Conditions: Solid Tumor, Adult Triple Negative Breast Cancer Head and Neck Squamous Cell Carcinoma Non Small Cell Lung Cancer
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 49
Healthy volunteers: no

Brief summary:
Approximately 90 male and female patients with documented solid tumor malignancies of epithelial origin that are locally advanced or metastatic, and either refractory to standard therapy or for whom no standard therapy is available, will be entered into this Phase 1a/2a, multicenter, open-label, dose-escalation, cohort study of AVID100. Phase 2a will include evaluation of patient with EGFR-overexpressing squamous histology non-small cell lung cancer, squamous cell carcinoma of the head and neck, and triple negative breast cancer

Detailed description:
On Day 1 of study, patients will receive study drug administered by 2-hour IV infusion. AVID100 will be administered once every 3 weeks (Q3W) with administration on Day 1 of the first week, followed by a 3-week recovery period. In Phase 2a AVID100 will be administered at a dose of 220 mg/m2.

Evidence of progressive disease at any point in the study will necessitate withdrawal of the patient from further participation so that alternative management of their malignancy may be considered. All patients will be followed to further evaluate safety as well as evidence of the anti-tumor effects of AVID100 in these selected patient populations. If anti-tumor activity is observed additional patients may be added to the planned Phase 2a patient populations to further characterize these effects.

Arms:
arm 1: Minimum of 1 to 3 patients per dose cohort; approximately 4 dose cohorts to be evaluated to establish the Maximum tolerated dose. arm 2: Addition of up to 15 patients in each of 2 subpopulations of patients with triple negative breast cancer (30 total). One group of 15 patients will have 3+ EGFR over-expression. The second group will have 2+ EGFR over-expression. arm 3: Addition of 15 patients with squamous head and neck carcinoma. Patients will have 3+ EGFR over-expression. arm 4: Addition of 15 patients with squamous histology non-small cell lung carcinoma. Patients will have 3+ EGFR over-expression

Interventions: intervention 1: AVID100 IV
Intervention descriptions: intervention 1: AVID100 is administered once every 3 weeks

Protocol document:
Prot_SAP_000.pdf: 
 
CLINICAL TRIAL PROTOCOL 
A Phase 1a/2a Cohort Dose Escalation Trial to Determine the Safety, Tolerance, Maximum 
Tolerated Dose, and Preliminary Antineoplastic Activity of AVID100, an Anti-Human 
Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Linked to the Maytansinoid 
DM1, in Patients with Advanced or Metastatic Solid Tumors of Epithelial Origin    
Product:  
 
 
AVID100 
Protocol Number: 
AVID100-01 
Short Title:   
 
AVID100 in Advanced Epithelial Carcinomas 
Phase:  
 
 
 
Phase 1a/2a 
 
 
IND Number:   
IND 125294 
 
 
CTA Number:   
e221762 
 
 
Version/Date: 
v11.0 / 30 May 2020 
 
 
Previous: 
v10.0 / 16 Nov 2019 
 
 
 
 
v9.0 / 15 May 2019 
 
 
 
 
v8.0 / 14 Nov 2018 
 
 
 
 
v7.0 / 31 Aug 2018 
 
 
 
 
v6.0 / 19 Jun 2018 
 
 
 
 
v5.0 / 26 Sep 2017  
 
 
 
 
v4.0 / 30 May 2017  
 
 
 
 
v3.0 / 12 May 2017  
 
 
 
 
v2.0 / 15 Mar 2017  
 
 
 
 
v1.2 / 09 Dec 2016  
 
 
 
 
v1.1 / 01 Dec 2016  
 
 
 
 
v1.0 / 27 Oct 2016  
Sponsor:  
 
 
Forbius (Formation Biologics)  
 
701Brazos Street, Suite 930 
 
Austin, Texas 78701 
USA 
 
CONFIDENTIAL AND PROPRIETARY 
This document is the confidential property of  Forbius (Formation Biologics; The Sponsor), and is intended solely for the guidance of this clinical 
investigation.  The information contained herein may not be disclosed to parties not associated with this clinical investigation without the written 
authorization of the Sponsor.  No part of this document may be reproduced, referenced, stored in a retrieval system, or transmitted, in any form or 
by any means, electronic, mechanical, photocopying, recording, or otherwise, without the written authorization of the Sponsor.  The foregoing 
shall not apply to disclosure required by applicable laws or governmental regulations; however, notice of any such disclosure will be given to the 
Sponsor as soon as practicable. 


 
 
 
 
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REPORTING SERIOUS AND UNEXPECTED ADVERSE EVENTS 
Any death or other serious adverse event (SAE), including any suspected unexpected serious 
adverse reaction (SUSAR) experienced by the patient from signing of informed consent* until 30 
days after receiving the final dose of study drug, or any SAE that occurs after 30 days of 
receiving the final dose of study drug and is believed to be study drug-related, must be promptly 
reported (within 24 hours of Investigator awareness).    
Unless otherwise instructed, SAE Reports are to be submitted electronically or by telefax to the 
Sponsor’s Safety agent, ProPharma Group.  Where indicated, additional communications may 
be made by telephone, telefax, or email; however, it is important that the primary route of 
transmission of SAE data be ProPharma Group.  This will enable all relevant parties to be 
made aware of the event in a timely fashion.   
Access information and training will be provided to participating study centers prior to or at the 
time of study initiation. 
Please see the Study Operations Manual (or other similar document) for further information on 
SAE Report submissions.   
 
SAE Submission (Safety Designee): 
 
ProPharma Group 
 
 
 
 
 
 
 
 
 
 
 
Fax: +01 (866) 681-1063 
 
 
 
 
 
 
 
 
 
 
 
Email:  clinicalsafety@propharmagroup.com 
 
 
Medical/Safety Contact(s): 
 
 
 
 
Debra L. Wood, MD  
Paul I. Nadler, MD 
Office: (973) 989-5010 or (973) 989-0046 
Fax: 
(973) 989-6960  
Email: dlwood@nadlerpharma.com 
Email:   pnadler@nadlerpharma.com 
 
 
 
 
Forbius Chief Medical Officer: 
 
 
 
Paul I. Nadler, MD 
Email: pnadler@nadlerpharma.com 
 
 
 
 
*Patients who sign informed consent and are subsequently deemed to be screen failures will be followed for the 
occurrence of SAEs/AEs until it is determined that they are will not be participating in this trial. 
 
 


 
 
 
 
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TABLE OF CONTENTS 
TITLE PAGE…………………………………………………………………………………..….1 
REPORTING SERIOUS AND UNEXPECTED ADVERSE EVENTS .........................................2 
2. 
SCIENTIFIC BACKGROUND AND RATIONALE ................................................30 
2.1. 
Background .................................................................................................................30 
2.1.1 
Overview of the Target:  EGFR ..................................................................................30 
2.1.2 
Overview of EGFR and Breast Cancer .......................................................................30 
2.1.3 
Overview of EGFR and Squamous Cell Carcinoma of the Head and Neck...............31 
2.1.4 
Overview of EGFR and Non-Small Cell Lung Carcinoma ........................................32 
2.1.5 
EGFR Extracellular Domain Mutations .....................................................................34 
2.1.6 
Overview of the Product:  AVID100 ..........................................................................34 
2.2. 
Nonclinical Studies .....................................................................................................35 
2.2.1 
Nonclinical Pharmacology Studies .............................................................................35 
2.2.1.1. 
In Vitro Pharmacology ................................................................................................35 
2.2.1.2. 
In Vivo Pharmacology .................................................................................................36 
2.2.2 
Nonclinical Pharmacokinetic Studies .........................................................................37 
2.2.2.1. 
Non-GLP Pharmacokinetic Study in Mice .................................................................37 
2.2.2.2. 
Non-GLP Pharmacokinetic Study in Primates ...........................................................37 
2.2.2.3. 
GLP Pharmacokinetic Study in Primates ...................................................................38 
2.2.3 
Nonclinical Toxicology Studies .................................................................................38 
2.2.3.1. 
Tissue Cross-Reactivity Studies .................................................................................38 
2.2.3.2. 
Non-GLP Toxicology Studies ....................................................................................39 
2.2.3.3. 
GLP Toxicology Studies .............................................................................................40 
2.2.4 
Other Safety Studies ...................................................................................................42 
2.2.4.1. 
Genotoxicity and Mutagenicity ..................................................................................42 
2.2.4.2. 
Carcinogenicity ...........................................................................................................42 
2.2.4.3. 
Immunogenicity ..........................................................................................................42 
2.2.4.4. 
Reproductive and Developmental Toxicity ................................................................42 
2.2.4.5. 
Pharmacologic Toxicity ..............................................................................................43 
2.2.4.6. 
Local Tolerance ..........................................................................................................43 
2.3. 
Clinical Experience .....................................................................................................43 


 
 
 
 
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2.3.1 
Clinical Experience with Agents Related to AVID100 ..............................................43 
2.3.1.1. 
Safety:  Emtansine-DM1 ............................................................................................43 
2.3.1.2. 
Safety:  Inhibition of EGFR ........................................................................................44 
2.3.1.3. 
Safety:  Clinical Adverse Effects of Anti-EGFR Antibodies .....................................44 
2.3.1.4. 
Safety:  Clinical Adverse Effect of Antibody-Drug Conjugates ................................44 
2.3.2 
Clinical Experience with AVID100 ............................................................................45 
2.3.2.1. 
AVID100-01:  Clinical Experience:  Phase 1a Dose Escalation ................................45 
2.3.2.2. 
AVID100-01:  Clinical Experience:  Phase 2a Dose Expansion ................................47 
2.4. 
Rationale for and Risks of Proposed Clinical Study ..................................................49 
2.4.1 
Rationale .....................................................................................................................49 
2.4.2 
Risks 
 ..............................................................................50 
2.5. 
Rationale for Starting Dose ........................................................................................51 
2.6. 
Justification for the Recommended Phase 2 Dose ......................................................51 
3. 
TRIAL OBJECTIVES AND DESIGN .......................................................................53 
3.1. 
Phase 1a: Dose-Escalation ..........................................................................................53 
3.1.1 
Primary Objective .......................................................................................................53 
3.1.2 
Secondary Objectives .................................................................................................53 
3.1.3 
Exploratory Objective .................................................................................................53 
3.2. 
Phase 2a:  Dose-Expansion .........................................................................................54 
3.2.1 
Primary Objective .......................................................................................................54 
3.2.2 
Secondary Objective ...................................................................................................54 
3.2.3 
Exploratory Objective .................................................................................................54 
3.3. 
Trial Design Summary ................................................................................................55 
4. 
PATIENT SELECTION .............................................................................................60 
4.1. 
Number of Patients .....................................................................................................60 
4.1.1 
Investigational Sites ....................................................................................................60 
4.1.2 
Number of Patients .....................................................................................................60 
4.2. 
Criteria for Inclusion ...................................................................................................61 
4.3. 
Criteria for Exclusion .................................................................................................63 
4.3.1 
Patients to be Excluded ...............................................................................................63 
4.3.2 
Drugs and Other Treatments to be Excluded ..............................................................66 
5. 
INVESTIGATIONAL DRUG ....................................................................................68 


 
 
 
 
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5.1. 
AVID100 ....................................................................................................................68 
5.2. 
Storage and Handling of  AVID100 ...........................................................................68 
5.3. 
Stability of AVID100 .................................................................................................68 
5.4. 
Labeling of AVID100 .................................................................................................69 
5.5. 
Packaging of AVID100 ..............................................................................................69 
5.6. 
Administration of AVID100 .......................................................................................69 
5.7. 
Dose Calculation .........................................................................................................69 
5.8. 
Dose Preparation .........................................................................................................70 
5.9. 
Accountability .............................................................................................................70 
5.10. 
Disposition of Used Supplies ......................................................................................70 
5.11. 
Inventory of Unused Supplies ....................................................................................70 
5.12. 
Destruction of Investigational Supplies ......................................................................71 
5.13. 
Resupply Requests ......................................................................................................71 
6. 
EXPERIMENTAL PLAN ..........................................................................................72 
6.1. 
Design Elements .........................................................................................................72 
6.2. 
Projected Recruitment Period for this Trial ................................................................72 
6.3. 
Cohort Management ...................................................................................................72 
6.3.1 
Prescreening for EGFR ...............................................................................................72 
6.3.2 
Patient Screening and Dose Cohort Assignment ........................................................72 
6.3.2.1. 
Screening of Potential Patients ...................................................................................73 
6.3.2.2. 
Submission of Patient Enrollment Documentation .....................................................73 
6.3.2.3. 
Patient Identification Code Assignment .....................................................................74 
6.3.2.4. 
Screening Failures ......................................................................................................74 
6.3.3 
Cohort Closure ............................................................................................................74 
6.4. 
Requirements for Patient Observation ........................................................................74 
6.5. 
Drug Treatment Regimen ...........................................................................................75 
6.5.1 
Study Start Day ...........................................................................................................75 
6.5.2 
Patient Availability During Cycle 1 ...........................................................................75 
6.5.3 
Therapy with AVID100 ..............................................................................................75 
6.5.3.1. 
Doses to be Administered ...........................................................................................75 
6.5.3.2. 
Route of Administration .............................................................................................77 
6.5.3.3. 
Duration of Infusion ...................................................................................................77 


 
 
 
 
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6.5.3.4. 
Volume of Infusion .....................................................................................................78 
6.5.3.5. 
Diluent ........................................................................................................................78 
6.5.3.6. 
Schedule ......................................................................................................................78 
6.6. 
Cycle 1 ........................................................................................................................78 
6.6.1 
Premedication .............................................................................................................79 
6.6.1.1. 
Premedication for Infusion-Related Reactions ...........................................................79 
6.6.1.2. 
Use of Other Premedications ......................................................................................79 
6.6.2 
Phase 1a:  Rules for Accrual .......................................................................................79 
6.6.2.1. 
Filling of Cohorts in Phase 1a ....................................................................................79 
6.6.2.2. 
Rules for Dose Escalation and Cohort Expansion in Phase 1a ...................................79 
6.6.2.3. 
Rules for Duration of Exposure Prior to Start of Next Patient and Start of Next 
Cohort in Phase 1a ......................................................................................................81 
6.6.2.4. 
Rules for Establishing the Recommended Phase 2 Dose ...........................................81 
6.6.3 
Phase 2a:  Rules for Accrual .......................................................................................81 
6.6.3.1. 
Filling of Cohorts in Phase 2a ....................................................................................81 
6.6.3.2. 
Rules for Patient Population to be Treated in Phase 2a ..............................................81 
6.6.3.3. 
Rules for Tolerability in Phase 2a ..............................................................................82 
6.7. 
Continued Therapy After Cycle 1 ...............................................................................82 
6.7.1 
Retreatment Guidelines ..............................................................................................82 
6.7.2 
Doses and Regimens ...................................................................................................82 
6.7.3 
Evaluation Schedules ..................................................................................................83 
6.7.4 
Duration of Treatment ................................................................................................83 
6.7.5 
Retreatment Following a Response ............................................................................83 
6.8. 
Toxicity and Dose Limiting Toxicity .........................................................................83 
6.8.1 
Toxicity Grading .........................................................................................................83 
6.8.2 
Toxicity Management and Dose Modification ...........................................................84 
6.8.3 
Definition of DLT .......................................................................................................84 
6.9. 
Definition of Maximum Tolerated Dose ....................................................................85 
6.10. 
Review of Safety Data During Study .........................................................................85 
6.11. 
Duration of Study Follow-Up .....................................................................................86 
6.12. 
Concurrent Treatments and Supportive Care..............................................................87 
7. 
STUDY ASSESSMENTS ..........................................................................................90 


 
 
 
 
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7.1. 
Consent and Medical History .....................................................................................91 
7.1.1 
Signing of Informed Consent/Assessment of Eligibility ............................................91 
7.1.2 
Past Medical History ...................................................................................................91 
7.1.3 
History of the Primary Malignancy ............................................................................91 
7.2. 
Safety Assessments (1) ...............................................................................................91 
7.2.1 
Medication Survey ......................................................................................................91 
7.2.2 
Adverse Event Assessment .........................................................................................92 
7.2.3 
Performance Status Evaluation ...................................................................................92 
7.2.4 
Vital Signs ..................................................................................................................92 
7.2.5 
Physical Examination .................................................................................................93 
7.2.6 
Hematology Panel .......................................................................................................94 
7.2.7 
Serum Chemistry Panel ..............................................................................................94 
7.2.8 
Coagulation Panel .......................................................................................................95 
7.2.9 
Urinalysis ....................................................................................................................95 
7.2.10 
Anti-Drug Antibody (ADA) to AVID100  (Central Lab)...........................................96 
7.2.11 
Pregnancy Testing ......................................................................................................96 
7.2.12 
Electrocardiogram .......................................................................................................97 
7.3. 
Safety Assessments (2) ...............................................................................................97 
7.3.1 
Ophthalmology Examination ......................................................................................97 
7.3.2 
MUGA Scan or Echocardiogram ................................................................................98 
7.3.3 
Pulmonary Function Testing .......................................................................................98 
7.3.4 
Chest Radiography ......................................................................................................98 
7.4. 
Disease Assessments ..................................................................................................98 
7.4.1 
EGFR Tumor Status Determination ...........................................................................99 
7.4.2 
Tumor Marker Measurement (Phase 1a only) ............................................................99 
7.4.3 
Diagnostic Imaging for Assessment of Disease (and Pulmonary Status) .................100 
7.4.4 
Response Assessment ...............................................................................................101 
7.5. 
Pharmacokinetic Assessments ..................................................................................101 
7.5.1 
Peripheral Blood Collection (Central Lab) ...............................................................101 
7.6. 
Biomarker Assessments ............................................................................................103 
7.6.1 
Exploratory EGFR Studies in Tumor Tissue (Central Lab) .....................................103 
7.6.2 
Exploratory EGFR Studies in ctDNA (Central Lab) (SCCHN patients only) ..........104 


 
 
 
 
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8. 
MANAGEMENT OF TOXICITY ...........................................................................105 
8.1. 
Determination of DLT versus Non-DLT ..................................................................105 
8.2. 
Premedication for Study Drug-Related Toxicities....................................................105 
8.2.1 
Infusion-Related Reactions .......................................................................................105 
8.2.2 
Premedication for IRRs ............................................................................................106 
8.2.3 
Other Study Drug-Related Toxicities .......................................................................106 
8.3. 
Dose Modification Options .......................................................................................106 
8.3.1 
Prolongation of Infusion Duration ............................................................................106 
8.3.2 
Temporary Dose Interruption (Delay) ......................................................................107 
8.3.2.1. 
Delay Between Dosing .............................................................................................107 
8.3.3 
Dose Reduction .........................................................................................................108 
8.3.4 
Schedule Alterations .................................................................................................108 
9. 
REMOVING PATIENTS FROM STUDY TREATMENT .....................................109 
9.1. 
Criteria for Treatment Discontinuation.....................................................................109 
9.2. 
Replacements ............................................................................................................110 
10. 
ADVERSE EVENTS ................................................................................................112 
10.1. 
Definitions ................................................................................................................112 
10.1.1 
Adverse Event ...........................................................................................................112 
10.1.2 
Suspected Adverse Reaction .....................................................................................112 
10.2. 
Evaluating Adverse Events .......................................................................................112 
10.2.1 
“Serious” Adverse Events and Suspected Adverse Reactions..................................112 
10.2.2 
“Unexpected” Serious Adverse Events and Suspected Unexpected Serious 
Adverse Reactions ....................................................................................................113 
10.2.3 
Non-Serious Adverse Events ....................................................................................114 
10.2.4 
Protocol-Related Adverse Events .............................................................................114 
10.3. 
Documenting Adverse Events ..................................................................................114 
10.3.1 
Information to be Provided for each AE ...................................................................114 
10.3.2 
Timeframe for Recording AEs .................................................................................116 
10.3.3 
Required Follow-up for AEs ....................................................................................116 
10.4. 
Reporting SAEs (Including Patient Deaths) and Unexpected SAEs ........................116 
10.4.1 
24-Hour Requirement for Reporting to the Sponsor ................................................116 
10.4.2 
Governing Regulatory Requirements Regarding Sponsor Review ..........................116 


 
 
 
 
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10.4.3 
Governing Regulatory Requirements Regarding Sponsor Reporting ......................117 
10.4.3.1. 
Reporting Criteria .....................................................................................................117 
10.4.3.2. 
Reporting Format ......................................................................................................117 
10.4.3.3. 
Reporting Timeframes ..............................................................................................118 
10.4.4 
Information to be Provided by the Investigator to the Sponsor ................................118 
10.4.4.1. 
Initial Information on an SAE ..................................................................................118 
10.4.4.2. 
Follow-up Information on an SAE ...........................................................................119 
10.4.4.3. 
SAE Review and Potential Impact On Trial Conduct ..............................................119 
10.5. 
Required Follow-up for All AEs and SAEs .............................................................119 
11. 
PRECAUTIONS WHEN DOSING WITH AVID100 .............................................121 
11.1. 
Precautions Regarding Procreation ...........................................................................121 
11.1.1 
Reproduction .............................................................................................................121 
11.1.2 
Contraception ............................................................................................................121 
11.1.3 
Pregnancy .................................................................................................................122 
11.1.4 
Breastfeeding ............................................................................................................122 
11.2. 
Additional Precautions ..............................................................................................122 
12. 
REGULATORY AND ETHICAL CONSIDERATIONS ........................................125 
12.1. 
Conditions of Testing ...............................................................................................125 
12.2. 
Institutional Review ..................................................................................................125 
12.3. 
Informed Consent .....................................................................................................126 
12.4. 
Conditions for Modifying or Terminating the Study ................................................126 
12.4.1 
Modification of the Study Protocol ..........................................................................126 
12.4.2 
Modification of the Informed Consent Document ....................................................127 
12.4.3 
Conditions for Termination of the Study ..................................................................127 
12.5. 
Deviation from the Protocol .....................................................................................127 
12.6. 
Documents to be Submitted to the Sponsor ..............................................................128 
12.7. 
Data Review During this Study ................................................................................129 
12.8. 
Trial Registration ......................................................................................................129 
13. 
INVESTIGATOR RESPONSIBILITIES .................................................................130 
13.1. 
Medical Supervision .................................................................................................130 
13.2. 
Confidentiality ..........................................................................................................130 
13.3. 
Use of Information and Publication ..........................................................................130 


 
 
 
 
