLTs observed during Cycle 1 according to the 3+3 design, and also by the 
frequency and severity of cumulative toxicities such as peripheral neuropathy. The SRC will 
continue to monitor the severity and frequency of acute and cumulative toxicities at regular 
intervals, i.e., every 3 months, to ensure acceptable tolerability of the selected RP2D and of the 
effectiveness of dose modification rules. The SRC will receive updated tabulations of recruitment, 
AEs, SAEs, clinical laboratory events, and dose modifications which will serve as the basis for 
their assessments. 
5.4 
INTERIM ANALYSIS 
There will not be any other formal interim analyses except for the one related to Simon’s two stage 
design described below; however, a description of the Dose-Escalation Phase and the selection 
of the RP2D may be written up for the purposes of a manuscript. 
Moreover, the cohort expansion portion of the study (Part B) will enrol up to 57 patients based on 
Simon’s two-stage design. The first stage will recruit up to 9 patients in each of three cohorts. If 
at least one objective response is observed, a second stage recruitment will occur with up to 10 
additional patients enrolled into that cohort, for a total of up to 19 patients per cohort. If at least 4 
objective responses are observed in the 19 patients, then OBI-999 will be considered worthy of 
further evaluation in that indication. Patients will be followed up to the 24-week scheduled 
response assessment for the purposes of counting objective responses for Simon’s two-stage 
design success criteria. A formal analysis will be performed to support it. 
Patient enrolment, patient disposition, baseline characteristics, cancer history, clinical benefit rate, 
exposure to OBI-999, AE and ECG summaries (all described in this document) will support this 
formal analysis at end of stage 1. 
If Simon’s two-stage design success criteria is not met, then the second stage recruitment will not 
occur, and analyses will be done for supporting an aCSR. 
The description above represents the initial interim analysis planning based on the protocol. In 
reality at the end of the first stage of Part B, four patients did not have a RECIST post-baseline 
assessment and so it has been decided to replace them to have enough data to perform the go/no-
go analysis.  2 'replacement' patients have been enrolled in the pancreatic cohort, while searching 
for 2 'replacement' patients in the colorectal cohort was in progress. On 10th November 2023, 
Sponsor stated they stop the study and elected to generate an aCSR and so formal go/no-go 
analysis never happened. 
6. 
RANDOMIZATION AND BLINDING 
The study is a Phase 1/2 open-label, dose escalation and cohort expansion study and does not 
involve randomization; patients and members of the clinical study team will not be blinded to 
treatment. 


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7. 
SAMPLE SIZE AND POWER CALCULATION 
This is a 2-part study: Part A (Dose-Escalation) and Part B (Cohort-Expansion). 
Up to 30 patients were to have been enrolled in the 3+3 dose-escalation portion of the study 
(Part A). 
The cohort-expansion portion of the study (Part B) will enroll up to 57 patients based on Simon’s 
two-stage design. The first stage will recruit up to 9 patients in each of three cohorts. If at least 1 
objective response is observed, a second stage recruitment will occur with up to 10 additional 
patients enrolled into that cohort, for a total of up to 19 patients per cohort. If at least 4 objective 
responses are observed in the 19 patients, then OBI-999 will be considered worthy of further 
evaluation in that indication. Patients will be followed up to the 24-week scheduled response 
assessment for the purposes of counting objective responses for Simon’s two-stage design 
success criteria. This design is based on a level of low interest for a treatment with an ORR of 
10% versus a level of high interest for a treatment with an ORR of 25%. The sample size is based 
on a one-sided alpha of 0.12 and 72% power. The two-stage design limits the number of patients 
treated for a treatment with low levels of activity. 
8. 
ANALYSIS ENDPOINTS 
Analysis endpoints are listed as per protocol. Only those endpoints marked with * will be analyzed 
in aCSR as per sponsor decision. Exploratory analyses are to be conducted by OBI Transnational 
Biology (or their designee) and may be included as appendices in the aCSR. 
8.1 
PRIMARY ENDPOINTS:   
Part A (Dose-Escalation): 
x 
AEs/ SAEs and laboratory abnormalities as graded by National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0*. 
x 
DLTs with OBI-999*.  
x 
MTD and RP2D of OBI-999. 
Part B (Cohort-Expansion): 
x 
Percentage of patients with objective response*, clinical benefit, DOR and PFS according 
to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. 
x 
Percentage of patients with ADAs in blood*. 
8.2 
SECONDARY ENDPOINTS:   
Part A (Dose-Escalation): 
x 
PK parameters of OBI-999 and its active metabolite MMAE*. 
Part B (Cohort-Expansion): 
x 
AEs/SAEs and laboratory abnormalities as graded by NCI CTCAE version 5.0*. 
x 
PK parameters of OBI-999 and its active metabolite MMAE*. 
8.3 
EXPLORATORY ENDPOINTS: 
Part A (Dose-Escalation): 


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x 
Potential predictive biomarkers for OBI-999 activity such as expression of Globo H and 
other tumor-associated glycans or tumor molecular phenotypes. 
Part B (Cohort-Expansion): 
x 
Potential predictive biomarkers for OBI-999 activity such as expression of Globo H and 
other tumor-associated glycans or tumor molecular phenotypes. 
9. 
ANALYSIS POPULATIONS 
Screen Failures Set: all patients who are considered screening failures. This analysis set will allow 
comparison of demographic and baseline characteristics for screen failures versus enrolled 
patients, to demonstrate that those who were excluded from the study were no different from those 
who had qualified and that there were no systemic biases in the enrollment of the study. 
Screened Population: all patients who have signed informed consent. 
Safety population: all enrolled patients who received at least 1 dose of study drug. This analysis 
set will be used for all safety endpoints. 
Efficacy population: all enrolled patients who received at least one dose of study drug and had at 
least one follow-up tumor assessment scan. The efficacy population will be used as primary for 
analysis of clinical activity.  
PK population: all enrolled patients who receive at least 1 dose of study drug and have sufficient 
PK samples (a sample at the end of administration and at least 3 samples during the elimination 
phase) to include in the PK assessments. This analysis set will be used for all PK endpoints. 
10. 
ANALYTICAL PLAN AND STATISTICAL METHODS  
10.1 GENERAL CONVENTIONS AND STATISTICAL CONSIDERATIONS 
All statistical analyses will be performed, and data appendices will be created using the SAS 
system version 9.4 or higher. 
Data collected in this study will be presented in patient data listings and summary tables. 
Descriptive statistics (number of patients with non-missing values, mean, standard deviation [SD], 
median, minimum, and maximum) will be presented for continuous variables. All raw data will be 
presented to the original number of decimal places. Means and medians will be presented to 1 
more decimal place than in the raw data. Standard deviations will be presented to 2 more decimal 
places than in the raw data. Descriptive summaries of time to event data will include medians and 
confidence intervals. 
All data will be listed for all patients. 
Frequency distributions (counts and percentages) together with mean and SD of ordinal scores 
will be presented for categorical variables. Discrete variables that are ordinal scaled (e.g., Eastern 
Cooperative Oncology Group [ECOG] performance score) will additionally be presented with 
mean scores and SD. If not specified otherwise, the number of observations with non-missing 
values will be the denominator for percentage calculation. Further details on the handling of 
missing observations are given in section 9.3. 
If days are converted to months, a factor of 30.4 days/month will be used. If days are converted 
to years, a factor of 365.25 days/year will be used. Time will be shown in study weeks, i.e., number 
of weeks from the first administration of any study drug. 


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Dose-Escalation (Part A). The dose-escalation analysis will be presented by OBI-999 dose (0.4, 
0.8, 1.2, and 1.6 mg/kg) cohorts and overall. The following cohorts and overall will be presented: 
x 
OBI-999 0.4 mg/kg 
x 
OBI-999 0.8 mg/kg 
x 
OBI-999 1.2 mg/kg  
x 
OBI-999 1.6 mg/kg 
x 
Dose-Escalation Total 
OBI-999 2.0 mg/kg was planned but Part A was closed before this dose was administered, and 
therefore there no patients in this cohort. For this reason, this cohort will not be presented in any 
of the analyses. 
Cohort-Expansion (Part B). The expansion part analysis will be presented by cancer type. The 
following cohorts and overall will be presented: 
x 
Cohort 1: Pancreatic cancer 
x 
Cohort 2: Colorectal cancer 
x 
Cohort 3: Basket (any solid tumor type other than those included in Cohorts 1 and 2) 
x 
Cohort-Expansion Total 
10.2 DEFINITION OF BASELINE, STUDY VISITS, AND VISIT WINDOWS 
Baseline for each assessment is defined as the last non-missing assessment prior to first dose of 
study drug. If scheduled and unscheduled assessments occurred on the same day and they both 
can qualify for being baseline, the value from the scheduled assessment should be considered as 
baseline. The baseline will be presented for each part. 
The data will be analyzed according to the visits recorded in the eCRF. No additional visit windows 
will be applied. In listings, any unscheduled visits will be inserted in the appropriate temporal 
sequence using visit date and time. 
10.3 HANDLING OF MISSING DATA 
Partial or missing start and end dates of AEs and concomitant medications will be imputed 
conservatively based on the rule described in Appendix II: Imputation rules for missing dates. The 
imputed dates will be used to allocate the AEs and concomitant medications to a study period, 
and to determine whether an AE is/is not treatment emergent. Listings of the AEs and concomitant 
medications will present the actual partial dates; imputed dates will not be shown in the listings. 
 
For ORR endpoint, patients with missing data (for any reason) will be included as non-responders 
in the statistical analysis for each related follow-up analysis. For analyses performed in the safety 
population, patients who discontinue due to toxicity or clinical progression prior to post-baseline 
tumor assessments will be considered as non-responders and retained in the denominator. 
 
