Conditions: NSCLC Stage IV
Keywords: Lung cancer Chemotherapy
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 35
Healthy volunteers: no

Brief summary:
This Phase II study will recruit 40 metastatic non-small cell lung cancer patients who failed treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. All recruited patients will receive AB-16B5 at a dose of 12 mg/kg once weekly combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks.

Detailed description:
This is an open-label, single-arm, multi-center Phase II trial of AB-16B5 in combination with docetaxel in previously treated subjects with metastatic non-small cell lung cancer who have experienced disease progression following treatment with a platinum-containing doublet treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or sequentially. Approximately 40 subjects will be enrolled in this trial and receive AB-16B5 at a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1. One cycle of treatment will consist of 21 days (3 weeks). The safety profile of the AB-16B5 and docetaxel combination will be examined during a safety lead-in period with the first 8 subjects completing one cycle of treatment. No dose escalation will be performed but a decision to de-escalate the AB-16B5 dose could be made using the modified toxicity probability interval method.

Subjects will be evaluated every 6 weeks with radiographic imaging to assess response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria for determination of the objective response rate (ORR) and progression free survival (PFS). Paired tumor biopsies (pre-treatment and on-treatment) will be collected in all subjects. Study treatment will continue until there is evidence of disease progression, treatment-related adverse events of unacceptable severity, subject request for discontinuation or Investigator determination that further treatment is not in the subject's best interest. Treatment through progression will be allowed if the Investigator considers the subject to be clinically stable. Subjects who must discontinue docetaxel due to toxicity will continue on AB-16B5.

Arms:
arm 1: AB-16B5 at a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1.

Interventions: intervention 1: AB-16B5 intervention 2: Docetaxel
Intervention descriptions: intervention 1: AB-16B5 is an inhibitor of the epithelial to mesenchymal transition. It is a fully humanized monoclonal antibody of IgG2 isotype against tumor-associated secreted clusterin (TA-sCLU). intervention 2: Docetaxel is an anticancer chemotherapy drug approved in the treatment of non-small cell lung cancer

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
Study Title: 
A Phase II Study of AB-16B5 combined with Docetaxel in 
Previously Treated Subjects with Metastatic Non-Small Cell 
Lung Cancer – EGIA-002 Study 
NCT Number: 
NCT04364620 
Protocol Date 
 30 October 2023 
 


 
 
 
 
 
Clinical Study Protocol  
AB-16B5-201 
 
Study Title: 
A Phase II Study of AB-16B5 combined with Docetaxel in 
Previously Treated Subjects with Metastatic Non-Small Cell 
Lung Cancer – EGIA-002 Study 
Study Number: 
AB-16B5-201 
Study Phase: 
II 
Indication: 
Treatment of metastatic non-small cell lung cancer (NSCLC) 
Principal Investigator: 
 
 
 
Sponsor: 
Alethia Biotherapeutics Inc. 
 
Sponsor Contact: 
Julie Laurin, B. Pharm., Ph.D. 
 
 
Sponsor Address: 
141 President-Kennedy Ave. 
Suite SB-5100, 5th floor 
Montreal, Quebec 
Canada H2X 1Y4 
 
 
Date 
Protocol: 
Amendment No. 4 
 
7 May 2020  
30 October 2023 
 
Confidentiality Statement 
 
This document contains proprietary and confidential information of the Sponsor. Acceptance 
of this document constitutes agreement by the recipient that no unpublished information 
contained herein will be published or disclosed without prior written approval from the 
Sponsor, except that this document may be disclosed to study personnel under your 
supervision who need to know the contents for conducting the study and appropriate 
Institutional Review Boards under the condition that they are requested to keep it 
confidential. The foregoing shall not apply to disclosure required by governmental 
regulations or laws; however, the Sponsor must be promptly informed of any such 
disclosure. 


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SPONSOR SIGNATURE PAGE 
Type of Document: 
 Protocol 
 
 
 Protocol amendment 
Protocol Title: 
A Phase II Study of AB-16B5 combined with Docetaxel in Previously 
Treated Subjects with Metastatic Non-Small Cell Lung Cancer 
Protocol Number: 
AB-16B5-201 
Protocol Date: 
30 October 2023 
This clinical study protocol was subject to critical review and has been approved by the Sponsor.  
 


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INVESTIGATOR’S AGREEMENT 
I will provide copies of the protocol, any subsequent amendments and access to all information 
provided by the Sponsor to the study personnel under my supervision. I will discuss this material 
with them to ensure that they are fully informed about the investigational study agent and the study 
protocol. I agree to conduct this clinical trial according to the protocol described herein, except 
when mutually agreed to in writing with the Sponsor. I also agree to conduct this study in 
compliance with Good Clinical Practice (GCP) standards as defined by the International 
Conference on Harmonisation (ICH) Guideline for Good Clinical Practice, all applicable national, 
state, and local regulations, as well as the requirements of the appropriate Research Ethics Board 
and any other institutional requirements. 
 
Principal Investigator: 
 
 
Signature: 
 
 
 
 
 
Date:  
 
 
 
 
 
 
 
 


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PRIMARY REASONS FOR THIS AMENDMENT 
 
 
 
 
  
 
 
 


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TABLE OF CONTENTS 
 
SPONSOR SIGNATURE PAGE ................................................................................................. 2 
INVESTIGATOR’S AGREEMENT ........................................................................................... 3 
PRIMARY REASONS FOR THIS AMENDMENT .................................................................. 4 
1. 
STUDY SYNOPSIS ............................................................................................................. 10 
2. 
LIST OF ABREVIATIONS ................................................................................................ 18 
3. 
INTRODUCTION ............................................................................................................... 22 
4. 
STUDY OBJECTIVES ....................................................................................................... 35 
4.1 
PRIMARY OBJECTIVES ................................................................................................... 35 
4.2 
SECONDARY OBJECTIVES .............................................................................................. 35 


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5. 
STUDY DESIGN ................................................................................................................. 35 
5.1 
SAFETY LEAD-IN PERIOD ............................................................................................... 36 
5.2 
FUTILITY ANALYSIS ....................................................................................................... 37 
5.3 
DATA SAFETY MONITORING BOARD ............................................................................. 38 
6. 
INCLUSION AND EXCLUSION CRITERIA ................................................................. 38 
6.1 
INCLUSION CRITERIA ..................................................................................................... 38 
6.2 
EXCLUSION CRITERIA .................................................................................................... 40 
7. 
STUDY TREATMENT ....................................................................................................... 41 
7.1.2 
Docetaxel ................................................................................................................ 42 
7.2 
TREATMENT DURATION ................................................................................................. 42 
7.3 
STUDY TREATMENT DOSE REDUCTION ......................................................................... 43 
7.3.2 
Docetaxel Dose Reduction ..................................................................................... 43 
7.4 
AB-16B5 AND DOCETAXEL DRUG ACCOUNTABILITY .................................................. 43 
8. 
STUDY FLOW CHART ..................................................................................................... 44 
9. 
STUDY PROCEDURES ..................................................................................................... 47 
9.1 
SUBJECT INFORMED CONSENT ...................................................................................... 47 
9.2 
INCLUSION/EXCLUSION CRITERIA ................................................................................ 47 
9.3 
MEDICAL HISTORY ........................................................................................................ 47 
9.4 
PRIOR AND CONCOMITANT MEDICATIONS ................................................................... 47 
9.4.1 
Prior Medications .................................................................................................. 47 
9.4.2 
Concomitant Medications ..................................................................................... 48 
9.4.3 
Subsequent Anti-Cancer Treatment .................................................................... 48 
9.5 
ADVERSE EVENT MONITORING ..................................................................................... 48 
9.6 
PHYSICAL EXAMINATION ............................................................................................... 48 
9.6.1 
Complete Physical Examination .......................................................................... 48 


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9.6.2 
Directed Physical Examination ............................................................................ 48 
9.7 
VITAL SIGNS, BODY WEIGHT AND HEIGHT .................................................................. 49 
9.8 
ELECTROCARDIOGRAM (ECG) ..................................................................................... 49 
9.9 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE SCALE .......... 49 
9.10 
TUMOR IMAGING AND ASSESSMENT OF DISEASE ...................................................... 49 
9.10.1 
Initial Tumor Imaging ....................................................................................... 49 
9.10.2 
Tumor Imaging During the Trial ..................................................................... 49 
9.10.3 
Assessment of Disease by RECIST 1.1 ............................................................. 50 
9.12 
SAFETY LABORATORY EVALUATIONS ....................................................................... 51 
9.13 
PHARMACOKINETIC/PHARMACODYNAMIC EVALUATIONS ....................................... 52 
9.13.1 
Blood Collection for Plasma AB-16B5 ............................................................. 52 
9.13.2 
Blood Collection for Anti-AB-16B5 Antibodies .............................................. 53 
10. 
VISIT REQUIREMENTS ............................................................................................... 53 
10.1 
SCREENING .................................................................................................................. 53 
10.2 
TREATMENT CYCLES .................................................................................................. 54 
10.3 
END OF TREATMENT ................................................................................................... 54 
10.4 
POST-TREATMENT ...................................................................................................... 54 
10.4.1 
Safety Follow-Up ................................................................................................ 54 
10.4.2 
Survival Follow-Up ............................................................................................ 54 
11. 
ADVERSE EVENT REPORTING ................................................................................. 54 
11.1 
DEFINITIONS ............................................................................................................... 54 
11.2 
REPORTING ADVERSE EVENTS TO THE SPONSOR ..................................................... 55 
11.3 
LABORATORY ABNORMALITIES AS ADVERSE EVENTS .............................................. 55 
11.4 
REPORTING A PREGNANCY ........................................................................................ 56 
11.5 
INVESTIGATOR EVALUATION OF ADVERSE EVENTS ................................................. 56 
11.6 
FOLLOW-UP OF ADVERSE EVENTS ............................................................................. 57 


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11.7 
REPORTING SERIOUS ADVERSE EVENTS TO THE RESEARCH ETHICS BOARD ......... 58 
12. 
STATISTICAL ANALYSIS ............................................................................................ 58 
12.2 
SAFETY LEAD-IN PERIOD ........................................................................................... 59 
12.3 
DATA HANDLING ........................................................................................................ 60 
12.4 
ANALYSIS POPULATIONS ............................................................................................ 60 
12.4.1 
Clinical Activity Evaluable Population ............................................................ 60 
12.4.2 
mITT Population ................................................................................................ 60 
12.4.3 
Safety Population ............................................................................................... 60 
12.4.4 
DLT Evaluable Population ............................................................................... 60 
12.4.5 
PK Evaluable Population .................................................................................. 61 
12.4.6 
Pharmacodynamic (PD) Evaluable Population .............................................. 61 
12.5 
EFFICACY ENDPOINTS DEFINITIONS AND ANALYSES ................................................ 61 
12.5.1 
Objective Response Rate ................................................................................... 61 
12.5.2 
Clinical Benefit Rate .......................................................................................... 61 
12.5.3 
Duration of Response ......................................................................................... 61 
12.5.4 
Duration of Clinical Benefit .............................................................................. 62 
12.5.5 
Duration of Stable Disease ................................................................................ 62 
12.5.6 
Progression-Free Survival ................................................................................. 62 
12.5.7 
Overall Survival ................................................................................................. 62 
12.5.9 
Subgroup Analyses ............................................................................................ 63 
12.6 
SAFETY DATA PRESENTATIONS AND SUMMARIES ..................................................... 63 
12.6.1 
Adverse Events ................................................................................................... 63 
12.6.2 
Prior and Concomitant Medications ................................................................ 63 
12.6.3 
Clinical and Laboratory Assessments .............................................................. 63 
12.6.4 
Subject Demographics, Baseline Characteristics and Disposition ................ 63 
12.6.5 
Analysis of Study Treatment Dosing ................................................................ 64 
12.7 
OTHER STUDY ENDPOINTS ......................................................................................... 64 