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13.4. 
Patient Screening Log ...............................................................................................131 
13.5. 
Drug Dispensing Inventory .......................................................................................131 
13.6. 
Handling and Disposal of Investigational Drug .......................................................131 
13.7. 
Recording and Processing of Data ............................................................................132 
13.8. 
Source Document Requirements ..............................................................................132 
13.9. 
Laboratory Reports ...................................................................................................132 
13.10. 
Record Retention ......................................................................................................133 
13.11. 
Monitoring of the Study ............................................................................................133 
13.12. 
Patient Confidentiality ..............................................................................................134 
13.13. 
Financing and Insurance ...........................................................................................134 
14. 
STATISTICAL ANALYSIS AND REPORTING OF DATA .................................135 
14.1. 
Statistical Considerations ..........................................................................................135 
14.2. 
Sample Size Considerations .....................................................................................135 
14.3. 
Statistical Analysis ....................................................................................................136 
14.3.1 
Analysis Sets .............................................................................................................137 
14.3.2 
Safety Analysis .........................................................................................................137 
14.3.2.1. 
Adverse Events .........................................................................................................137 
14.3.2.2. 
Laboratory Determinations .......................................................................................138 
14.3.2.3. 
Vital Signs, Body Weight, Physical Exam Findings ................................................138 
14.3.2.4. 
ECG Findings ...........................................................................................................138 
14.3.2.5. 
Other Safety Data .....................................................................................................138 
14.3.2.6. 
Maximum Tolerated Dose ........................................................................................138 
14.3.3 
Other Analyses ..........................................................................................................138 
14.3.3.1. 
Antineoplastic Activity .............................................................................................138 
14.3.3.2. 
Pharmacokinetic Parameters .....................................................................................139 
14.3.3.3. 
Biomarker Parameters ..............................................................................................140 
14.4. 
Clinical Study Report ...............................................................................................140 
APPENDIX A ..............................................................................................................................141 
Study Assessments .......................................................................................................................141 
APPENDIX B ..............................................................................................................................146 
Performance Status Evaluation ....................................................................................................146 
APPENDIX C ..............................................................................................................................147 


 
 
 
 
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New York Heart Association’s Functional Criteria .....................................................................147 
APPENDIX D ..............................................................................................................................148 
Adverse Event Grading Scale ......................................................................................................148 
APPENDIX E ..............................................................................................................................149 
Clinical Adverse Events:  Determining Relationship to Study Drug ..........................................149 
APPENDIX F...............................................................................................................................150 
Measurement of Effect .................................................................................................................150 
APPENDIX G ..............................................................................................................................155 
Grading and Management of Infusion Reactions ........................................................................155 
APPENDIX H ..............................................................................................................................157 
Recommendations for Management of Keratitis and Rash .........................................................157 
APPENDIX I ...............................................................................................................................158 
Sample Size Considerations .........................................................................................................158 
REFERENCES ............................................................................................................................161 


 
 
 
 
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TABLES AND FIGURES 
 
TABLE 1:  AVID100-01 (PHASE 1A DOSE-ESCALATION) ...................................................47 
TABLE 2:  AVID100-01 (PHASE 2A DOSE-ESCALATION) ...................................................48 
TABLE 3:  RECOMMENDED PREMEDICATION REGIMEN ..............................................106 
TABLE 4:  DOSE REDUCTION SCHEDULE FOR AVID100 ................................................108 
TABLE 5:  TEST OF NULL AT 0.05 LEVEL (TWO SIDED) USING NORMAL 
APPROXIMATION .................................................................................................136 
TABLE 6:  SMALLEST VALUE OF P (%) FOR STATISTICAL SIGNIFICANCE ...............136 
TABLE 7:  STUDY ASSESSMENTS SCHEDULE...................................................................141 
TABLE 8:  PHARMACOKINETIC SAMPLING SCHEDULE.................................................144 
TABLE 9:  MAXIMUM TOTAL BLOOD COLLECTION VOLUMES...................................145 
TABLE 10:  MEASURES OF PERFORMANCE STATUS ......................................................146 
TABLE 11:  NEW YORK HEART ASSOCIATION FUNCTIONAL CRITERIA ...................147 
TABLE 12:  CLINICAL ADVERSE EVENT GRADING .........................................................148 
TABLE 13:  CLINICAL ADVERSE EVENTS:  DETERMINING RELATIONSHIP TO 
STUDY DRUG .........................................................................................................149 
TABLE 14:  RESPONSE CRITERIA FOR SOLID TUMORS ..................................................150 
TABLE 15:  GRADING OF INFUSION REACTIONS .............................................................155 
TABLE 16:  MANAGEMENT OF INFUSION REACTIONS ..................................................156 
 
 
Figure 1:  Dose Escalation Schema ...............................................................................................57 
Figure 2:  Expansion Cohorts .....................................................................................................58 
 
 
 


 
 
 
 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Expanded Term 
1M FUP 
1 month follow-up 
Ab 
antibody 
ACSL 
access-controlled secure location 
ADA 
anti-drug antibody 
ADC 
antibody-drug conjugate 
ADCC 
antibody dependent cellular cytotoxicity 
AE 
adverse event 
Akt 
protein kinase B (PKB) 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase (SGPT) 
ANC 
absolute neutrophil count 
aPTT 
ARDS 
activated partial thromboplastin time 
acute respiratory distress syndrome 
AST 
aspartate aminotransferase (SGOT) 
AUC 
area under the plasma concentration-time curve 
AUClast 
area under the plasma concentration curve at the last measurable concentration 
AVID100 
anti-human EGFR mAb linked to the maytansinoid DM1 
BC 
breast cancer 
β-hCG 
beta-human chorionic gonadotropin 
BP 
blood pressure 
BID 
2 times per day 
BSA 
body surface area 
BUN 
blood urea nitrogen 
C 
Centigrade, Celsius, Cycle 
Ca 
calcium 
CBC 
complete blood count 
CFR 
Code of Federal Regulations 
CHF 
congestive heart failure 
CI 
confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CIS 
carcinoma in situ 
CK 
creatine kinase 
Cl 
chloride 
Cl 
clearance 
Cmax 
maximum (peak) concentration 
Cmin 
minimum (trough) concentration 
CNS 
central nervous system 
COPD 
chronic obstructive pulmonary disease 
CR 
complete response 
CRC 
colorectal carcinoma 
CrCl 
creatinine clearance 
CRF 
case report form 
CS 
clinically significant 
CT 
computerized tomography 
CTCAE 
Common Terminology Criteria for Adverse Events (NCI, Version 5.0) 
ctDNA 
circulating tumor deoxyribonucleic acid 
CV 
curriculum vitae 
CXR 
chest X-ray 
D, d 
day 
DCR 
disease control rate 


 
 
 
 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Expanded Term 
DEHP 
di(2-ethylhexyl)phthalate  
dL 
deciliter 
DLCO 
diffusion capacity of carbon monoxide 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DVT 
deep vein thrombosis 
EC 
Ethics Committee 
ECD 
extracellular domain 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
electronic data capture 
eGFR 
estimated glomerular filtration rate 
EGFR 
epidermal growth factor receptor 
EGFRi 
epidermal growth factor inhibitors 
EGFRvIII 
EGFR mutant type III variant 
EMT 
epithelial mesenchymal transition 
EOI 
end of infusion 
EOT 
end of treatment 
ER 
estrogen receptor 
F 
Fahrenheit 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed, paraffin-embedded 
FISH 
fluorescence in situ hybridization 
FSH 
follicle-stimulating hormone 
FVC 
forced vital capacity 
FWA 
Federal-Wide Assurance  
GCP 
Good Clinical Practices 
GI 
gastrointestinal 
GLP 
Good Laboratory Practices 
H, h 
hour 
HBV 
hepatitis B virus 
hCG 
human chorionic gonadotropin 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HL 
Hodgkin’s lymphoma 
HIV 
human immunodeficiency virus 
HRT 
hormone replacement therapy 
HNSTD 
highest non-severely toxic dose 
hpf 
high power field 
IB 
Investigator’s Brochure 
IC50 
half maximal inhibitory concentration 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IHC 
immunohistochemistry 
ILD 
interstitial lung disease 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IP 
intraperitoneal 
IRB 
Institutional Review Board   
IRR 
infusion-related reaction 
IU 
international units 


 
 
 
 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Expanded Term 
IV, i.v. 
intravenous 
K 
potassium 
kg 
kilogram 
KO 
knock out 
KRAS 
Kirsten ras oncogene homolog 
LLN 
lower limit of normal 
LVEF 
left ventricular ejection fraction 
M, m 
month, molar, meter 
mAb 
monoclonal antibody 
MAB100 
unconjugated monoclonal anti-EGFR antibody precursor of AVID100 
MAD 
maximum administered dose 
MAPK 
mitogen activated protein kinase 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
magnesium 
mg 
milligram 
MI 
myocardial infarction 
min 
minute 
mL 
milliliter 
mm 
millimeter 
MMAE 
monomethyl aurostatin E 
MRI 
magnetic resonance imaging 
msec 
millisecond 
MTD 
maximum tolerated dose 
mTNBC 
metastatic triple-negative breast cancer 
MUGA 
multiple gated acquisition scan 
n 
nano 
Na 
sodium 
NaCl 
sodium chloride 
NCS 
not clinically significant 
ng 
nanogram 
NGS 
next generation sequencing 
nM 
nanomolar 
NS 
normal saline 
NSCLC 
non-small cell lung carcinoma 
NYHA 
New York Heart Association 
OR 
objective response 
ORR 
objective response rate 
OS 
overall survival 
OTC 
over the counter 
P 
phosphorus 
PA 
posterior to anterior 
PBS 
phosphate buffered saline 
PC 
pancreatic carcinoma 
PD 
pharmacodynamic 
PD 
progressive disease 
PE 
physical examination 
PE 
pulmonary embolism 
PET 
positron emission tomography 
PFS 
progression free survival 
PFT 
pulmonary function test 
PK 
pharmacokinetic 
PO, p.o. 
per os 


 
 
 
 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Expanded Term 
PR 
partial response 
PR 
progesterone receptor 
PS 
performance status 
PSA 
prostate specific antigen 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
Q3W 
QT 
once every 3 weeks 
ECG interval between onset of QRS complex to end of the T wave (QT interval) 
QTc 
QT interval corrected for heart rate 
RBC 
red blood cell 
RECIST 
response evaluation criteria in solid tumors 
RP2D 
recommended phase 2 dose 
RTK 
receptor tyrosine kinases 
SAE 
serious adverse event 
sALCL 
systemic anaplastic large cell lymphoma 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SC 
subcutaneous 
SCCHN 
squamous cell carcinoma of the head and neck 
SD 
stable disease 
SOI 
start of infusion 
SOP 
standard operating procedure 
Sq-NSCLC 
squamous histology non-small cell lung carcinoma 
SUSAR 
suspected unexpected serious adverse reaction 
T1/2 
half-life 
TBD 
to be determined 
TK 
toxicokinetic 
TKI 
tyrosine kinase inhibitor 
Tmax 
time to peak plasma concentration 
TNBC 
triple negative breast cancer 
TSC 
tumoristatic concentration 
TTP 
time to progression 
ULN 
upper limit of normal 
µg 
micogram 
µM 
micromolar 
Vd 
volume of distribution 
Vol 
volume 
VS 
vital signs 
W, w 
week 
WBC 
white blood cell 
WOCBP 
women of child-bearing potential 
WNL 
within normal limits 
Y, y 
year 
 


 
 
 
 
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1. 
TRIAL SYNOPSIS  
PROTOCOL 
Title 
A Phase 1a/2a Cohort Dose Escalation Trial to Determine the Safety, Tolerance, Maximum 
Tolerated Dose, and Preliminary Antineoplastic Activity of AVID100, an Anti-Human 
Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody Linked to the 
Maytansinoid DM1, in Patients with Advanced or Metastatic Solid Tumors of Epithelial 
Origin  
Number  
AVID100-01 
Date 
30 May 2020 
Version 
10.0 
Development Phase  
1a/2a 
Compound Code 
TBD 
IP Code 
AVID100 
IND Number 
IND125294 
Investigational Drug 
Description 
AVID100, an anti-human EGFR monoclonal antibody linked to the maytansinoid 
DM1(emtansine) 
OBJECTIVES 
Phase 1a  
(dose escalation portion of study) 
Primary  
To determine the safety and tolerability, dose-limiting toxicities (DLTs), maximum 
tolerated dose (MTD), and recommended Phase 2 dose (RP2D)** of sequential escalating 
doses of AVID100 when administered once every 3 weeks (Q3W) by 2-hour* intravenous 
(IV) infusions to patient cohorts with locally advanced/unresectable or metastatic solid 
tumor malignancies of epithelial origin  
*Protocol v5.0:  Extended from 1 hour to 1.5 hours due to Grade 3 IRR observed in Cohort 3 (80 
mg/m2); effective 20Jul2017 and documented in a study Note to File dated 21Jul2017 (see Section 
2.3.2.1; AVID100-01: Clinical Experience) 
*Protocol v6.0:  Extended from 1.5 hours to 2 hours due to Grade 2 IRRs observed in Cohort 4(120 
mg/m2); effective 21Dec2017 and documented in a study Note to File dated 28Dec2017 (see Section 
2.3.2.1; AVID100-01: Clinical Experience) 
**Protocol v6.0:  The MTD and RP2D has been determined to be 220 mg/m2 
Secondary 
• 
Characterization of the pharmacokinetic (PK) profile of total antibody (AVID100 plus 
MAB100), AVID100, and DM1  
• 
Evaluation of the preliminary antineoplastic effects of AVID100 including: 
o 
Evidence of objective response (OR) or stable disease (SD)* 
o 
Duration of OR or SD* 
o 
Time to progression (TTP) of disease* 
*As assessed by modified Response Evaluation Criteria in Solid Tumors (RECIST, v1.1)   
Exploratory  
Tests to assess potential biomarkers and response predictors will be conducted and may 
include: 
• 
Evaluation by immunohistochemistry (IHC) and/or fluorescence in situ hybridization 
(FISH) (or similar assay) of tumor EGFR-expression in archival, formalin-fixed, 
paraffin-embedded (FFPE) samples obtained from a previous diagnostic or surgical 
procedure (if available) 
Phase 2a 
(enrollment of additional patient 
cohorts at the RP2D) 
Primary 
To further evaluate the safety, tolerability, and preliminary antineoplastic effect of 
AVID100 when administered at the RP2D in 3 expansion cohorts  of patients with locally 
advanced/unresectable or metastatic solid tumor malignancies of epithelial origin, and 
expressing the EGFR The tumor types to be evaluated in these expansion cohorts are 
metastatic triple negative breast cancer (mTNBC), squamous cell carcinoma of the head 
and neck (SCCHN), and squamous histology non-small cell lung carcinoma (Sq-NSCLC). 
Note:  To be eligible for study enrollment, analytical results documenting EGFR expression positivity 
by IHC must be documented by a central laboratory in archival FFPE samples obtained from a 


 
 
 
 
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previous diagnostic or surgical procedure.  In the mTNBC cohort results must be 3+ intensity in 
≥ 50% of tumor cells or ≥ 2+ intensity in ≥ 75% of tumor cells.  In the SCCHN and Sq-NSCLC 
cohorts results must be 3+ intensity in ≥ 50% of tumor cells.  If tissue is unavailable, patients 
must have primary or metastatic tumor sites(s) considered safely accessible for biopsy, and 
must be willing to undergo tumor biopsy. 
Sufficient FFPE tumor tissue from either a prior procedure or a recent biopsy must also be available for 
submission to a central laboratory for other study-related evaluations as planned per protocol. 
Secondary 
Further characterization of the PK profile of total antibody (AVID100 plus MAB100), 
AVID100, and DM1  
Exploratory 
Tests to assess potential biomarkers and response predictors will be conducted and may 
include but are not limited to: 
• 
Evaluation by FISH (or similar assay) of tumor EGFR-expression and other potential 
biomarkers in archival, FFPE samples obtained from a either a previous diagnostic or 
surgical procedure or a recent biopsy (required at Screening, optional thereafter) 
• 
Evaluation of circulating tumor DNA (ctDNA) for EGFR extracellular domain (EGFR-
ECD) mutation status and EGFR mutant type III variant (EGFRvIII) deletions (SCCHN 
only), as well as evaluation of other potential biomarkers of interest (required for all 
indications) 
PATIENT SELECTION 
Investigational Sites 
Phase 1a:  Single center planned (up to 2 centers may participate based on accrual) 
Phase 2a:  Approximately 6-12 participating centers; number of sites TBD based on tumor 
type selection and anticipated accrual 
Number of Patients 
Approximately 90 patients to be entered during Phase 1a and Phase 2a    
Phase 1a:  Approximately 30 patients in escalating dose cohorts 
• 
Minimum of 1 to 3 patients per dose cohort; approximately 4 dose cohorts to be 
evaluated to establish the MTD and/or RP2D 
• 
Expansion of any cohort to 6 patients in the event of a Cycle 1 DLT in any of the initial 
1 to 3 patients  
• 
Minimum of 6 patients to be treated at the MTD (or maximum administered dose 
[MAD]); expansion of this cohort (or any other) up to 12 patients may be considered to 
further evaluate tolerability 
Phase 2a:  Approximately 60 patients in 3 expansion cohorts (approximately 30 patients in 
the mTNBC cohort and 15 patients each in the SCCHN and Sq-NSCLC cohorts); more 
patients may be entered if fewer than 30 patients are required to establish the RP2D in 
Phase 1a  
There is potential for entry of additional patients in the Phase 1a portion of the study to:   
• Assure sufficient evaluable patients per cohort by adding an additional patient to a 
cohort  
• Evaluate > 4 dose cohorts should this be necessary to identify the RP2D 
• Expand a lower dose cohort(s) if an initially identified MTD is expanded and found to 
exceed tolerability either with single or repeated cycles of therapy  
• Evaluate a previously unexamined intermediate dose, if indicated 
There is potential for additional expansion cohorts in the Phase 2a portion of the trial (by 
amendment only) 
Eligibility 
 
 
Patients to be Included (patients must meet all of the following criteria) 
1. 
Male or female patients, ≥ 18 years   
2. 
Patients with a documented (histologically- or cytologically-proven) solid tumor 
epithelial carcinoma that is locally advanced or metastatic 
3. 
Patients with a malignancy that is either refractory to standard therapy, or for which no 
standard therapy is available 
4. 
Patients with a malignancy that is currently not amenable to surgical intervention due 
to either medical contraindications or non-resectability of the tumor 
5. 
Phase 1a Dose-Escalation Cohorts:  Patients with measurable or non-measurable 
disease according to RECIST, v1.1 criteria. To include patients reasonably likely to 
express EGFR.  


 
 
 
 
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6. 
Phase 2a Expansion Cohorts ONLY:  Patients with mTNBC, SCCHN, or Sq-NSCLC 
and with:   
• 
Measurable disease per RECIST, v1.1 criteria  
• 
An EGFR-expressing solid tumor documented by central laboratory assessment to 
be positive by immunohistochemistry (IHC)* as follows: 
o mTNBC Cohort**:  3+ intensity in ≥ 50% of tumor cells or ≥ 2+ intensity in ≥ 
75% of tumor cells (~15 patients each) 
o SCCHN Cohort:  3+ intensity in ≥ 50% of tumor cells (~15 patients) 
o Sq-NSCLC Cohort:  3+ intensity in ≥ 50% of tumor cells (~15 patients) 
** Recruitment in mTNBC cohort subgroups will be halted after enrollment of 15 patients in 
order to assess activity. 
• EGFR assessment to be made using: 
o An archival FFPE tumor specimen (as recent as possible), or  
o Surgical or biopsy specimens if archival tumor tissue results are not available 
• 
Availability of FFPE tumor tissue from either a prior procedure or a recent biopsy 
for submission to a central laboratory for other study-related evaluations 
*DAKO EGFRpharmDX IHC kit system technology to be utilized.  For this study, EGFR-
positive staining is defined as 3+ intensity in  ≥ 50% of tumor cells  or ≥ 2+ intensity in ≥ 75% of 
tumor cells for mTNBC; or 3+ intensity in ≥ 50% of tumor cells for SSCHN and Sq-NSCLC, 
whether it is complete or incomplete circumferential staining.   
7. 
Patients with an Eastern Cooperative Oncology Group (ECOG) performance status as 
follows, and an anticipated life expectancy of > 3 months  
• Phase 1a Dose-Escalation Cohort Patients:  0, 1, or 2 
• Phase 2a Expansion Cohort Patients:  0 or 1 
8. 
Women of childbearing potential (WOCBP) and fertile men with a partner of 
childbearing potential agreeing to use a highly effective method of contraception 
during the study and for 3 months after the last dose of study drug; male patients must 
also agree to refrain from sperm donation during this period.   
9. 
Patients with the ability to understand and give written informed consent for 
participation in this trial, including all evaluations and procedures as specified by this 
protocol.  Informed consent must be obtained prior to patient screening, and before 
any evaluations or procedures specifically related to this study are performed. 
Patients to be Excluded (patients must not meet any of the following criteria) 
1. 
Women who are pregnant or intending to become pregnant during or within 3 months 
after the last dose of study drug; women who are breastfeeding; WOCBP and fertile 
men with a WOCBP partner not using and not willing to use a highly effective method 
of contraception 
2. 
Patients with known central nervous system (CNS) or leptomeningeal metastases, or 
spinal cord compression not controlled by prior surgery or radiotherapy, or patients 
with symptoms suggesting CNS involvement for which treatment is required  
3. 
Patients with a malignancy other than that of epithelial origin 
4. 
Phase 2a Expansion Cohorts ONLY:  Patients with an active second malignancy or 
history of another malignancy within the last 2 years with the exception of: 
• 
Treated non-melanoma skin cancers 
• 
Treated carcinoma in situ  
• 
Controlled, superficial carcinoma of the bladder  
• 
T1a carcinoma of the prostate comprising < 5% of resected tissue and prostate 
specific antigen (PSA) within normal limits (WNL) since resection 
5.  Patients with any of the following hematologic abnormalities at baseline: 
• 
Hemoglobin < 9.0 g/dL 
• 
Absolute neutrophil count (ANC) < 1,500 per mm3 
• 
Platelet count < 100,000 per mm3 
6. 
Patients with any of the following serum chemistry abnormalities at baseline: 
• 
Total bilirubin > 1.5 × the upper limit of normal (ULN) for the institution  
• 
AST or ALT > 3 × the ULN for the institution (> 5× ULN if due to hepatic 
involvement by tumor) 
• 
Serum creatinine > 1.5 × ULN  
7. 
Patients with any of the following coagulation parameter abnormalities at baseline as 