For CBR endpoint, patients with missing data (for any reason) will be included as non-responders 
in the statistical analysis for each related follow-up analysis. 
10.4 PATIENT DISPOSITION 
The number of patients screened and the reasons for screen failure from main consent, including 


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exclusion criteria met and inclusion criteria not met, will be tabulated overall in the screened 
population (all patients who have signed main informed consent) by Parts A and B. 
Patients in each analysis population, as well as patients who complete the treatment, complete 
the study, and patients who prematurely discontinue from treatment and from the study, together 
with number of enrolled patients, will be tabulated as indicated in section 9.1. The number and 
percentage within each category will be presented by Parts A and B and by cohort (by dose level 
in Part A and by cancer type in Part B). 
The number and percentage of patients included in the safety, efficacy and PK populations will 
also be conducted by study part and by cohort (by dose level in Part A and by cancer type in 
Part B). 
A listing with all enrolled patients (all patients who have been screened and are eligible) will be 
generated for the study to describe country/study center, patient number, study part, cohort, date 
of Globo-H screening consent, Globo-H screening consent version, date of main informed 
consent, informed consent version, was informed consent withdrawn, date of withdrawal, first and 
last study drug dosing dates, total duration of study drug dosing, the reason for discontinuing study 
drug dosing, end of study (completion or discontinuation) date, and reason for discontinuing the 
study. 
10.5 PROTOCOL DEVIATIONS 
Protocol deviations will be classified as major and minor as specified in the Protocol Deviations 
Management Plan. Patients with major protocol deviations will be identified and documented 
before the database lock. 
 
The number and percentage of patients with at least one major protocol deviation and the 
categories of the major protocol deviations will be summarized by study part and by cohort (by 
dose level in Part A and by cancer type in Part B) using the safety and efficacy populations. 
 
The number and percentages of patients with at least one major protocol deviation related to 
COVID-19 will be summarized too. 
 
Protocol deviations related to COVID-19 will be listed. 
10.6 PATIENT CHARACTERISTICS 
 
Baseline and demographic characteristics will be summarized for the screen failures population 
and by study part and by cohort (by dose level in Part A and by cancer type in Part B) using the 
safety population. Medical history, prior and concomitant medications will be summarized by study 
part and by cohort (by dose level in Part A and by cancer type in Part B) using the safety and 
efficacy populations. 
 
10.6.1 BASELINE AND DEMOGRAPHIC CHARACTERISTICS 
Descriptive statistics for continuous variables (age at screening, height at screening, weight at 
baseline, body mass index [BMI] at baseline, and Globo H score) and frequency counts and 
percentages for categorical demographic variables (child-bearing status, sex, ethnicity, race, 
Globo H [positive/negative] and ECOG performance) will be summarized by study part, and by 


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cohort (by dose level in Part A and by cancer type in Part B) using the safety and efficacy 
populations. 
BMI will be derived as: BMI [kg/m2] =weight[kg]/(height[cm]/100)2. 
 
Height reported in inches will be converted to centimeters as: Height [cm] = height [in] * 2.54. 
 
Baseline and demographic characteristics will be provided in a listing. 
10.6.2 MEDICAL HISTORY AND CURRENT MEDICAL CONDITIONS 
Medical history (conditions not ongoing at screening) and concomitant conditions (ongoing at 
screening or unknown) will be coded using Medical Dictionary for Drug Regulatory Activities 
(MedDRA®) version 23.0 or newer. The number and percentage of patients reporting a history of 
any medical condition, as recorded on the eCRF, will be summarized by study part, by cohort (by 
dose level in Part A and by cancer type in Part B), by System Organ Class (SOC) and preferred 
term (PT) in the safety and efficacy populations. Patients having the same medical condition 
(based on SOC and PT) more than once will be counted only once for a particular SOC and PT. 
Medical history, disease characteristics, surgical and medical procedures will be listed.  
 
10.6.3 PRIOR AND CONCOMITANT MEDICATIONS 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study will be documented as AEs on the eCRF. 
All prior and concomitant medications will be coded using September 2019 Format Global B3 
version of World Health Organization Drug Dictionary Enhanced (WHO-DD) and will be further 
classified to the appropriate Anatomical Therapeutic Chemical (ATC) code. The exact version of 
the dictionary is subject to change. 
The number and percentages of patients with at least one prior or concomitant medication will be 
summarized by ATC level 4 and ATC level 2 classes and WHO-DD preferred term (PT). Prior and 
concomitant medications will be summarized by study part, and by cohort (by dose level in Part A 
and by cancer type in Part B) in the safety and efficacy populations. These summaries will be 
done separately.  
A medication is considered prior if the end date of the medication is prior to the first study drug 
dose date. A medication is considered concomitant if it is administered before the first study drug 
dose date and is continuing at the time of the first dose of study drug, or if it is administered on or 
after the first study drug dose date up to 28 days after patient’s last study drug dose. 
Patients receiving the same medication more than once will be counted only once for a particular 
medication class, where applicable. 
Medications having both start and end dates missing will be considered concomitant; in the case 
of a missing start date and not a missing end date the medication will be considered concomitant 
unless the end date is prior to the date of the first dose.  
All prior and concomitant medications will be provided in a listing. 


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10.6.4 CANCER HISTORY 
Location of primary tumor, histological/molecular subtype of cancer, elevation of tumor-specific 
serum markers observed prior to study entry, tumor marker elevated (if elevation observed), TNM 
stage at study entry, TNM stage at diagnosis of advanced disease, metastatic sites and previous 
cancer therapies will be tabulated. Data will be summarized in the safety and efficacy populations 
by study part, and by cohort (by dose level in Part A and by cancer type in Part B). 
Cancer history will be listed. 
10.6.5 OTHER MEDICAL HISTORY 
Medical history terms, start/end dates, ongoing status, active treatment at study entry will be 
presented in a listing. 
10.6.6 PRIOR CANCER SURGERIES 
Prior cancer surgery description and date will be presented in a listing. 
10.6.7 PRIOR CANCER RADIOTHERAPY 
Radiation field (anatomic site), first and last dose dates, and total dose with units will be 
presented in a listing. 
10.6.8 PRIOR CANCER MEDICATION THERAPY 
Treatment setting, best response to treatment, and reason to stop treatment will be tabulated.   
Data will be summarized in the safety and efficacy populations by study part, and by cohort (by 
dose level in Part A and by cancer type in Part B). 
Prior cancer medication therapies will be presented in a listing. 
10.6.9 SMOKING HISTORY 
Substance type, usage status, frequency, length of usage and smoking exposure will be tabulated; 
descriptive statistics for continuous variable (‘Number used’ eCRF field) will be summarized by 
study part, and by cohort (by dose level in Part A and by cancer type in Part B) using the safety 
and efficacy populations.  
Length of usage, presented in years, will be calculated as the difference in stop and start dates of 
usage/365.25.  
Quantification of smoking exposure will be expressed as “pack-years”. Pack-years will be 
calculated as follows:  number of years participant smoked*number of cigarettes smoked per day 
divided by 20. The following rules will be applied to calculate “pack-years”: 
x 
1 pipe = 2.5 cigarettes. 
x 
1 cigar = 2.5 cigarettes. 
x 
20 cigarettes a day for 1 year = 1 pack-year. 
x 
8 pipes a day for 1 year = 1 pack-year. 
x 
8 cigars a day for 1 year = 1 pack-year. 
 


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Smoking history will be provided in a listing. 
10.7 ANALYSIS OF STUDY ENDPOINTS 
This section describes analysis of primary, secondary and exploratory endpoints as per protocol. 
All endpoints will be analyzed using planned treatments. Summaries will be presented for safety 
population in Part A and Part B. Summaries for anti-OBI 999 antibodies (ADA) in Part B will be 
presented in PK and safety populations. 
Only those analyses marked with * will be analyzed in aCSR as per sponsor decision.  
10.7.1 PRIMARY ENDPOINTS 
PART A (DOSE-ESCALATION) 
A. AEs/ SAEs and laboratory abnormalities as graded by NCI CTCAE version 5.0*. 
Treatment emergent adverse events (TEAEs) are defined as AEs with onset dates on or after the 
start of study drug until 28 days after the last dose of study drug or if it is present prior to receipt 
of the study treatment but worsens in severity or increases in frequency on or after the first dose. 
AEs having both onset and end dates missing will be considered as TEAEs. 
TEAEs will be summarized by study part, cohort (by dose level in Part A and by cancer type in 
Part B), SOC, PT, severity grade, and relationship to treatment. SAEs, deaths, and AEs leading 
to early treatment discontinuation (collected on Adverse Events eCRF page) will be summarized. 
The summaries will be sorted by decreasing order of overall incidence of SOCs and decreasing 
order of overall incidence of PTs within SOCs. 
Events reported as “Unrelated” or “Unlikely related” to study drug will be considered as unrelated 
to the study drug. Events reported as “Possibly related”, “Probably related”, “Definitely related” to 
study drug or without relationship information will be considered as related to the respective 
treatment. 
Overview summaries of the number and percentages of patients and number of events within the 
following categories will be provided by study part and by cohort (by dose level in Part A and by 
cancer type in Part B): 
x 
Any TEAE 
x 
Any TEAE grade ≥ 3 
x 
Any TEAE related to OBI-999 
x 
Any Serious TEAE 
x 
Any Non-Serious TEAE 
x 
Any Serious TEAE related to OBI-999 
x 
Any TEAE leading to death 
x 
Any TEAE leading to discontinuation of OBI-999 (defined as AE with an action taken 
equals to “Drug Withdrawn”) 
x 
Any Serious TEAE leading to discontinuation of OBI-999 (defined as AE with an action 
taken equals to “Drug Withdrawn”) 
x 
Any TEAE leading to study discontinuation (defined as AE flagged as Grade 4 infusion 
reactions and OBI-999 related toxicity, or intercurrent illness in the “End of Study” eCRF 