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12.7.1 
Pharmacokinetic Analysis ................................................................................. 64 
12.7.2 
12.8 
INTERIM ANALYSES .................................................................................................... 64 
13. 
STUDY ADMINISTRATION ......................................................................................... 64 
13.1 
INFORMED CONSENT .................................................................................................. 64 
13.2 
RESEARCH ETHIC BOARD REVIEW AND APPROVAL ................................................. 65 
13.3 
PROTOCOL COMPLIANCE ........................................................................................... 65 
13.4 
PROTOCOL REVISIONS ............................................................................................... 65 
13.5 
DATA ENTRY INTO ECRF ........................................................................................... 65 
13.6 
STUDY MONITORING .................................................................................................. 66 
13.7 
RETENTION OF RECORDS ........................................................................................... 66 
13.8 
FINANCIAL DISCLOSURE ............................................................................................ 67 
13.9 
STUDY OR STUDY SITE TERMINATION ....................................................................... 67 
13.10 
CLINICAL STUDY REPORT .......................................................................................... 67 
14. 
REFERENCES ................................................................................................................. 68 
 
 
 
 
 
 
 
 


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1. STUDY SYNOPSIS 
Study Title: A Phase II Study of AB-16B5 combined with Docetaxel in Previously Treated 
Subjects with Metastatic Non-Small Cell Lung Cancer – EGIA-002 Study 
Abbreviated Title: AB-16B5 combined with Docetaxel in NSCLC 
Study Number: AB-16B5-201  
Study Phase: II 
Study Period: 2020-2021 
Study Design: 
This is an open-label, single-arm, multi-center Phase II trial of AB-16B5 in combination with 
docetaxel in previously treated subjects with metastatic non-small cell lung cancer who have 
experienced disease progression following treatment with a platinum-containing doublet 
treatment and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously 
or sequentially. Approximately 40 subjects will be enrolled in this trial and receive AB-16B5 at 
a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 
75 mg/m2 once every 3 weeks on Day 1. One cycle of treatment will consist of 21 days 
(3 weeks). The safety profile of the AB-16B5 and docetaxel combination will be examined 
during a safety lead-in period with the first 8 subjects completing one cycle of treatment or 
experiencing a DLT during Cycle 1 and being part of the DLT Evaluable population (as defined 
in Section 12.4.4). No dose escalation will be performed but a decision to de-escalate the AB-
16B5 dose could be made using the modified toxicity probability interval method.  
Radiographic imaging will be performed every 6 weeks until disease progression to assess 
response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria 
for determination of the objective response rate (ORR) and progression free survival (PFS). 
Paired tumor biopsies (pre-treatment and on-treatment) will be collected in all subjects. Adverse 
events will be monitored throughout the study and graded for severity according to the NCI 
Common Terminology Criteria for Adverse Events (CTCAE). Study treatment will continue 
until there is evidence of disease progression (defined according to RECIST 1.1), treatment-
related adverse events of unacceptable severity, subject request for discontinuation or 
Investigator determination that further treatment is not in the subject’s best interest. Treatment 
through progression will be allowed if the Investigator considers the subject to be clinically 
stable (see Section 7.2 for definition of clinically stable).  
Subjects who must discontinue AB-16B5 or docetaxel due to toxicity or any reasons other than 
progressive disease will continue the other treatment (AB-16B5 or docetaxel). Subjects who 
must discontinue both AB-16B5 and docetaxel for reasons other than progressive disease will 
remain in the study to obtain tumor imaging until disease progression. 
A futility analysis will also be conducted with a minimum of 10 evaluable subjects (i.e., subjects 
who are part of the Clinical Activity Evaluable Population as defined in Section 12.4.1). 


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Monitoring of responses will be done every 8 subjects thereafter until up to 34 evaluable subjects 
are obtained or the trial is stopped for futility. The trial will be stopped for futility if either 0 
confirmed response out of 10 subjects, 1 confirmed response out of 18, 2 confirmed responses 
out of 26 or 6 confirmed responses out of 34 are obtained. If more than 6 confirmed responses 
are obtained out of 34 evaluable subjects, AB-16B5 in combination with docetaxel will be 
considered promising. 
Objectives: 
Primary Objectives:  
• To determine the objective response rate (ORR) per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the safety and tolerability of the combination of AB-16B5 and docetaxel 
Secondary Objectives: 
• To determine the clinical benefit rate (complete response (CR), partial response (PR) and 
stable disease (SD)) per RECIST 1.1 and the duration of clinical benefit in subjects receiving 
the combination of AB-16B5 and docetaxel 
• To determine the duration of response (CR and PR) per RECIST 1.1 in subjects receiving 
the combination of AB-16B5 and docetaxel 
• To determine the duration of stable disease per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the progression free survival (PFS) per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the overall survival (OS) in subjects receiving the combination of AB-16B5 
and docetaxel 
• To determine the pharmacokinetics of AB-16B5 in this subject population 
 
 
 
 
 


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Diagnosis and Criteria for Inclusion: 
Inclusion Criteria 
Subjects enrolled in the study must meet the following inclusion criteria: 
1. Subjects (male or non-pregnant female) must be ³ 18 years of age on the day of signing 
the informed consent.  
2. Subjects with a histologically or cytologically confirmed diagnosis of (Stage III-IV) non-
small cell lung cancer (NSCLC) and with at least one measurable lesion defined by 
RECIST 1.1.  
3. Subjects must have experienced a disease progression following treatment with an  
anti-PD1 or PD-L1 immune checkpoint antibody and a platinum-containing doublet 
treatment, administered simultaneously or sequentially.  
4. Subjects with a targetable driver mutation in EGFR or ALK gene will be allowed on trial 
after failing all available targeted therapies and having experienced a disease progression 
following treatment with an anti-PD1 or PD-L1 immune checkpoint antibody and a 
platinum-containing doublet treatment, administered simultaneously or sequentially. 
5. Subjects must have adequate organ and immune function as indicated in the table below 
 
 


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System 
Laboratory Value 
Hematological 
Absolute neutrophil count (ANC) 
³ 1.5 X 109/L (1,500 cells/mm3) 
Platelets 
³ 100 X 109/L (100,000 cells/mm3) 
Hemoglobin 
³ 90 g/L 
Hepatic 
Total bilirubin 
£ ULN 
AST (SGOT) and ALT (SGPT) 
£ 1.5 X ULN, unless secondary to liver metastases 
Alkaline phosphatase 
£ 2.5 X ULN 
Renal 
Creatinine clearancea 
³ 50 mL/min 
Coagulation 
International Normalized Ratio (INR)  
£ 1.5 X ULNb 
Creatinine clearance should be calculated using the Cockcroft-Gault Method:  
Formula to use when serum creatinine is expressed in mg/dL: 
CrCl = [(140-age) X weight (kg) X (0.85 for females only)] / (72 X serum creatinine (mg/dL)) 
Formula to use when serum creatinine is expressed in µmol/L: 
CrCl = 1.23 X [(140-age) X weight (kg) X (0.85 for females only)] / (serum creatinine (µmol/L))  
bif subject is receiving anticoagulant therapy, then INR must be within therapeutic range. 
6. Subjects must have a tumor lesion amenable for biopsies with no contraindication for 
biopsy.  
7. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance 
status of £ 2. 
8. Subjects must have a life expectancy of at least 3 months. 
9. Subjects must have recovered from the toxic effects resulting from the most recent 
cancer treatment to Grade 1 or less. If the subjects underwent major surgery or received 
radiation therapy, they must have recovered from the complications and/or toxicity. 
10. Female subjects of childbearing potential must have a negative serum pregnancy test 
within 72 hours prior to the first dose of study treatment.  
11. Subjects (both male and female) of reproductive potential must be willing to practice 
highly effective methods of contraception throughout the study and for up to 90 days 


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after the last dose of study medication. Abstinence is acceptable if this is the subject’s 
usual lifestyle. 
12. Female subjects are not considered of childbearing potential if they have a history of 
surgical sterility or evidence of post-menopausal status defined as any of the following: 
o ³ 45 years of age and has not had menses for more than 2 years. 
o Amenorrhoeic for < 2 years without hysterectomy and oophorectomy and a 
follicle stimulating hormone (FSH) value in the postmenopausal range at 
screening. 
o Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy 
or oophorectomy must be confirmed with medical records of the actual procedure 
or by ultrasound. Tubal ligation must be confirmed with medical records of the 
actual procedure. 
13. Subjects must understand and be able and willing and likely to fully comply with the 
study procedures, including scheduled follow-up, and restrictions. 
14. Subjects must have given written personally signed and dated informed consent to 
participate in the study in accordance with the International Conference on 
Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any 
study related procedures. 
Exclusion Criteria 
1) Subjects who have received prior therapy with AB-16B5. 
2) Subjects who have received prior therapy with docetaxel for the treatment of NSCLC. 
3) Subjects who are currently participating or has participated in a study of an 
investigational agent or using an investigational device within 21 days of the first dose 
of study treatment. The 21-day window should be calculated using the last dose of an 
antineoplastic investigational agent or last use of an investigational device with 
antineoplastic intent. 
4) Subjects who have received any anti-cancer treatment within 3 weeks or radiation 
therapy within 2 weeks prior to receiving the first dose of study treatment or who have 
not recovered from adverse events to Grade 1 or less. Subjects with alopecia are eligible 
to participate. 
5) Subjects who are expected to require any other form of systemic or localized 
antineoplastic therapy while on the trial. This includes maintenance therapy with another 
agent or radiation therapy. 