 
 
 
 
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determined by the Investigator: 
• 
PT (or INR) > 1.5 × ULN for the institution (> 3× ULN for the institution if 
anticoagulated) 
• 
PTT (or aPTT) > 1.5 × ULN for the institution (> 3× ULN for the institution if 
anticoagulated) 
8. 
Patients with: 
• 
Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary 
embolism (PE) within 4 weeks prior to first study drug administration;  
• 
Active uncontrolled bleeding or a known bleeding diathesis 
9. 
Patients with a significant cardiovascular disease or condition, including: 
• 
 Congestive heart failure (CHF) currently requiring therapy 
• 
Need for anti-arrhythmic medical therapy for a ventricular arrhythmia or other 
uncontrolled arrhythmia (patients with controlled atrial fibrillation (heart rate 
[HR] < 90) for > 30 days prior to study entry are eligible) 
• 
Severe conduction disturbances (e.g., 3rd degree heart block) 
• 
Angina pectoris requiring therapy 
• 
Left ventricular ejection fraction (LVEF) known to be below the lower limit of 
normal (LLN) for the center, or  < 50% by MUGA or echocardiogram if no LLN 
is defined by the site  
• 
QTc interval > 480 msec  
• 
Uncontrolled hypertension (per the Investigator’s discretion) 
• 
Class III or IV cardiovascular disease according to the New York Heart 
Association’s (NYHA) Functional Criteria 
• 
History of acute coronary syndromes (including myocardial infarction [MI] and 
unstable angina), coronary angioplasty, stenting, or bypass grafting within 6 
months prior to first study drug administration 
10. Patients with a significant ocular disease or condition, including: 
• 
History of ocular inflammatory disease 
• 
History of disorders of the cornea, including current evidence of keratitis 
11. Patients with a significant pulmonary disease or condition, including: 
• 
Significant symptomatic chronic obstructive pulmonary disease (COPD), as 
assessed by the Investigator 
• 
History or any current evidence on imaging studies prior to or during study of 
interstitial lung disease (ILD), pulmonary fibrosis 
• 
History of pulmonary inflammatory disease, pneumonitis, acute respiratory 
distress syndrome (ARDS) 
12. Patients with significant gastrointestinal (GI) abnormalities, including but not limited 
to: 
• 
History of inflammatory bowel disease 
• 
Diarrhea > Grade 2 within 2 weeks prior to first study drug administration 
13. Patients with non-healing wounds on any part of the body 
14. Patients with a known or suspected hypersensitivity to any of the excipients of 
formulated AVID100  
15. Patients with any other serious/active/uncontrolled infection, any infection requiring 
parenteral antibiotics, or unexplained fever  >38º C within 2 weeks prior to first study 
drug administration  
16. Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic 
therapy with the exception of persistent Grade 2 alopecia, peripheral neuropathy, 
decreased hemoglobin, hypomagnesemia, lymphopenia, and/or end-organ failure 
being adequately managed by hormone replacement therapy  
17. Patients with inadequate recovery from any prior surgical procedure, or patients 
having undergone any major surgical procedure within 4 weeks prior to first study 
drug administration 
18. Patients with any other serious, life-threatening, or unstable pre-existing medical 
condition (aside from the underlying malignancy) including significant organ system 
dysfunction, or clinically significant laboratory abnormality (ies), which, in the 
opinion of the Investigator, would either compromise the patient’s safety or interfere with 
obtaining informed consent, compliance with study procedures, or evaluation of the 


 
 
 
 
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safety of the study drug 
19. Patients with a psychiatric disorder or altered mental status that would preclude 
understanding of the informed consent process and/or completion of the necessary 
study-related evaluations 
20. Patients with the inability or with foreseeable incapacity, in the opinion of the 
investigator, to comply with the protocol requirements 
Drugs and Other Treatments to be Excluded (patients must not be receiving any of the 
following) 
1. 
Any antineoplastic agent for the primary malignancy (standard or investigational) 
without delayed toxicity within 2 weeks  
(See patients to be excluded for criteria on recovery from prior antineoplastic therapy) 
2. 
Any other investigational treatments during study.  This includes participation in any 
medical device or other therapeutic intervention clinical trials.    
3. 
Radiotherapy against target lesions within 4 weeks prior to first study drug 
administration and during study 
4. 
Strong inhibitors and/or inducers of cytochrome P450 (CYP) isoenzyme 3A4 within 2 
weeks prior to first study drug administration and during study 
5. 
Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone or 
equivalent) within 2 weeks prior to first study drug administration and during study  
(exceptions are provided). 
6. 
Prophylactic use of hematopoietic growth factors within 1 week prior to first study 
drug administration and during Cycle 1 of study; thereafter-prophylactic use of growth 
factors is allowed as clinically indicated.  Use of growth factors as treatment is 
permitted at any time after initiation of study drug as clinically indicated.  
Transfusions are permitted as needed. 
Questions regarding patient eligibility must be addressed and resolved by the Investigator 
in consultation with the Medical Monitor prior to enrollment. 
INVESTIGATIONAL DRUG 
AVID-100 
 
Labeled supplies will be provided.  Each single-use glass vial contains study drug: 
• 
as a liquid formulation for intravenous (IV) injection in a total volume of 10 mL  
• 
at a concentration of 6 mg/mL for a total vial content of  60 mg. 
Formulation Excipients 
20 mM sodium succinate, 10% w/v trehalose dihydrate, and 0.02% w/v polysorbate 20, pH 
5.5 
Storage 
Refrigerate (2ºC to 8ºC); store in an access-controlled, secure location 
Stability 
Once diluted for IV administration (in 0.9 % NaCl solution), AVID100 to be administered 
within 4 hours 
EXPERIMENTAL PLAN 
Design Elements 
• 
Uncontrolled, open-label, non-randomized 
• 
Enrollment in the order of confirmation of eligibility 
• 
Escalating doses of study drug in sequential patient cohorts (Phase 1a) 
• 
Cohort expansion at the MTD or R2PD and in other cohorts based on safety (Phase 1a) 
• 
Addition of expansion cohorts of defined patient populations (Phase 2a)  
Observation Requirements 
Patients will be treated and followed on an outpatient basis. 
• 
Phase 1a Dose-Escalation Cohorts: Patients will be observed for a minimum of 4 
hours following completion of the first administration of study drug (Day 1) and a 
minimum of 1 hour following completion of subsequent infusions.   
• 
Phase 2a Expansion Cohorts: Patients will be observed for a minimum of 2 hours 
following completion of the first administration of study drug (Day 1), and a minimum 
of 1 hour following completion of subsequent infusions.  
At the end of each infusion, the IV line must remain in place for at least 1 hour to allow 
administration of IV drugs, if necessary.  
Study Start Day / Scheduling 
and Patient Availability 
Initial dose of study drug to be administered on Day 1 of Cycle 1 
 
Combination Agent 
None 


 
 
 
 
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INVESTIGATIONAL DRUG ADMINISTRATION 
Doses to be Administered 
Doses to be Evaluated During Phase 1a 
Dose cohorts will be numbered and entered sequentially.  The number of cohorts evaluated 
will be based upon toxicities experienced during Cycle 1.   
The initial dose of AVID-100 to be evaluated will be 20 mg/m2/dose (with the maximum 
dose to be administered in this trial not to exceed 330 mg/m2/dose).  An accelerated 
titration design (1 patient per cohort) will be used for dose-escalation for up to 2 cohorts or 
until the occurrence of an event that activates a stopping rule.  Thereafter, dose-escalation 
will follow a standard 3+3 design with a target toxicity level of 33.3% or less as determined 
by DLTs.  Doses will be calculated as follows: 
• 
Dose Part A: Up to 2 cohorts will receive consecutive 100% increases in dose until:   
o 
A study drug-associated* ≥ Grade 2 toxicity or accrual to Cohort 3, whichever 
occurs first (commence Part B)  
o A study drug-associated* DLT (commence Part C) 
• 
Dose Part B:  cohorts will receive consecutive 50% increases in dose until:   
o A study drug-associated* DLT (commence Part C) 
o > 1 patient with a study drug-associated DLT (stop dose escalation) 
• 
Dose Part C:  cohorts will receive consecutive 25% increases in dose until:   
o 
> 1 patient with a study drug-associated DLT (stop dose escalation) 
*study drug-associated:  AEs considered possibly related, probably related, or related to study drug 
Note:  Based on emerging tolerability data the Sponsor may choose to escalate the dose between 
cohorts at an  increment less than the percent increase allowed above in an effort to protect 
patient safety. 
Dose to be Administered During Phase 2a 
Patients entered to the Phase 2a portion of this study will receive study drug at the RP2D 
established during the Phase 1a portion of the study. The MTD and RP2D has been 
determined to be 220 mg/m2 
Ongoing safety evaluations will continue during accrual of patients to the Phase 2a 
expansion cohorts to determine whether any newly identified AEs necessitate modifications 
to the protocol or discontinuation of accrual to patients within any cohort. 
Changes in Dose to be Administered 
Patients will continue to be treated with study drug at that same dose level throughout the 
duration of their time on study, unless dose reduction is necessary due to the occurrence of 
a DLT or other toxicity warranting dose reduction at the Investigator’s discretion. There 
will be no intra-patient dose-escalation.  
Dose adjustments should be made in the event of noted weight change (± 10%; less at the site’s 
discretion or if required by institution procedures) at visits that require weight measurement.   
Route of Administration 
IV infusion via indwelling venous access catheter, utilizing a controlled infusion device 
Dose Preparation 
Infusion sets made of DEHP-free material, containing a 0.22 micron in-line filter 
Infusion Duration 
2 hours (+ 10 minutes) 
Infusion Volume  
Doses ≤ 180 mg/m2:  100 mL 
Doses > 180 mg/m2:  200 to 250 mL; this may include either: 
• 
100 mL × 2 (dose to be divided between two 100 mL infusion volumes to be 
administered sequentially) 
• 
Up to 250 mL (using a single flexible IV bag) 
Diluent 
Commercially available sterile 0.9 % NaCl solution for IV infusion  
Schedule 
Study drug is to be administered once every 3 weeks (Q3W) on Day 1 of each cycle (3 
weeks [21 days] equals 1 dosing cycle).   
End of Cycle 1 (EOC1) assessments are to be performed no sooner than C1/D21 (-2 days).  
Subsequent cycles may be administered Q3W (± 2 days), unless further delay is required to 
allow for amelioration of toxicities 
STUDY DESIGN 
Cycle 1 
 
A minimum of 1 cycle of AVID100 will be administered, if tolerated.  Determinations 
regarding cohort escalation, DLTs, and MTD will be based on toxicities observed during 


 
 
 
 
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this 3 week (Cycle 1) of treatment.  
• 
Patients completing Cycle 1, in the absence of a DLT, will be considered to have 
tolerated the regimen.   
• 
Patients must receive their full planned dose of AVID100 during Cycle 1 in order to be 
considered evaluable for safety and tolerability, unless dose reduction, interruption, or 
discontinuation was the result of a DLT.   
• 
Dose-Escalation Cohorts:  Patients will be replaced, if necessary (e.g., received < 1 full 
dose of AVID100 plus follow-up through EOC1 [C1/D21 {- 2 days}]) for any reason 
other than a DLT), to allow for a thorough assessment of the tolerability in any dose 
cohort.   
• 
All enrolled patients will be considered in the assessment of safety and tolerability. 
Premedication 
Beginning with the first dose, all patients must be premedicated with standard therapies 
prior to each dose of AVID100 to reduce the risk of infusion-related reactions (IRRs) 
associated with study drug.   
The recommended premedication regimen includes administration of dexamethasone 12 
hours and 6 hours prior to each dose, as well as administration to begin at minimum 30 
minutes prior to each infusion of a glucocorticoid (e.g., dexamethasone) as well as an H1 
(e.g., diphenhydramine/hydroxyzine) and an H2-blocker (e.g., ranitidine/famotidine).   
In the event of other study-drug associated reactions (e.g., nausea, vomiting, diarrhea, etc.), 
patients may be premedicated with standard therapies in order to reduce the potential for 
such reactions in the future.   
Mandatory premedication will be implemented for all patients should a pattern begin to 
emerge of mild-to-moderate study drug-related reactions that are amenable to prophylaxis 
with standard agents.   
Phase 1a:  Rules for Accrual 
 
 
Rules for Dose Escalation and Cohort Expansion 
Dose escalation of AVID100 is based on demonstrated tolerability during Cycle 1 (i.e., the 
initial 3 weeks of dosing) and the occurrence of DLTs thought to be associated with (i.e., 
possibly related, probably related, or related to) study drug.  The rules for dose escalation 
and identification of the MTD(s) in this study are as follows: 
Establishment of the MTD 
1. Dose Part A:  Minimum of 1 patient entered into dose Cohort 1 and 2 ONLY; dose 
escalation between cohorts will be 100% (until at most Cohort 3).   
• If during Cycle 1, a patient experiences any > Grade 2 toxicity considered 
associated with study drug, the cohort will be expanded to 3 patients and Part B will 
commence.  
• If during Cycle 1, the patient experiences a DLT considered associated with study 
drug, the cohort will be expanded to 6 patients and Part C will commence. 
2. Dose Part B:  Minimum of 3 patients entered to each cohort; dose escalation between 
cohorts will be 50%.   
• If during Cycle 1, any 1 patient experiences a DLT considered associated with 
study drug, the cohort will be expanded to 6 patients and Part C will commence. 
• If during Cycle 1, > 1 patient experiences a DLT dose escalation will STOP.  This 
will indicate that the MTD has been exceeded. 
3. Dose Part C:  Minimum of 6 patients entered into any cohort where a DLT is observed 
in any of the first 3 patients, otherwise a minimum of 3 patients per cohort; dose 
escalation between cohorts will be 25%. 
• If during Cycle 1, > 1 patient experiences a DLT, dose escalation will STOP.  This 
will indicate that the MTD has been exceeded. 
4. If it is determined that a dose level is not tolerated, the previous lower dose cohort will 
be expanded to 6 patients (if this has not already been accomplished) as a total of 6 
patients must be treated before establishing a dose as the MTD. 
5. Once the MTD (or maximum dose to be studied) is achieved and the RP2D is 
identified, that cohort may be expanded up to 12 patients to more fully evaluate safety 
and tolerability at that dose level at the Sponsor’s discretion.  
6. Should the DLT rate equal or exceed 33.3% in an expanded MTD cohort, it will be 
determined that the dose is not tolerated.  If this occurs, the previous lower dose cohort 
may be expanded.  Therefore: 


 
 
 
 
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• There is potential for expansion of lower dose cohort(s) if the initially identified 
MTD is not tolerated (either with single or repeat cycles of therapy), and 
• There is potential to evaluate and expand a previously unexamined intermediate 
dose level(s) between 2 established dose levels to more fully characterize 
tolerability. 
Note:  Based on emerging tolerability data the Sponsor may choose to escalate the dose between 
cohorts at an  increment less than the percent increase allowed above in an effort to protect 
patient safety. 
Rules for Duration of Exposure Prior to Start of Next Patient and Start of Next 
Cohort 
Dose escalation and accrual to the next cohort will occur only after the minimum number of 
patients required for tolerability assessment in the current cohort have completed Cycle 1, 
and only after acceptable tolerance has been demonstrated in at least 1 of 1, 3 of 3, or 5 of 6 
patients treated in the current cohort (depending on cohort size), and after consultation with 
the Sponsor's Medical Monitor(s).   
In cohorts with > 1 patient enrollment will be staggered between the first and second patient 
by at minimum 24 hours in order to assess for IRRs; thereafter patients within a cohort may 
be added concurrently. 
For all patients, EOC1 assessments are to be performed no sooner than C1/D21 (-2 days). 
Rules for Establishing the 
RP2D 
The MTD (or a dose lower than the MTD) will be identified as the RP2D, provided a 
minimum of 6 patients have been treated at that dose, and provided acceptable tolerance has 
been demonstrated in at least 5 of 6 patients treated.   
 
The RP2D choice will be based on the MTD evaluation as well as other toxicities observed 
in the study, including observations in later cycles of administration of AVID100, as well as 
on PK and other data. 
Phase 2a:  Rules for Accrual  
Once the RP2D has been identified, approximately 60 patients in 3 expansion will be 
enrolled to the Phase 2a portion of the study. 
• 
Accrual to Phase 2a may begin once the RP2D has been established and a minimum of 
6 patients have been treated at that dose.   
• 
If the Phase 1a MTD Cohort is to be expanded up to 12 patients to more fully evaluate 
safety and tolerability at that dose level, accrual to Phase 2a may begin concurrent with 
accrual of the additional up to 6 patients to that cohort.     
Rules for Patient Population to be Treated  
Patients will be accrued to 3 expansion cohorts.  The tumor types to be evaluated in these 
expansion cohorts are mTNBC (~30 patients), SCCHN (~15 patients), and Sq-NSCLC (~15 
patients).   
Criteria for eligibility will be as described above with the additional requirement that 
patient tumors must have been documented to express EGFR by IHC (3+ intensity in ≥ 
50% of tumor cells or ≥ 2+ intensity in ≥ 75% of tumor cells in mTNBC; 3+ intensity in ≥ 
50% of tumor cells in SCCHN and Sq-NSCLC) in a central laboratory.   Further, FFPE 
tumor tissue from either a prior procedure or a recent biopsy must be available for 
submission to a central laboratory for other study-related evaluations. 
Rules for Tolerability  
The criteria for tolerability during Phase 1a will apply to Phase 2a Expansion Cohorts.  
Safety will be reviewed on an ongoing basis to determine if the dose and schedule chosen 
based on the Phase 1a dose escalation is safe and well-tolerated in expanded populations of 
patients with the tumor types selected for the expansion cohorts (mTNBC, SCCHN, and 
Sq-NSCLC). Should it be determined that the dose is not well-tolerated (i.e., > 33.3% of 
patients in an expansion cohort experience a Cycle 1 DLT), the safety of that dose level will 
be re-evaluated and the next lower dose with established tolerability in Phase 1a will be 
administered to subsequent patients. 
An exception will be the occurrence of toxicity suggesting organ damage (e.g., pulmonary 
fibrosis, drug-induced liver injury) occurring in > 2 patients within an expanded cohort, in 
which case further accrual to that cohort will be discontinued. 
Continued Therapy after  
Cycle 1 
Upon completion of Cycle 1, in the absence of unacceptable toxicity or documented disease 
progression, patients may continue to be treated with study drug Q3W (± 2 days) unless 


 
 
 
 
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further delay is required to allow for amelioration of toxicities.  Administration will be at 
the same dose and infusion duration established for the patient during Cycle 1, and on the 
same schedule (unless dose reduction is necessary), provided retreatment guidelines are 
met.  Additional cycles should be initiated within approximately 2 weeks of the completion 
of the previous cycle, if feasible. 
Retreatment Guidelines:  In order to start any new cycle a patient must meet the following 
criteria: 
• 
ANC > 1,000 per mm3 
• 
Platelets > 75,000 per mm3 
• 
Ongoing AEs (study drug-associated) should NOT meet the criteria for DLT 
• 
Any ongoing AEs should have either ameliorated to < Grade 1 severity, returned to 
baseline status, or resolved, with the exceptions of Grade 2 alopecia, clinical events that 
are being adequately controlled with best supportive care (e.g., nausea, vomiting, 
diarrhea, fatigue), and asymptomatic laboratory abnormalities that are considered 
clinically insignificant or that are resolving with medical therapy  
Duration of Treatment 
 
Additional cycles of AVID100 may continue to be administered if tolerated and in the 
absence of documented disease progression, at the Investigator’s discretion, provided 
retreatment criteria have been met.   
Retreatment Following a 
Response 
Treatment with AVID100 may be restarted in a patient who:  
• 
Previously achieved a documented OR or prolonged SD on this study, stopped 
treatment, and subsequently progresses, or  
• 
Discontinued therapy for a reason other than a DLT or PD, and in whom documented 
OR or prolonged SD is subsequently noted.   
Such action may be taken at the Investigator’s discretion, following discussion with the 
Medical Monitor, provided retreatment criteria are met, no anti-cancer treatment was 
administered since the last dose of AVID100, and the trial is still open.  This option for 
retreatment does not apply to patients who previously experienced an unacceptable toxicity 
that required permanent discontinuation of study drug. 
TOXICITY and DLT 
Toxicity Grading 
Common Terminology Criteria for Adverse Events [CTCAE Version 5.0] to be used for 
grading toxicities  
Toxicity Management/ Dose 
Modification 
Management of Dose-Limiting Toxicities 
Toxicity that meets the protocol definition of DLT will be managed by either discontinuing 
the patient from further participation in the study, or the patient may continue on study if 
there is evidence of response or other clinical benefit, but must do so at a reduced dose of 
study drug, and ONLY following discussion with the Sponsor’s Medical Monitor(s).  
Patients may not be retreated following the occurrence of a DLT until retreatment criteria 
have been met. 
Exceptions to continuing on study at a reduced dose include evidence of pulmonary, neuro-, 
ocular, nephro-, or hepatotoxicity as detailed in the protocol Criteria for Treatment 
Discontinuation.  In such instances patients must be permanently discontinued from 
treatment with study drug.     
Management of Other Toxicities 
Toxicity that does not meet the protocol definition of DLT, but nevertheless warrants dose 
modification may be managed by either dose reduction or temporary interruption of study 
drug in order to allow for amelioration of the toxicity.  
DLT Definition 
 
Any of the following toxicities, if judged to be associated with study drug (i.e., possibly 
related, probably related, or related), will be considered a DLT for the purposes of this trial.  
1. 
Evidence of pulmonary fibrosis, any grade (patient must be permanently discontinued) 
2. 
Grade 3 non-hematologic toxicity regardless of duration with the exceptions of:  
• 
Grade 3 nausea, vomiting, diarrhea, or fatigue lasting < 2 days with best 
supportive care 
• 
Grade 3 asymptomatic electrolyte abnormalities lasting < 3 days that are not 
considered clinically relevant by the Investigator and that resolve with medical 
therapy 
3. 
AST and/or ALT elevation > 3 × ULN (or > 3 × baseline if elevated at study entry as 
allowed by study eligibility criteria), with total bilirubin > 2 × ULN without initial 


 
 
 
 