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page) 
x 
Any Serious TEAE leading to study discontinuation (defined as AE flagged as Grade 4 
infusion reactions and OBI-999 related toxicity, or intercurrent illness in the “End of Study” 
eCRF page) 
Tables by SOC and PT will be displayed for following AEs. Only those AEs marked with * will be 
analyzed in the aCSR as per sponsor decision. 
x 
TEAEs* 
x 
TEAEs grade ≥ 3* 
x 
TEAEs related to OBI-999* 
x 
Serious TEAEs* 
x 
Non-Serious TEAEs 
x 
Serious TEAEs related to OBI-999* 
x 
TEAEs leading to death* 
x 
TEAEs leading to discontinuation of OBI-999* 
x 
Serious TEAEs leading to discontinuation of OBI-999* 
x 
TEAEs leading to study discontinuation* 
x 
Serious TEAEs leading to study discontinuation* 
Tables by SOC and PT will display the incidence of events (number of events, number and 
percentage of patients with any event, number of events of each specific SOC, number and 
percentage of patients with any event of each specific SOC, number of events of each specific PT 
and number and percentage of patients with any event of each specific PT).  
Tables of TEAEs and serious TEAEs by SOC, PT and worst CTCAE grade (per summarization 
level) will be presented and will display number and percentage of patients with any event of each 
specific SOC/PT/CTCAE grade. Number of events will not be displayed. If a patient has multiple 
AEs with the same SOC or SOC and PT respectively and one of them has missing severity, the 
highest severity will be used. If the severity is missing for all AEs with the same SOC or SOC and 
PT, a “missing” category will be added in the summary table. 
The following listings will be prepared for AEs. Only those AEs marked with * will be listed in the 
aCSR as per sponsor decision. 
x 
Pre-treatment AEs 
x 
All TEAEs* 
x 
All TESAEs* 
x 
All TEAEs related to OBI-999* 
x 
TEAEs leading to death (with Grade 5 or “Fatal” as an outcome)* 
x 
All TEAEs leading to discontinuation of OBI-999* 
x 
All TEAEs leading to study discontinuation 
x 
Post-treatment AEs 
Number and percentage of patients with laboratory abnormalities with grade ≥ 3 will be provided 
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B. Dose-limiting toxicities (DLTs) with OBI-999* 
A DLT is defined as the occurrence of any of the following events, within the first cycle of treatment 
that is considered to be at least possibly related to OBI-999: 
x 
Grade 4 neutropenia lasting more than 7 days. 
x 
Febrile neutropenia. 
x 
Grade 4 thrombocytopenia. 
x 
Grade 3 thrombocytopenia with ≥ Grade 2 bleeding requiring platelet transfusions. 
x 
≥ Grade 3 fatigue, nausea and vomiting or diarrhea for more than 72 hours despite optimal 
supportive care. 
x 
Any Grade 4 gastrointestinal toxicity. 
x 
Any ≥ Grade 3 non-hematological toxicity (except Grade 3 fatigue, nausea, vomiting, or 
diarrhea lasting < 24 hours with optimal therapy, Grade 3 non-hematologic laboratory 
abnormalities that resolve to Grade 1 or baseline within 14 days). 
 
All TEAEs, unless they are determined to be not related to study drug will be taken into 
consideration in determining DLTs. The period for DLT observation is 21 days from the start of 
first dose of OBI-999 (i.e., Day 1). 
 
DLTs (not to be programmatically derived; will be analyzed as collected on eCRF) will be displayed 
by dose level in a frequency table in decreasing order of incidence. AEs will be graded according 
to the NCI CTCAE V5.0. All TEAEs unless they have been determined to be not related to study 
drug will be DLTs and will be summarized by dose, SOC and PT. A listing of DLTs will be prepared. 
C. MTD and RP2D of OBI-999 
At the time of this version of the SAP, Part A (Dose-Escalation) was completed. The RP2D of 1.2 
mg/kg was identified during SRC review. 
PART B (COHORT-EXPANSION) 
A. Objective Response* 
Overall tumor response (not to be programmatically derived; will be analyzed as collected on 
eCRF) will be listed by cancer type and visit. For each patient, best overall response (BOR) is 
defined as the best overall tumor response (complete response [CR], partial response [PR)] stable 
disease [SD], and progressive disease [PD], or not evaluable [NE]) from the start of treatment until 
disease progression, recurrence or end of study. In general, the patient’s best response 
assignment will depend on both the tumor measurement and confirmation criteria.  
If an NE response is determined at a time point, this response will be ignored and subsequent 
non-NE responses will be used for the confirmation. For example, the sequence of tumor 
assessments: PR, NE, NE, CR, SD, that had more than two consecutive NEs, the third 
subsequent non-NE response (CR) is used as the confirmation of the first PR for best overall 
response derivation. 
A requirement for SD is that it should be met at least once ≥ 6 weeks after the first dose of trial 
treatment, otherwise the best response will be NE.  
The criteria for confirmation of the response are summarized in the following table (Eisenhauer 




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If the BOR used for ORR based on unconfirmed and confirmed overall responses differs by 10%, 
then we will present the same summary for ORR based on unconfirmed overall responses as a 
sensitivity analysis. 
B. Clinical Benefit Rate 
Clinical benefit rate (CBR) is defined as the percentage of patients with confirmed CR, PR, or SD 
among all the patients of the safety and efficacy populations. A confirmed response will be defined 
as two or more consecutive assessments separated by at least 3 weeks. Patients who discontinue 
prior to post-baseline tumor assessments will be considered as non-responders and retained in 
the denominator. This analysis is similar to ORR. 
If the BOR used for CBR based on unconfirmed and confirmed overall responses differs by 10%, 
then we will present the same summary for CBR based on unconfirmed overall responses as a 
sensitivity analysis. 
C. Duration of Response 
DOR is defined as the time from date of confirmed PR or CR to date of progression or death due 
to any cause and will be expressed in months. For patients who are alive and progression-free at 
the time of analysis, DOR will be censored at the last tumor assessment date. The DOR will only 
be evaluated for the subgroup of patients with a confirmed PR/CR using the Kaplan Meier method.  
A summary of the patients with disease progression, or death, or the number of patients censored 
will be presented by the median time, Q1, Q3 and survival rates along with 95% CI, minimum and 
maximum will be provided. 
Patients who discontinue from the study without experiencing any pre-defined events or patients 
who completed the study period without experiencing any pre-defined events will be included in 
statistical analysis as censored. 
Sample code for duration of response is provided below: 
ods output Quartiles=QUARTS;  
proc lifetest data=DATA method=km OUTSURV=KMEST;  
by COHORT;  
time AVAL*CENSOR(1);  
run;  
ods output close; 
 
D. Progression Free Survival 
PFS is defined as the time from first dose of study drug until radiographically determined disease 
progression or death due to any cause, whichever occurs first. Patients who are still alive or who 
have no progressive disease reported at analysis will be censored at the last evaluable tumor 
assessment date. 
Patients who discontinue from the study without experiencing any pre-defined events or patients 
who completed the study period without experiencing any pre-defined events will be included in 


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the statistical analysis as censored. 
A summary of the patients with progression, or death, or the number of patients censored, 
presenting the median time, Q1, Q3 and survival rates along with 95% CI, minimum and maximum 
will be provided. 
DOR and PFS summaries will be presented for safety and efficacy populations. 
As additional analysis, ORR, CBR, DOR and PFS will be summarized for patients from Part A for 
safety and efficacy populations. 
E. Percentage of patients with anti-OBI-999 antibodies (ADAs) in blood* 
The number and percentage of patients with final ADA results in the blood will be summarized. 
ADAs titers over time will be summarized by cancer type in Part B using descriptive statistics, 
including percent coefficient of variation (CV%), geometric mean, and geometric SD using safety, 
and PK populations. Data listings will be produced for all ADA data. 
10.7.2 SECONDARY ENDPOINTS 
PART A (DOSE-ESCALATION) 
 
A. PK parameters of OBI-999 and its active metabolite MMAE. 
PK analyses will be conducted by OBI Pharma, Inc. Please refer to the SAP developed by OBI 
for PK parameters (Appendix III). 
PART B (COHORT-EXPANSION) 
A. TEAEs/TESAEs and laboratory abnormalities as graded by NCI CTCAE version 
5.0*. 
Please refer to the analysis presented to Section 9.7.1. 
B. PK parameters of OBI-999 and its active metabolite MMAE.  
PK analyses will be conducted by OBI Pharma, Inc. Please refer to statistical analysis plan 
developed by OBI for PK parameters (Appendix III).  
10.7.3 EXPLORATORY ENDPOINTS 
A. Potential predictive biomarkers for OBI-999 activity such as expression of Globo H and 
other tumor-associated glycans or tumor molecular phenotypes. 
The above analysis will be conducted by OBI Translational Biology (or their designee). Details of 
these analyses will be provided in separate document(s). The results will be compiled into a 
separate appendix in Section 14 of the Clinical Study Report (CSR). 
10.8 SAFETY ENDPOINTS 
This section describes the safety endpoints that are not part of the primary, secondary or 