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6) Subjects who are receiving a dose > 10 mg/day of prednisone (or equivalent) within 
7 days prior to the first dose of study treatment or any other form of immunosuppressive 
medication (corticosteroid pre-treatment and/or post-treatment of docetaxel is allowed).  
7) Subjects who require treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, 
itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, 
saquinavir, telithromycin and voriconazole). Subjects may be included if there is an 
alternate treatment with a weak CYP3A4 inhibitor and they are willing to change at least 
7 days prior to the first dose of study treatment.  
8) Subjects who have another malignancy that is progressing or requires active treatment. 
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin 
or in situ cervical cancer. 
9) Subjects who have known active central nervous system metastases and/or 
carcinomatous meningitis. Subjects with previously treated brain metastases may 
participate if they have been clinically stable for at least 2 weeks prior to the first dose 
of study treatment, if they have no evidence of new or enlarging brain metastases and if 
they are not receiving a dose > 10 mg/day of prednisone (or equivalent) within 7 days 
prior to the first dose of study treatment. 
10) Subjects with clinically significant ECG abnormalities.  
11) Subjects who have received or will receive a live vaccine within 30 days prior to the first 
dose of study treatment.  
12) Subjects with a known history of human immunodeficiency (HIV). 
13) Subjects with an active Hepatitis B or C infection. 
14) Subjects with an active infection requiring antibiotic therapy. 
15) Subjects with a known history of alcohol or other substance abuse within the last year. 
16) Subjects with known hypersensitivity to docetaxel or drugs formulated with polysorbate 
80. 
17) Subjects who have a history or current evidence of any condition, therapy or laboratory 
abnormalities that may confound the results of the trial, interfere with the subject’s 
participation for the full duration of the trial or if it is not in the best interest of the subject 
to participate in the trial. 
18) Subjects with medical, social or psychosocial factors that, in the opinion of the treating 
Investigator, could impact the safety or compliance with study procedures. 
19) Subjects who are pregnant or lactating or who are expecting to conceive or father 
children within the projected duration of the trial through 90 days after the last dose of 
AB-16B5 or the last dose of docetaxel. 


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Statistical Methodology: 
This is a single arm Phase II study with a safety lead-in period and a futility analysis. To assess 
efficacy, the primary endpoint ORR will use a Predictive Probability Design (PPD)1. The PPD 
is a flexible design that allows for the possibility to stop before the end of the trial if the treatment 
is not efficacious enough (futility). 
 
 
 
 
  
 
 
 
 
 
Safety Lead-in Period 
The assumptions to be applied in establishing the mTPI2 methodology are: 
• the maximum tolerated dose (MTD) is defined to have 0.30 probability of toxicity; and 
• the acceptable variance around the MTD is ± 0.05 (i.e., the region of the MTD is 25% to 
35% incidence of dose limiting toxicity (DLT)). 
The mTPI model will determine the number of toxicities relative to subjects enrolled in the 
safety lead-in before the dose de-escalation decision is made. No dose escalation will be allowed. 
The number of subjects with DLTs observed relative to the number of subjects treated at a 
specific dose determines whether dose de-escalation is needed. The treatment will be considered 
acceptable if no more than 3 subjects experienced a DLT during the first cycle in the first 8 
subjects treated and being part of the DLT Evaluable population. De-escalation to AB-16B5 9 


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mg/kg will be performed if more than 3 subjects experienced a DLT in the first 8 subjects treated. 
The next three subjects will then be evaluated at this lower dose. If 0 or 1 subject experienced a 
DLT during the first cycle in these 3 subjects, the AB-16B5 9 mg/kg dose will be considered 
acceptable. A final de-escalation of AB-16B5 to 6 mg/kg will be performed if more than 1 
subject experienced a DLT at 9 mg/kg and the safety profile will be evaluated using the same 
process as described above. 
For these purposes, a DLT will be defined as a ≥ Grade 3 non-hematologic toxicity occurring 
during Cycle 1 of therapy. In addition, the following hematologic toxicities will be considered 
as a DLT: 
• Grade ≥ 4 neutropenia or thrombocytopenia > 7 days 
• Grade ≥ 3 thrombocytopenia with bleeding 
• Grade ≥ 3 febrile neutropenia 
Toxicities that are clearly and incontrovertibly due to disease progression or to extraneous 
causes will not be considered DLTs. In addition, the following non-hematologic toxicities will 
not be considered DLTs: 
• Grade 3 arthralgia or myalgia which returns to Grade ≤ 1 within < 7 days with 
appropriate supportive care 
• Grade 3 nausea, vomiting or diarrhea which returns to Grade ≤ 1 within < 72 hours with 
appropriate supportive care 
• Grade 3 fatigue lasting < 7 days 
• Grade 3 electrolyte abnormalities that last less than 72 hours and are not associated with 
clinical symptoms 
• Grade 3 amylase or lipase elevation which is not associated with symptoms or clinical 
manifestations of pancreatitis 
Statistical Analyses 
The primary endpoint of ORR will be tested using PPD. Descriptive statistics including the 
number of evaluable subjects, the percentage of subjects, and the 95% confidence interval will 
be presented for ORR and clinical benefit rate. Duration of response, duration of stable disease, 
duration of clinical benefit, PFS and OS will be analyzed using Kaplan-Meier method to account 
for censoring data. 
Pharmacokinetic Analyses 
Noncompartmental analysis (NCA) of pharmacokinetic data will be conducted using standard 
approaches which will be defined in a separate analysis plan. If feasible, the peak concentration 
(Cmax), area under the concentration time curve (AUC), clearance (CL), volume of distribution 
(Vz) and half-life will be reported.  Summary statistics will be provided. 
The pharmacokinetic data may also be evaluated using a population pharmacokinetics approach. 


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2. LIST OF ABREVIATIONS 
 
 
 
 
 
 
 
 
 


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3. INTRODUCTION 
 
 
 
 
 
 
 
 
 
 


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4. STUDY OBJECTIVES 
4.1 
PRIMARY OBJECTIVES 
The primary objectives of this study are: 
• To determine the objective response rate (ORR) per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the safety and tolerability of the combination of AB-16B5 and docetaxel 
4.2 
SECONDARY OBJECTIVES  
The secondary objectives of this study are: 
• To determine the clinical benefit rate (complete response (CR), partial response (PR) and stable 
disease (SD)) per RECIST 1.1 and the duration of clinical benefit in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the duration of response (CR and PR) per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the duration of stable disease per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the progression free survival (PFS) per RECIST 1.1 in subjects receiving the 
combination of AB-16B5 and docetaxel 
• To determine the overall survival (OS) in subjects receiving the combination of AB-16B5 and 
docetaxel 
• To determine the pharmacokinetics of AB-16B5 in this subject population 
 
 
 
 
  
5. STUDY DESIGN 
This is an open-label, single-arm, multi-center Phase II trial of AB-16B5 in combination with 
docetaxel in previously treated subjects with metastatic non-small cell lung cancer who have 
experienced disease progression following treatment with a platinum-containing doublet treatment 
and an anti-PD1 or PD-L1 immune checkpoint antibody, administered simultaneously or 


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sequentially. Approximately 40 subjects will be enrolled in this trial and receive AB-16B5 at a 
dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 
once every 3 weeks on Day 1. One cycle of treatment will consist of 21 days (3 weeks). The safety 
profile of the AB-16B5 and docetaxel combination will be examined during a safety lead-in period 
with the first 8 subjects completing one cycle of treatment or experiencing a DLT during Cycle 1 
and being part of the DLT Evaluable population (as defined in Section 12.4.4).  
Radiographic imaging will be performed every 6 weeks until disease progression to assess 
response to treatment using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria 
for determination of the objective response rate (ORR) and progression free survival (PFS). A 
futility analysis will be conducted to minimize subject exposure to an ineffective treatment. Paired 
tumor biopsies (pre-treatment and on-treatment) will be collected in all subjects. Adverse events 
will be monitored throughout the study and graded for severity according to the NCI Common 
Terminology Criteria for Adverse Events (CTCAE). Study treatment will continue until there is 
evidence of disease progression (defined according to RECIST 1.1), treatment-related adverse 
events of unacceptable severity, subject request for discontinuation or Investigator determination 
that further treatment is not in the subject’s best interest. Treatment beyond progression will be 
allowed if the Investigator considers the subject to be clinically stable (see Section 7.2 for 
definition of clinically stable).  
Subjects who must discontinue AB-16B5 or docetaxel due to toxicity or any reasons other than 
progressive disease will continue on the other treatment (AB-16B5 or docetaxel). Subjects who 
must discontinue both AB-16B5 and docetaxel for reasons other than progressive disease will 
remain in the study to obtain tumor imaging until disease progression. 
5.1 
SAFETY LEAD-IN PERIOD 
The safety profile of AB-16B5 at a dose of 12 mg/kg administered once weekly on Days 1, 8 and 
15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1 will be examined 
during a safety lead-in period with the first 8 subjects completing one cycle of treatment or 
experiencing a DLT during Cycle 1 and being part of the DLT Evaluable population. No dose 
escalation will be performed but a decision to de-escalate the dose of AB-16B5 could be made 
using the modified toxicity probability interval method (mTPI)2. 
The study treatment will be considered acceptable if no more than 3 subjects experienced a DLT 
during the first cycle in the first 8 subjects treated.  
For these purposes, a DLT will be defined as a Grade ≥ 3 non-hematologic toxicity occurring 
during Cycle 1 of therapy. In addition, the following hematologic toxicities will be considered as 
a DLT: 
• Grade ≥ 4 neutropenia or thrombocytopenia > 7 days 
• Grade ≥ 3 thrombocytopenia with bleeding 


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• Grade ≥ 3 febrile neutropenia 
Toxicities that are clearly and incontrovertibly due to disease progression or to extraneous causes 
will not be considered DLTs. In addition, the following non-hematologic toxicities will not be 
considered DLTs: 
• Grade 3 arthralgia or myalgia which returns to Grade ≤ 1 within < 7 days with appropriate 
supportive care 
• Grade 3 nausea, vomiting or diarrhea which returns to Grade ≤ 1 within < 72 hours with 
appropriate supportive care 
• Grade 3 fatigue lasting < 7 days 
• Grade 3 electrolyte abnormalities that last less than 72 hours and are not associated with 
clinical symptoms 
• Grade 3 amylase or lipase elevation which is not associated with symptoms or clinical 
manifestations of pancreatitis 
De-escalation of AB-16B5 will be performed if more than 3 subjects experienced a DLT in the 
first 8 subjects treated.  
The next three subjects will then be treated with AB-16B5 at 9 mg/kg AB-16B5 administered once 
weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks 
on Day 1. If 0 or 1 subject experienced a DLT during the first cycle in these 3 subjects, AB-16B5 
at the 9 mg/kg dose will be considered acceptable.  
If more than 1 subject experienced a DLT, a final de-escalation of AB-16B5 to 6 mg/kg will be 
performed and the safety profile will be evaluated using the same process as described above. 
5.2 
FUTILITY ANALYSIS 
A futility analysis will also be conducted with a minimum of 10 evaluable subjects (i.e., subjects 
who are part of the Clinical Activity Evaluable Population as defined in Section 12.4.1). 
Monitoring of responses will be done every 8 subjects thereafter until up to 34 evaluable subjects 
are obtained or the trial is stopped for futility. The trial will be stopped for futility if either 0 
confirmed response out of 10 subjects, 1 confirmed response out of 18, 2 confirmed responses out 
of 26 or 6 confirmed responses out of 34 are obtained. If more than 6 confirmed responses are 
obtained out of 34 evaluable subjects, AB-16B5 in combination with docetaxel will be considered 
promising.   
Futility will be assessed once the number of evaluable patients is obtained at each review of the 
data. If the confirmation of a response is crucial for the decision making (e.g., if there is only one 
unconfirmed response out of the 10 first evaluable patients), the decision to stop for futility will 
be postponed until there is a second scan for confirmation. A detailed set of rules and review 