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findings of cholestasis (i.e., no elevation in serum alkaline phosphatase [ALP]), that 
cannot be explained by other factors 
4. 
Any Grade 4 non-hematologic toxicity with the exception of: 
• 
Grade 4 asymptomatic electrolyte abnormalities lasting < 7 days that are not 
considered clinically significant by the Investigator and that are controlled with 
medical therapy 
5. 
Neutropenia that is: 
• 
> Grade 3 and associated with fever (ANC < 1000 per mm3, temperature > 38.3ºC 
[101ºF] or a sustained temperature of ≥ 38ºC [100.4ºF] for > 1 hour) (i.e., febrile 
neutropenia)  
• 
Grade 4 and sustained (ANC < 500 per mm3, duration > 5 days) 
6. 
Thrombocytopenia that is: 
• 
Grade 3 with clinically significant hemorrhage or requirement for transfusion 
• 
Grade 4 (platelets < 25,000 per mm3) 
7. 
Inability to complete Cycle 1 at the assigned dose (i.e., receipt of < 1 full planned dose 
of study drug plus 3 weeks of follow-up due to ≥ Grade 3 toxicity) 
8. 
Treatment delays > 2 weeks from the scheduled “next dose” due to > Grade 3 toxicity  
Other toxicities may be considered a DLT as determined by the Investigator in 
conjunction with the Medical Monitor. 
The above criteria will be used to make individual patient determinations regarding dose 
reductions, interruptions, or discontinuation throughout the course of the trial, but only 
those DLTs occurring during Cycle 1 will be used to make decisions regarding dose 
escalation and tolerability. 
Events occurring after Cycle 1 will also be evaluated by the Investigator and Medical 
Monitor and taken into consideration when deciding upon further doses to be assessed as 
well as to establishment of the RP2D. 
MTD Definition 
In the Phase 1a portion of this trial, MTD will be defined as the dose below that which 
produces, during Cycle 1 of treatment, any of the indicated DLTs either in > 1 patient in a 3 
to 6 patient cohort, or in > 33.3% of patients in the event of an expanded 7 to 12 patient 
cohort. 
The MTD will not be established until all patients entered into the cohort under evaluation 
have either completed Cycle 1, discontinued further participation in the trial, or had their 
dose reduced due to the occurrence of a DLT. 
Previously established tolerability of a dose level will be reevaluated if DLTs thought to be 
possibly related, probably related, or related to study drug are observed in later cycles.  
Safety Monitoring  
The Investigator(s) and Sponsor's Medical Representatives will comprise a Study Safety 
Committee.  Clinical and laboratory safety data will be reviewed on an ongoing basis in 
order to make decisions regarding the advisability of continuing accrual and dose 
escalation.  To do so: 
1. 
The following will be promptly reported to the Sponsor or designee: 
• 
SAEs, within 24 hours of Investigator awareness 
• 
AEs resulting in permanent discontinuation from study, regardless of seriousness 
or relationship to study drug 
• 
DLTs 
• 
Dose modifications (i.e., dose reductions, temporary dose interruptions)  
2. 
AEs will be recorded on the electronic case report form (eCRF) in a timely manner 
following a patient completing (or being discontinued from) each dosing cycle. 
3. 
The Investigator will make critical laboratory safety data available in a timely manner.  
4. 
Patients will be carefully evaluated for evidence of all AEs, including potential 
cumulative and/or delayed toxicities, throughout the duration of their time on study.   
5. 
During Phase 1a:  Biweekly safety teleconferences will be held between the 
Investigational Site(s) and the Sponsor and/or designee; frequency may fluctuate 
based on accrual and study activity. 
6. 
During Phase 2a:  Monthly safety teleconferences will be held between the 
Investigational Site(s) and the Sponsor and/or designee; frequency may fluctuate 
based on accrual and study activity, as indicated 
Availability of these data also will enable the Sponsor (or designee) to notify regulatory 


 
 
 
 
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authorities, as well as Investigators who may be participating at other sites or in other 
clinical trials of the study drug, of events occurring during the trial. 
PARAMETERS TO BE MEASURED 
Prescreening 
• 
The trial site will prescreen patients for EGFR Tumor Status Determination before 
entering patients into screening for the treatment portion of the trial.  The site should 
use a separate prescreening informed consent form.  Prescreening may be performed 
outside the 28 (+ 2) day screening period to allow adequate turnaround time for 
receipt of results, provided separate informed consent has been obtained. 
Screening  
(Within 14 days prior to 1st dose 
unless otherwise stipulated) 
• 
Informed consent 
• 
Eligibility assessment 
• 
Past medical history 
• 
History of the primary malignancy (including data on best response to prior therapy, if 
available) 
Safety Assessment 
Patients to be monitored throughout the treatment and follow-up period for occurrence of 
adverse events (AEs) (acute, delayed, and/or cumulative), as well as for changes in clinical 
status, vital signs (VS), and laboratory data.   
Safety Assessments (1) (Within 14 days prior to 1st dose unless otherwise stipulated) 
• 
Medication survey 
• 
Adverse events (collection of data from 1st dose to 30 days after final dose) 
• 
Performance status evaluation (ECOG) 
• 
Vital signs (including temperature, pulse, respiratory rate, BP, and O2 saturation by 
pulse oximetry) 
• 
Physical examination (including weight and pulmonary assessment at each visit) 
• 
Hematologic parameters 
• 
Serum chemistries 
• 
Coagulation parameters 
• 
Urinalyses 
• 
Anti-drug antibody (ADA) to AVID100 (Central Lab) 
• 
Pregnancy testing (if applicable) (serum test within 14 days, urine or serum test 
repeated within 2 working days prior to 1st dose) 
• 
12-Lead ECGs 
Safety Assessments (2) (within 28 days [+2 days] prior to first dose of study drug, 
provided no antineoplastic therapy has been delivered between safety assessment and first 
dose of study drug) 
• 
Ophthalmology exam (complete)  
• 
MUGA scan or Echocardiogram (follow-up ONLY in patients with a history of CHF, 
or in patients developing clinical findings suggestive of cardiac dysfunction at any 
point during the study or the follow-up period) 
• 
Pulmonary function testing (to include spirometry and DLCO) 
• 
Chest X-Ray (PA and lateral) 
Disease Assessment 
(within 28 days [+ 2 days] prior to 
1st dose) 
Disease Assessments 
• 
EGFR tumor status determination (by local or central evaluation of archival formalin-
fixed paraffin-embedded [FFPE] tumor tissue or verification by previous pathology 
report during Phase 1a and by central evaluation of FFPE tumor tissue [archival or 
from recent biopsy] during Phase 2a) 
o 
Phase 1a Dose-Escalation Cohorts:  Optional   
o 
Phase 2a Expansion Cohorts:  Required; tumor must be EGFR-positive by IHC as 
specified (3+ intensity in ≥ 50% of tumor cells or ≥ 2+ intensity in ≥ 75% of 
tumor cells in mTNBC; 3+ intensity in ≥ 50% of tumor cells in SCCHN and Sq-
NSCLC) for patient to be eligible for enrollment  
• 
Tumor marker measurement (as indicated by tumor type) (Phase 1a only) 
• 
Diagnostic imaging for assessment of disease (and pulmonary status) (CT/MRI)  
o For Phase 2a patients must have documented measurable disease 
o For safety (all patients), imaging of the chest required at each evaluation 
• 
Response assessment (per RECIST 1.1).  Data on evidence of and duration of any OR 
or SD, as well as the TTP to be collected (all patients)   


 
 
 
 
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Pharmacokinetics  
(Central Lab) 
Serum sampling to assess the PK profiles of total antibody (AVID100 plus MAB100), 
AVID100, and DM1; to be performed throughout the trial (all patients)   
Biomarker Studies (Central 
Lab) 
• 
Tumor sample submission: for evaluation of tumor EGFR-expression by FISH and 
other potential biomarkers; in archival or recently obtained FFPE tumor tissue 
o Phase 1a Dose-Escalation Cohorts:  If available 
o Phase 2a Expansion Cohorts:   
 
Required at Screening; if not available patient must be willing to undergo 
tumor biopsy.   
 
Optional Post-Dosing if tumor tissue is available from an interval surgery, in 
the event of a documented objective response if the patient has accessible 
tumor or prolonged disease stabilization > 8 weeks, and upon request of the 
Sponsor based on other study findings (after discussion with the 
Investigator). 
• 
Peripheral blood collection: for evaluation of EGFR ctDNA for EGFR-ECD mutation 
status and EGFRvIII deletions (SCCHN patients only), as well as assessment of other 
potential biomarkers of interest (required for all indications) 
STUDY COMPLETION 
Criteria for Treatment 
Discontinuation 
Patients will be discontinued from further treatment with study drug in the event of any of 
the following:  
1. 
Patient must be permanently discontinued in the event of any major, potentially 
irreversible organ system DLT , including: 
• Pulmonary toxicity defined as: 
o Evidence of pulmonary fibrosis, any grade  
o Reduction of forced vital capacity (FVC) or DLCO > Grade 3  
• Neurotoxicity defined as peripheral neuropathy > Grade 3 
• Any ocular toxicity  > Grade 3  
• Nephrotoxicity defined as: 
o Acute kidney disease > Grade 3 (i.e., creatinine > 3 × baseline or > 4.0 mg/dL) 
o Chronic kidney disease > Grade 3 (i.e., estimated glomerular filtration rate 
[eGFR] or creatinine clearance [CrCl] 29-15 mL/min/1.73 m2) 
o Proteinuria > Grade 3 (i.e., > 3.5 g/24 hours) 
• Hepatotoxicity suggestive of drug-induced liver injury, as characterized by the 
following 3 criteria: 
o AST and/or ALT elevation > 3 × ULN (or > 3 × baseline if elevated at study 
entry as allowed by study eligibility criteria)  
o Total bilirubin > 2 × ULN without initial findings of cholestasis (i.e., no 
elevation in serum ALP) 
o No explanation for the above findings, such as:  viral hepatitis A, B, or C; 
preexisting or acute liver disease; or another drug capable of causing the 
observed injury 
Adapted from:  Hy’s Law. Drug–induced liver injury: premarketing clinical evaluation. 
Guidance for Industry. U.S. Department of HHS, FDA, CDER, CBER, 2009. 
2. 
Any other DLT considered by the Investigator to require treatment discontinuation. 
Note:  Patients experiencing a DLT not listed in #1 above may continue at a reduced dose if there 
is evidence of an OR, SD, or other clinical benefit, and ONLY following discussion with 
the Sponsor’s Medical Monitor(s).    
3. 
Another AE not meeting the criteria for a DLT, yet considered by the Investigator to 
require treatment discontinuation. 
4. 
Documented progressive disease at any time during the study 
5. 
Treatment failure not meeting the criteria for progressive disease, but considered by 
the Investigator to require treatment discontinuation. 
6. 
Requirement for a significant surgical procedure  
7. 
An intercurrent illness which, in the opinion of the Investigator, would prevent 
completion of study-related evaluations 
8. 
Significant deviation from the protocol or eligibility criteria.  Such patients will be 
considered protocol violations and will be discontinued from treatment 
9. 
Pregnancy 
10. Noncompliance with study or follow-up procedures 


 
 
 
 
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11. Patient withdrawal of consent and election to discontinue treatment with study drug. 
(Patients may leave the study at any time for any reason if they wish to do so, without 
any consequence.) 
12. Termination of the study by the Sponsor 
Any other reason which, in the opinion of the Investigator, would justify treatment 
discontinuation. 
Follow-up 
• 
End of Treatment (EOT) evaluations to be conducted within approximately 10 days 
following the decision to discontinue the patient from further treatment    
• 
1 Month Follow-up (1M FUP) evaluations to be conducted approximately 30 days (+7 
days) following the last dose of study drug.   
• 
If an observed toxicity thought to be associated with study drug has not resolved by the 
1M FUP evaluation, an additional follow-up AE assessment will be conducted 
approximately 3 months (may be repeated at 6 months if needed) following the last 
dose of study drug, if feasible, in order to confirm that the event has either resolved, 
returned to baseline status, or been adequately explained, and that no longer term 
deleterious effects have become evident.   
Any patient who develops pulmonary fibrosis will be followed at approximately 3 month 
intervals for up to 2 years to assess the course of the disease and evaluate potential 
reversibility of this finding. 
• 
In the event of an ongoing OR or SD at the EOT, response assessments based on tumor 
marker and imaging studies will continue to be performed every 3 months during the 
first year and every 6 months thereafter, until PD or another therapeutic intervention is 
initiated, so that data may be collected on the duration of stabilization or response, as 
well as on the overall TTP.  
ANALYSIS PLAN 
Safety/Tolerability 
Safety analyses are to be conducted on patients receiving any amount of a dose of 
AVID100. 
Antineoplastic Activity 
Patients who complete Cycle 2 (6 weeks) of treatment, receive at least 2 planned doses 
during that period, and have a follow-up assessment of disease status will be considered 
evaluable for assessment of antineoplastic activity.  Patients who are withdrawn from the 
study before completion of Cycle 2 because of progressive disease also will be included in 
assessments of antineoplastic activity. 
TRIAL REPORTING 
Final Study Report 
Final integrated clinical/statistical study report to be prepared following study completion. 
 


 
 
 
 
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2. 
SCIENTIFIC BACKGROUND AND RATIONALE 
 
Background 
2.1.1 
Overview of the Target:  EGFR 
Several members of the HER-ERBB family of Type 1 receptor tyrosine kinases (RTK) 
(including EGFR/HER1/ERBB1, HER2/ERBB2, HER3/ERBB3, and HER4/ERBB4) have been 
proven to be important targets for cancer therapy (1-5).  EGFR has been shown to be highly 
expressed or in some cases mutated in a variety of human malignancies.  Activation of the EGFR 
pathway results in cell proliferation and inhibition of apoptosis as well as affecting angiogenesis 
and the metastatic process.  EGFR (HER1, ERBB1) has been clinically validated as a target, with 
marketed products including both tyrosine kinase inhibitors and monoclonal antibodies directed 
to this cellular receptor shown to be effective therapy for selected human malignancies.  EGFR 
tyrosine kinase inhibitors have been shown to be effective in the treatment of patients with 
malignancies including non-small cell lung carcinoma (NSCLC) and pancreatic carcinoma (PC), 
whereas anti-EGFR antibodies have been approved for treatment of colorectal carcinoma (CRC), 
squamous cell carcinoma of the head and neck (SCCHN), and squamous histology NSCLC (Sq-
NSCLC) (6, 7).   EGFR inhibitors (EGFRi) have been studied in a wide variety of other 
indications including but not limited to: ovarian cancer, renal cell cancer, hepatocellular cancer, 
and breast cancer.  In these and other indications limited EGFRi activity was observed either as 
single agents or in combination with other therapies including chemotherapy, thereby precluding 
their being developed further. 
2.1.2 
Overview of EGFR and Breast Cancer 
The role of EGFR gene and protein expression as well as activation of EGFR and downstream 
signaling in patients with subtypes of breast cancer (BC) has been studied intensively but there is 
no current consensus on the importance of inhibiting this pathway in the treatment of patients 
with this malignancy.  A wide variety of published studies have been performed over nearly 
three decades evaluating EGFR expression in BC using varied techniques to assess cell surface 
receptor expression and activation as well as gene amplification (8-16).  EGFR expression has 
been detected in estrogen receptor/progesterone receptor (ER/PR) positive tumors (11) and 
HER2 amplified and non-amplified tumors (9).  The majority of studies suggest that 
overexpression is most commonly observed in patients with poorly differentiated, inflammatory, 
basal, and/or triple-negative BC (TNBC) (8, 10-16) although some studies suggested greater 
expression in HER2+ tumors than in ER-positive BC or TNBC (9, 10, 15).  The proportion of 
patients who are positive varies depending on the patient subset evaluated and the technique(s) 
used for assessment.  Recent studies have been undertaken utilizing a validated modification of 
the DAKO PharmDx IHC assay to evaluate the proportion of patients with various levels of 
EGFR expression on several different tumor types.  Based on nearly 250 triple TNBC tissue 
samples it has been determined that: (a) 25% of TNBC cases were either 2+ or 3+ in ≥ 50% of 
tumor cells; (b) 19% of TNBC cases were 2+ in ≥ 50% of tumor cells; (c) 13% of TNBC cases 
were 2+ in ≥ 75% of tumor cells and; (d) 6% of TNBC cases were 3+ in ≥ 50% of tumor  cells. 
EGFR signaling has been shown to play a role in the development and pathogenesis of BC (17) 
including aspects of bone metastases (18). The role of EGFR on the epithelial-mesenchymal 
transition (EMT) associated with tumor invasiveness, angiogenesis, and metastasis has also been 


 
 
 
 
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documented (19). In addition, hetero-dimerization of EGFR with HER2 and HER3 or with non 
ERBB family receptors (e.g., MET) may also have a role in either the pathogenesis of subsets of 
patients with BC or in their resistance to therapy (19). 
 
Very limited activity has been observed in patients with metastatic BC treated with either anti-
EGFR monoclonal antibodies (mAbs) or EGFR tyrosine kinase inhibitors (TKI) as single agents 
(19-23).  Some evidence of increased activity of chemotherapy plus the anti-EGFR mAb 
cetuximab vs. chemotherapy alone has been documented in patients with TNBC but thus far no 
definitive evidence of efficacy has been presented for any regimen containing an EGFRi (24, 
25).  These data suggested a need to develop biomarkers to assess potential responses earlier or 
to select patients with TNBC and other subtypes of BC who may be more responsive to novel 
therapies (19).   
Preclinical data document the potent activity of AVID100 both in vitro and in vivo in models of 
BC including TNBC (Section 2.3.1.1 and Investigator’s Brochure).  In this clinical study one 
expansion cohort will enroll patients with BC who have not received ado-trastuzumab emtansine 
(Kadcyla®) and have been prescreened for EGFR overexpression using a validated bioassay.  
Strong overexpression of EGFR, i.e., ≥ 3+ intensity by immunohistochemistry (IHC)  in ≥ 50% 
of tumor cells or ≥ 2+ intensity in ≥ 75% of tumor cells will be utilized as the provisional cut-off 
for patient entry into this study.  Evaluation of EGFR gene expression will also be evaluated in 
parallel using a validated FISH assay but these results will not be used for selection of patients.   
The choice of cell surface expression of EGFR and the high cut-off value was based on the 
primary mechanism of antitumor activity of AVID100 which is dependent on the delivery of the 
DM1 cytotoxic payload to EGFR-expressing cells. The relatively limited activity of cetuximab, 
demonstration that cetuximab activity is increased by the addition of chemotherapy, and the 
strong data that tubulin-targeted agents (e.g. Paclitaxel, docetaxel, ixabepilone, eribulin, and 
DM1) are active in many patients with BC provide the rationale for testing AVID100 in patients 
who show a high degree of overexpression of EGFR.  Patients with levels of HER2 that are 
below the level required for treatment with trastuzumab or ado-trastuzumab emtansine and who 
meet the criteria for EGFR-overexpression may be considered for enrollment. 
2.1.3 
Overview of EGFR and Squamous Cell Carcinoma of the Head and Neck 
The EGFR pathway is a validated target for therapy of patients with SCCHN (26-29).  Multiple 
studies have documented that EGFR is highly expressed in more than 90% of SCCHN tumor 
samples compared to normal squamous epithelium from non-malignant tissue (26-29) with the 
majority of specimens being graded 2+ or 3+ by IHC (29).  Increased production of transforming 
growth factor alpha (TGF-), an EGFR ligand, has also been documented to be increased in 
SCCHN samples compared to normal mucosa (29). Higher levels of EGFR expression in patients 
with SCCHN are associated with poor prognosis (26, 27, 29) as well as poor local control of the 
tumor and reduced responsiveness to cetuximab (29).  EGFR mutant type III variant (EGFRvIII) 
mutations are present in up to 40% of patients with SCCHN and may contribute to resistance to 
therapy with anti-EGFR mAbs (28-30) despite documentation that cetuximab binds to, down-
modulates, and ultimately inhibits signaling via this mutant receptor (31, 32).  KRAS mutations 
occur in less than 5% of patients with SCCHN and their impact on prognosis or response to 
therapy has not been established (29) 


 
 
 
 
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Multiple clinical trials evaluating both anti-EGFR mAbs and EGFR-TKI have been completed 
over the last two decades.  Relatively limited antitumor activity has been observed in patients 
treated with EGFR-TKI and none of these agents has been approved for treatment of SCCHN 
(26-28, 33-35).  In contrast, activity has been observed with some anti-EGFR mAbs and 
cetuximab has been approved as a single agent as well as in combination with either 
chemotherapy or radiotherapy for the treatment of selected patients with SCCHN (33-36).  In 
patients who recently progressed on a platinum-based chemotherapy regimen approximately 
13% of recipients of cetuximab achieved a partial response (PR) with a median duration of 
response of 5.8 months (36, 37). Addition of cetuximab to a regimen of cisplatin or carboplatin 
plus 5-FU in patients with untreated recurrent or metastatic SCCHN improved OS from 7.4 
months in the chemotherapy alone group to 10.1 months in the group receiving chemotherapy 
and cetuximab (38).  Progression-free survival (PFS) was increased by 2.3 months (from 3.3 to 
5.6 months) and 36% of the patients treated with cetuximab and chemotherapy experienced 
objective responses compared to a 20% response rate in recipients of chemotherapy alone (38).  
Preliminary data have been presented or published on the clinical activity of other anti-EGFR 
mAbs as well as on EGFR-TKI.  Activity has been observed with many of these agents (33, 34) 
but thus far the only agent with proven safety and efficacy is cetuximab (36-38).  The single 
agent activity of cetuximab is limited but addition of cetuximab to chemotherapy in a P3 
registration study resulted in an incremental improvement in response rate, PFS and OS. Studies 
of chemotherapy regimens including either paclitaxel or docetaxel plus cetuximab have shown 
promise (39), both of these approved taxanes have activity in the treatment of SCCHN and 
docetaxel is approved for this indication (40).  These data provide support for treatment of 
patients with SCCHN with AVID100, an ADC targeting EGFR with a DM1 payload that is a 
more potent microtubule-targeted agent than available taxanes.  AVID100 has shown greater 
activity that the unconjugated antibody (MAB100) in a variety of in vitro cell lines derived from 
patients with SCCHN (Section 2.2.1.1.1 and Investigator’s Brochure).  The preclinical data 
with AVID100, the documented single agent activity of cetuximab, and the documented role of 
paclitaxel and docetaxel in patients with SCCHN provides a strong rationale for the evaluation of 
AVID100 in this patient population. 
2.1.4 
Overview of EGFR and Non-Small Cell Lung Carcinoma 
EGFR has been documented to be a crucial target for specific subsets of patients with NSCLC 
(4).  EGFR tyrosine kinase inhibitors (TKI) (erlotinib, gefitinib, afatinib) have been documented 
to be active in patients with activating EGFR mutations and superior to first line chemotherapy 
in this patient population (41). Mutations resistant to the approved EGFR TKIs, including 
T790M, limit their long term benefits.  Recently osimertinib has been approved and shown to be 
active in patients resistant to first generation inhibitors and more active than available 
chemotherapy in first line treatment of patients with T790M mutation-positive NSCLC (42).   
The evaluation of anti-EGFR mAbs in patients with NSCLC has been more complex with 
numerous studies and subanalyses required to ultimately delineate a potentially sensitive patient 
population.  Cetuximab, a mouse-human chimeric anti-EGFR mAb, was initially shown to be 
active in a subset of both EGFR-wild type and EGFR-mutated NSCLC lines in vitro and in vivo 
both alone and in combination with chemotherapeutic agents; these data supported subsequent 
clinical evaluation (43). 