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exploratory endpoints previously described in section 9.7. 
All safety endpoints will be analyzed using the safety population. 
Safety will be evaluated by presenting summaries of exposure to study treatment, laboratory 
evaluations 
(hematology, 
chemistry, 
coagulation, 
and 
urine 
analysis), 
vital 
signs, 
electrocardiogram (ECG) and other parameters. 
10.8.1 EXPOSURE TO STUDY TREATMENT AND TREATMENT COMPLIANCE 
The number of doses received, number of doses adjusted along with reasons of dose adjustment, 
total actual dose received in mg, total planned dose in mg, percentage of compliance (defined 
below), number of infusions interrupted along with reasons for infusion interruptions; number of 
infusions prematurely discontinued along with reasons for infusion prematurely discontinued, and 
the extent of exposure (calculated as last dose date – first dose date +1), will be summarized 
using descriptive statistics by study part, cohort, and overall.  
Percentage of compliance for a patient will be defined as the total actual dose received divided by 
the total planned dose multiplied by 100. 
ܲ݁ݎܿ݁݊ݐܽ݃݁݋݂ܿ݋݉݌݈݅ܽ݊ܿ݁ሺΨሻൌܶ݋ݐ݈ܽܽܿݐݑ݈ܽ݀݋ݏ݁ݎ݁ܿ݁݅ݒ݁݀݅݊݉݃
ܶ݋ݐ݈ܽ݌݈ܽ݊݊݁݀݀݋ݏ݁݅݊݉݃
ݔͳͲͲ 
Extent of exposure will also be summarized categorically by number and percentages for each of 
the following categories and cumulatively according to these categories: 
x 
> 0 and ≤ 3 weeks 
x 
> 3 and ≤ 6 weeks 
x 
> 9 and ≤ 12 weeks 
x 
> 12 and ≤ 18 weeks 
x 
> 18 and ≤ 24 weeks 
x 
> 24 and ≤ 36 weeks 
x 
> 36 and ≤ 48 weeks 
x 
> 48 weeks 
In addition, the percentages of compliance will be presented by the specific ranges for each study 
part and cohort: 
x 
< 80% 
x 
≥ 80% to < 120% 
x 
≥ 120% 
Data listings will be produced for all study drug administration data. 
10.8.2 LABORATORY DATA 
Baseline results, worst post baseline values (minimum or maximum value as determined by the 
specific analyte), change from baseline to worst post baseline values for hematology and serum 
chemistry collected by local laboratories, will be summarized using descriptive statistics, by study 
part, cohort and overall, in the safety population. Hematology will include Hemoglobin, Hematocrit, 


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, Platelet count, and White blood cell count with differential. Serum chemistry will include Albumin, 
Alanine aminotransferase, Alkaline phosphatase, Aspartate aminotransferase, Blood urea 
nitrogen or Urea, Bicarbonate, Creatinine, Creatine kinase, Electrolytes (Na, K, Cl, Ca, P, Mg), 
Glucose, Lactate dehydrogenase, Total bilirubin, Total protein, and Uric acid. 
  
Results of coagulation tests (prothrombin time, international normalized ratio, activated partial 
thromboplastin time), urine analysis data will be summarized at each scheduled visit. Actual 
laboratory values, and changes from baseline in laboratory values, will be summarized in SI units 
using descriptive statistics, by study part, dose group, cohort and overall, in the safety population. 
 
For coagulation tests, descriptive statistics will include CV%, geometric mean and geometric SD, 
calculated as: geometric SD = exp (SQRT(v)) where v is the squared standard deviation of the 
log-transformed values. 
 
Shift tables classified by CTCAE grades (grade 0, grade 1, grade 2, grade 3, grade 4, grade 5) 
from baseline to worst post-baseline grade per cohort, may be presented by selected laboratory 
tests, where applicable. For laboratory tests for which grades of severity are not defined by 
CTCAE, results will be graded by the low/normal/high classifications based on laboratory normal 
ranges. 
Urinalysis and microscopic analysis of the urine will be presented in a listing. 
For laboratory results reported with a prefix, i.e., “<”, “<=”, “=>” or “>”, the value derived from 
reported results without a prefix will be analyzed. 
Change from baseline scatter plot for selected laboratory analytes will be provided. 
Data listings will be produced for all collected laboratory data, including pregnancy test results. 
10.8.3 VITAL SIGNS  
Vital signs assessments (body temperature, pulse, systolic and diastolic blood pressure) and 
weight will be tabulated by visit. 
Baseline results, change from baseline results of vital signs (systolic and diastolic blood pressure 
[mmHg], pulse [beats per minute]), temperature [degree C]) signs will be summarized by study 
part, by cohort (by dose level in Part A and by cancer type in Part B) using descriptive statistics.  
In addition, number and percentages of patients by categories (abnormal low, normal, abnormal 
high) by visit and overall will be calculated and summarized for each of Part A and Part B. 
Data listings will be produced for all collected vital sign data.  
10.8.4 ELECTROCARDIOGRAM 
ECG results will be summarized by study part, by cohort (by dose level in Part A and by cancer 
type in Part B) and scheduled visit. QTc interval in msec (Fredericia) will be summarized using 
descriptive statistics and ECG interpretation will be summarized by number and percentage. 
ECG interpretation will be tabulated by a shift table (baseline vs. worst post baseline observation 
including unscheduled visits). 


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QTcF will be categorized using the FDA guidance thresholds as follows: > 450 msec, > 480 msec 
and > 500 msec. Frequency and proportion of patients that exceed the FDA guidance thresholds 
will be summarized by visit and overall, for Part A and Part B. Frequency and proportion of patients 
with increase from baseline of more than 30 msec and more than 60 msec will be summarized by 
visit and overall for Part A and Part B. 
10.8.5 OTHER SAFETY PARAMETERS 
ECOG categories will be tabulated by visit and a shift table (baseline vs. worst post baseline 
observation including unscheduled visits). 
Physical examination results (normal/abnormal-not clinically significant/abnormal-clinically 
significant/not evaluable/not done) will be listed and a shift table (baseline vs. worst post baseline 
observation, including unscheduled visits) will be displayed for each body system. 
Ophthalmological examination categories will be listed by study part, by cohort (by dose level in 
Part A and by cancer type in Part B) and scheduled visit. 
 
11. 
DEVIATIONS FROM ANALYSIS AS DESCRIBED IN THE 
PROTOCOL 
In the section §14.2 of the protocol the safety population is defined as all enrolled patients who 
receive at least 1 dose of study drug. The population used for analysis of clinical activity is defined 
as all enrolled patients who received at least one dose of study drug and had at least one follow-
up tumor assessment scan, but it was not clearly stated this is the efficacy population. We clearly 
defined it in section §8 of the SAP. 
The DOR is defined in section 14.3 of the protocol as the time from date of confirmed PR or CR 
to date of progression, but as we are applying a censoring rule to patients who are alive at the 
time of the analysis, we updated the definition in section 9.7.1 of the SAP to time from date of 
confirmed PR or CR to date of progression or death (from any cause). 
OBI-999 2.0 mg/kg was planned to be administered in Part A but this dose was not administered 
to any subjects in Part A due to the toxicity observed with the 1.6 mg/kg dose. For this reason, 
this cohort will not be presented. 
Efficacy endpoints will be analyzed in the safety and efficacy populations, because the definition 
of the efficacy population specifies that patients must have at least one follow-up assessment 
scan and so is closer to a per protocol population.  
DLTs will not be derived and will be presented as collected on the eCRF. The following DLTs have 
been updated: 
x 
“≥ Grade 3 fatigue, nausea and vomiting or diarrhea that does not resolve to Grade 1 or 
Baseline within 72 hours despite optimal supportive care” has been revised to “≥ Grade 3 
fatigue, nausea and vomiting or diarrhea for more than 72 hours despite optimal supportive 
care”. 
x 
“Any other Grade 3 or Grade 4 non-hematological toxicity (except Grade 3 fatigue, nausea, 
vomiting, or diarrhea lasting < 24 hours with optimal therapy, Grade 3 non-hematologic 
laboratory abnormalities that resolve to Grade 1 or baseline within 14 days)” has been 


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revised to. Any ≥ Grade 3 non-hematological toxicity (except Grade 3 fatigue, nausea, 
vomiting, or diarrhea lasting < 24 hours with optimal therapy, Grade 3 non-hematologic 
laboratory abnormalities that resolve to Grade 1 or baseline within 14 days)”. 
On 10 November 2023, Sponsor stated they stop the OBI-999-001 study and elected to generate 
an aCSR. Therefore, as per sponsor decision, the planned analyses have been changed to: 
x 
In section §10.5, the protocol deviations will neither be summarized nor listed. 
x 
In section §10.6.1, the baseline and demographic characteristics will be summarized 
using only the safety population and listed. 
x 
In section §10.6.2, the medical history and current medical conditions will neither be 
summarized nor listed. 
x 
In section §10.6.3, the prior and concomitant medications will neither be summarized nor 
listed. 
x 
In section §10.6.4, the cancer history will be summarized using only the safety 
population and listed. 
x 
In section §10.6.5, other medical history will not be listed. 
x 
In section §10.6.6, prior cancer surgeries will neither be summarized nor listed. 
x 
In section §10.6.7, prior cancer radiotherapy will neither be summarized nor listed. 
x 
In section §10.6.8, prior cancer medication therapy will neither be summarized nor listed. 
x 
In section §10.6.9, smoking history will neither be summarized nor listed. 
x 
In section §10.7.1, adverse events that will be analyzed and listed have been marked 
with asterisks. Only ORR analysis using safety population and ADA analysis using safety 
and PK populations have been selected as CBR, DOR and PFS analyses will no longer 
be conducted for the aCSR. Only waterfall plot (bar plot) showing the best reduction in 
target lesion therapy will be presented for Cohort-Expansion patients. 
x 
In section §10.8.1, only extent of exposure will be summarized, and all study drug 
administration data will be listed. 
x 
In section §10.8.2, laboratory data will only be listed. OBI decided not to conduct 
normalization of local laboratory assessments; therefore, data will be listed as recorded. 
x 
In section §10.8.3, vital signs data will only be listed. 
x 
In section §10.8.4, electrocardiogram data will only be listed. 
x 
In section §10.8.5, ECOG, physical examination and ophthalmological data will neither 
be summarized nor listed. 
12. PROGRAMMING SPECIFICATIONS 
All outputs will be produced using SAS version 9.4 or a later version. 
The margins should be at least 1.50 inches for the binding edge and 1.0 inches for all other edges.  
In the top left portion of each table/listing, the sponsor’s name, protocol number, type of analysis 
(Draft or Final) will be presented. In the top right portion of each table/listing, page X of Y will be 
presented. On the next line, a table/listing number followed by the title of the table/listing and 