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timelines will be presented in a futility assessment charter which will be completed prior to the 
enrollment of the tenth patient in the study. 
5.3 
DATA SAFETY MONITORING BOARD 
A Data Safety Monitoring Board (DSMB) composed of an independent oncologist, the Principal 
Investigator, the medical monitor, the biostatistician and a sponsor representative will meet to 
review the safety lead-in data and to determine the safe dose to continue the study enrollment.   
6. INCLUSION AND EXCLUSION CRITERIA 
6.1 
INCLUSION CRITERIA 
Subjects enrolled in the study must meet the following inclusion criteria: 
1) Subjects (male or non-pregnant female) must be ³ 18 years of age on the day of signing 
the informed consent.  
2) Subjects with a histologically or cytologically confirmed diagnosis of (Stage III-IV) non-
small cell lung cancer (NSCLC) and with at least one measurable lesion defined by 
RECIST 1.1.  
3) Subjects must have experienced a disease progression following treatment with an anti-
PD1 or PD-L1 immune checkpoint antibody and a platinum-containing doublet treatment, 
administered simultaneously or sequentially. 
4) Subjects with a targetable driver mutation in EGFR or ALK gene will be allowed on trial 
after failing all available targeted therapies and having experienced a disease progression 
following treatment with an anti-PD1 or PD-L1 immune checkpoint antibody and a 
platinum-containing doublet treatment, administered simultaneously or sequentially. 
5) Subjects must have adequate organ and immune function as indicated in the table below:  
System 
Laboratory Value 
Hematological 
Absolute neutrophil count (ANC) 
³ 1.5 X 109/L (1,500 cells/mm3) 
Platelets 
³ 100 X 109/L (100,000 cells/mm3) 
Hemoglobin 
³ 90 g/L 
Hepatic 
Total bilirubin 
£ ULN 
AST (SGOT) and ALT (SGPT) 
£ 1.5 X ULN, unless secondary to liver 
metastases 
Alkaline phosphatase 
£ 2.5 X ULN 
Renal 


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Creatinine clearancea 
³ 50 mL/min 
Coagulation 
International Normalized Ratio (INR)  
£ 1.5 X ULNb 
aCreatinine clearance should be calculated using the Cockcroft-Gault Method:  
Formula to use when serum creatinine is expressed in mg/dL: 
CrCl = [(140-age) X weight (kg) X (0.85 for females only)] / (72 X serum creatinine (mg/dL)) 
Formula to use when serum creatinine is expressed in µmol/L: 
CrCl = 1.23 X [(140-age) X weight (kg) X (0.85 for females only)] / (serum creatinine (µmol/L)) 
bif subject is receiving anticoagulant therapy, then INR must be within therapeutic range. 
6) Subjects must have a tumor lesion amenable for biopsies with no contraindication for 
biopsy.  
7) Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status 
of £ 2. 
8) Subjects must have a life expectancy of at least 3 months. 
9) Subjects must have recovered from the toxic effects resulting from the most recent cancer 
treatment to Grade 1 or less. If the subjects underwent major surgery or received radiation 
therapy, they must have recovered from the complications and/or toxicity. 
10) Female subjects of childbearing potential must have a negative serum pregnancy test within 
72 hours prior to the first dose of study treatment.  
11) Subjects (both male and female) of reproductive potential must be willing to practice highly 
effective methods of contraception throughout the study and for up to 90 days after the last 
dose of study medication. Abstinence is acceptable if this is the subject’s usual lifestyle. 
12) Female subjects are not considered of childbearing potential if they have a history of 
surgical sterility or evidence of post-menopausal status defined as any of the following: 
o ³ 45 years of age and has not had menses for more than 2 years. 
o Amenorrhoeic for < 2 years without hysterectomy and oophorectomy and a follicle 
stimulating hormone (FSH) value in the postmenopausal range at screening. 
o Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or 
oophorectomy must be confirmed with medical records of the actual procedure or 
by ultrasound. Tubal ligation must be confirmed with medical records of the actual 
procedure. 
13) Subjects must understand and be able and willing and likely to fully comply with the study 
procedures, including scheduled follow-up, and restrictions. 
14) Subjects must have given written personally signed and dated informed consent to 
participate in the study in accordance with the International Conference on Harmonization 


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(ICH) Good Clinical Practice (GCP) Guidelines, before completing any study related 
procedures. 
6.2 
EXCLUSION CRITERIA 
Subjects enrolled in the study must not meet the following exclusion criteria: 
1) Subjects who have received prior therapy with AB-16B5. 
2) Subjects who have received prior therapy with docetaxel for the treatment of NSCLC. 
3) Subjects who are currently participating or has participated in a study of an investigational 
agent or using an investigational device within 21 days prior to the first dose of study 
treatment. The 21-day window should be calculated using the last dose of an antineoplastic 
investigational agent or last use of an investigational device with antineoplastic intent. 
4) Subjects who have received any anti-cancer treatment within 3 weeks or radiation therapy 
within 2 weeks prior to receiving the first dose of study treatment or who have not 
recovered from adverse events to Grade 1 or less. Subjects with alopecia are eligible to 
participate. 
5) Subjects who are expected to require any other form of systemic or localized antineoplastic 
therapy while on the trial. This includes maintenance therapy with another agent or 
radiation therapy. 
6) Subjects who are receiving a dose > 10 mg/day of prednisone (or equivalent) within 7 days 
prior to the first dose of study treatment or any other form of immunosuppressive 
medication (corticosteroid pre-treatment and/or post-treatment of docetaxel is allowed).  
7) Subjects who require treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, 
itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, 
saquinavir, telithromycin and voriconazole). Subjects may be included if there is an 
alternate treatment with a weak CYP3A4 inhibitor and they are willing to change at least 
7 days prior to the first dose of study treatment.  
8) Subjects who have another malignancy that is progressing or requires active treatment. 
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin 
or in situ cervical cancer. 
9) Subjects who have known active central nervous system metastases and/or carcinomatous 
meningitis. Subjects with previously treated brain metastases may participate if they have 
been clinically stable for at least 2 weeks prior to the first dose of study treatment, if they 
have no evidence of new or enlarging brain metastases and if they are not receiving a dose 
> 10 mg/day of prednisone (or equivalent) within 7 days prior to the first dose of study 
treatment.  
10) Subjects with clinically significant ECG abnormalities.  


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11) Subjects who have received or will receive a live vaccine within 30 days prior to the first 
dose of study treatment.  
12) Subjects with a known history of human immunodeficiency (HIV). 
13) Subjects with an active Hepatitis B or C infection. 
14) Subjects with an active infection requiring antibiotic therapy. 
15) Subjects with a known history of alcohol or other substance abuse within the last year. 
16) Subjects with known hypersensitivity to docetaxel or drugs formulated with polysorbate 
80. 
17) Subjects who have a history or current evidence of any condition, therapy or laboratory 
abnormalities that may confound the results of the trial, interfere with the subject’s 
participation for the full duration of the trial or if it is not in the best interest of the subject 
to participate in the trial. 
18) Subjects with medical, social or psychosocial factors that, in the opinion of the treating 
Investigator, could impact the safety or compliance with study procedures. 
19) Subjects who are pregnant or lactating or who are expecting to conceive or father children 
within the projected duration of the trial through 90 days after the last dose of AB-16B5 or 
the last dose of docetaxel. 
7. STUDY TREATMENT 
7.1 
 
 
 
  
 
  
 
 


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7.1.2 
Docetaxel 
Docetaxel will be administered at the dosage of 75 mg/m2 by a 60-minute IV infusion once every 
3 weeks on Day 1. Docetaxel will be prepared and administered as per approved product 
label/monograph and hospital standard practices.  
All subjects should be premedicated with corticosteroids as per hospital standard practices. Vein 
extravasation and accidental spillages should be dealt with according to the hospital standard 
practices.   
7.2 
TREATMENT DURATION 
One cycle of treatment will consist of 21 days (3 weeks).   
Study treatment will continue until there is evidence of disease progression, unacceptable toxicity, 
subject requests discontinuation of study treatment, or the Investigator feels that further treatment 
is not in the subject’s best interest. Subjects who must discontinue AB-16B5 or docetaxel due to 
toxicity or any reasons other than progressive disease may continue on the other treatment (AB-
16B5 or docetaxel). 
Treatment beyond progression will be allowed if the Investigator considers the subject to be 
clinically stable. The clinical judgment decision by the site should be based on the clinical stability 
of the subjects as defined below:  
Clinical stability is defined as the following:  
• Absence of symptoms and signs indicating clinically significant progression of disease, 
including worsening of laboratory values  
• No decline in ECOG performance status  
• Absence of rapid progression of disease  
• Absence of progressive tumor at critical anatomical sites (e.g., cord compression) 
requiring urgent alternative medical intervention 


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Any subject deemed clinically unstable should be discontinued from trial treatment at first 
radiologic evidence of PD.  
Subjects who must discontinue both AB-16B5 and docetaxel for reasons other than progressive 
disease will remain in the study to obtain tumor imaging until disease progression. 
7.3 
STUDY TREATMENT DOSE REDUCTION 
 
 
 
 
 
 
 
7.3.2 
Docetaxel Dose Reduction 
Subjects who experience either febrile neutropenia, neutrophils < 500 cells/mm3 for more than one 
week, severe or cumulative cutaneous reactions, or other Grade ≥ 3 non-hematological toxicities 
that is judged to be related to docetaxel should have treatment withheld until resolution of the 
toxicity and then resumed at 60 mg/m2. Based upon subject’s condition, treatment with AB-16B5 
may continue during this cycle and the start of a new cycle could be delayed by one week. In this 
case, a fourth dose of AB-16B5 would be administered in the cycle.  
Subjects who develop Grade ≥ 3 peripheral neuropathy should have docetaxel discontinued.  
7.4 
AB-16B5 AND DOCETAXEL DRUG ACCOUNTABILITY 
Accurate records of all drug shipments reconstituted and dispensed AB-16B5, and record of all 
drug that is returned must be accounted for on an AB-16B5 Study Drug Accountability Form 
provided to the Investigator by the Sponsor. This inventory record must be available for inspection 


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by the Study Monitor during regular monitoring visits. AB-16B5 Drug supplies are to be used only 
in accordance with this protocol and under the supervision of the Investigator. 
Any study drug requiring destruction must be destroyed according to the hospital standard 
practices. At the end of the study, the final drug accountability reconciliation will take place. The 
overall number of vials shipped to the center, and the number of vials destroyed or returned will 
be provided by the pharmacy, and an account given of any discrepancy.  
Docetaxel accountability should also be maintained as per the hospital standard practice.  
8. STUDY FLOW CHART 
The Study Flow Chart (Table 5) summarizes the trial procedures to be performed at each visit. 
Individual trial procedures are described in detail below. It may be necessary to perform these 
procedures at unscheduled time points if deemed clinically necessary by the Investigator. 
Furthermore, additional evaluations/testing may be deemed necessary by the Investigator and or 
the Sponsor for reasons related to subject safety. In these cases, such evaluations/testing will be 
performed as per standard clinical practices. 