 
 
 
 
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Several studies evaluated cetuximab in combination with chemotherapy as a first-line therapy of 
NSCLC with mixed results (44). Two Phase 3 studies yielded similar efficacy outcomes but 
disparate results with respect to statistical significance.  A modest median OS advantage of 1.2 
months (HR 0.87, [95% CI 0.762-0.996], p=0.044) was observed in the FLEX study (1125 
patients enrolled) evaluating the addition of cetuximab to cisplatin and vinorelbine versus the 
chemotherapy combination alone (45).  Although the increment in OS was similar, the 1.3 month 
increase was not statistically significant in the smaller BMS099 study (676 patients enrolled) 
comparing a taxane and carboplatin regimen with or without the addition of cetuximab (HR 0.89 
[95% CI 0.754-1.051], p=0.169) (46). The minor increments in OS and the failure to achieve a 
statistically significant result in both studies precluded approval of cetuximab in this setting.  
Subsequent subanalyses of the FLEX trial suggested that patients who received cetuximab in 
addition to the designated platinum doublet who developed first cycle rash had prolonged OS, 
PFS and increased responses rates compared to patients who received chemotherapy alone (47).  
In a separate retrospective subanalysis, the median OS was assessed comparing patients whose 
EGFR tumor expression denoted by immunohistochemistry H-scores were low (< 200) (69% of 
patients) compared to those who were high (≥ 200) (31% of patients) (48).  Median OS for 
patients receiving cetuximab plus chemotherapy with high H-scores was 12.0 months [95% CI 
10.2-15.2] compared to 9.6 months ([7.6-10.6]; HR 0.73, 0.58-0.93, p=0.011) for patients with 
high H-Scores who received chemotherapy alone.  No effect on OS was observed when 
comparing the two regimens in patients who had low H-scores (9.8 vs. 10.3 months for the 
combination vs. the chemotherapy regimen only, respectively, HR 0.99, p=0.88).  Many other 
studies have been completed evaluating the potential efficacy of cetuximab in patients with 
NSCLC, but none have prospectively confirmed the potential for enrichment based on the EGFR 
expression criteria delineated by the retrospective analysis of the FLEX trial although some 
subsequent reviews, meta-analyses and commentaries support the efficacy of cetuximab in the 
treatment of NSCLC despite the lack of confirmatory evidence (44). 
Based on a promising Phase 2 trial, a Phase 3 trial adding cetuximab to either docetaxel or 
pemetrexed in patients with previously treated NSCLC was undertaken (49).  No impact was 
observed in median PFS in patients treated with cetuximab plus either chemotherapy regimen 
compared to the single agent chemotherapeutics in this trial of second line therapy. Additional 
studies have been performed to evaluate the efficacy of cetuximab in treatment-refractory 
NSCLC.  These studies documented that cetuximab as salvage therapy has little or no 
demonstrable activity in the treatment of previously treated NSCLC patients with or without 
evidence of EGFR mutations (50, 51). 
Two Phase 3 studies have been completed with the second generation recombinant human anti-
EGFR monoclonal antibody, necitumumab, resulting in an approval for this agent in combination 
with chemotherapy for patients with Sq-NSCLC.  In the first of two completed Phase 3 trials, 
INSPIRE, no benefit was observed as a result of the addition of cetuximab to a pemetrexed-
cisplatin regimen in patients with Stage IV non-squamous NSCLC (52, 53).  In the Phase 3 
SQUIRE study, the addition of cetuximab to gemcitabine and cisplatin resulted in an 
improvement in median OS compared to patients receiving this chemotherapy regimen alone (7, 
54).  The addition of necitumumab to first-line chemotherapy in this study resulted in a 
prolongation of the median OS to 11.5 months [95% CI 10.4-12.6] compared to 9.9 months [8.9-
11.1] with chemotherapy alone (HR 0.84, [95% CI 0.74-0.96], p=0.01).  This survival benefit 


 
 
 
 
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was consonant with the observations in FLEX where the best HR for median OS was observed in 
patients with Sq-NSCLC (47).  Although the authors of the SQUIRE study did not find that the 
cutoff of <200 or >=200 H-scores to be discriminatory, there was a difference in median OS 
survival between the necitumumab plus chemotherapy-treated and chemotherapy alone groups in 
patients with high (>= 200) H-score values (12.0 months vs. 9.7 months; HR 0.75 [95% CI 0.60-
0.94], p=0.01). For patients with low (<200) H-Scores median OS for patients receiving 
cetuximab and chemotherapy was 11.1 months compared to 9.7 months for the chemotherapy 
arm; HR 0.90 [95% CI 0.75-1.07], p=0.23. 
The data outlined above along with data on the potent and superior activity of AVID100 
compared to cetuximab in in vitro and in vivo models including models of NSCLC support its 
evaluation in patients with treatment-refractory NSCLC.  The initial study will focus on patients 
with Sq-NSCLC.  This choice based on the known higher EGFR expression in patient with 
squamous histology compared to patients with non-squamous NSCLC as well as the documented 
albeit limited activity observed with necitumumab in a Phase 3 trial.  If sufficient activity is 
documented in this patient population additional studies may be conducted in patients with non-
squamous NSCLC. 
2.1.5 
EGFR Extracellular Domain Mutations 
Recent studies have documented that one mechanism of resistance to anti-EGFR mAbs in 
patients with CRC is the emergence of EGFR extracellular domain mutations (mEGFR-ECD) 
with reduced binding for the administered mAb and, in some cases, other mAbs targeting EGFR 
(56, 57).  EGFRvIII mutations resulting from a deletion in EGFR exons 2-7 have been observed 
in multiple tumors and are associated with resistance to cetuximab in patients with SCCHN (58, 
28).  EGFRvIII expression has been observed in variable numbers of patients with SCCHN with 
some estimates varying from 0.31% to 42% (28, 58). EGFR tyrosine kinase domain mutations 
have also been observed in patients with SCCHN but have not been associated with resistance to 
cetuximab (59, 60).  A single documented point mutation in the EGFR-ECD has recently been 
detected in a patient with SCCHN (61).  Given the availability of ctDNA and next-generation 
sequencing (NGS) technology to document the presence of mEGFR-ECD these evaluations may 
be of use in understanding either innate or acquired resistance to AVID100 in patients with 
SCCHN previously treated with cetuximab. 
2.1.6 
Overview of the Product:  AVID100 
Forbius (formerly Formation Biologics, AvidBiologics) has developed AVID100, an antibody-
drug conjugate (ADC), consisting of a novel IgG1 anti-EGFR antibody, MAB100, conjugated to 
the microtubule inhibitory drug DM1, mertansine (a derivative of maytansine), via a stable 
linker.  MAB100 has the same variable region primary sequence as cetuximab. Accordingly, its 
specificity for EGFR is expected to be identical to this marketed anti-EGFR antibody. MAB100 
differs from cetuximab by two amino acid residues in its Fc region. Also, due to its production in 
CHO cells, the glycosylation of MAB100 is different from that of cetuximab. There are 
approximately 3.5 DM1 moieties per molecule of antibody (Ab). 
Maytansine and its derivatives (“maytansinoids”) bind to tubulin and are potent inhibitors of 
mitosis (62).  Maytansine binds to a unique site on ß-tubulin despite evidence of cross-inhibition 
of binding between vinca alkaloid antineoplastic agents and this agent (62).  Synthetic 
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(63).  DM1 is a highly potent maytansine analog that has been conjugated to monoclonal 
antibodies (63) including an approved agent, ado-trastuzimab emtansine, a HER2-targeted ADC 
(64).  DM1 has been utilized as the cytotoxic moiety conjugated to an anti-EGFR antibody 
incorporated in the investigational medical product AVID100. 
The binding affinity of AVID100 for the recombinant ectodomain of EGFR is approximately 2 
nM.  AVID100 inhibits ligand binding to EGFR with concomitant inhibition of phosphorylation 
of this receptor as well as downstream kinases involved in the EGFR pathway (Mitogen 
Activated Protein Kinase [MAPK] and Akt [Protein Kinase B, PKB])  (Data on File; 
Forbius/Formation Biologics).  AVID100 has also been shown to mediate antibody-dependent 
cellular cytotoxicity (ADCC) in vitro.  Upon binding to the extracellular domain III of EGFR, 
AVID100 is presumed to undergo receptor-mediated internalization and subsequent lysosomal 
degradation, resulting in intracellular release of DM1-containing cytotoxic catabolites. Binding 
of DM1 to tubulin disrupts microtubule assembly, which results in cell cycle arrest and apoptotic 
cell death (65-67).  This latter mechanism is presumed to predominate and is responsible for its 
potent preclinical activity, as demonstrated by its superior activity in in vitro and in vivo studies 
compared to unconjugated anti-EGFR antibodies including MAB100 (the AVID100 antibody 
prior to conjugation to DM1) and cetuximab. AVID100 is being developed as a therapeutic 
candidate for EGFR-expressing solid tumors. 
 
Nonclinical Studies  
2.2.1 
Nonclinical Pharmacology Studies 
2.2.1.1. 
In Vitro Pharmacology 
2.2.1.1.1. 
Activity Against Tumor Cell Lines 
In vitro studies have been undertaken in a variety of tumor cells lines.  AVID100 demonstrated 
activity in over 30 cell lines.  Preliminary studies documented that AVID100 was significantly 
more active than MAB100 in human cell lines derived from: (a) squamous cell carcinoma of the 
head and neck; (b) gastric carcinoma; (c) pancreatic carcinoma; (d) squamous cell carcinoma of 
the lung; and (e) breast carcinoma.  In contrast, the colorectal carcinoma cell lines that were 
tested were resistant to both AVID100 and MAB100.  
In many of the cell lines studied AVID100 was more active than MAB100 as denoted by the fold 
difference in the IC50s.  AVID100 was documented to be more active than MAB100 in the head 
and neck cancer cell lines including: FaDu (pharynx squamous cell carcinoma; 10,000 x); Detroit 
562 (pharyngeal cell carcinoma; 1,250 x); Cal 27 (tongue squamous cell carcinoma; 100 x); and 
SCC9 (tongue squamous cell carcinoma; 100 x).  Increased activity was also documented in a 
variety of pancreatic adenocarcinoma cell lines including: ASPc-1 (100 x); BxPC-2 (2,500 x); 
Capan-1 (12.5 x); and PANC-02.13 (140 x) as well as a pancreatic epithelioid carcinoma, 
PANC-1 (50 x).  AVID100 also showed increased potency compared to MAB100 in squamous 
cell lung carcinoma cell lines (H226; 10,000 x and H292; 1000 x), as well as cell lines derived 
from gastric malignancies (gastric adenocarcinoma, AGS; 50 x or gastric carcinoma, N87; 25 x). 
More detailed studies of the in vitro antitumor effects of AVID100 were performed in several 
tumor cell lines and immortalized EGFR-expressing human keratinocytes.  More potent growth 


 
 
 
 
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inhibition was observed in the MDA-MB-468 (breast) and NCI-H292 (lung) cancer cell lines 
treated with AVID100 compared to MAB100 or to cetuximab.  In contrast, AVID100 cytotoxic 
potency on HaCaT immortalized normal human keratinocytes was similar to that observed with 
either MAB100 or cetuximab.  These results documented that the DM1-conjugated ADC, 
AVID100, was more active than the tested unconjugated anti-EGFR antibodies against tumor 
cell lines in vitro, whereas there was no significant increase in its activity on immortalized 
human keratinocytes suggesting that it may have enhanced activity against certain EGFR-bearing 
tumors without markedly enhancing cutaneous toxicity. 
2.2.1.1.2. 
Antibody Dependent Cellular Cytotoxicity  
The potential of AVID100 to mediate antibody dependent cellular cytotoxicity (ADCC) was 
evaluated using effector cell lines expressing either high or low affinity FcγRIIIA.  No evidence 
of ADCC was observed in experiments using the low affinity FcR-expressing cells.  AVID100 
mediated ADCC when using high affinity FcγR-expressing cells as the effector cells. 
2.2.1.1.3. 
Inhibition of EGFR Signal Transduction 
In vitro experiments documented that pretreatment with AVID100 inhibited ligand-dependent 
activation of EGFR.  Exposure of three EGFR-expressing cell lines (HaCaT, NCI-H292, and 
MDA-MB-468) to AVID100 in the presence of an EGFR ligand, epidermal growth factor (EGF), 
resulted in inhibition of phosphorylation of EGFR in vitro.  Inhibition was observed in a cell line 
with evidence of constitutive activation of EGFR presumed to be due to autocrine production of 
EGFR ligands, MDA-MB-468, as well as cell lines in which EGFR phosphorylation was only 
observed after exposure to exogenous ligand  (HaCaT, NCI-292).  In addition to inhibition of 
EGFR activation, pretreatment of the MDA-MB-468 cell line with AVID100 also resulted in 
reduction of phosphorylation of MAPK and Akt, two critical downstream signaling targets 
activated by EGFR. 
2.2.1.2. 
In Vivo Pharmacology 
Antitumor activity of AVID100 and MAB100 was evaluated in vivo in a tumor xenograft model 
using the EGFR-expressing MDA-MB-468 human breast adenocarcinoma in athymic nude mice.  
Single doses of MAB100 administered subcutaneously (SC) at 5 and 10 mg/kg resulted in a 
delay in the rate of tumor growth compared to phosphate buffered saline (PBS) controls, but 
there was no evidence of tumor regression.  In contrast, administration of single doses of either 5 
or 10 mg/kg of AVID100 by the SC route resulted in a more marked effect on tumor growth with 
complete remissions observed in all treated animals (12/12 in each group).  No evidence of 
recurrence in tumors was observed through the end of the study on Day 144. A subsequent 
experiment evaluated repeated intraperitoneal (IP) doses of AVID100, MAB100, and PBS in the 
MDA-MB-468 model.  Tumor growth inhibition was observed in all animals receiving either 
AVID100 or MAB100 when compared to control animals receiving PBS.  A dose-response 
relationship was observed with minimal effects being observed with 0.625 mg/kg of AVID100 
compared to increasing antitumor effects at doses of 1.25, 2.5, and 5 mg/kg. Ablation of all 
tumors was observed in animals receiving either 2.5 or 5 mg/kg of AVID100 on this schedule. 
A NSCLC model utilizing EGFR-expressing human H292 cells was evaluated using IP doses of 
1.5, 3.0,7.5, or 15 mg/kg of AVID100 on Days 0, 7, 11, 15, and 19.  Administration of AVID100 


 
 
 
 
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was effective in reducing tumor volumes at all doses levels compared to the control group 
receiving PBS.  All dosing levels of AVID100 resulted in complete tumor regression in some of 
the mice, with a trend toward a greater percentage of complete regression at the higher doses.  In 
an additional H292 xenograft study, serum concentration profiles showed that exposure to 
AVID100 (total and conjugated Ab) were approximately proportional to dose, and increased 
with increasing administered dose. In addition, serum concentrations of conjugated antibody 
were only slightly lower than total antibody. This indicates AVID100 is stable in the circulation 
and that a relatively small amount of deconjugation occurs in vivo. This is consistent with the PK 
profiles of other ADCs conjugated with a SMCC-DM1 payload (68).  
Based on the efficacy (anti-tumor activity)/pharmacodynamics (PD) and PK of AVID100 
observed in this H292 xenograft tumor study, a PK/PD model was generated to determine a 
concentration-effect relationship and a potential target tumoristatic concentration (TSC), which 
is defined as the predicted concentration at which there is no net tumor growth in this model. 
Based on this xenograft model, the TSC for AVID100 was estimated to be 1.7 μg/mL with a 
95% confidence interval ranging from 0.3 to 3.1 μg/mL. 
2.2.2 
Nonclinical Pharmacokinetic Studies 
The PK profile of AVID100  has been evaluated not only in a non-GLP efficacy study in mice, 
but also in non-GLP and GLP toxicology studies in cynomolgus monkeys.   
2.2.2.1. 
Non-GLP Pharmacokinetic Study in Mice 
The results of the PK and PD study in tumor-bearing mice receiving AVID100 is discussed in 
Section 2.2.1.2. 
2.2.2.2. 
Non-GLP Pharmacokinetic Study in Primates 
PK data from the pilot study of administration of 10 mg/kg of AVID100 by one hour IV infusion 
once every 3 weeks to cynomolgus monkeys revealed that AVID100 exhibited either a bi- or tri-
phasic serum elimination profile when using either total antibody or conjugated antibody 
detection methods.  The serum concentration for AVID100 rapidly declined for the first 3 hours 
after the end of infusion of AVID100, followed by a slower decrease over the subsequent 6 hours 
post-dose.  For AVID100, the terminal half-lives for both total and conjugated antibody were 
similar, at 34.0 and 37.2 hours, respectively. The average volume of distribution was between 
35.1 and 47.8 mL/kg, which suggest that the total and conjugated antibody were distributed 
primarily within the central compartment.   In general, the measured and derived PK parameters 
between total antibody and conjugated antibody were similar.  An additional pilot study 
evaluating toxicity and PK in cynomolgus monkeys receiving weekly doses of either 10 or 20 
mg/kg of AVID100 was performed.  In this study the terminal half-life (T½) of conjugated 
antibody ranged from 30.03 hours to 48.50 hours depending on dose, whereas for the total 
antibody, the T½ ranged from 34.7 and 62.28 hours depending on dose level and week of dosing. 
Low to no anti-drug antibody (ADA) responses were detected in either animal, and there was no 
evidence of increased clearance of AVID100 related to the development of ADA responses.  
Thus, exposure to AVID100 was maintained throughout the study with once weekly dosing.  In 
addition, serum levels of the catabolite, DM1, were measured and remained low throughout the 
duration of the study indicating AVID100 remains intact in vivo.  By correlating the PK results 


 
 
 
 
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from this cynomolgus monkey study with the PK/PD model generated from the H292 xenograft 
tumor study, it can be concluded that the serum concentrations of total and conjugated antibody 
in this once weekly cynomolgus monkey study exceeded the predicted therapeutic range (as 
defined by the 95% confidence interval around the TSC derived from the mouse xenograft 
study). 
2.2.2.3. 
GLP Pharmacokinetic Study in Primates 
As part of a 4 week GLP toxicology study the toxicokinetics (TK) of the conjugated and total 
antibody in male and female Cynomolgus monkey serum was evaluated following IV 
administration of AVID100 at dose levels of 10 and 25 mg/kg. Peak serum concentrations were 
observed between 1 and 8 hours and between 1 and 4 hours post start of infusion (SOI) for 
conjugated and total antibody, respectively. The estimated T½ ranged from 43.7 to 72.5 hours 
for conjugated antibody and from 55.8 to 68.1 hours for total antibody. The mean estimated 
clearance (CL) and volume of distribution (Vd) ranged from 0.703 to 1.01 mL/hr/kg and from 
69.6 to 86.2 mL/kg across dose levels for the conjugated antibody. For total antibody, the mean 
estimated CL and Vd ranged from 0.754 to 0.887 mL/hr/kg and from 72.1 to 81.6 mL/kg, 
respectively. Systemic exposure to the conjugated antibody and total antibody increased with 
increasing dose in a dose proportional manner between 10 and 25 mg/kg on Day 1. No notable 
gender differences in exposure were observed for either ADC or total Ab. In general, after 
repeated administration of AVID100, similar exposure to conjugated and total antibody was 
observed relative to Day 1, except for some animals where total antibody exposure increased on 
Day 22 compared to Day 1. The AUC(0-t) ratio of total Ab relative to conjugated antibody 
ranged from 1.00 to 1.55 and appeared to increase slightly following repeated administration of 
AVID100. Overall, the antibody generally remained conjugated in the blood. 
2.2.3 
Nonclinical Toxicology Studies 
2.2.3.1. 
Tissue Cross-Reactivity Studies 
AVID100 cross-reactivity on a variety of human tissues was evaluated in detail.  AVID100 was 
used for staining in this study. Since AVID100 has the same variable region primary sequences 
as cetuximab, its binding affinity and specificity for EGFR is expected to be identical to this 
marketed anti-EGFR antibody. AVID100 stained a variety of tissue elements including 
epithelium, mesothelium, spindle cells, perineurium, endoneurium, neural/glial cell processes, 
pituicytes, arachnoid cap cells, retinal cells, vascular and intrinsic smooth myocytes, 
mononuclear cells, cells of the glomerular tuft, decidual cells, extracellular proteinaceous 
material (placenta only), endometrial stromal cells, and testicular interstitial cells.  All observed 
staining with AVID100 was judged expected based on literature reports of broad EGFR 
expression by a variety of tissue elements.  No unexpected AVID100 staining was observed in 
any of the human tissues. 
Cross-reactivity of AVID100 on human, cynomolgus monkey and rat EGFR ectodomain was 
also evaluated.  Human and cynomolgus monkey EGFR share 99% sequence homology, while 
the sequence homology between human and rat EGFR is only 89% (Protein Blast, ACN#: 
Human CAA25240.1, Monkey SP005549616.1, and Rat ADT91285.1).  The studies documented 
comparable binding of AVID100 to the human and cynomolgus EGFR but not to rat EGFR. 