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population information will be displayed. Horizontal lines will appear after the column heading of 
the table/listing. Footnotes will be put under the main body of text at the bottom of the page. The 
source listing number will be displayed for all tables. The SAS program name, Source Data, 
Extract date and Cut-off date will appear bottom left in a string of each table/listing. The date and 
time of creation of table/listing will appear bottom left under to the SAS program name line.  
Times New Roman, proportional 8-point bold font will be used for all tables and listings. Usually, 
a landscape layout is suggested for both tables and listings, but it is not mandatory. Any date 
information in the listing will use the date9. format, for example, 07MAY2002. 
Shells for unique tables and listings are provided in a separate Mock-Up TFLs document. 
13. 
LIST OF TABLES, LISTINGS, AND FIGURES 
Shells for unique tables, listings and figures are provided in a separate Mock-Up tables, figures, 
and listings (TFLs) document. 
14. 
REFERENCES 
Patrick Therasse, Susan G. Arbuck, Elizabeth A. Eisenhauer, et al. New Guidelines to Evaluate 
the Response to Treatment in Solid Tumors Journal of the National Cancer Institute, Vol. 92, 
No. 3, February 2, 2000. 






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h. 12-lead ECG with assessment of QTcF: at screening, Cycle 1 Day 1, Cycle 1 Day 3 (48r 2 hours after the end of the Cycle 1 Day 1 OBI-
999 infusion) and EoS/ET. The ECG testing on C1D4 could be tested 24 hours before but no later than C1D4. 
i. 
Pregnancy testing should be performed in females of childbearing potential only. A serum pregnancy test is required during screening. A 
urine or serum pregnancy test is acceptable end of study or early termination 
j. 
Tumor biopsy samples are mandatory at screening visit. Fresh (preferred) tissue or archival tissue is acceptable. A minimum of 5 slides are 
required for the central laboratory Globo H assay for determination of eligibility in Part B. Up to 10 unstained additional slides should be 
provided, depending on availability, for the protocol defined exploratory studies. 
k. Hematology and Serum chemistry (Laboratory Assessments: Protocol Table 12-1). Blood draw is prior to OBI-999 infusion. For C2D1 and 
each cycle after, laboratory assessments may be drawn 72 hours in an advance of infusion. 
Hematology: hematocrit, hemoglobin, erythrocyte count, white blood count, absolute counts of leukocytes, neutrophils, lymphocytes, 
monocytes, eosinophils, basophils, and platelet count.  
Serum chemistry: sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, calcium, phosphorus, magnesium, 
total protein, albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine kinase, lactate 
dehydrogenase, total bilirubin, and uric acid. Creatinine clearance will be calculated by Cockcroft Gault equation at screen visit, week 1 and 
EoS/ET.  
l. 
Coagulation, and Urinalysis (Laboratory Assessments: Protocol Table 12-1). Blood draw and urine collection is prior to OBI-999 infusion. 
Only urinalysis will be collected at Day 1 of Cycles 2-35. 
Coagulation: prothrombin time, activated partial thromboplastin time, and international normalized ratio.  
Urinalysis: specific gravity, pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, nitrite, leukocyte esterase as assessed by dipstick. 
A microscopic urinalysis (only if needed) evaluating white blood cells, red blood cells, epithelial cells, bacteria, cast and crystals 
m. OBI-999 is given on Day 1 of each 21-day cycle until DLT, disease progression, unacceptable toxicity, or withdrawal of consent, whichever 
occurs earlier. 
n. Pharmacokinetic: (for analysis of serum concentration of OBI-999 total antibody, ADC and free MMAE). Detailed sampling schedule in 
Table 14.2 (Part A) and Table 14.3 (Part B). 
o. Immunogenicity studies (ADA) - ADA samples will be collected. Detailed sampling schedule in Table 14.2 (Part A) and Table 14.3 (Part B). 
For patients with persistent antibodies at end of study, an additional ADA sample will be collected at 4 months after the end of study visit. 
p. Radiology (CT or MRI scan) evaluations of tumor response: Performed during screening and during the study every 6 weeks for the first 
3 months, and then every 9 weeks until discontinuation of study treatment, disease progression, death, or initiation of further systemic 
cancer therapy, including radiation therapy, whichever occurs earlier. CT or MRI scan will be performed within 1 week prior to the start of 
the next cycle. Unscheduled scan can be performed anytime, if needed to confirm disease progression. Radiology assessment for early 


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termination/end of study, should ONLY be performed if ≥9 weeks have passed from the previous scheduled CT/MRI scan. Same 
assessment method and same technique should be used on each patient while on study.  




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e. If there is change of the infusion rate or interruption of infusion, the PK sampling on Day 1 is to be collected from the exact time of completion 
of infusion to obtain the post-infusion samples after the end of infusion. Exact time of sample collection and the reason for interruption should 
be documented in the eCRF. 
f. 
ADA samples will be collected along with pre-infusion PK samples. No post-infusion ADA samples will be collected. For subjects with 
persistent antibodies at end of study, an additional ADA sample will be collected at 4 months after the end of study visit. 




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16. 
APPENDIX II 
IMPUTATION RULES FOR MISSING DATES 
Algorithm for Treatment-emergent Adverse Events 
AE Start Date AE Stop Date 
Action 
Known 
Known 
If start date < study drug start date, then not TEAE 
If start date ≥ study drug start date, then TEAE 
Partial 
If start date < study drug start date, then not TEAE 
If start date ≥ study drug start date, then TEAE 
Missing or 
Unknown 
If start date < study drug start date, then not TEAE 
If start date ≥ study drug start date, then TEAE 
Partial, but the 
known date 
components 
show that it 
cannot be on or 
after study drug 
start date 
Known 
Not TEAE  
Partial 
Not TEAE  
Missing or 
Unknown 
Not TEAE  
Partial, could 
be on or after 
study drug start 
date 
Known 
If stop date < study drug start date, then not TEAE  
If stop date ≥ study drug start date, then TEAE  
Partial 
Impute stop date as latest possible date (i.e., last day of month if day is 
unknown or 31-Dec if day and month are unknown), then:  
If stop date < study drug start date, then not TEAE  
If stop date ≥ study drug start date, then TEAE  
Missing or 
Unknown 
Assumed TEAE  
Missing or 
Unknown 
Known 
If stop date < study drug start date, then not TEAE  
If stop date ≥ study drug start date, then TEAE  
Partial 
Impute stop date as latest possible date (i.e., last day of month if day is 
unknown or 31st December if day and month are unknown), then:  
If stop date < study drug start date, then not TEAE  
If stop date ≥ study drug start date, then TEAE  
Missing or 
Unknown 
Assumed TEAE 
Algorithm for Concomitant Medications 


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CM Start Date 
CM Stop Date 
Action 
Known 
Known 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Partial 
Impute stop date as latest possible date (i.e., last day of month if day unknown 
or 31-Dec if day and month are unknown), then: 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Missing or 
Unknown 
Assign as CONCOMITANT 
Partial 
Known 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Partial 
Impute stop date as latest possible date (i.e., last day of month if day unknown 
or 31-Dec if day and month are unknown), then: 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Missing or 
Unknown 
Assign as CONCOMITANT  
Missing or 
Unknown 
Known 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Partial 
Impute stop date as latest possible date (i.e., last day of month if day unknown 
or 31-Dec if day and month are unknown), then: 
If stop date < study drug start date, assign as PRIOR 
If stop date ≥ study drug start date, assign as CONCOMITANT 
Missing or 
Unknown 
Assign as CONCOMITANT 
 


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17. 
APPENDIX III 
PHARMACOKINETIC ANALYSIS PLAN 
 
 
Pharmacokinetic Analysis Plan 
 
A Phase 1/2, Open-Label, Dose-Escalation and Cohort-
Expansion Study Evaluating the Safety, Pharmacokinetics, 
and Therapeutic Activity of OBI-999 in Patients With 
Advanced Solid Tumors 
 
 
Version 1.0 
DATE: 30 NOV 2021 
 
 
 
 
 
Property of OBI Pharma, Inc. 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of OBI 
 


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PHARMACOKINETIC ANALYSIS PLAN SIGNATURE PAGE 
Pharmacokinetic Analysis Plan V1.0 (Dated 30NOV 2021) for Protocol OBI-999-001. 
 
 
Name 
Signature 
Date 
Author: 
 
 
DDMMMYYYY 
 
Position: 
 
 
Company: 
 
 
Upon review of this document, the undersigned approves this version of the Statistical 
Analysis Plan, authorizing that the content is acceptable for the reporting of this study. 
 