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Table 5: 
Schedule of Study Procedures/Assessments 
 
Screening 
Phase 
Treatment Cycles (21-Day Cycles)1 
End of 
Treatment 
Post-Treatment3 
Treatment Cycle 
Screening  
12 
22 
32 
42 
52 
62 
72 
8 and 
beyond2 
Discontinuation 
(DC) 
Safety 
Follow-Up 
Survival 
Follow-Up 
Scheduling Window (Days) 
-28 to -1 
 
 
 
 
 
 
 
 
At time of DC 
30 Days 
Post Last 
Treatment 
Every 12 
Weeks 
Informed Consent 
x 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
x 
 
 
 
 
 
 
 
 
 
 
 
Demographics and Medical History 
x 
 
 
 
 
 
 
 
 
 
 
 
Prior and Concomitant Medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
NSCLC Disease and Prior Treatment 
x 
 
 
 
 
 
 
 
 
 
 
 
Subsequent Anti-Cancer Treatment 
 
 
 
 
 
 
 
 
 
 
x 
x 
Survival Status 
 
 
 
 
 
 
 
 
 
 
 
x 
Clinical Procedures/Assessments 
Review of Adverse Events 
 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Complete Physical Examination 
x 
 
 
 
 
 
 
 
 
x 
 
 
Directed Physical Examination 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Vitals Signs4 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Body Weight 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Height 
x 
 
 
 
 
 
 
 
 
 
 
 
12-Lead ECG5 
x 
 
 
 
 
 
 
 
 
 
 
 
ECOG 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
 
Efficacy Measurement 
Tumor Imaging6 
x 
 
x 
 
x 
 
x 
 
x 
x 
 
 
Laboratory Procedures/Assessments (Local Laboratory) 
Pregnancy Test8 
x 
 
 
 
 
 
 
 
 
x 
 
 
Coagulation Test 
x 
 
 
 
 
 
 
 
 
 
 
 
Hematology   
x 
x9 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Clinical Biochemistry 
x 
x9 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
Urinalysis 
x 
 
x 
 
x 
 
x 
 
x10 
 
 
 
Laboratory Procedures/Assessments (Central Laboratory) 
AB-16B5 Pharmacokinetics11 
 
x 
x 
 
x 
 
 
 
x11 
 
 
 
Anti-AB-16B5 Antibodies12 
 
x 
x 
 
x 
 
 
 
x12 
x 
 
 


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Study Treatment Administration 
AB-16B513 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
Docetaxel14 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
 
 
 
 
 
 
 
 
 
 


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9. STUDY PROCEDURES 
9.1 
SUBJECT INFORMED CONSENT 
The Investigator must obtain documented consent from each potential subject or each subject’s 
legally acceptable representative prior to participating in a clinical study.  
Informed consent form must be documented by the subject’s dated signature or by the subject’s 
legally acceptable representative’s dated signature on a consent form along with the dated 
signature of the person conducting the consent discussion. A copy of the signed and dated informed 
consent form should be given to the subject before participation in the study. 
The initial informed consent form, any subsequent revised written informed consent form and any 
written information provided to the subject must receive the IRB/EC’s approval/favorable opinion 
in advance of use. The subject or his/her legally acceptable representative should be informed in a 
timely manner if new information becomes available that may be relevant to the subject’s 
willingness to continue participation in the study. The communication of this information will be 
provided and documented via a revised consent form or addendum to the original consent form 
that captures the subject’s dated signature or by the subject’s legally acceptable representative’s 
dated signature. 
The informed consent will adhere to IRB/EC requirements, applicable laws and regulations and 
Sponsor requirements. 
9.2 
INCLUSION/EXCLUSION CRITERIA 
All inclusion and exclusion criteria will be reviewed by the Investigator to ensure that the subject 
qualifies for the study. 
9.3 
MEDICAL HISTORY 
A medical history will be obtained by the Investigator. Medical history will include all active 
conditions and any condition diagnosed within the prior 10 years that are considered to be 
clinically significant by the Investigator.  
The Investigator will obtain prior and current details regarding the subject’s lung cancer. These 
details will be recorded separately and not listed as medical history. 
9.4 
PRIOR AND CONCOMITANT MEDICATIONS 
9.4.1 
Prior Medications 
The Investigator will review and record prior medication taken by the subject within 1 month prior 
to study treatment start.  
The Investigator will review and record all prior anti-cancer treatments including systemic 
treatments, radiation, and surgeries, regardless of the time prior to first dose of trial treatment. 


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Prior anti-cancer treatment for NSCLC will be recorded separately and not listed as a prior 
medication.  
9.4.2 
Concomitant Medications 
The Investigator will record all concomitant medications taken by the subjects during the study.  
The subject must not receive other anti-cancer therapy or investigational drugs while on study. 
Palliative radiotherapy may be given; however, the irradiated lesions will not be evaluated for 
response. Supportive treatments will be given according to label instructions as medically 
indicated for subjects.   
During the post-treatment period, only concomitant medications related to adverse events 
requiring a follow-up will be recorded.  
9.4.3 
Subsequent Anti-Cancer Treatment 
The Investigator will review all new anti-cancer therapy initiated after the last dose of study 
treatment. If a subject initiates a new anti-cancer therapy within 30 days after the end of treatment, 
the 30-day Safety Follow-Up visit must occur before the first new dose of the new therapy. Once 
new anti-cancer therapy has been initiated, the subject will move into Survival Follow-Up.  
9.5 
ADVERSE EVENT MONITORING 
Safety will be assessed by physical examination, measurement of vital signs, clinical laboratory 
evaluations and electrocardiogram. Clinically significant changes in these parameters will be 
captured as adverse events (AEs).  
The Investigator is responsible for the appropriate medical care and the safety of subjects who 
have entered this study. The Investigator must document all AEs and notify the Sponsor of any 
serious adverse event (SAE) experienced by subjects who have entered this study. 
Refer to Section 11 for detailed information regarding the assessment and recording of AEs.  
9.6 
PHYSICAL EXAMINATION 
9.6.1 
Complete Physical Examination 
The Investigator will perform a complete physical exam during the screening period. Clinically 
significant abnormal findings should be recorded as medical history. After the first dose of trial 
treatment, new clinically significant abnormal findings should be recorded as AEs. A complete 
physical exam will also be performed at the end of treatment. 
9.6.2 
Directed Physical Examination 
For treatment cycles, the Investigator will perform a directed physical exam as clinically indicated 
prior to trial treatment administration. New clinically significant abnormal findings should be 
recorded as AEs.  


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9.7 
VITAL SIGNS, BODY WEIGHT AND HEIGHT 
Vitals signs will be measured at screening, within 48 hours prior to each study treatment 
administration (i.e., Day 1, Day 8 and Day 15 of each cycle) and at the end of treatment. Vital 
signs will include temperature, pulse, respiratory rate and blood pressure. Body weight will be 
measured at screening, within 48 hours prior to Day 1 of each cycle and at the end of treatment. 
Height will be measured at screening only. 
9.8 
ELECTROCARDIOGRAM (ECG) 
12-lead ECG assessments will be performed after resting for 5 minutes and will include heart rate, 
PR, QRS, RR, QT, QTc. This test will be performed at screening only. Additional 12-lead ECG 
assessments may be performed as clinically indicated. 
9.9 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE SCALE 
The Investigator will assess ECOG status at screening, within 48 hours prior to the study treatment 
administration on Day 1 of each cycle, at the end of treatment and during the Safety Follow-Up.  
9.10 
TUMOR IMAGING AND ASSESSMENT OF DISEASE  
Tumor imaging should be acquired by computed tomography (CT, strongly preferred). Magnetic 
resonance imaging (MRI) should be used when CT is contraindicated or for imaging in the brain. 
The same imaging technique regarding modality and use of contrast should be used in a subject 
throughout the trial to optimize the visualization of existing and new tumor burden.  
Local site Investigator/radiology assessment based on RECIST 1.1 will be used to determine 
subject eligibility.  
9.10.1 
Initial Tumor Imaging  
Initial tumor imaging at screening must be performed within 28 days prior to the study treatment 
start. The site study team must review screening images to confirm the subject has measurable 
disease per RECIST 1.1.  
Scans performed as part of routine clinical management are acceptable for use as screening tumor 
imaging if they are of diagnostic quality and performed within 28 days prior to the date of study 
treatment start.  
9.10.2 
Tumor Imaging During the Trial  
Tumor assessments during study treatment will be performed every 6 weeks at the end (between 
Day 16 and Day 21) of every even numbered cycle of treatment (i.e., Cycles 2, 4, 6, etc.) or more 
frequently if clinically indicated.  
In subjects who discontinue the study treatment due to documented disease progression, no 
additional tumor imaging is required.  


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Subjects who discontinue both AB-16B5 and docetaxel for reasons other than progressive disease 
will be re-evaluated at the time of treatment discontinuation unless a tumor assessment was 
performed within the previous four weeks. Additional tumor imaging will then be performed 
approximately every 6 weeks after the last tumor imaging until disease progression (unless the 
Investigator elects to continue treatment beyond progression), the start of new anti-cancer 
treatment or withdrawal of consent, whichever occurs first. 
Partial and complete response should be confirmed by a repeat tumor imaging assessment. The 
tumor imaging for confirmation of response will be performed at the earliest 4 weeks after the first 
indication or at the next scheduled scan, whichever is clinically indicated.  
9.10.3 
Assessment of Disease by RECIST 1.1 
RECIST 1.1 will be used as the primary measure for assessment of the objective response rate 
(ORR), clinical benefit rate, duration of response, duration of stable disease and progression free 
survival (PFS).  
 