 
 
 
 
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These data supported the use of cynomolgus monkeys as a relevant species to explore the safety 
and tolerability of AVID100. 
2.2.3.2. 
Non-GLP Toxicology Studies 
2.2.3.2.1. 
Single Dose Toxicology Study 
A single dose non-GLP pilot toxicology study was completed with two cynomolgus monkeys 
treated with a 10 mg/kg single injection of AVD100. The drug was well-tolerated with no 
notable toxicities. 
2.2.3.2.2. 
Multiple Dose  Toxicology Study  
A repeat dose non-GLP pilot toxicology study was performed with AVID100 in cynomolgus 
monkeys.  Three monkeys received 4 one hour IV infusions of 10 mg/kg of AVID 100 every 3 
weeks for a total of 12 weeks (4 doses, days 1, 22, 43, and 64).  All of the animals survived until 
the end of the study although decreased activity, decreased appetite, and dehydration requiring 
IV fluids were observed.  Skin changes considered treatment-related were observed in all 
animals, and included hyperkeratosis, dryness, and erythema over the bridge of the nose which 
was noted after the first or second dose and progressed in severity as dosing continued.  Other 
skin changes included hyperpigmentation, facial rash, and in one animal, ulcerative skin lesions 
were noted after the last dose and required topical treatment and systemic antibiotics.  In general, 
the observed skin changes resolved within 10 days after dosing, indicating that the treatment-
related dermal effects were transient and reversible.  All skin changes observed in this study 
were consistent with the known toxicity profile observed with cetuximab or panitumumab in 
cynomolgus monkeys.  Diarrhea and weight loss were observed in one animal.  Mild to moderate 
increases in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were observed in 
all animals, however, these increases were transient and ALT and ALP levels returned to or near 
baseline levels before the next cycle of drug administration or by the end of the study.  No 
changes considered directly related to AVID100 in hematology or urinalysis parameters 
considered of toxicological relevance were noted in this study.  At necropsy, treatment-related 
findings were limited to dermal changes, such as hyperkeratosis and flaky skin around the nose 
bridge, hands, feet, and tail base, and dark pigmentation around the mouth, eyes, and penis.  
Histopathological changes considered treatment-related were observed in the skin of most 
animals.  These dermal changes observed across (but not all) animals included mild, focal 
acanthosis, hyperkeratosis, fibrosis, and lymphocytic infiltrates.  Mild hyperplasia was observed 
in the colon or jejunum in most animals, with mild lymphoplasmacytic infiltrates in the colon of 
some animals.  These microscopic changes observed in the skin and jejunum/colon are consistent 
with the toxicity profile of cetuximab, and were considered treatment-related.  
An additional pilot repeat dose non-GLP toxicology study evaluated weekly dosing for 4 weeks 
of either 10 or 20 mg/kg one hour IV infusions of AVID100 in female cynomolgus monkeys.  
Only two monkeys were included in this preliminary study.  Administration of AVID100 once 
weekly for 4 weeks was clinically well tolerated, and both animals survived to the end of the 
study.  Treatment-related skin changes were observed in both animals, and included mild to 
moderate erythema, hyperpigmentation, and hyperkeratosis, all of which are consistent with the 
known toxicity profile of cetuximab.  By the last dose fragile skin and skin abrasions were noted 
in the high-dose animal.  A slight decrease in food consumption was observed after the second 


 
 
 
 
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dose in the low-dose animal, which was likely secondary to the discomfort associated with the 
skin effects of AVID100.  A mild decrease in body weight was also observed in the high-dose 
animal.  A decrease in platelet counts was observed in both animals, which ranged from 1.5 to 2-
fold below baseline; platelet counts, however, recovered between weekly dosing cycles, 
indicating this change was reversible.  The decrease in platelet counts observed in this study is 
consistent with the effects of DM1, and thus, are likely treatment-related (69).  Consistent with 
the previous studies, mild elevations (in comparison to pre-study values) in ALT and ALP were 
observed in both animals (72 hours post-dose at each cycle), but despite these elevations, the 
ALT and ALP levels for both animals were only slightly above the normal range for cynomolgus 
monkeys. Primary treatment-related changes were observed microscopically in the skin, and 
characterized as vacuolation of melanocytes in the basal layer of the epidermis with occasional 
dead cells, mild acanthosis, and orthokeratotic hyperkeratosis, all of which are consistent with 
the known dermal effects of EGFR inhibitors, such as cetuximab.  An increase in mitotic figures 
in epithelial cells within the collecting ducts of the kidneys and in the crypts of the small 
intestine was also observed in the 20 mg/kg animal, which is likely treatment-related since this 
change is consistent with the effects associated with DM1, which is an anti-mitotic microtubule 
inhibitor (69, 70). 
2.2.3.3. 
GLP Toxicology Studies 
2.2.3.3.1. 
Single Dose Toxicology Study 
The objective of this study was to determine the potential toxicity of AVID100 given once by 
intravenous (IV) infusion to cynomolgus monkeys followed by a 14-day observation period. 
Three male and three female cynomolgus monkeys received a single IV dose of 25 mg/kg of 
AVID 100.  All animals survived to the end of the study. 
AVID100-related findings were generally consistent with the expected pharmacology/toxicology 
of an antibody-mertansine conjugate targeting the EGF receptor and were similar to those 
reported for currently approved anti-EGFR antibodies and/or antibody-mertansine conjugates 
(71, 72). 
These findings included adverse skin reactions (reddening, flaking, lesion, scab formation) and 
microscopic findings of single cell necrosis/increased mitosis predominantly affecting the 
epithelia of the skin, eyes (cornea), and gastrointestinal (esophagus, stomach, small and large 
intestines) and urinary tracts (renal pelvic urothelium and bladder).  Non-epithelial AVID100-
related findings were present in the brain (focal area of minimal glial single cell 
necrosis/increased mitosis in one female), liver (minimal to mild single cell necrosis/increased 
mitosis) and spleen (minimal single cell necrosis/increased mitosis within the red pulp stroma). 
In addition, minimal to mild lymphoid hyperplasia was noted in various lymph nodes and there 
was minimal to mild lymphoid depletion in the thymus.   
Changes in clinical pathology parameters were transient and largely consistent with an 
inflammatory response or hepatic toxicity. 
In conclusion, administration of AVID100 to cynomolgus monkeys by 1-hour IV infusion at a 
single dose of 25 mg/kg followed by a 14-day observation period resulted primarily in 
microscopic findings attributable to mitotic arrest in the epithelia of various organs and tissues 


 
 
 
 
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consistent with the known pharmacological activity of AVID100 and with the 
pharmacology/toxicology of approved antibodies targeting EGFR and/or antibody-mertansine 
conjugates. Since the majority of findings were graded minimal in severity and/or could 
reasonably be expected to show reversibility and did not result in dose-limiting clinical toxicity, 
a single dose of 25 mg/kg was considered to represent the highest non-severely-toxic-dose 
(HNSTD) in this study. 
2.2.3.3.2. 
Multiple Dose Toxicology Study  
The objectives of this study were to determine the potential toxicity of AVID100  when given 
once weekly by IV infusion for a total of 5 weekly doses to cynomolgus monkeys. In addition, 
the toxicokinetic characteristics of AVID100 were determined.  
Two dose levels of AVID100, a mid-dose of 10 mg/kg and a high dose of 25 mg/kg, were 
compared to a reference control in male and female monkeys. 
All animals at 25 mg/kg were euthanized in poor and/or deteriorating condition on Days 13 to 15 
(depending on cohort) prior to administration of the third dose. Animals first presented with skin 
rash (dry, flaking, reddening, lesion with/without discharge) on the limbs, torso and face, and 
subsequent clinical signs including excessive scratching, reduced activity, reduce appetite, 
hunched posture, pallor, and suspected dehydration. Similar clinical signs were noted in animals 
at 10 mg/kg all of which survived to scheduled euthanasia after 5 weekly doses, but in general 
were later in onset and slower to progress.  
In addition to clinical signs, principal AVID100-related findings were generally consistent with 
the expected pharmacology of an antibody-mertansine conjugate targeting the EGF receptor, and 
were similar to those reported for currently approved unconjugated anti-EGFR antibodies 
(cetuximab, panitumumab, necitumumab) or the approved anti-HER2 antibody drug conjugate 
(ado-trastuzumab emantsine). The most prevalent microscopic findings at 25 mg/kg (2 doses) 
were epithelial single cell necrosis/increased mitosis predominantly affecting the epithelia of 
various organs and tissues including the skin, eye (cornea and conjunctiva), digestive tract, 
trachea, liver, kidney, mammary gland and reproductive tract and was graded as minimal with 
the exception of the skin where it was graded minimal to mild. Also present in the kidneys were 
minimal to mild vacuolation of the pelvic epithelium, minimal tubular degeneration and minimal 
to mild mononuclear cell inflammation in the pelvic region. In the reproductive tract tissues in 
addition to the single cell necrosis/increased mitosis there was moderate atrophy in the vagina 
and mild decrease in the corpora lutea and follicles that were considered AVID100-related.  
Non-epithelial AVID100-related changes at 25 mg/kg/dose (2 doses) were present in the bone 
marrow (minimal to moderate reduced cellularity), lymphoid tissues (minimal to marked 
lymphoid depletion), heart (minimal myocardial degeneration and increased incidence of 
minimal mononuclear cell infiltration), liver (minimal to mild hepatocellular hypertrophy and 
minimal hepatocellular vacuolation) and femur (moderate to marked decreased cellularity of the 
osteoblasts).  
AVID100-related findings at 10 mg/kg (5 doses) were similar to those seen at 25 mg/kg (2 
doses) with the most prevalent microscopic finding being epithelial single cell necrosis/increased 
mitosis. However, at 10 mg/kg the findings were generally of a lower severity and involved 
fewer organs. 


 
 
 
 
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Various changes in hematology and clinical chemistry parameters were either consistent with the 
microscopic findings or considered secondary to the inflammatory response.  
There were no AVID100-related effects on any of the other parameters evaluated in this study.  
In conclusion, administration of AVID100 to cynomolgus monkeys by weekly 1-hour IV 
infusion at 10 or 25 mg/kg/dose resulted in adverse clinical signs primarily affecting the skin that 
necessitated the euthanasia of animals following a second dose of 25 mg/kg. Microscopic 
examination showed increased cellular mitotic arrest/single cell necrosis in the epithelial of the 
skin and various other organs and tissues and evidence of potential hepatic, renal, cardiac and 
lymphoid toxicity. However, none of the findings described, with the exception of those in the 
skin, were considered to have contributed to the adverse clinical findings that resulted in the 
decision to euthanize the animals after 2 doses of 25 mg/kg/dose.  
All animals at 10 mg/kg/dose survived to scheduled euthanasia after having received 5 weekly 
doses. Microscopic findings were similar to those described in animals after 2 doses of 25 
mg/kg/dose but generally were of a lower severity and/or involved fewer organs and tissues and 
the majority of observed changes could reasonably be expected to be reversible. Although 
moderate myocardial degeneration/necrosis was observed in 1 out of 6 animals at 10 mg/kg dose, 
based on the low incidence of the finding, a weekly dose of 10 mg/kg for 5 doses was  
considered to represent the highest non-severely-toxic-dose (HNSTD) in this study. 
2.2.4 
Other Safety Studies 
2.2.4.1. 
Genotoxicity and Mutagenicity 
No studies have been performed with AVID100 or MAB100.  DM1, the cytotoxic conjugate of 
AVID100 as well as the prototypical maytansinoid, maytansine, have been shown to be 
genotoxic. 
2.2.4.2. 
Carcinogenicity 
No studies have been performed with AVID100 or MAB100. 
2.2.4.3. 
Immunogenicity 
Immunogenicity was not directly monitored in the GLP toxicology studies. However, no effects 
on AVID100 pharmacokinetics indicative of the presence of anti-drug-antibodies were observed 
over time in repeat dose studies. 
2.2.4.4. 
Reproductive and Developmental Toxicity 
No studies on the potential effects of AVID100 on reproduction function or on embryo-fetal 
development have been performed.  Ovarian weights were decreased in the weekly repeat dose 
toxicology study and this finding correlated with decreased corpora lutea and decreased follicles.  
Testicular weight was decreased and reductions in the epididymis and sperm were also observed. 
Although directed to ErbB2 (HER2), ado-trastuzumab emtansine is an approved ADC utilizing 
the same cytotoxic conjugate as AVID100.  Exposure to this ADC may result in embryo-fetal 
death or birth defects.  Patients are advised to utilized adequate contraception during treatment 
and for a period of time after discontinuing this ADC (72). 


 
 
 
 
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2.2.4.5. 
Pharmacologic Toxicity 
No formal pharmacologic toxicity studies were performed. As noted above, toxicities expected 
based on inhibition of EGFR in tissues and organs were observed.  Evaluation of 
electrocardiograms, heart rate, respiratory rate, indirect blood pressure, and neurological 
examinations including evaluation of behavior was undertaken in the single and multiple dose 
GLP toxicology studies.  
Sinus tachycardia was observed in several animals but there was no clear evidence of a dose-
response relationship.  Sinus bradycardia was observed in a single animal receiving 10 mg/kg of 
AVID100.  Neither was considered to be test item-related although the single animal 
experiencing bradycardia also had evidence of minimal myocardial degeneration and minimal 
mononuclear cell infiltration in the heart.  Aside from the instances of sinus tachycardia and 
sinus bradycardia, all of the electrocardiograms evaluated were qualitatively and quantitatively 
normal.  Heart rate was lower and the RR and QT intervals were shorter in male animals on day 
2 following the 10 mg/kg dose.  At Day 30, the QTc interval was longer in male and female 
animals receiving the lower dose (10 mg/kg) than those receiving the reference item by 10.84 
and 11.48%, respectively.  There were no dose-related changes in the QTc interval and 
evaluation of within group comparisons from pretreatment to Day 2 showed no clear evidence of 
changes in the QTc interval in either the low or high dose group animals. 
There were no AVID100-related effects on indirect mean arterial blood pressure or respiratory 
rate.  There were no effects on neurological assessment parameters that were considered to be 
definitively related to treatment with AVID100.  Decreased proprioceptive positioning of the left 
hind limb was observed in 2 out of 3 females in the 10 mg/kg dose group at week 4 but was not 
observed in the other hind limb or in male animals receiving this dose and was considered of 
equivocal toxicological significance. 
2.2.4.6. 
Local Tolerance 
No abnormalities were observed at the sites of injection. 
 
Clinical Experience 
2.3.1 
Clinical Experience with Agents Related to AVID100 
2.3.1.1. 
Safety:  Emtansine-DM1 
The maytansinoid DM1 is an analog of maytansine, a natural product of ansamycin antibiotic 
(benzoansamacrolide).  Maytansine, the prototypic maytansinoid was found to bind to tubulin, 
potently inhibit its polymerization at subnanomolar concentrations, and inhibit mitosis.  Despite 
preclinical activity in vivo over a wide range of doses in murine models, evaluation in clinical 
studies was disappointing with very limited evidence of clinical activity as well as 
documentation of significant toxicities at the defined IV maximal tolerated dose (MTD) of 2 
mg/m2 administered every 3 weeks (66, 67).  Gastrointestinal (GI) toxicity including nausea, 
vomiting, abdominal pain and diarrhea were observed, and depending on the study, GI toxicity 
along with either central nervous system (CNS) toxicity (e.g., weakness) or liver function 
abnormalities (primarily ALT elevations) were considered to have been dose-limiting in patients 


 
 
 
 
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with cancer receiving this agent.  Mild hematological toxicity (primarily thrombocytopenia) was 
also observed in some but not all clinical studies of maytansine. 
2.3.1.2. 
Safety:  Inhibition of EGFR 
Numerous preclinical and clinical studies have been performed with inhibitors of EGFR 
including monoclonal anti-EGFR antibodies, TKIs, and other agents including EGFR-based 
vaccines and intratumoral injections of antisense to EGFR (1-6, 73-74).  EGFR is expressed 
primarily on normal and tumor cells of ectodermal and mesodermal origin (75).  EGFR signaling 
is involved in the development of epithelial organs and tissues with major abnormalities 
observed in development in EGFR knock-out (KO) mice (76, 77). The abnormalities observed in 
the GI tract, skin, eye, lung, kidneys, liver, and brain in KO mice lacking functional EGFR 
provide insight into the potential for adverse effects observed after administration of agents 
inhibiting this signaling pathway. 
2.3.1.3. 
Safety:  Clinical Adverse Effects of Anti-EGFR Antibodies 
The safety and tolerability of unconjugated monoclonal anti-EGFR antibodies has been well-
studied and detailed data about the 3 U.S. FDA-approved products (Erbitux-cetuximab, Vectibix-
pantitumumab, and Portrazza-necitumuab) are available (71, 78, 79).  The most frequent and 
severe toxicities commonly observed in patients receiving therapy with these 3 antibodies 
include EGFR inhibitor-induced dermatologic (skin and skin appendage) and mucosal changes, 
infusion-related reactions (IRR) including fatal reactions, electrolyte depletion (hypomagnesemia 
> hypocalcemia and hypokalemia), ocular toxicity (keratitis), pulmonary toxicity (pulmonary 
fibrosis/interstitial lung disease [ILD]), headache, infection, and gastrointestinal disorders 
including  nausea, diarrhea, stomatitis and dyspepsia (71, 78, 79). Certain AEs were observed 
more frequently with the individual antibodies alone and in combination with other 
antineoplastic therapies and are detailed in the accompanying prescribing information for these 
products (71, 78, 79). 
2.3.1.4. 
Safety:  Clinical Adverse Effect of Antibody-Drug Conjugates 
Several ADCs have been approved for human use and their safety and tolerability have been 
dependent on both the target of the antibody as well as the drug conjugate used in the construct.  
Gemtuzumab ozogamicin (Mylotarg), a conjugate of calicheamicin and an anti-CD33 antibody 
was approved for treatment of elderly patients with acute myeloid leukemia (AML), was 
subsequently withdrawn from the market and has recently been approved again for AML patients 
using a different dose and schedule.  Brentuximab vedotin (Adcetris), an anti-CD30 
monoclonal antibody conjugated to a microtubule disrupting agent, monomethyl aurostatin E 
(MMAE), is approved for the treatment of Hodgkin’s lymphoma (HL) and systemic anaplastic 
large cell lymphoma (sALCL) (80).  Ado-trastuzumab emtansine (Kadcyla) is a conjugate of 
DM1, (an analog of maytansine) linked through an SMCC linker with trastuzumab 
(Herceptin), an anti-HER2 monoclonal antibody approved for the treatment of patients with 
breast cancer overexpressing HER2 (72).  The safety profile of this latter antibody may provide 
some relevant background since it and AVID100 are both DM1 conjugates with the SMCC 
linker.  The most common adverse event seen in patients receiving ado-trastuzumab emtansine 
that is likely to be related to the DM1 moiety (i.e., not commonly observed with trastuzumab 


 
 
 
 
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alone) was hepatotoxicity including cases of liver failure.  Pulmonary toxicity manifest as 
interstitial lung disease and infusion-related reactions were also observed in patients receiving 
this anti-HER2 ADC.  Several other toxicities not commonly associated with trastuzumab were 
observed with ado-trastuzumab emtansine including: fatigue, headache, constipation, 
thrombocytopenia (the dose-limiting toxicity observed with Kadcyla® administration), 
hemorrhage, and neurotoxicity manifest as peripheral neuropathy.   
2.3.2 
Clinical Experience with AVID100 
Three antibody-drug conjugates ADC have current approvals by regulatory authorities and a 
wide variety of ADC with varying specificities, linkers, and cytotoxic components are in clinical 
development.  Several ADCs with antibodies specific for EGFR and different linkers are in 
clinical development but only limited information is available on these potential products. 
2.3.2.1. 
AVID100-01:  Clinical Experience:  Phase 1a Dose Escalation  
This is the first clinical study of AVID100.  A total of 24 patients were entered and treated in the 
completed Phase 1a dose escalation portion of this trial:  1 patient each at Dose Level 1 and 2 (20 
and 40 mg/m2), after which the protocol transitioned from single-patient cohorts to a 3+3 design 
and 3 patients each were entered at Dose Level 3, 4, 5, and 6 (80, 120, 180, and 220 mg/m2, 
respectively); each dose level was considered to be tolerated according to protocol definitions.  
Accrual to Dose Level 7 (270 mg/m2) followed; 7 patients were entered, 2 of whom experienced 
Cycle 1 dose-limiting toxicities (DLTs) (Grade 4 asymptomatic platelet count decreased and 
Grade 3 asymptomatic lipase increase), indicating the dose of 270 mg/m2 was not well tolerated 
and had exceeded the MTD in this Phase 1 patient population.  A trial-drug-related serious 
adverse event (SAE) also occurred in a patient assigned to the 270 mg/m2 cohort; a 73 year old 
female with primary peritoneal carcinoma experienced Grade 3 pneumonitis during Cycle 4 of 
treatment which improved with glucocorticoid therapy and was considered resolved at the time 
of most recent follow-up.  Three (3) additional patients were entered to the previous Dose Level 
6; each tolerated dosing, thus confirming 220 mg/m2 as the maximum tolerated dose (MTD) of 
AVID100.  This dose level was selected as the recommended Phase 2 dose (R2PD). 
All patients were dosed on an every 3 weeks (Q3W) schedule (3 weeks equals 1 cycle).  During 
the dose escalation period, toxicities most frequently observed were Grade 1 to 2 in severity, 
occurred across all dose levels, and included the following in greater than one patient:  rash, 
including acneiform rash in 16 patients; nausea in 10 patients; fatigue in 7 patients, vomiting in 5 
patients with Grade 3 severity reported in 1 patient; diarrhea, dry skin, and headache in 3 patients 
each; and allergic conjuntivitis, mucositis, and anorexia in 2 patients each.    
Laboratory abnormalities observed in greater than one patient were: asymptomatic platelet count 
decreases in 5 patients during Cycle 1, including a single Grade 4 event (at 270 mg/m2 and 
meeting study DLT criteria for the dose cohort, see above), three Grade 3 events (at 120, 220, 
and 270 mg/m2), and one Grade 2 event (at 80 mg/m2);  asymptomatic lipase elevations in 4 
patients, including a single Grade 4 event during Cycle 8 (at 180 mg/m2), and three Grade 3 
events, one during Cycle 1 (at 270 mg/m2 and meeting study DLT criteria for the dose cohort, 
see above), one during Cycle 2 (at 220 mg/m2), one during Cycle 4 (at 80 mg/m2); and aspartate 
aminotransferase (AST) elevations of Grade 3 severity in 2 patients, reported during Cycle 1 for 
one patient, and Cycles 3, 4, and 5 for the second patient (at 220 and 180 mg/m2, respectively). 