Name 
Signature 
Date 
Approved By: 
 
 
DDMMMYYYY 
 
Position: 
 
 
Company: 
 
 
Approved By: 
 
 
DDMMMYYYY 
 
Position: 
 
 
Company: 
 
 
Approved By: 
 
 
DDMMMYYYY 
 
Position: 
 
 
Company: 
 


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MODIFICATION HISTORY 
 
Unique 
Identifier for 
this Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorized Version 
1.0 
 
 
Not Applicable – First Version 
 
 


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TABLE OF CONTENTS 
1. 
INTRODUCTION ........................................................................................................................................................... 44 
2. 
CLINICAL STUDY METHODS ...................................................................................................................................... 44 
2.1. 
Analysis Groups ................................................................................................................................................ 44 
2.2. 
Dose Administration .......................................................................................................................................... 44 
2.3. 
PK Sampling Schedule ..................................................................................................................................... 44 
2.4. 
Analytical Methods ............................................................................................................................................ 45 
3. 
PHARMACOKINETIC AN ALYSIS METHODS ............................................................................................................. 45 
3.1. 
Analysis Population and Handling of Missing Time Points ................................................................................. 45 
3.2. 
Demographic and Baseline Characteristics ....................................................................................................... 45 
3.3. 
Dosing and Pharmacokinetic Sampling Summary ............................................................................................. 46 
3.4. 
Definition and Estimation of Individual NCA PK Parameters .............................................................................. 46 
3.5. 
Descriptive Statistics ......................................................................................................................................... 49 
4. 
LISTING OF PROPOSED TABLES, FIGURES, AND LISTINGS .................................................................................. 49 
 
 


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ACRONYMS AND ABBREVIATIONS 
Standard acronyms and abbreviations are listed below. 
 
Abbreviation  
Definition 
AUC  
Area Under the Concentration-Time Curve 
AUC(0-last)  
AUC to the Last Measurable Concentration 
AUC(0-t)  
AUC from 0 to time t 
AUC(0-∞)  
AUC Extrapolated to Infinity 
ADC 
Antibody drug conjugate 
BMI  
Body Mass Index 
BQL  
Below the Quantification Limit 
Clast  
Last Measurable Concentration (above the quantification limit) 
CL 
Clearance 
cm  
Centimeter(s) 
Cmax  
Maximum Serum Concentration 
CSR  
Clinical Study Report 
CV  
Coefficient of Variation 
ECL 
Electrochemiluminescence 
EDC  
Electronic Data Capture 
g  
Gram(s) 
GM  
Geometric Mean 
GSD  
Geometric Standard Deviation 
h  
Hour(s) 
Ke  
Terminal Phase Elimination Rate Constant 
kg  
Kilogram(s) 
L  
Liter(s) 
LLOQ  
Lower Limit of Quantification 
Max  
Maximum 
Min  
Minimum 
min  
Minute(s) 
mL  
Milliliter(s) 
MMAE 
monomethyl auristatin E 
NCA  
Noncompartmental Analysis 
μg  
Microgram(s) 
PK  
Pharmacokinetic(s) 
SD  
Standard Deviation 
t1/2  
Apparent Terminal Elimination Half-Life 
Tlast  
Time of Last Measurable Concentration 
Tmax  
Time to Maximum Serum Concentration (Cmax) 
Vz 
Apparent Volume of Distribution During Terminal Phase 
 
 
 


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1. INTRODUCTION  
This pharmacokinetic analysis plan describes the rules and conventions to be used in the 
presentation and analysis of PK data to be presented for Protocol [OBI-999-001]. This 
document is based on protocol, version 7.0, dated 21 July 2021.      
This document reiterates key PK elements in the study design of Protocol OBI-999-
001and thoroughly describes the presentations and summaries of PK data as well as the 
noncompartmental analysis (NCA) to be included in the PK Report and summarized in 
the clinical study report (CSR) for this protocol. Shells and mockups are given for all PK-
related tables, figures, and listings planned for inclusion in the CSR and/or PK Report. At 
minimum, mean PK plots as well as listings and summaries of OBI-999 concentrations 
and PK parameters will be included in the CSR, while all tables, figures, and listings 
described in this document will be included in the PK Report.  
2. CLINICAL STUDY METHODS 
2.1. Analysis Groups 
This is a Phase I, open-label, dose-escalation (Part A) and cohort expansion (Part B) 
study of OBI-999, an antibody drug conjugate (ADC), targeting Globo H in patients with 
locally advanced or metastatic solid tumors.  Part A is designed to establish the MTD and 
RP2D of OBI-999. Part B is intended to further characterize the safety and clinical activity 
profile of the RP2D dose of OBI-999 administered as monotherapy in patients with 
advanced solid tumors. 
2.2. Dose Administration 
OBI-999 were administered as a 60-minute intravenous (IV) infusion on Days 1of each 
21-day cycle for the initial 2 cycles (Cycle 1 and Cycle 2). The infusion duration for Cycles 
3 and beyond may be reduced, at the Investigator’s discretion, to 30 minutes if no infusion 
related AEs occur during the first 2 cycles. For Part A (Dose-Escalation), OBI-999 was 
planned to be given at doses of 0.4, 0.8, 1.2, 1.6, and 2.0 mg/kg (capping calculations at 
a maximum of 100 kg) using a 3+3 design to identify the MTD and RP2D. For Part B 
(Cohort-Expansion), OBI-999 will be given at the RP2D of 1.2 mg/kg (capping 
administered dose to a maximum of 120 mg for 100 kg) 
2.3. PK Sampling Schedule 
Blood (serum) samples will be collected at the following time points: C1D1 Pre-infusion 
(within 1 day prior-to the infusion), post infusion samples at the end of infusion and at 0.5 
(±15 min), 2 (±15 min), 4 (±15 min), 8 (±15 min), 24 (± 2 h, on Day2), 72 (±2 h, on Day4), 


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168 (±2 h, on Day8),   240 (±2 h, on Day11 ) and 336 hours (±2 h, on Day15) after the 
end of the infusion.   
 
 
2.4. Analytical Methods 
As OBI-999 is an antibody drug conjugate (ADC) and composed of a humanized monoclonal 
IgG1antibody conjugated with monomethyl auristatin E (MMAE, vedotin) targeting Globo H. The 
concentration of OBI-999 and total antibody in the serum samples were determined using a 
validated electrochemiluminescence (ECL) method with assay ranges of 15 to 24000 ng/mL and 
100 to 15000 ng/mL, respectively.  The concentration of MMAE in the serum samples were 
determined using a validated LC/MS/MS method with an assay range of 2 to 4000 pg/mL.  
 
3. PHARMACOKINETIC AN ALYSIS METHODS 
3.1. Analysis Population and Handling of Missing Time Points 
The PK population will include all enrolled subjects who receive at least 1 dose of study 
drug 
and have sufficient PK samples (a sample at the end of administration and at least 3 
samples 
during the elimination phase) to include in the PK assessments.  Generally, only values 
above the lower limit of quantification (LLOQ) are used for the estimation of PK 
parameters. Unless otherwise specified below, missing sampling or concentration values 
should not be imputed, but left missing in the calculation of derived PK parameters. If the 
actual sampling time is missing, but a valid concentration value has been measured, the 
scheduled protocol time may be used for the calculation of derived PK parameters.  
Collection of serum samples outside of the protocol defined time window for the time point 
will not result in exclusion of the sample result from NCA. Values below the lower limit of 
quantification (LLOQ) will be referred to as below the quantification limit (BQL). BQL 
values that precede the first PK concentration above the LLOQ will be imputed as 0 for 
linear plots and for all calculations including NCA and summary statistics. All other BQL 
values will be treated as missing for all analyses.  
3.2. Demographic and Baseline Characteristics 
Sex, race, age, weight, height, and body mass index (BMI) of subjects in the PK analysis 
population will be listed and summarized (PK Table 1, PK Listing 1). 


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3.3. Dosing and Pharmacokinetic Sampling Summary 
Subject dose administration times will be presented (PK Listing 2). Cases that potentially 
affect the analysis will be discussed. Protocol deviations related to dosing or PK sampling 
will be listed (PK Listing 3) and summarized in the PK Report text. Deviations to be 
included in the PK Report include: 
• Blood specimen not collected 
• Serum specimen result not obtained 
• Specimen temperature excursion 
• Required specimen collected out of window 
• Any other deviation determined by the PK analyst to be potentially affect PK 
Serum concentrations will be listed by subject (PK Listing 4-6), with nominal and actual 
time associated with the sample indicated (nominal time is defined as the time in h since 
the start time of the dose). Both laboratory reported concentration values, and modified 
concentration values used for analysis (for instance, imputation of 0 for a BQL value at 
baseline) will be included, as separate columns, in the listing. Serum drug concentrations 
will also be summarized (PK Table 2-4) and plotted. PK Figure 1 to PK Figure 12 will plot 
all individual subject and mean serum PK profiles, as linear and semi-logarithmic plots, 
respectively. Subject ID for each individual profile in these figures will be shown in a 
legend.  
3.4. Definition and Estimation of Individual NCA PK Parameters 
PK parameters will be estimated through a NCA using version 8.3 or later of Phoenix® 
WinNonlin® 
(Pharsight Corporation, Cary, NC). Actual post-dose time will be used for the estimation 
of PK parameters instead of nominal time. Individual PK parameter estimates will be 
listed (PK Listing 7-9). 
Phoenix® WinNonlin® NCA will use the following settings to compute parameters from 
plasma PK data:   
• Linear Up Log Down calculation method 
• Uniform weighting 
• Intravenous dose 
• Plasma Model Type 