 
 
 
 
 
  


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9.12 
SAFETY LABORATORY EVALUATIONS 
Clinical laboratory tests will be performed locally at the clinical center. Laboratory tests for 
screening must be performed within 28 days prior to the first dose of study treatment. A serum 
pregnancy test will be done within 72 hours prior to the first cycle of treatment (Cycle 1) and at 
the end of treatment for all females with an intact uterus, regardless of age, unless amenorrhoeic 
for the previous 12 months. A coagulation test will be performed at screening only. However, 
subjects receiving anticoagulant therapy must be monitored closely during the study.  
During Cycle 1, hematology and clinical biochemistry will be performed within 48 hours prior to 
each study treatment administration (i.e., Day 1, Day 8 and Day 15). From Cycle 2 and onward, 
hematology and clinical biochemistry will be performed within 48 hours prior to the study 
treatment administration on Day 1 only. Urinalysis will be performed at every 2 cycles.  
Laboratory results must be known and acceptable prior to dosing on Day 1 of each cycle.  
The following laboratory parameters will be evaluated: 
Hematology 
Clinical Biochemistry 
Urinalysis 
Other 
Absolute neutrophil count 
Albumin 
Blood 
INR 
Hemoglobin 
Alkaline phosphatase 
Glucose 
aPTT/PTT 
Hematocrit 
ALT 
Microscopic exam  
(if abnormal results are 
noted) 
 
Platelet count 
Amylase 
 
Red blood cell count 
AST 
Protein 
 
White blood cell count  
(total and differential) 
Bicarbonate 
Specific gravity 
 
Calcium 
 
 
 
Chloride 
 
 
 
Creatinine 
 
 
 
Creatinine clearance 
 
 
 
Glucose 
 
 
 
Lipase 
 
 
 
Magnesium 
 
 
 
Phosphate 
 
 
 
Potassium 
 
 
 
Sodium 
 
 
 
Total Bilirubin 
 
 
 
Total Protein 
 
 
 
Urea 
 
 
 
Uric acid 
 
 


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9.13 
PHARMACOKINETIC/PHARMACODYNAMIC EVALUATIONS 
9.13.1 
Blood Collection for Plasma AB-16B5  
Blood samples (approximately 10 mL per sample) for the assay of AB-16B5 will be collected from 
all subjects to define the pharmacokinetic properties of AB-16B5 when administered intravenously 
once weekly. Blood samples will be collected throughout the study at the following time-points: 
   Cycle 
   Day 
Time-point 
1 
1 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
2 hours after starting AB-16B5 infusion 
3 
48 hours after starting AB-16B5 infusion  
8 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
15 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
2 
1 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
2 hours after starting AB-16B5 infusion 
8 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
15 
Prior to starting AB-16B5 infusion 
0.5 hour after starting AB-16B5 infusion  
1 hour (immediately prior to the end of AB-16B5 infusion)  
16-21 
On the day of the scan or the biopsy 
4 
1 
Prior to starting AB-16B5 infusion 
8 
1 
Prior to starting AB-16B5 infusion 
Every 4 cycles 
thereafter 
1 
Prior to starting AB-16B5 infusion 
There will be no pharmacokinetic blood samples collected beyond Cycle 36. Clinical staff is 
encouraged to take the blood samples at the scheduled time-point; however, deviations from the 
scheduled sample times are not considered protocol deviations. Blood should not be collected from 


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the same vein used to administer AB-16B5. Samples should be stored at the clinical site at -70°C 
until shipment to the assigned bioanalytical laboratory for analysis.   
9.13.2 
Blood Collection for Anti-AB-16B5 Antibodies 
Blood samples (approximately 5 mL per sample) will be collected from all subjects to determine 
the presence of anti-AB-16B5 antibodies (ADA).   
Anti-AB-16B5 antibody (ADA) samples will be collected prior to the infusion of AB-16B5 on 
Day 1, Day 8 and Day 15 of Cycle 1, on Day 1 of Cycles 2 and 4 and on Day 1 of every 4 cycles 
thereafter. An ADA sample will also be collected at the End of Treatment visit. 
   Cycle 
   Day 
Time-point 
1 
1 
Prior to starting AB-16B5 infusion 
8 
Prior to starting AB-16B5 infusion 
15 
Prior to starting AB-16B5 infusion 
2 
1 
Prior to starting AB-16B5 infusion 
4 
1 
Prior to starting AB-16B5 infusion 
Every 4 cycles thereafter 
1 
Prior to starting AB-16B5 infusion 
There will be no ADA blood samples collected beyond Cycle 36. Similarly, no ADA blood 
samples will be collected at End of Treatment visit for subjects continuing treatment beyond Cycle 
36. Samples should be stored at the clinical site at -70°C until shipment to the assigned 
bioanalytical laboratory for analysis.  
 
 
10. VISIT REQUIREMENTS 
10.1 
SCREENING 
Visit requirements are outlined in Section 8 - Study Flow Chart. Specific procedure-related details 
are provided above in Section 9 - Study Procedures. 
Approximately 28 days prior to randomization, potential subjects will be evaluated to determine 
that they fulfill the entry requirements as set forth in Section 6. Screening procedures may be 
repeated after consultation with the Sponsor. 
Written consent must be obtained prior to performing any protocol specific procedure. Results of 
a test performed prior to the subject signing consent as part of routine clinical management are 
acceptable in lieu of a screening test if performed within the specified time frame. Screening 


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procedures are to be completed within 28 days prior to the first dose of study treatment except for 
the following: 
• For women of reproductive potential, a pregnancy test will be performed within 
72 hours prior to first dose of study treatment.  
10.2 
TREATMENT CYCLES 
Visit requirements are outlined in Section 8 - Study Flow Chart. Specific procedure-related details 
are provided above in Section 9 - Study Procedures. 
10.3 
END OF TREATMENT 
The End of Treatment visit should be conducted when both AB-16B5 and docetaxel are 
discontinued. Visit requirements are outlined in Section 8 - Study Flow Chart. Specific procedure-
related details are provided above in Section 9 - Study Procedures. 
10.4 
POST-TREATMENT 
10.4.1 
Safety Follow-Up 
The mandatory Safety Follow-Up Visit should be conducted approximately 30 days (± 7 days) 
after the last dose of study treatment or before the initiation of a new anti-cancer treatment, 
whichever comes first.  
10.4.2 
Survival Follow-Up 
Survival Follow-Up contacts by telephone will be made every 12 weeks (± 2 weeks) after the 
Safety Follow-Up Visit to assess survival for survival status. Subjects with a related AE of Grade 
³ 2 will be further followed until the resolution of the AE to Grade £ 1 or until beginning of a new 
anti-cancer treatment, whichever occurs first. Survival Follow-Up contacts will continue until 
either death, withdrawal of consent, or the end of the study, whichever occurs first.  
11. ADVERSE EVENT REPORTING 
11.1 
DEFINITIONS 
Adverse Event (AE): Any unfavorable or unintended sign, symptom, or disease that is temporally 
associated with the use of a study treatment but is not necessarily caused by the study treatment.  
This includes worsening (e.g., increase in frequency or severity) of pre-existing conditions.  
Serious Adverse Event (SAE): An adverse event resulting in any of the following outcomes: 
• death 
• is life-threatening (i.e. an immediate threat to life) 
• insubject hospitalization* 
• prolongation of an existing hospitalization 


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• persistent or significant disability/incapacity 
• congenital anomaly/birth defect 
• is medically important+ 
*An insubject hospitalization is defined as an admission for any length of time.  A hospitalization 
for the administration of study treatment, for routine or planned clinical procedures, or for “social” 
reasons (not the result of any adverse change in the subject’s condition) should not be considered 
an adverse event and should not be reported as a serious adverse event. If the subject experiences 
any adverse change in condition during hospitalization, the condition must be reported as an 
adverse event or serious adverse event according to the above definitions.  
+Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately life-
threatening or result in death or result in hospitalization but may jeopardize the subject or may 
require intervention to prevent one of the other outcomes listed above.  
Unexpected Adverse Event: An adverse event, the nature or severity of which is not consistent 
with the applicable product information (e.g. Investigator’s Brochure for an unapproved study 
agent or package insert/summary of product characteristics for an approved product). Expected 
means that the event has previously been observed with the study treatment and is identified and/or 
described in the applicable product information. It does not mean that the event is expected with 
the underlying disease(s) or concomitant medications. 
11.2 
REPORTING ADVERSE EVENTS TO THE SPONSOR 
All adverse events that are identified from the start of study treatment administration (Day 1) 
through 30 days following administration of the last dose of study treatment will be recorded on 
the Adverse Event Electronic Case Report Form (AE eCRF). All data fields on the AE eCRF must 
be completed.  
Serious Adverse Events must also be recorded on the SAE Worksheet and sent to the Drug Safety 
designee within 24 hours of site personnel becoming aware of the SAE. The SAE Worksheet 
should be completed as much as possible but should not be held until all information is available.  
Additional information, follow-up information, and corrections should be provided on subsequent 
updates of the SAE Worksheet that are clearly identified as follow-up (#1, #2, etc.) reports. The 
SAE Worksheets should be sent to the Sponsor using the Drug Safety contact information and 
process as provided on the SAE Worksheet. 
Drug Safety personnel will be available to answer questions and assist site personnel in 
documenting SAEs and completing the SAE worksheet.  
11.3 
LABORATORY ABNORMALITIES AS ADVERSE EVENTS 
A laboratory abnormality should be reported as an adverse event if it is associated with an 
intervention. Intervention includes, but is not limited to, discontinuation of treatment, dose 


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reduction/delay, or concomitant therapy. In addition, any medically important laboratory 
abnormality may be reported as an adverse event at the discretion of the Investigator. This includes 
laboratory abnormalities for which there is no intervention, but the abnormal value(s) suggests a 
disease or organ toxicity. If clinical sequelae are associated with a laboratory abnormality, the 
diagnosis or medical condition should be reported (e.g., renal failure, hematuria) not the laboratory 
abnormality (e.g., elevated creatinine, urine RBC increased). 
11.4 
REPORTING A PREGNANCY 
All pregnancies are reported up to 30 days following the last dose of study treatment. A pregnancy 
must be reported to the Drug Safety designee as soon as the site becomes aware of the pregnancy. 
The Drug Safety designee will send an acknowledgement memorandum to the Investigator along 
with a Pregnancy Assessment Form. A follow-up Pregnancy Assessment Form will be sent to the 
site every 3 months. Pregnancy Assessment Forms must be completed by the Investigator until 
delivery, elective termination of the pregnancy, or miscarriage. The Investigator is responsible for 
following the subject’s pregnancy to final outcome.  
Pregnancies are not considered adverse events. Complications or medical problems associated 
with a pregnancy are considered AEs and may be SAEs. Complications or medical problems are 
reported as AEs/SAEs if they occur during the study follow-up period (30 days after the last dose 
of study treatment) according to the procedure described in Section 11.2. 
11.5 
INVESTIGATOR EVALUATION OF ADVERSE EVENTS 
Severity will be graded using the NCI CTCAE Version 5.0. The CTCAE Version 5.0 may be 
downloaded 
from 
the 
Cancer 
Treatment 
Evaluation 
Program 
(CTEP) 
website 
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf). In the event that an AE does not have a CTCAE code, the following severity 
classifications will be used: 
Severity: 
Grade 
Severity 
Description 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated.  
2 
Moderate 
Minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL). 
Instrumental ADL refer to preparing meals, shopping for groceries 
and clothes, using the telephone, managing money, etc.  
3 
Severe 
Severe or medically significant but not immediately life-
threatening; hospitalization or prolongation of hospitalization 
indicated; disabling; limiting self-care ADL. Self-care ADL refer to 
bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden.  
4 
Life-threatening* 
Life-threatening consequences; urgent intervention indicated.  