 
 
 
 
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A total of 5 patients experienced infusion-related reactions (IRR), one an SAE of Grade 3 
severity during Cycle 4 (at 80 mg/m2), and four of Grade 2 severity during Cycles 2, 4, 6 and 7 
(at doses of 120, 80, 120, and 180 mg/m2, respectively).  The Grade 3 reaction was characterized 
by dyspnea, bronchospasm, tachycardia, and chest pain; this event was dose-limiting for the 
patient, the infusion was stopped, and the patient was discontinued from further participation in 
the trial.  The Grade 2 events responded to infusion interruption, symptomatic therapy and were 
generally restarted at a slower rate and completed.  As a result of these events, infusions were 
lengthened for all patients from 1 hour to 1.5 hours following the Grade 3 event, and then from 
1.5 hours to 2 hours following the occurrence of two Grade 2 events within a cohort, as required 
per protocol*; further, mandatory premedication was implemented (per protocol v5.0). 
Other adverse events of note that occurred in single patients included: Grade 3 dyspnea in the 
patient with pneumonitis, Grade 3 lymphopenia, Grade 3 proteinuria; individual instances of 
Grade 2 keratitis, watering eyes, abdominal pain, myalgia, weight loss, sinusitis, infections of the 
oral mucosa and bladder; and Grade 1 dry eyes, pruritus, alopecia, peripheral sensory 
neuropathy, restless legs/twitching, oral candidiasis, fungal rash, cough, flu-like symptoms, viral 
upper respriatory infection, dehydration, and hypokalemia in individual patients (TABLE 1).   
With the MTD and RP2D determined, accrual to the Phase 2a portion began at the RP2D of 220 
mg/m2. 
*This action to prolong infusions in the event of a Grade 3 IRR in a cohort or a Grade 2 IRR in ≥ two thirds of the 
patients entered to a cohort  is stipulated per protocol (see Section 6.5.3.3; Duration of Infusion).    
• 
In response to the above described Grade 3 event of 19Jul2017 in Cohort 3 (80 mg/m2), and effective 20Jul 
2017, infusions in all future patients were extended from 1 hour to 1.5 hours.  Ongoing patients receiving 
AVID100 over 1 hour were allowed to continue to do so per protocol, or Investigators could opt to extend 
infusions to 1.5 hours (or longer), at their discretion.  Sites were notified of these instructions in writing 
20Jul17.  The action was documented in a study Note to File dated 21Jul2017, and cited in protocol v5.0. 
• 
In response to two Grade 2 events in Cohort 4 (120 mg/m2), and effective 21Dec2017, infusions in all 
future patients were extended from 1.5 hours to 2 hours.  Ongoing patients receiving AVID100 over 1.5 
hours were allowed to continue to do so per protocol, or Investigators could opt to extend infusions to 2 
hours (or longer), at their discretion.  The action was documented in a study Note to File dated 
28Dec2017, and cited in protocol v6.0. 
Note:  Effective with protocol v5.0, in order to decrease the risk of IRRs all patients will be premedicated with 
standard therapies prior to each infusion, at minimum through and including Cycle 4.  A recommended 
premedication regimen is provided (see Section 8.2; Premedication of Study Drug-Related Toxicities). 
 
 
 
 
 


 
 
 
 
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TABLE 1:  AVID100-01 (PHASE 1A DOSE-ESCALATION)   
PATIENTS WITH TREATMENT-RELATED ADVERSE EVENTS 
Adverse Event Term (in > 1 patient) 
(N-24*) 
Maximum Grade Per Patient 
1 
2 
3 
4 
Total (%) 
  
  
 
 
  
Rash (including acneiform, maculopapular, & not specified) 
14 
2 
 
 
16 (66.7) 
Nausea 
6 
4 
 
 
10 (41.7) 
Fatigue 
5 
2 
 
 
7 (29.2) 
Infusion reaction 
 
4 
1** 
 
5 (20.8) 
Platelet count decreased 
 
1 
3 
1 
5 (20.8) 
Vomiting 
3 
1 
1 
 
5 (20.8) 
Lipase increased 
 
 
3 
1 
4 (16.7) 
Diarrhea 
2 
1 
 
 
3 (12.5) 
Dry skin 
2 
1 
 
 
3 (12.5) 
Headache 
3 
 
 
 
3 (12.5) 
Allergic conjunctivitis 
1 
1 
 
 
2 (8.3) 
Mucositis 
1 
1 
 
 
2 (8.3) 
Anorexia 
1 
1 
 
 
2 (8.3) 
AST increased 
 
 
2 
 
2 (8.3) 
Also reported, single episodes of: 
Grade 3 
dyspnea, lymphocyte count decreased, pneumonitis**, proteinuria 
Grade 2 
abdominal pain, bladder infection, keratitis, myalgia, oral mucosal infection, sinusitis, watering 
eyes, weight loss 
Grade 1 
alopecia, cough, dehydration, dry eyes, flu-like symptoms, fungal intertrigo rash, hypokalemia, 
oral candidiasis, peripheral sensory neuropathy, photophobia, pruritus, restless legs/twitching, 
viral upper respiratory infection 
*Pts with at least 1 treatment-related AE = 21 of 24 
**SAE 
2.3.2.2. 
AVID100-01:  Clinical Experience:  Phase 2a Dose Expansion 
As of 15 Apr 2020 data are available for a total of 18 patients1 entered and treated in the ongoing 
Phase 2a dose expansion portion of this trial to cohorts of the 3 tumor types being evaluated: 4 
patients to the TNBC cohort; 12 patients to the SCCHN cohort, and 2 patients to the Sq-NSCLC 
cohort.  All patients are being treated at the RP2D of 220 mg/m2; study drug is being 
administered by 2-hour IV infusion on the Q3W schedule evaluated in Phase 1a.  Three (3)2 
patients in the SCCHN cohort have experienced study drug-related SAEs/DLTs: Grade 4 
AST/ALT elevation during Cycle 2 and Grade 4 IRR during Cycle 6 in one patient; Grade 3 
mucositis during Cycle 2 in one patient, and Grade 2 subdural hemorrahges during Cycle 1 in a 
patient with Grade 3 decreased platelets who had a fall hitting his head. The first patient 
underwent dose reduction to 180 mg/m2 and continued on study after resolution of the AST/ALT 
 
1 A total of 22 patients were entered and treated as of this data cutoff date, however data entry was delayed due to 
coronavirus pandemic mitigations. 
2 Two (2) additional patients, one in the SCCHN cohort and one in the TNBC cohort, experienced study drug-related 
SAEs/DLTs prior to the data cutoff date, however the events do not appear in the study database due to data entry 
delays secondary to coronavirus pandemic mitigations: Grade 3 platelet decrease during Cycle 1in one patient and 
Grade 3 AST increase during Cycle 1 in one patient.  The SCCHN patient underwent dose reduction to 180 mg/m2 
and continued on study after resolution of decreased platelets, but was discontinued from study participation as a 
result of disease progression after 2 cycles at the reduced dose.   The TNBC patient was planned to undergo dose 
reduction to 180 mg/m2 but discontinued study participation due to disease progression.   


 
 
 
 
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elevation, but was discontinued from study participation as a result of the IRR that followed 4 
cycles later.  The other two patients underwent dose reduction to 180 mg/m2 and continued on 
study following resolution of their events per protocol; both patients discontinued from study 
participation due to disease progression after 3 and 4 additional cycles, respectively, of treatment 
at the lower dose.  One (1) patient in the SCCHN cohort experienced the SAE of Grade 3 
pneumonitis considered possibly related to treatment, with onset after study discontinuation due 
to disease progression (56 days after last dose); at last report the event was was resolving.   
Thus far the treatment-related clinical AEs that have been reported for greater than one patient 
have included:  fatigue in 6 patients; rash, including acneiform rash in 5 patients; dry skin and 
watering eyes in 4 patients each; and mucositis (including the Grade 3 event meeting DLT 
criteria, mentioned above), keratitis, nausea, and anemia in 2 patients each. 
Treatment-related laboratory abnormalities observed in greater than one patient have included: 
platelet count decreases in 5 patients (including the Grade 3 event that occurred in the patient 
with subdural hemorrhages, mentioned above); AST elevations in 3 patients (including the Grade 
4 event meeting DLT criteria, mentioned above); proteinuria in 3 patients; and alkaline 
phosphatase increase and hypomagnesemia in 2 patients each.  The grades of all events, and 
other adverse events of note that occurred in single patients are noted in TABLE 2.  
Accrual to the Phase 2a portion of the study is ongoing. 
 
TABLE 2:  AVID100-01 (PHASE 2A DOSE-ESCALATION)   
PATIENTS WITH TREATMENT-RELATED ADVERSE EVENTS 
Adverse Event Term (in > 1 patient) 
(N-18*) 
Maximum Grade Per Patient 
1 
2 
3 
4 
Total (%) 
 
 
Fatigue 
2 
3 
1 
 
6 (33.3) 
Rash (including acneiform and not specified) 
5 
 
 
 
5 (27.8) 
Platelet count decrease 
3 
1 
1^ 
 
5 (27.8) 
Dry skin 
4 
 
 
 
4 (22.2) 
Watering eyes 
3 
1 
 
 
4 (22.2) 
AST increase 
1 
1 
 
1**^ 
3 (16.7) 
Proteinuria 
1 
2 
 
 
3 (16.7) 
Hypomagnesemia  
2 
 
 
 
2 (11.1) 
Keratitis 
 
2 
 
 
2 (11.1) 
Mucositis  
 
1 
1**^ 
 
2 (11.1) 
Nausea 
2 
 
 
 
2 (11.1) 
Anemia 
 
2 
 
 
2 (11.1) 
Alkaline phosphatase increase 
 
2 
 
 
2 (11.1) 
Also reported, single episodes of: 
Grade 4 
ALT increase**^, AST increase**^, IRR**^ 
Grade 3 
Lipase increase, pneumonitis** 
Grade 2 
 
Anorexia, asthma exacerbation, conjunctival injection, cough, eye pain/irritation, uveitis, 
hyperhidrosis, malaise, incision site discharge, subdural hemorrhages**^, bilirubin increase, 
hypoalbuminemia, hypokalemia 
Grade 1 
Diarrhea, dry mouth, dysgeusia, epistaxis, pruritus, forced expiratory flow reduced, WBC count 
decrease, PTT prolonged, amylase increase, hyperuricemia, hyponatremia 
*Pts with at least 1 treatment-related AE = 10 of 13 (data as of 15Apr2020) 
**SAE, ^DLT   


 
 
 
 
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Rationale for and Risks of Proposed Clinical Study 
2.4.1 
Rationale 
The clinical utility of a variety of unconjugated anti-EGFR antibodies (cetuximab, panitumumab, 
necitumumab) has been established in a variety of clinical indications including CRC, SCCHN, 
and Sq-NSCLC.  Despite the documentation of activity of these monoclonal antibodies alone or 
in combination with standard therapies in these indications, most patients treated with these 
products do not respond and resistance eventually develops in the majority of patients who 
derive initial benefit.  Conjugation of the anti-EGFR antibody MAB100 to DM1 via a stable 
linker has resulted in increased antitumor activity in vitro and in vivo in a variety of tumor 
models including models using tumor lines that are resistant to cetuximab. Based on prior 
validation of EGFR as a target as well as the evidence that AVID100 may provide superior 
antitumor activity based on nonclinical models, this trial aims to evaluate the safety and 
tolerability of escalating doses of this novel conjugated anti-EGFR antibody followed by a 
preliminary evaluation of its clinical activity in selected patients with EGFR-overexpressing 
tumors. 
The three indications identified for further study in the Phase 2a segment of the study are patients 
with mTNBC, SCCHN, and Sq-NSCLC without alternative therapeutic options.  The detailed 
rationale for the choice of each indication is provided (see Section 2.1.2, Section 2.1.3, Section 
2.1.4).  For the purposes of this study the original DAKO PharmDx assay has been revalidated 
for the assessment of higher levels of EGFR expression to facilitate enrichment of patient 
populations that may be appropriate targets for AVID100. 
Briefly, the EGFR pathway has been documented to play an important role in metastatic BC.  
EGFR-overexpression is observed in subsets of patients with metastatic BC (most commonly 
associated with TNBC) and, although limited activity has been observed with single agent 
therapy with EGFRi, addition of chemotherapy to cetuximab has shown increased activity in 
Phase 2 studies.  The DM1 moiety coupled to trastuzumab has shown activity and is approved 
for treatment of patients with HER2 over-expressing BC.  There is also strong evidence of 
activity for other tubulin-targeted agents suggesting that AVID100 may be active in the triple-
negative subset of patients with metastatic BC who overexpress EGFR (3+ overexpression in ≥ 
50% of cells in approximately 6% of patients tested with the validated assay and 2+ 
overexpression in ≥75% of cells in approximately 13% of cases) (Data on File, 
Forbius/Formation Biologics).   
Cetuximab, an unconjugated chimeric anti-EGFR mAb is approved alone and in combination 
with radiotherapy and chemotherapy in selected patients with SCCHN.  Phase 3 studies of  
chemotherapy, compared to cetuximab plus chemotherapy, documented increased ORR, PFS, 
and OS for the combination compared to chemotherapy alone.  EGFR overexpression is common 
in patients with SCCHN (3+ overexpression in ≥ 50% of cells in  approximately 22% of patients 
tested using a validated assay) (Data on File, Forbius/Formation Biologics) . The role of the 
EGFR pathway in this malignancy has been well-documented.  In addition, other microtubule-
targeting agents have been shown to be active in the treatment of patients with SCCHN.  The 
documented therapeutic efficacy of anti-EGFR mAbs and taxanes in the treatment of SCCHN, as 


 
 
 
 
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well as the significant population of patients whose tumors overexpress EGFR, provides a strong 
rationale for the evaluation of AVID100 as a potential therapy for patients with this malignancy. 
Cetuximab showed variable activity in combination with chemotherapy in the first line treatment 
of NSCLC.  Necitumab, a recombinant human IgG1 monoclonal anti-EGFR antibody, has been 
shown to be safe and effective in combination with chemotherapy in the treatment of patients 
with squamous histology but was ineffective in patients with non-squamous histology NSCLC.  
The incremental activity observed in this setting is modest suggesting that there is room for 
improved efficacy.  The majority of patients with NSCLC overexpress EGFR (3+_ 
overexpression in ≥ 50% of cells in approximately 22% of patients with NSCLC tested using a 
validated assay) (Data on File, Forbius/Formation Biologics).  Anti-EGFR antibodies have 
activity in patients with NSCLC including an approved indication in patients with squamous 
histology NSCLC. Since squamous NSCLC is also sensitive to tubulin-targeted agents in various 
lines of therapy (paclitaxel, docetaxel, and vinorelbine) there is a strong rationale for targeting 
patients with this malignancy with an anti-EGFR antibody-DM1 conjugate. 
2.4.2 
Risks 
The potential risks to patients enrolled in this trial have been outlined in sections describing the 
potential adverse events associated with: (a) maytansine and its analog, DM1; (b) inhibition of 
EGFR; (c) inhibition of EGFR by anti-EGFR monoclonal antibodies; and (d) antibody-drug 
conjugates (ADC).  Nonclinical toxicology studies have been performed in cynomolgus monkeys 
to evaluate potential safety issues that may emerge in patients treated with AVID100 and these 
studies have been utilized to define a starting dose for the first clinical study.  A cohort dose 
escalation plan has been included to rapidly escalate the dose of AVID100 initially, but decrease 
the incremental increases and increase the patient sample size in subsequent cohorts.  Escalation 
to each subsequent higher dose cohort will require demonstration of safety and tolerability in the 
preceding cohort until a safe recommended Phase 2 dose (R2PD) and schedule can be 
established.  In the event of certain toxicities the infusions may be slowed, premedications or 
other supportive measures may be instituted, doses may be decreased,  or AVID100 may be 
discontinued.  Premedications for infusion-related reactions are not required, but can be 
instituted in patients who experience such adverse reactions during any cycle and, premedication 
for all patients may be instituted if the frequency and/or severity of AEs suggest that this would 
improve patient safety and the tolerability of AVID100.  
Note:   Effective with protocol v5.0, in order to decrease the risk of IRRs all patients will be premedicated with 
standard therapies prior to each infusion, at minimum through and including Cycle 4.  A recommended 
premedication regimen is provided (see Section 8.2; Premedication of Study Drug-Related Toxicities). 
Because of the risk of pulmonary toxicity that has been observed with ADCs and agents 
inhibiting EGFR, and because a single patient on the Phase 1a segment of this trial receiving a 
dose of 270 mg/m2 developed pneumonitis considered related to AVID100, patients with a 
history of or evidence of interstitial fibrosis will continue to be excluded from entry into the trial.   
Patients will be assessed using chest CT every 6 weeks (when disease assessments are 
scheduled) regardless of whether these imaging studies are required for tumor assessment.  
Patients will also be evaluated by regular evaluation of oxygen saturation using pulse oximetry, 
physical exams and queries regarding all adverse events with a detailed assessment of potential 


 
 
 
 
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pulmonary adverse events.  Pulse oximetry will be conducted prior to and following all infusions 
of AVID100 throughout the study, and decreases in oxygen saturation will require further 
evaluation.  In the event of patient-reported symptoms of pulmonary toxicity or Investigator-
assessed symptoms or signs of potential pulmonary adverse effects, additional studies including 
interval chest imaging studies will be performed.  If pulmonary findings on imaging studies (e.g., 
evidence of pulmonary fibrosis, interstitial pneumonitis, acute respiratory distress syndrome) or 
clinical evidence of pulmonary adverse effects are detected, administration of AVID100 will be 
permanently discontinued and pulmonary consultation will be obtained to consider additional 
appropriate diagnostic procedures and/or therapeutic interventions. 
 
Rationale for Starting Dose 
The starting dose is based on the observed safety and tolerability of  AVID100 in the single dose 
GLP toxicology study that simulates the intermittent (every 3 week) schedule to be evaluated in 
this Phase 1a study as well as in the planned Phase 2a expansion cohorts.  The 25 mg/kg dose in 
this study was determined to be the HNSTD.  One sixth the HNSTD adjusted for body surface 
area (BSA) is 1.3 mg/kg.  In order to minimize the variability of PK parameters observed when 
dosing monoclonal antibodies on a mg/kg basis, particularly in obese patients, dosing of 
AVID100 will be based on a per m2 basis.  The proposed starting dose is 20 mg/m2.  Data from 
the multidose GLP study and other pilot toxicology studies were also considered in the 
determination of the initial dose to be used in this first study in patients.  In addition, data on the 
pharmacokinetic profile of AVID100 as well as studies in tumor models were considered in the 
choice of the starting dose and escalation scheme.  The original maximum dose to be 
administered in this trial was not to exceed 220 mg/m2/dose, based on the initial rate of infusion 
of AVID100 over 1 hour.  Since the infusion rate has been extended the maximum dose to be 
administered in this trial was adjusted accordingly to 330 mg/m2. 
 
Justification for the Recommended Phase 2 Dose 
The R2PD has been determined to be 220 mg/m2 based on observed DLTs at the highest dose 
level studied, 270 mg/m2.  Seven patients were treated at a dose of 270 mg/m2 on an every three 
week (Q3W) schedule. One patient was not evaluable for safety because of the development of 
brain metastases secondary to primary breast cancer, diagnosed during Cycle 1.  Two Grade 3 
toxicities were observed at this dose level during Cycle 1 (asymptomatic Grade 3 lipase elevation 
without evidence of pancreatitis and Grade 4 thrombocytopenia without sequelae).  The 
occurrence of two DLTs in Cycle 1 determined that this dose level exceeded the MTD.  Because 
of this finding, an additional three patients were added to the previous dose level of 220 mg/m2, a 
dose level that had been tolerated without any ≥ Grade 3 AE that met the DLT criteria in the 
initial 3 patients evaluated (one patient had experienced Grade 3 elevation of AST but this did 
not meet the protocol-specified criteria for DLT).  No DLTs were observed in Cycle 1 in the 
additional 3 patients treated at this dose level. 
Based on safety and tolerability of the 6 patients evaluated, 220 mg/m2 was determined to be the 
MTD and has been selected as the R2PD to be evaluated in three expansion cohorts in patients 
with metastatic TNBC, SCCHN, and Sq-NSCLC, each with high expression of EGFR as 
determined by standardized immunohistochemistry (IHC) testing. 


 
 
 
 
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Historically, the efficacy of ADCs is dependent upon multiple factors including the relative 
expression of the target antigen on tumor and normal tissues as well as the delivery of the ADC 
to the tumor. The latter parameter depends on the delivery of the highest feasible dose given the 
relatively low proportion of the ADC that is delivered to the tumor. Given the nature of patients 
enrolled in the Phase 1a segment (refractory to multiple prior therapy and the requirement that 
they were epithelial tumors potentially responsive to EGFR inhibitors but were not required to 
overexpress EGFR) a relatively small number of patients were treated on multiple cycles of 
AVID100.  For this reason, it may be necessary to reevaluate the dose utilized in the Phase 2a 
expansion cohorts based on observed acute and/or longer term tolerability as more experience 
with the safety and tolerability of AVID100 is obtained. 
 