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• Lambda Z Acceptance Criteria 
x Rsq_adjusted ≥ 0.80 
x Span ≥ 2.0 half-lives 
x Includes ≥ 3 timepoints after Tmax 
 
Tmax (hour): Time to reach the maximum concentration 
- 
directly taken from the observed concentration 
Cmax (μg/mL): Maximum concentration 
- 
directly taken from the observed concentration 
Clast (μg/mL): Concentration at last quantifiable time point 
- 
directly taken from the observed concentration 
λ (1/h): Elimination rate constant associated with the terminal phase 
- 
estimated terminal slope of the linear regression of log-transformed 
concentration vs time 
- 
The regression analysis should contain data from at least 3 different time 
points in the terminal phase and as many data points as possible, always 
including the last quantifiable concentration but excluding the concentration 
at Tmax.  
- 
The coefficient of determination Adj_RSq2 should be larger than or equal to 
0.80. If at least one of these three conditions is not fulfilled, the terminal half-
life and the parameters depending on t½ will be listed but flagged as not 
reliably calculated. They will generally be excluded from descriptive 
statistics and statistical testing procedures. 
t½ (h): Terminal elimination half-life 
- 
ݐଵȀଶൌ
௟௢௚೐ଶ
஛ 
AUClast (h*μg/mL): Area under the concentration-time curve from time zero to time the 
last quantifiable time, calculated by log-linear trapezoidal rule. 
AUC∞ (h*μg/mL): Area under the concentration-time curve from time zero to infinite time 
- 
The percentage of extrapolated AUC should not exceed 20% of AUC∞ for 
each individual profile. If the percentage of extrapolated AUC is more than 


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20%, the individual AUC∞ result and the parameters depending on AUC∞ 
will be listed but flagged as not reliably calculated. They will generally not 
be included in descriptive statistics and statistical testing procedures. 
AUMClast (h2*μg/mL): Area under the first moment of the concentration time curve from 
time zero to time the last quantifiable time, calculated by log-linear 
trapezoidal rule. 
AUMC∞ (h2*μg/mL): Area under the first moment of the concentration-time curve from 
time zero to infinite time 
CL (mL/h): Total body clearance following iv administration 
- 
ܥܮൌ
்௢௧௔௟஽௢௦௘஺ௗ௠௜௡௜௦௧௥௔௧௘ௗ௜௡̶ρ௚̶
஺௎஼ಮ
 
Vz (mL): Volume of distribution following iv administration 
- 
ܸ௭ൌܥܮɉ
ൗ 
Vss (mL): Volume of distribution at steady-state following iv administration 
- 
ܸ௦௦ൌ
்௢௧௔௟஽௢௦௘஺ௗ௠௜௡௜௦௧௥௔௧௘ௗ௜௡̶ρ௚̶ൈ஺௎ெ஼
ሺ஺௎஼ಮሻమ
 
Dose proportionality 
- 
To investigate the dose proportionality of AUC and Cmax, a statistical 
analysis using the power model will be conducted. The power model will 
have the form: 
- 
Y = a*(dose)b , where Y is the PK parameter, and a and b are the coefficient 
and exponent, respectively, of the power equation. 
- 
By taking the natural logarithm (ln), the power model can be analyzed using 
linear regression and has the form: 
- 
ln(Y) = ln(a)+b*ln(dose) + error =α + β*ln(dose) + error, 
- 
where α is the intercept, and β is the slope, and ln(dose) is based on the 
dose size for each subject. 
- 
Estimates of slope and intercept along with their 90% confidence intervals 
will be reported. A minimum of 3 values per dose must be available for a 
given parameter to estimate dose proportionality using the power model. 
All calculations will use the actual post-dose times recorded on the CRF. All computed 
PK parameters will be listed by subject and summarized by doses group in the Escalation 
Phase and by disease cohort in the Expansion Phase (mean, standard deviation, 


Statistical Analysis Plan: OBI-999-001 
Review Status: FINAL  
  
Version: 2.0 
 
Version Date: 12-JUL-2024 
 
Page 49 of 62 
 
coefficient of variation, minimum, maximum, number of observations). Individual and 
mean (by time) concentrations versus time will be plotted for each dose on both linear 
and natural logarithm scales.  
3.5. Descriptive Statistics 
Subject-specific PK parameter estimates will be listed (PK Listing 4-6). PK estimates will 
be summarized in PK Table 5-7. Summary statistics will include mean, standard deviation 
(SD), minimum, maximum, median, coefficient of variation as a percent (CV%), GM, and 
geometric standard deviation (GSD) 
 
4. LISTING OF PROPOSED TABLES, FIGURES, AND 
LISTINGS 
PK Table 1: Summary of Demographic and Baseline Characteristics of Subjects Included in the PK 
Analysis Population 
Parameter 
PK Analysis Population 
(N=X) 
Sex – N (%) 
 
Male 
 
Female 
 
Age (years) 
 
Mean (SD) 
 
Median 
 
Min, Max 
 
Height (cm) 
 
Mean (SD) 
 
Median 
 
Min, Max 
 
Weight (kg) 
 
Mean (SD) 
 
Median 
 
Min, Max 
 
BMI (kg/m2) 
 
Mean (SD) 
 
Median 
 
Min, Max 
 
Race – N (%) 
 
American Indian or Alaska Native 
 
Asian 
 
Black or African American 
 
Native Hawaiian or other Pacific 
Islander 
 
White 
 
Other or Unknown 
 
 
PK Table 2: Summary Statistics for Concentrations of OBI-999 by Nominal Time 
 


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Subject ID 
OBI-999 Concentration (μg/mL) by Nominal Time1 After Dose (h) 
0 
1.5 
3 
5 
9 
25 
73 
169 
241 
337 
UXX-001 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-002 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-003 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
…  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Statistics 
 
 
 
 
 
 
 
 
 
 
N2  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Mean  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
SD  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
GM  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
(Min, Max)  
(x, x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, x)  
(x, x)  
(x, x)  
1 Times are relative to time of dosing. 
2 Number of data points used to compute the summary statistics. For calculation of summary statistics, BQL values 
were imputed as 0 if they did not come after a PK sample concentration that is above the LLOQ and treated as 
missing otherwise. 
PK Table 3: Summary Statistics for Concentrations of total antibody by Nominal Time 
 
Subject ID 
Total Antibody Concentration (μg/mL) by Nominal Time1 After Dose (h) 
0 
1.5 
3 
5 
9 
25 
73 
169 
241 
337 
UXX-001 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-002 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-003 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
…  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Statistics 
 
 
 
 
 
 
 
 
 
 
N2  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Mean  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
SD  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
GM  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
(Min, Max)  
(x, x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, 
x)  
(x, x)  
(x, x)  
(x, x)  
1 Times are relative to time of dosing. 
2 Number of data points used to compute the summary statistics. For calculation of summary statistics, BQL values 
were imputed as 0 if they did not come after a PK sample concentration that is above the LLOQ and treated as 
missing otherwise. 
PK Table 4: Summary Statistics for Concentrations of MMAE by Nominal Time 
Subject ID 
MMAE (ng/mL) by Nominal Time1 After Dose (h) 
0 
1.5 
3 
5 
9 
25 
73 
169 
241 
337 
UXX-001 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-002 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
UXX-003 
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
…  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Statistics 
 
 
 
 
 
 
 
 
 
 
N2  
x  
x  
x  
x  
x  
x  
x  
x  
x  
x  
Mean  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
SD  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
GM  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
x.x  
(Min, Max)  
(x, x)  
(x, 
(x, 
(x, 
(x, 
(x, 
(x, 
(x, x)  
(x, x)  
(x, x)  


Statistical Analysis Plan: OBI-999-001 
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Page 51 of 62 
 
x)  
x)  
x)  
x)  
x)  
x)  
1 Times are relative to time of dosing. 
2 Number of data points used to compute the summary statistics. For calculation of summary statistics, BQL values 
were imputed as 0 if they did not come after a PK sample concentration that is above the LLOQ and treated as 
missing otherwise. 
PK Table 5: Summary Statistics for PK Parameters of OBI-999 
Statistic 
Tmax 
(h) 
Cmax 
(μg/mL) 
Cmax_D 
(μg/mL/mg) 
AUC(0-last) 
(h×μg/mL) 
AUC(0-last)__D 
(h×μg/mL/mg) 
CL 
(L/h) 
t1/2 
(h) 
Vss 
(L) 
N 
 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
 
SD 
 
 
 
 
 
 
 
 
Min 
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
CV % 
 
 
 
 
 
 
 
 
GM 
 
 
 
 
 
 
 
 
GSD 
 
 
 
 
 
 
 
 
 
PK Table 6: Summary Statistics for PK Parameters of total antibody 
Statistic 
Tmax 
(h) 
Cmax 
(μg/mL) 
Cmax_D 
(μg/mL/mg) 
AUC(0-last) 
(h×μg/mL) 
AUC(0-last)__D 
(h×μg/mL/mg) 
CL 
(L/h) 
t1/2 
(h) 
Vss 
(L) 
N 
 
 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
 
 
SD 
 
 
 
 
 
 
 
 
Min 
 
 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
 
 
CV % 
 
 
 
 
 
 
 
 
GM 
 
 
 
 
 
 
 
 
GSD 
 
 
 
 
 
 
 
 
 
PK Table 7: Summary Statistics for PK Parameters of MMAE 
Statistic 
Tmax 
(h) 
Cmax 
(ng/mL) 
Cmax_D 
(ng/mL/mg) 
AUC(0-last) 
(h×ng/mL) 
AUC(0-last)__D 
(h×ng/mL/mg) 
t1/2 
(h) 
N 
 
 
 
 
 