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Grade 
Severity 
Description 
5 
Death 
Death related to AE. 
*Note – a severity assessment of life-threatening is not necessarily the same as the seriousness 
criterion of life-threatening. The former means that the event is a potential threat to life. The latter 
means that the event is an immediate threat to life. 
Causality: 
For each AE, the Investigator should determine and document whether there exists a reasonable 
possibility that any component of the study treatment caused or contributed to the AE. The 
Investigator’s assessment should be recorded in the source document. If the Investigator does not 
know whether or not the study treatment is causally related to the event, reporting for study 
purposes will be as at least “possibly related” to study treatment. The initial causality assessment 
may be revised as new information becomes available (see table below). 
Relationship to Drug  
Description  
Definitely Related  
Exhibits previously known toxicity of agent; or  
Follows a reasonable temporal sequence from administration of the 
drug;  
Follows a known or expected response pattern to the suspected drug;  
Is confirmed by stopping or reducing the dosage of the drug; and  
Is not explained by any other reasonable hypothesis. 
Probably Related 
Follows a reasonable temporal sequence from the time of study drug 
administration; and/or  
Follows a known response pattern to the study drug. 
Possibly Related  
Follows a reasonable temporal sequence from the time of study drug 
administration; and/or  
Follows a known response pattern to the study drug; but could have 
been produced by other factors such as the patient’s clinical state, 
therapeutic intervention, or concomitant therapy. 
Unlikely Related  
Does not follow a reasonable temporal sequence from the time of 
study drug administration; and  
Was likely produced by other factors such as the patient’s clinical 
state, therapeutic intervention or concomitant therapy, but for which 
relationship cannot be definitely ruled out. 
Not related 
The adverse event can be determined with certainty to have no 
relationship to the study drug. 
11.6 
FOLLOW-UP OF ADVERSE EVENTS 
Adverse events that have not resolved by the end of the safety follow-up period will be recorded 
as ongoing. However, subjects with a related AE of Grade ³ 2 will be further followed (during 
Survival Follow-Up) until the resolution of the AE to Grade £ 1 or until beginning of a new anti-
cancer treatment, whichever occurs first. 
SAEs that have not resolved by the end of the safety follow-up period are followed until final 
outcome is known. If it is not possible to obtain a final outcome for a SAE (e.g., the subject is lost 
to follow up), the reason that a final outcome could not be obtained will be documented by the 
Investigator. 


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SAEs that occur after the safety follow-up (i.e., 30 days after the last dose of the study treatment) 
that are assessed by the Investigator to be related to study agent must be reported to the Drug 
Safety designee on the SAE worksheet.  
11.7 
REPORTING SERIOUS ADVERSE EVENTS TO THE RESEARCH ETHICS BOARD 
All SAEs that are considered unexpected and related to the study agent will be reported by the 
Sponsor or designee as expedited (i.e., 15-Day) reports to the appropriate regulatory authorities 
AND to all participating Investigators. In addition, the Sponsor or designee follows all applicable 
local and national regulatory requirements regarding safety reporting. Each Investigator must also 
comply with the applicable regulatory requirements related to the reporting of SAEs to the 
Institutional Review Board/Ethics Committee (IRB/EC) responsible for reviewing the study at 
their site, as well as the regulatory authority(ies) (if applicable). 
12. STATISTICAL ANALYSIS 
Final statistical analyses (excluding interim analyses) will be performed once that last enrolled 
subject has completed 4 cycles of treatment or has progressed, whichever comes first, and that the 
database has been locked.  
 
  
 
 
 


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12.2 
SAFETY LEAD-IN PERIOD 
The assumptions to be applied in establishing the mTPI2 methodology are: 
• the maximum tolerated dose (MTD) is defined to have 0.30 probability of toxicity; and 
• the acceptable variance around the MTD is ± 0.05 (i.e., the region of the MTD is 25% to 
35% incidence of dose limiting toxicity (DLT)). 
The mTPI model will determine the number of toxicities relative to subjects enrolled in the safety 
lead-in before the dose de-escalation decision is made. No dose escalation will be allowed. The 
number of subjects with DLTs observed relative to the number of subjects treated at a specific 
dose determines whether dose de-escalation is needed. The treatment will be considered acceptable 
if no more than 3 subjects experienced a DLT during the first cycle in the first 8 subjects treated 
and being part of the DLT Evaluable population. De-escalation to AB-16B5 9 mg/kg dose will be 
performed if more than 3 subjects experienced a DLT in the first 8 subjects treated. The next three 
subjects will then be evaluated at this lower dose. If 0 or 1 subject experienced a DLT during the 
first cycle in these 3 subjects, the AB-16B5 9 mg/kg dose will be considered acceptable. A final 
de-escalation of AB-16B5 to 6 mg/kg will be performed if more than 1 subject experienced a DLT 
at 9 mg/kg and the safety profile will be evaluated using the same process as described above.  
For these purposes, a DLT will be defined as a Grade ≥ 3 non-hematologic toxicity occurring 
during Cycle 1 of therapy. In addition, the following hematologic toxicities will be considered as 
a DLT: 
• Grade ≥ 4 neutropenia or thrombocytopenia > 7 days 
• Grade ≥ 3 thrombocytopenia with bleeding 
• Grade ≥ 3 febrile neutropenia 
Toxicities that are clearly and incontrovertibly due to disease progression or to extraneous causes 
will not be considered DLTs. In addition, the following non-hematologic toxicities will not be 
considered DLTs: 
• Grade 3 arthralgia or myalgia which returns to Grade ≤ 1 within < 7 days with appropriate 
supportive care 
• Grade 3 nausea, vomiting or diarrhea which returns to Grade ≤ 1 within < 72 hours with 
appropriate supportive care 
• Grade 3 fatigue lasting < 7 days 
• Grade 3 electrolyte abnormalities that last less than 72 hours and are not associated with 
clinical symptoms 


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• Grade 3 amylase or lipase elevation which is not associated with symptoms or clinical 
manifestations of pancreatitis 
12.3 
DATA HANDLING 
Listings of all subject data will be prepared. Data summaries will be presented in tabular and/or 
graphical format and summarized descriptively, where appropriate. Detailed analyses will be 
described in the SAP. 
For all variables, only the observed data from subjects will be used in the statistical analyses; there 
is no plan to estimate missing data. Subjects without a valid clinical response assessment will be 
assigned a best overall response of not evaluable (NE). Data from subjects who are lost to follow-
up or have missing observations before reaching an endpoint in any of the time-to-event analyses 
will be treated as censored with specific rules defined in the SAP. 
12.4 
ANALYSIS POPULATIONS 
12.4.1 
Clinical Activity Evaluable Population 
The Clinical Activity Evaluable population will include all subjects who receive at least one dose 
of each study treatment drug (AB-16B5 and Docetaxel) and have at least one on-study disease 
assessment (post-dose) or develop early progression and discontinue study treatment prior to the 
first planned on-study disease assessment. Subjects who discontinue both study treatment drugs 
due to any other reason prior to their on-study disease assessment will not be included in the 
Clinical Activity Evaluable population.  
This population will be used to evaluate futility rules as per PPD, to present tumor responses data 
and summary statistics. 
12.4.2 
mITT Population 
The modified Intent-to-Treat (mITT) population will include subjects who receive at least one 
dose of each study treatment (AB-16B5 and Docetaxel).  
This population will be used to present PFS and OS. 
12.4.3 
Safety Population 
The Safety population is defined as all subjects who received at least one dose of any study 
treatment drug (i.e., AB-16B5 or Docetaxel). The Safety population will be used for all safety 
analyses. 
12.4.4 
DLT Evaluable Population  
The DLT Evaluable population is defined as all subjects enrolled in the safety lead-in period who 
experienced a DLT during Cycle 1 or who completed one cycle of treatment (all 3 complete doses 
of AB-16B5 and 1 complete dose of Docetaxel). Subjects who are not evaluable for DLT will be 


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replaced. The DLT Evaluable population will be used to present the DLT AEs and for dose de-
escalation decisions during the safety lead-in period. 
12.4.5 
PK Evaluable Population 
The PK Evaluable population for the noncompartmental analysis is defined as all subjects who 
received AB-16B5 and have at least 3 measurable and adequately documented concentrations. 
The PK Evaluable population for the population pharmacokinetic analysis is defined as all subjects 
who received AB-16B5 and have at least one adequately documented concentration. 
12.4.6 
Pharmacodynamic (PD) Evaluable Population 
The PD Evaluable population will include all subjects who receive at least one dose of AB-16B5 
and have at least one measurable biomarker. 
12.5 
EFFICACY ENDPOINTS DEFINITIONS AND ANALYSES 
12.5.1 
Objective Response Rate 
Objective disease response will be categorized in accordance with RECIST 1.1.  
Objective response rate (ORR) is defined as the percent of subjects documented to have a 
confirmed complete response (CR) or partial response (PR).  
The primary endpoint of ORR will be tested using PPD. Descriptive statistics (frequency, 
percentage, and 95% CI) for ORR and best overall response (CR, PR, SD, PD, NE) will be 
presented.  
12.5.2 
Clinical Benefit Rate 
Clinical benefit rate (CBR) is defined as the percentage of subjects documented to have a 
confirmed complete response (CR) or partial response (PR), or stable disease (SD) documented 
during at least 2 on-study assessments and including at least 10 weeks on study (i.e., allowance for 
2-week window around Week 12 assessment).  
Descriptive statistics (frequency, percentage, and 95% CI) for CBR will be presented.  
12.5.3 
Duration of Response 
Duration of response (DOR) is defined as the time from date of the first documentation of objective 
tumor response (CR or PR) to the first documentation of objective progression of disease (PD) or 
to death due to any cause in the absence of documented PD. DOR will only be calculated for the 
subgroup of subjects achieving a confirmed CR or PR. The Kaplan Meier method will be used to 
estimate median DOR. Subjects with objective tumor response, and alive without PD at the end of 
the study will be censored at the date of their last tumor assessment. Other rules and time points 
for censoring for DOR will be specified in SAP. 


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12.5.4 
Duration of Clinical Benefit 
Duration of clinical benefit is defined as the time from date of the first documentation of clinical 
benefit to the first documentation of objective progression of disease (PD) or to death due to any 
cause in the absence of documented PD. Duration of clinical benefit will only be calculated for the 
subgroup of subjects achieving a clinical benefit. The Kaplan Meier method will be used to 
estimate median duration of clinical benefit. Subjects with clinical benefit, and alive without PD 
at the end of the study will be censored at the date of their last tumor assessment. Other rules and 
time points for censoring for duration of stable disease will be specified in SAP. 
12.5.5 
Duration of Stable Disease 
Duration of stable disease is defined as the time from date of the first documentation of stable 
disease to the first documentation of objective progression of disease (PD) or to death due to any 
cause in the absence of documented PD. Duration of stable disease will only be calculated for the 
subgroup of subjects achieving a stable disease as their best overall response. The Kaplan Meier 
method will be used to estimate median duration of stable disease. Subjects with stable disease, 
and alive without PD at the end of the study will be censored at the date of their last tumor 
assessment. Other rules and time points for censoring for duration of stable disease will be 
specified in SAP. 
12.5.6 
Progression-Free Survival 
Progression-free survival (PFS) is defined as the time from date of first study treatment to first PD 
or death due to any cause in the absence of documented PD. Censoring for the PFS endpoint will 
be assigned on the date of the last tumor assessment if no assessment of tumor progression is 
identified and the subject does not die while on study. For subjects in whom two or more sequential 
assessments are missed, followed by the finding of tumor progression, the PFS endpoint will be 
censored on the date of the last tumor assessment before the gap. Subjects lacking an evaluation 
of disease after first study treatment will have their PFS time censored on the date of first dose 
with duration of 1 day. Subjects who start a new anti-cancer therapy prior to documented PD will 
have the endpoint censored at the date of the last tumor assessment prior to the start of the new 
therapy. The Kaplan-Meier method will be used to obtain the estimate of median progression-free 
survival time.  
12.5.7 
Overall Survival 
Overall survival (OS) is defined as the time from date of first study treatment to death due to any 
cause. The Kaplan-Meier method will be used to estimate the median OS and 1-year Survival Rate. 
The 95% CI of the 1-year survival rate will also be reported. Censoring for the survival endpoint 
will be assigned on the date of the last on study follow-up that the subject is reported to be alive.  


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12.5.9 
Subgroup Analyses 
There will be no subgroup analyses. 
12.6 
SAFETY DATA PRESENTATIONS AND SUMMARIES 
12.6.1 
Adverse Events 
AEs will be classified using the medical dictionary for regulatory activities (MedDRA) 
classification system. Listings will include the verbatim term, Preferred Term (PT), and System 
Organ Class (SOC). The number of subjects with AEs and the incidence of AEs by SOC and PT 
will be summarized. AEs will be summarized by maximum intensity and relationship to study 
therapy. Separate summaries will be provided for AEs, SAEs, treatment-related AEs, treatment 
related SAEs, and other significant AEs (e.g., AEs leading to study discontinuation).  
12.6.2 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization (WHO) 
medical dictionary; subjects who received these medications will be listed and summarized.  
12.6.3 
Clinical and Laboratory Assessments 
Clinical and laboratory assessments include clinical laboratory tests (hematology, biochemistry, 
urinalysis and coagulation), vital signs, physical exams, ECOG, and 12 lead ECGs.  
All clinical laboratory results will be listed by subject. Hematology, biochemistry and urinalysis 
will be summarized descriptively, which will include a display of change from baseline. Selected 
parameters will be presented in shift tables of baseline (from normal to abnormal, abnormal to 
normal, etc.). Laboratory values outside of the normal ranges will be identified.  
Vital signs and ECG measurements will be listed for each subject at each available visit. For vital 
signs, descriptive statistics of observed values and changes from baseline will be summarized by 
treatment group. 
ECOG will be presented in terms of number and percentage of subjects in each category, by visit. 
12.6.4 
Subject Demographics, Baseline Characteristics and Disposition 
Demographic, baseline disease characteristics, medical history, primary disease history and prior 
systemic therapies/surgeries will be summarized and listed based on safety population. Subject 


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enrollment and disposition including reasons for study withdrawal and reasons for treatment 
discontinuation will be summarized. 
12.6.5 
Analysis of Study Treatment Dosing 
Study treatment administration will be described in terms of the duration of exposure, total number 
of cycles administered, for each agent separately and for the combination, compliance, cumulative 
dose and reasons for the deviations from planned therapy. 
12.7 
OTHER STUDY ENDPOINTS 
12.7.1 
Pharmacokinetic Analysis 
Noncompartmental analysis (NCA) of pharmacokinetic data will be conducted using standard 
approaches which will be defined in a separate analysis plan.  If feasible, the peak concentration 
(Cmax), area under the concentration time curve (AUC), clearance (CL), volume of distribution 
(Vz) and half-life will be reported.  Summary statistics will be provided. 
The pharmacokinetic data may also be evaluated using a population pharmacokinetics approach.   
 
 
 
 
12.8 
INTERIM ANALYSES 
Interim safety evaluation will be conducted once 8 evaluable subjects (i.e., part of the DLT-
evaluable population) are obtained. 
Interim futility evaluations will be conducted once 10 evaluable subjects (i.e., part of the Clinical 
Activity Evaluable population) are obtained and every 8 evaluable subjects thereafter. 
13. STUDY ADMINISTRATION 
13.1 
INFORMED CONSENT 
A copy of the proposed informed consent document must be submitted to the Sponsor or designee 
for review and comment prior to submission to the reviewing IRB/EC. The consent form must be 
approved by the IRB/EC and contain all elements required by national, state, local, and 
institutional regulations or requirements. 
It is the responsibility of the Investigator to provide each subject with full and adequate verbal and 
written information using the IRB/EC approved informed consent document(s), including the 
objective and procedures of the study and the possible risks involved before inclusion in the study. 


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Each subject must voluntarily provide written informed consent (including consent for the use and 
disclosure of research-related health information). The consent must be obtained prior to 
performing any study-related procedures that are not part of normal subject care, including 
screening and changes in medications including any washout of medications. A copy of the signed 
informed consent must be given to the study subject. 
13.2 
RESEARCH ETHIC BOARD REVIEW AND APPROVAL 
The Investigator or Sponsor shall assure that the IRB/EC, constituted in accordance with the ICH 
Guideline for Good Clinical Practice (GCP), will provide initial and continuing review of the 
study. Prior to shipment of the study treatment and enrollment of study subjects, documented 
IRB/REC approval of the protocol, informed consent form must be obtained and provided to the 
Sponsor or designee. 
The IRB/EC must also be informed of all protocol amendments prior to implementation. The 
Investigator must provide reports of any change in research activity (i.e. the completion, 
termination, or discontinuation of a study) to the IRB/EC. 
13.3 
PROTOCOL COMPLIANCE 
Except for a change that is intended to eliminate an apparent immediate hazard to a study subject, 
the protocol shall be conducted as described. Any such change must be reported immediately to 
the Sponsor and to the IRB/EC. 
13.4 
PROTOCOL REVISIONS 
Protocol amendments will be prepared and approved by the Sponsor. All protocol amendments 
will be signed by the Investigator and submitted to the IRB/EC for review prior to implementation. 
Documentation of IRB/EC approval must be forwarded to the Sponsor or designee. If an 
amendment significantly alters the study design, increases potential risk to the subject or otherwise 
affects statements in the informed consent form, the informed consent form must be revised 
accordingly and submitted to the IRB/EC for review and approval. The approved consent form 
must be used to obtain informed consent from new subjects prior to enrollment and must be used 
to obtain informed consent from subjects already enrolled if they are affected by the amendment. 
13.5 
DATA ENTRY INTO ECRF 
Study-specific eCRFs will be made available to the site. Study data, contained in source 
documentation, will be entered into the eCRFs for all subjects enrolled in the study. All pertinent 
data records are to be submitted to the sponsor during and/or at completion or termination of the 
study. 
The Investigator agrees that qualified representatives of the sponsor and regulatory agencies will 
have the right, both during and after this study, to conduct inspections and to audit and review 
medical records pertinent to the clinical study as permitted by the regulations. Subjects will not be 


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identified by name in any reports stemming from the study, and confidentiality of information in 
medical records will be preserved. The confidentiality of the subject will be maintained unless 
disclosure is required by regulations. Accordingly, the following statement (or similar statement) 
that permits the release of the subject’s medical records will be included in the informed consent 
document: Representatives of regulatory agencies, IRB/EC, the sponsor, and the subject’s 
personal physician may review the subject medical records and all information related to this 
study as permitted by law. Subject identity will remain confidential unless disclosure is required 
by law. 
13.6 
STUDY MONITORING 
The Sponsor or designee will monitor the study. Study monitors representing the Sponsor will 
routinely visit study sites throughout the trial.   
Routine monitoring visits will be conducted to: 
• Assure compliance with the study protocol; 
• Verify that the informed consent process was conducted before initiation of any screening 
procedures that are performed solely for the purpose of determining eligibility for the study 
and prior to the provision of study medication; 
• Verify that the protocol, protocol amendments, and safety information are submitted to the 
IRBs/EC and approved by the IRBs/EC in a timely manner; 
• Review the eCRFs and source documents to ensure that reported study data are accurate, 
complete, and verifiable from source documents; 
• Verify that the investigational products are stored properly and under the proper conditions, 
that they are in sufficient supply, and that receipt, use, and return of investigational 
products at the study centers are controlled and documented adequately; 
• Verify that the Investigator and study center personnel remain adequately qualified 
throughout the study; and 
• Verify that the research facilities, including laboratories and equipment, are maintained 
adequately to safely and properly conduct the study. 
Auditors representing the Sponsor may also evaluate the study and its monitors. For these 
purposes, the Investigator will make eCRFs and source documents available when requested.  
In addition, the study may be evaluated by representatives of the regulatory authorities, who will 
also be allowed access to study documents. The Investigator should promptly notify the Sponsor 
of any audits they have scheduled with any regulatory authority. 
13.7 
RETENTION OF RECORDS 
The Investigator shall retain all records and source documents pertaining to the study, including 
any films, tracings, computer discs or tapes. They will be retained for the longer of the maximum 


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period required by the country and institution in which the study is conducted, or the period 
specified by the Sponsor at the time the study is completed, terminated or discontinued. 
If the Investigator leaves the institution, the records shall be transferred to an appropriate designee 
who accepts the responsibility for record retention. Notice of such transfer shall be documented in 
writing and provided to the Sponsor. 
13.8 
FINANCIAL DISCLOSURE 
The Investigator will provide the Sponsor sufficient and accurate information on financial interests 
(proprietary or equity interests, payments exclusive of clinical trial costs) to allow complete 
disclosure to regulatory authorities. The Investigator shall promptly update this information if any 
relevant changes occur during the course of the investigation and for a period of 1 year following 
study completion. 
13.9 
STUDY OR STUDY SITE TERMINATION 
If the Sponsor, the Investigator, IRB/EC or a regulatory authority discovers conditions arising 
during the study that indicate that the study should be halted or that the study center should be 
terminated, this action may be taken after appropriate consultation between the Sponsor and the 
Investigator. Conditions that may warrant termination of the study include, but are not limited to, 
the following: 
• The discovery of an unexpected, serious, or unacceptable risk to the subjects enrolled in the 
study. 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product. 
The study site may warrant termination under the following conditions: 
• Failure of the Investigator to enroll subjects into the study at an acceptable rate. 
• Failure of the Investigator to comply with pertinent regulatory authority regulations. 
• Submission of knowingly false information from the research facility to the Sponsor, study 
monitor, or the regulatory authority. 
• Insufficient adherence to protocol requirements. 
13.10 CLINICAL STUDY REPORT 
The final CSR will be issued when all subjects enrolled in the study will have ended their 
participation in the trial. 
 


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14. REFERENCES 
 
 


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