 
Mean 
 
 
 
 
 
 
SD 
 
 
 
 
 
 
Min 
 
 
 
 
 
 
Median 
 
 
 
 
 
 
Max 
 
 
 
 
 
 
CV % 
 
 
 
 
 
 
GM 
 
 
 
 
 
 
GSD 
 
 
 
 
 
 
 
 
 


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Page 52 of 62 
 
APPENDIX 1. LIST OF PROPOSED PK FIGURES LIST OF PK FIGURES 
PK Figure 1: Concentration Profiles of OBI-999 for All Subjects by 
Time.................................14 
PK Figure 2: Semi-log Concentration Profiles of OBI-999 for All Subjects by 
Time..................14 
PK Figure 3: Mean Concentration of OBI-999 by Nominal Time 
...............................................15 
PK Figure 4: Mean Concentration of OBI-999 by Nominal Time (Semi-Log) 
...........................15 
PK Figure 5: Concentration Profiles of total antibody for All Subjects by Time 
........................16 
PK Figure 6: Semi-log Concentration Profiles of total antibody for All Subjects by 
Time..........16 
PK Figure 7: Mean Concentration of total antibody by Nominal Time 
.......................................17 
PK Figure 8: Mean Concentration of total antibody by Nominal Time (Semi-Log) 
...................17 
PK Figure 9: Concentration Profiles of MMAE for All Subjects by Time 
..................................18 
PK Figure 10: Semi-log Concentration Profiles of MMAE for All Subjects by 
Time.................18 
PK Figure 11: Mean Concentration of MMAE by Nominal Time 
...............................................19 
PK Figure 12: Mean Concentration of MMAE by Nominal Time (Semi-Log) 
...........................19 
 
PK Figure 1: Concentration Profiles of OBI-999 for All Subjects by Time 


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PK Figure 2: Semi-log Concentration Profiles of OBI-999 for All Subjects by Time 
 
PK Figure 3: Mean Concentration of OBI-999 by Nominal Time 


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PK Figure 4: Mean Concentration of OBI-999 by Nominal Time (Semi-Log) 
 


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PK Figure 5: Concentration Profiles of total antibody for All Subjects by Time 
 
PK Figure 6: Semi-log Concentration Profiles of total antibody for All Subjects by 
Time 
 


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PK Figure 7: Mean Concentration of total antibody by Nominal Time 
 
PK Figure 8: Mean Concentration of total antibody by Nominal Time (Semi-Log) 
 


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PK Figure 9: Concentration Profiles of MMAE for All Subjects by Time 
 
PK Figure 10: Semi-log Concentration Profiles of MMAE for All Subjects by Time 
 
PK Figure 11: Mean Concentration of MMAE by Nominal Time  


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PK Figure 12: Mean Concentration of MMAE by Nominal Time (Semi-Log) 
 
 
 
 


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APPENDIX 2. LIST OF PROPOSED PK LISTINGS TABLE OF PK LISTINGS 
PK 
Listing 
1: 
Subject 
Level 
Demographic 
and 
Baseline 
Characteristics 
.......................................21 
PK 
Listing 
2: 
OBI-999 
Dosing.......................................................................................................21 
PK 
Listing 
3: 
Protocol 
Deviations 
Related 
to 
Dosing 
or 
PK 
Samples.............................................21 
PK 
Listing 
4: 
Subject 
Level 
OBI-999 
Concentrations 
in 
Serum.....................................................21 
PK 
Listing 
5: 
Subject 
Level 
total 
antibody 
Concentrations 
in 
Serum.............................................22 
PK 
Listing 
6: 
Subject 
Level 
MMAE 
Concentrations 
in 
Serum.......................................................22 
PK 
Listing 
7: 
Subject-Specific 
Pharmacokinetic 
Parameters 
of 
OBI-
999.....................................22 
PK 
Listing 
8: 
Subject-Specific 
Pharmacokinetic 
Parameters 
of 
total 
antibody..............................22 
PK 
Listing 
9: 
Subject-Specific 
Pharmacokinetic 
Parameters 
of 
MMAE........................................23 
 
 


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PK Listing 1: Subject Level Demographic and Baseline Characteristics 
Subject ID  Sex  
Race 
Age 
(years) 
Height 
(cm) 
Weight 
(kg) 
BMI 
(kg/m2) 
UXX-001 
 
 
 
 
 
 
UXX-002 
 
 
 
 
 
 
UXX-003 
 
 
 
 
 
 
….. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Listing 2: OBI-999 Dosing 
Subject ID  
Dose 
(mg)  
Date of Infusion  Start Time  
End Time  
UXX-001 
 
 
 
 
UXX-002 
 
 
 
 
UXX-003 
 
 
 
 
 
 
 
 
 
 
PK Listing 3: Protocol Deviations Related to Dosing or PK Samples 
Subject 
ID 
DV 
Number 
Deviation 
Description 
Study 
Day 
Reason 
for 
Deviation 
Deviation 
Resulted 
in AE? 
Deviation 
Resulted in 
Subject 
Termination? 
Deviation 
Affected 
Product 
Stability? 
Specimen 
Type 
Affected 
Visit 
Number 
Deviat
Catego
UXX-
001 
 
 
 
 
 
 
 
 
 
 
UXX-
002 
 
 
 
 
 
 
 
 
 
 
UXX-
003 
 
 
 
 
 
 
 
 
 
 
Note: This listing contains a subset of the protocol deviations in the clinical database relevant to the PK analysis 
PK Listing 4: Subject Level OBI-999 Concentrations in Serum 
Subjec
t ID 
Nomina
l Time1 
(h) 
Actua
l 
Time1 
(h) 
Lab Reported 
Drug 
Concentratio
n 
(μg/mL) 
Analysis 
Drug 
Concentratio
n 
(μg/mL) 
Used in Ke 
Calculation
s 
Exclude
d 
from 
NCA 
Reason 
for 
Exclusio
n from 
NCA 
UXX-
001 
0  
0  
BQL  
0  
No  
No 
 
UXX-
002 
0.5  
0.5  
50.1  
50.1  
No  
No 
 
UXX-
003 
1.5 
1.52  
BQL  
missing  
No  
No 
 
… 
 
 
 
 
 
 
 
1Times are relative to time of dose. For Actual Times, out-of-window times are indicated by an asterisk 


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PK Listing 5: Subject Level Total Antibody Concentrations in Serum 
Subjec
t ID 
Nomina
l Time1 
(h) 
Actua
l 
Time1 
(h) 
Lab Reported 
Drug 
Concentratio
n 
(μg/mL) 
Analysis 
Drug 
Concentratio
n 
(μg/mL) 
Used in Ke 
Calculation
s 
Exclude
d 
from 
NCA 
Reason 
for 
Exclusio
n from 
NCA 
UXX-
001 
0  
0  
BQL  
0  
No  
No 
 
UXX-
002 
0.5  
0.5  
50.1  
50.1  
No  
No 
 
UXX-
003 
1.5 
1.52  
BQL  
missing  
No  
No 
 
… 
 
 
 
 
 
 
 
1Times are relative to time of dose. For Actual Times, out-of-window times are indicated by an asterisk 
PK Listing 6: Subject Level MMAE Concentrations in Serum 
Subjec
t ID 
Nomina
l Time1 
(h) 
Actua
l 
Time1 
(h) 
Lab Reported 
Drug 
Concentratio
n 
(ng/mL) 
Analysis 
Drug 
Concentratio
n 
(ng/mL) 
Used in Ke 
Calculation
s 
Exclude
d 
from 
NCA 
Reason 
for 
Exclusio
n from 
NCA 
UXX-
001 
0  
0  
BQL  
0  
No  
No 
 
UXX-
002 
0.5  
0.5  
50.1  
50.1  
No  
No 
 
UXX-
003 
1.5 
1.52  
BQL  
missing  
No  
No 
 
… 
 
 
 
 
 
 
 
1Times are relative to time of dose. For Actual Times, out-of-window times are indicated by an asterisk 
PK Listing 7: Subject-Specific Pharmacokinetic Parameters for OBI-999 
Subject 
ID 
Tmax 
(h) 
Cmax 
(μg/mL) 
Cmax_D 
(μg/mL/mg) 
AUC(0-last) 
(h×μg/mL) 
AUC(0-last)__D 
(h×μg/mL/mg) 
CL 
(L/h) 
Ke 
(1/h) 
t1/2 
(h) 
Vss 
(L) 
UXX-001 
 
 
 
 
 
 
 
 
 
UXX-002 
 
 
 
 
 
 
 
 
 
UXX-003 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Listing 8: Subject-Specific Pharmacokinetic Parameters for total antibody 
Subject 
Tmax 
Cmax 
Cmax_D 
AUC(0-last) 
AUC(0-last)__D 
CL 
Ke 
t1/2 
Vss 


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ID 
(h) 
(μg/mL) 
(μg/mL/mg) 
(h×μg/mL) 
(h×μg/mL/mg) 
(L/h) 
(1/h) 
(h) 
(L) 
UXX-001 
 
 
 
 
 
 
 
 
 
UXX-002 
 
 
 
 
 
 
 
 
 
UXX-003 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK Listing 9: Subject-Specific Pharmacokinetic Parameters for MMAE 
Subject ID 
Tmax 
(h) 
Cmax 
(ng/mL) 
Cmax_D 
(ng/mL/mg) 
AUC(0-last) 
(h×ng/mL) 
AUC(0-last)__D 
(h×ng/mL/mg) 
t1/2 
(h) 
UXX-001 
 
 
 
 
 
 
UXX-002 
 
 
 
 
 
 
UXX-003 
 
 
 
 
 
 
…