FOR ADDITIONAL INFORMATION, PLEASE REFER TO THE INVESTIGATOR’S 
BROCHURE (IB) 


 
 
 
 
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3. 
TRIAL OBJECTIVES AND DESIGN 
 
Phase 1a: Dose-Escalation 
3.1.1 
Primary Objective  
To determine the safety and tolerability, dose-limiting toxicities (DLTs), and the maximum 
tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D)** of sequential escalating 
doses of AVID100 when administered once every 3 weeks (Q3W) by 2-hour* intravenous (IV) 
infusions to patient cohorts with locally advanced/unresectable or metastatic solid tumor 
malignancies of epithelial origin   
*Protocol v5.0:  Extended from 1 hour to 1.5 hours due to Grade 3 IRR observed in Cohort 3 (80 mg/m2); effective 
20Jul2017 and documented in a study Note to File dated 21Jul2017 (see Section 2.3.2.1;  AVID100-01: Clinical 
Experience) 
*Protocol v6.0:  Extended from 1.5 hours to 2 hours due to Grade 2 IRRs observed in Cohort 4 (120 mg/m2); 
effective 21Dec2017 and documented in a study Note to File dated 28Dec2017 (see Section 2.3.2.1; AVID100-01: 
Clinical Experience) 
**Protocol v6.0:  The MTD and RP2D has been determined to be 220 mg/m2 
3.1.2 
Secondary Objectives  
• Characterization of the pharmacokinetic (PK) profile of total antibody (AVID100 plus 
MAB100), AVID100, and DM1 in this patient population (all patients)   
• Evaluation of the preliminary antineoplastic effects of AVID100 in this patient 
population (all patients), including:  
o Evidence of objective response (OR) or stable disease (SD)*   
o Duration of OR or SD*  
o Time to progression (TTP) of disease*  
*As assessed by standard response criteria (see Appendix F; Measurement of Effect; Response Evaluation 
Criteria for Solid Tumors [RECIST] v1.1) 
3.1.3 
Exploratory Objective  
Tests to assess potential biomarkers and response predictors will be conducted and may include: 
• Evaluation by immunohistochemistry (IHC) and/or fluorescence in situ hybridization 
(FISH) (or similar assay) of tumor EGFR-expression and other potential biomarkers of 
pathway activation in archival, formalin-fixed, paraffin-embedded (FFPE) samples 
obtained from a previous diagnostic or surgical procedure (if available) 
Note:   Biopsies for confirmation of EGFR status and performance of biomarker assessments are 
permissible in Phase 1a patients on a case-by-case basis, if considered safe, following discussion 
between the Investigator and the Sponsor’s Medical Monitor(s). 


 
 
 
 
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Phase 2a:  Dose-Expansion  
3.2.1 
Primary Objective 
To further evaluate the safety, tolerability, and preliminary antineoplastic effect* of AVID100 
when administered at the RP2D** and schedule in 3 expansion cohorts  of patients with locally 
advanced/unresectable or metastatic solid tumor malignancies of epithelial origin, that are 
measurable, and that express the epidermal growth factor receptor (EGFR).  The tumor types to 
be evaluated in these expansion cohorts are metastatic triple-negative breast cancer (mTNBC), 
squamous cell carcinoma of the head and neck (SCCHN), and squamous histology non-small cell 
lung carcinoma (Sq-NSCLC).  
*As assessed RECIST v1.1 
**May be equal to or less than the MTD 
Note:  
To be eligible for study enrollment, analytical results documenting EGFR expression positivity by IHC 
must be documented by a central laboratory in archival FFPE samples obtained from a previous diagnostic 
or surgical procedure.  In the mTNBC cohort results must be 3+ intensity in ≥ 50% of tumor cells or ≥ 2+ 
intensity in ≥ 75% of tumor cells.  In the SCCHN and Sq-NSCLC cohorts results must be 3+ intensity in ≥ 
50% of tumor cells.  If tissue is unavailable, patients must have primary or metastatic tumor sites(s) 
considered safely accessible for biopsy, and must be willing to undergo tumor biopsy in order to document 
EGFR expression positivity to verify study eligibility. 
Sufficient FFPE tumor tissue from either a prior procedure or a recent biopsy must also be available for 
submission to a central laboratory for other study-related evaluations as planned per protocol (see Section 
3.2.3; Exploratory Objective).  
3.2.2 
Secondary Objective  
Further characterization of the PK profile of total antibody (AVID100 plus MAB100), 
AVID100, and DM1 in this patient population   
3.2.3 
Exploratory Objective  
Tests to assess potential biomarkers and response predictors will be conducted and may include 
but are not limited to: 
• Evaluation by FISH (or similar assay) of tumor EGFR-expression and other potential 
biomarkers in archival, FFPE samples obtained from either a previous diagnostic or 
surgical procedure or a recent biopsy (required at Screening, optional at other indicated 
timepoints) 
• Evaluation of circulating tumor DNA (ctDNA) for EGFR extracellular domain (EGFR-
ECD) mutation status and EGFR mutant type III variant (EGFRvIII) deletions (SCCHN 
only), as well as evaluation of other potential biomarkers of interest (required for all 
indications) 


 
 
 
 
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Trial Design Summary  
Patient Population and Objectives 
Approximately 90 male and female patients with documented solid tumor malignancies of 
epithelial origin that are locally advanced or metastatic, and either refractory to standard therapy 
or for whom no standard therapy is available, will be entered into this Phase 1a/2a, multicenter, 
open-label, dose-escalation, cohort study of AVID100, an anti-human EGFR monoclonal 
antibody (mAb) linked to the maytansinoid DM1.   
The initial Phase 1a Dose-Escalation portion of the trial (approximately 30 patients) is designed 
to evaluate the safety and  tolerability, as well as identify the DLT(s), MTD, and RP2D of 
sequential escalating doses of AVID100 (study drug), when administered to patients with tumors 
reasonably likely to express EGFR; secondary objectives include characterization of the PK 
profile of  total antibody (AVID100 plus MAB100), AVID100, and DM1, as well as preliminary 
assessment of the antineoplastic activity of AVID100.   
Once the MTD and/or RP2D is identified, 3 expansion cohorts of patients (approximately 60 
patients total; approximately 30 patients in the mTNBC cohort* distributed equally to enroll 15 
patients to each of two cohort subgroups [i.e., either 3+ intensity in ≥ 50% of tumor cells or ≥ 2+ 
intensity in ≥ 75% of tumor cells], and 15 patients to each of the SCCHN and Sq-NSCLC 
cohorts) with measurable disease and confirmed EGFR-positive tumors will be accrued during 
the subsequent Phase 2a Dose-Expansion portion of the trial where the goal will be to further 
evaluate the safety, tolerability, and antineoplastic activity of AVID100 when administered at the 
RP2D; a secondary objective is to further characterize the PK profile of  total antibody, 
AVID100, and DM1 (PK evaluation will be less extensive in Phase 2a when compared to Phase 
1a).  The tumor types to be evaluated in these expansion cohorts are mTNBC, SCCHN, and Sq-
NSCLC. 
An exploratory objective in both the Phase 1a and Phase 2a portions of the trial will be 
evaluation of the utility of potential biomarkers and response predictors of AVID100 activity in 
FFPE tumor tissue (optional in Phase 1a patients, required in Phase 2a patients) and peripheral 
blood (in Phase 2a patients).  In addition, SCCHN patients enrolled to Phase 2a will be evaluated 
for EGFR-ECD mutation status and EGFRvIII) deletions.  Patients will be treated and followed 
on an outpatient basis throughout the trial, unless hospitalization is required for other reasons, or 
to assure patient safety.   
*Recruitment in mTNBC cohort subgroups will be halted after enrollment of 15 patients in order to assess activity. 
Dosing Schedule and Treatment Duration 
• Beginning with the first dose, all patients must be premedicated with standard therapies 
prior to each dose of AVID100 to reduce the risk of infusion-related reactions (IRRs). 
Mandatory premedication for other adverse events will be implemented for all patients 
should a pattern begin to emerge of mild-to-moderate study drug-related reactions that 
are amenable to prophylaxis with standard agents.      
• On Day 1 of study, patients will receive study drug administered by 2-hour IV infusion.  
Patients receiving doses ≤ 180 mg/m2 will receive study drug in a fixed 100 mL volume; 


 
 
 
 
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patients receiving doses > 180 mg/m2 will receive study drug in a volume of 200 to 250 
mL (dose to be divided between two 100 mL infusion volumes [i.e., 100 mL × 2] to be 
administered sequentially, or delivered in a larger volume up to 250 mL using a single 
flexible IV bag). AVID100 will be administered once every 3 weeks (Q3W) with 
administration on Day 1 of the first week, followed by a 3-week recovery period.  This 3 
week (21 day) period will be considered Cycle 1.  In Phase 1a, determinations regarding 
cohort escalation, DLTs, and MTD will be based on the toxicities observed during this 
initial cycle.  Patients must receive their full planned dose of AVID100, plus complete 
the designated follow-up period, in order to be considered evaluable for tolerability, 
unless dose reduction, interruption, or discontinuation was the result of a DLT.  End of 
Cycle 1 (EOC1) assessments are to be performed no sooner than C1/D21 (-2 days).   
•  In all patients entered, a minimum of at least Cycle 1 of study will be completed, if 
tolerated, after which, in the absence of documented disease progression or unacceptable 
toxicity, a patient may continue to receive additional cycles of study drug Q3W (± 2 
days), at the same dose and infusion duration established for the patient during Cycle 1, 
and on the same schedule.  These additional 3 week cycles may continue, if tolerated and 
in the absence of documented disease progression, at the Investigator’s discretion, 
provided specified retreatment criteria have been met.  Evidence of progressive disease at 
any point in the study will necessitate withdrawal of the patient from further participation 
so that alternative management of their malignancy may be considered.   
Doses to be Evaluated 
At study entry, patients will be sequentially assigned to fill escalating dose cohorts of AVID100 
beginning at the dose of 20 mg/m2/dose.    
An accelerated titration design (1 patient per cohort) with 100% incremental increases in dose 
will be used for dose-escalation for up to 2 cohorts (until at most Cohort 3) or until the 
occurrence of an event that activates a stopping rule.  Thereafter, dose-escalation will follow a 
standard 3+3 design, with 50% and then 25% incremental increases in dose, and with a target 
toxicity level of 33.3% or less as determined by DLTs.  The number of cohorts evaluated and the 
maximum administered dose (MAD) will depend upon the observed tolerability of AVID100 
during Cycle 1 of patient treatment; however, the maximum dose to be administered in this trial 
is not to exceed 330 mg/m2/dose.  Doses will be calculated as shown (Figure 1).   
The Investigator(s) and Sponsor's Medical Monitor(s) will comprise a Study Safety Committee, 
and will review clinical and laboratory safety data on an ongoing basis throughout the study and 
make decisions regarding the advisability of continuing accrual to a particular dose cohort, 
and/or escalating the dose and allowing accrual to a higher dose cohort.  


 
 
 
 
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Figure 1:  Dose Escalation Schema 
Abbreviations (in alphabetical order):  DLT, dose-limiting toxicity; Gr, grade; pts, patients 
 
Filling of Cohorts 
Phase 1a Dose-escalation:  In cohorts with > 1 patient enrollment will be staggered between the 
first and second patient by at minimum 24 hours in order to assess for IRRs; thereafter patients 
within a cohort may be added concurrently.  Dose escalation and accrual to the next cohort will 
occur after the minimum number of patients required for tolerability assessment in the current 
cohort have completed Cycle 1, and only after acceptable tolerance has been demonstrated in at 
least 1 of 1, 3 of 3, or 5 of 6 patients treated in the current cohort (depending on cohort size), and 
review of the data with the Sponsor's Medical Monitor(s).   
Phase 2a Expansion:  Once the MTD (or maximum dose to be studied) is identified, and the 
RP2D is determined, patients will be enrolled to the Phase 2a portion of the study to receive the 
RP2D.  Patients will be accrued to one of 3 expansion cohorts, by tumor type (Figure 2).  The 
tumor types to be evaluated in these expansion cohorts are mTNBC (with 2 subgroups), SCCHN, 
and Sq-NSCLC.  Patients will be identified using the same eligibility criteria except as specified; 
however, patients must also have measurable disease and documented EGFR-positive tumors as 
specified, and if patients do not have sufficient archival tumor tissue to submit to a central lab in 
order to establish EGFR status and be available for completion of biomarker evaluations, they 
must have primary or metastatic tumor site(s) considered safely accessible for biopsy, and be 
willing to give consent for biopsy collection of additional tissue.   


 
 
 
 
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If the R2PD is not tolerated and a Cycle 1 DLT is experienced in ≥ 33% of patients entered into 
an expansion cohort, the next lower dose with established tolerability in Phase 1a will be 
administered to subsequent patients.   
*Biopsies for confirmation of EGFR status and performance of biomarker assessments are permissible in Phase 1a 
patients on a case-by-case basis, if considered safe, following discussion between the Investigator and the Sponsor’s 
Medical Monitor(s). 
 
Figure 2:  Expansion Cohorts 
Abbreviations (in alphabetical order):  MTD, maximum tolerated dose; mTNBC, metastatic triple-negative breast cancer,; pts, patients; RP2D, 
recommended phase 2 dose; SCCHN, squamous cell carcinoma of the head and neck, Sq-NSCLC, squamous histology non-small cell lung 
carcinoma. 
 
Study Assessments 
For safety, patients will be monitored throughout the treatment and 1 month follow-up period for 
evidence of AEs, including changes in clinical status, laboratory data, ECG findings, and either 
MUGA scans or echocardiograms in patients with a history of CHF. Evaluation of patients for 
interstitial pulmonary fibrosis or other pulmonary disorders will include evaluation of related 
signs and symptoms, reported adverse effects, pulse oximetry, pulmonary function tests, and 
radiographic imaging of the chest (X-ray and CT); evidence of pulmonary fibrosis of any grade 
at any point in the trial will result in immediate discontinuation from treatment with study drug.  
Patients will also be evaluated for evidence of antibody formation to AVID100.  Patients 
experiencing a DLT regarded as associated with study drug at any point during treatment will 
either be discontinued from treatment with study drug, or may continue if there is evidence of an 
OR, disease stabilization, or other clinical benefit, but must do so at a reduced dose of AVID100 
(see Section 8.3.2; Dose Reduction), and ONLY following discussion with the Sponsor’s 
Medical Monitor(s).  Patients may not be retreated following the occurrence of a DLT until 


 
 
 
 
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retreatment criteria have been met.  Only DLTs occurring during Cycle 1 will be used to make 
determinations regarding dose escalation and tolerability.  Exceptions to continuing on study at a 
reduced dose include evidence of pulmonary, neuro-, ocular, nephro-, or hepatotoxicity as 
detailed in Section 9.1 (Criteria for Treatment Discontinuation).  In such instances patients must 
be permanently discontinued from treatment with study drug.   
 
 
 
 


 
 
 
 
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4. 
PATIENT SELECTION 
 
Number of Patients 
4.1.1 
Investigational Sites 
This is a multicenter trial.   
• Phase 1a:  Single center planned (up to 2 centers may participate based on accrual) 
• Phase 2a:  Accrual to be divided between approximately 6-12 participating centers; 
number of sites TBD based on tumor type selection and anticipated accrual   
4.1.2 
Number of Patients  
Approximately 90 patients to be entered during the combined Phase 1a and Phase 2a portions of 
the trial.   
Considerations for estimating the number of patients to be entered are as follows: 
• Phase 1a:  Approximately 30 patients in escalating dose cohorts 
o Minimum of 1 to 3 patients per dose cohort; assume approximately 4 dose cohorts 
to be evaluated to establish the MTD and/or RP2D  
o Expansion of any cohort to 6 patients in the event of a Cycle 1 DLT in any of the 
initial 1 to 3 patients 
o Minimum of 6 patients to be treated at the MTD (or maximum administered dose 
[MAD]); expansion of this cohort (or any other) up to 12 patients may be 
considered to further evaluate tolerability 
 
• Phase 2a:  Approximately 60 patients in 3 expansion cohorts (approximately 30 patients 
in the mTNBC cohort and 15 patients each in the SCCHN and Sq-NSCLC cohorts); more 
patients may be entered if fewer than 30 patients are required to establish the RP2D in 
Phase 1a 
There is potential for entry of additional patients in the Phase 1a portion of the trial to: 
• Assure sufficient evaluable patients per cohort by entering an additional patient to a 
cohort (e.g., increase a 1 patient cohort to 2 patients, a 3 patient cohort to 4 patients, or a 
6 patient cohort to 7 patients)   
Note:   Should this action be taken, cohort tolerability assessment and subsequent dose escalation will 
occur when the minimum number of patients required to evaluate tolerability have completed 
Cycle 1.  However, if any additional patient experiences an event that would, per protocol, result 
in either cohort expansion or the halting of dose escalation, protocol rules as outlined herein will 
be followed (see Section 6.6.2.2; Rules for Escalation and Cohort Expansion in Phase 1a). 
• Evaluate > 4 dose cohorts should this be necessary to identify the RP2D 
• Expand a lower dose cohort(s) if an initially identified MTD cohort is expanded and is 
found to exceed tolerability either with single or repeated cycles of therapy  


 
 
 
 
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• Evaluate a previously unexamined intermediate dose level(s) between 2 established dose 
levels to further characterize safety and tolerability, if indicated 
Note: 
This action would be taken in the event of an unacceptably high frequency of toxicities observed 
in patients treated at one dose, considered to be in marked contrast to the tolerability noted in the 
immediately preceding dose cohort. 
There is potential for additional expansion cohorts within the Phase 2a portion of the trial (by 
amendment only). 
Expanded accrual in any cohort will take place at the Sponsor discretion, after discussion with 
the Investigator(s). 
 
Criteria for Inclusion 
Patients must meet all of the following criteria to be eligible for participation in the trial: 
1. Male or female patients, > 18 years of age at the time of obtaining informed consent 
2. Patients with a documented (histologically- or cytologically-proven) solid tumor 
epithelial carcinoma that is locally advanced or metastatic   
3. Patients with a malignancy that is either refractory to standard therapy or for which no 
standard therapy is available   
4. Patients with a malignancy that is currently not amenable to surgical intervention due to 
either medical contraindications or non-resectability of the tumor  
5. Phase 1a Dose-Escalation Cohorts:  Patients with measurable or non-measurable disease 
according to RECIST, v1.1 (see Appendix F; Measurement of Effect).  To include 
patients reasonably likely to express EGFR*  
*Includes patients with breast, ovarian, endometrial, cervical, esophageal, gastric, colorectal, biliary, 
hepatocellular, pancreatic, prostate, renal cell, bladder carcinoma or gliomas.  Patients with squamous cell 
carcinoma of the head and neck (SCCHN) and NSCLC may only be entered after careful evaluation of 
their smoking history, pulmonary function, and imaging studies to rule out pulmonary dysfunction, and 
after discussion with the Medical Monitor. 
6. Phase 2a Expansion Cohorts ONLY:  Patients with mTNBC, SCCHN, or Sq-NSCLC and 
with:  
• Measurable disease according to RECIST, v1.1 (determined as 1 or more lesions 
as assessed by computerized tomography [CT] or magnetic resonance imaging 
[MRI]).   
Note:  Any lesions which have been subjected to locoregional therapies or radiotherapy should not 
be considered measurable unless the lesion has clearly progressed (per RECIST v1.1) since 
the procedure. 
• An EGFR-expressing solid tumor documented by central laboratory assessment to 
be positive by IHC* as follows: 


 
 
 
 
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o mTNBC Cohort**:  3+ intensity in ≥ 50% of cells or ≥ 2+ intensity in ≥ 
75% of cells (~15 patients in each subgroup) 
o SCCHN Cohort:  3+ intensity in ≥ 50% of tumor cells (~15 patients) 
o Sq-NSCLC Cohort:  3+ intensity in ≥ 50% of tumor cells (~15 patients) 
** Recruitment in mTNBC cohort subgroups will be halted after enrollment of 15 
patients in order to assess activity   
• EGFR assessment to be made using:  
o An archival FFPE tumor specimen (as recent as possible; sufficient  FFPE 
tissue must be available for submission to a central analytical laboratory 
in order to confirm EGFR status as well as be available for other study-
related evaluations), or 
o Surgical or biopsy specimens if archival tumor tissue results are not 
available (patients must be willing to undergo a pre-dosing biopsy from a 
primary or metastatic tumor site(s) considered safely accessible for 
biopsy).   
*DAKO EGFRpharmDX IHC kit system technology to be utilized.  For this study, EGFR-positive 
staining is defined as noted above for each cohort.   
7. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 
(or equivalent Karnofsky Performance Status; see Appendix B; Performance Status 
Evaluation) as follows, and an anticipated life expectancy of ≥ 3 months: 
• Phase 1a Dose-Escalation Cohort Patients:  0, 1, or 2 
• Phase 2a Expansion Cohort Patients:  0 or 1 
8. Women of childbearing potential (WOCBP) and fertile men with a partner of 
childbearing potential agreeing to use a highly effective method of contraception during 
the study and for 3 months after the last dose of study drug; male patients must also agree 
to refrain from sperm donation during this period.   
Note: 
Women are considered of childbearing potential if they have experienced menarche, and they have 
not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy), or are not postmenopausal. Post-menopause is defined as: 1) amenorrhea for > 12 
months with no other cause, or 2) irregular menstrual periods, on hormone replacement therapy 
(HRT), with a documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL. In 
women under 55 years who have not been surgically sterilized, post-menopausal status should be 
confirmed by evaluation of serum FSH. 
Men are considered fertile unless they have undergone surgical sterilization (bilateral vasectomy 
or a bilateral orchiectomy).  
A highly effective method of contraception is defined as true abstinence or non-hormonal 
contraception equivalent to a double-barrier method, or intrauterine device (see Section 11.1; 
Precautions Regarding Procreation).  
9. Patients with the ability to understand and give written informed consent for participation 
in this trial, including all evaluations and procedures as specified by this protocol 


 
 
 
 
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Note: 
Informed consent must be obtained prior to patient screening, and before any evaluations or 
procedures specifically related to this study are performed. 
 
Criteria for Exclusion 
Patients meeting any of the following criteria are ineligible for participation in the trial.  
4.3.1 
Patients to be Excluded  
1. Women who are pregnant or intending to become pregnant during or within 3 months 
after the last dose of study drug; women who are breastfeeding; WOCBP and fertile men 
with a WOCBP partner not using and not willing to use a highly effective method of 
contraception.  
Note:  
WOCBP and fertile men will be informed as to the potential risk of procreation while participating 
in this trial.  A pregnancy test must be performed on, and the results reviewed for, each WOCBP 
prior to first study drug administration (serum at screening, serum or urine thereafter).  A negative 
pregnancy test performed within ≤ 2 working days prior to first study drug administration must be 
documented on the patient’s electronic case report form (eCRF) (see Section 11.1; Precautions 
Regarding Procreation). 
2. Patients with known central nervous system (CNS) or leptomeningeal metastases, or 
spinal cord compression not controlled by prior surgery or radiotherapy, or patients with 
symptoms suggesting CNS involvement for which treatment is required  
Note: 
Patients previously treated for these conditions that have stable CNS disease (verified with 2 
consecutive imaging studies performed at least 4 weeks apart with the most recent study 
performed within 12 weeks prior to first study drug administration), are asymptomatic and are not 
currently taking corticosteroids, or are on a stable dose of corticosteroids for at least 4 weeks prior 
to Day 1 of the study, are permitted. Prophylactic anticonvulsant medications are allowed. 
 
Patients with newly identified CNS disease during study treatment will be considered to have 
disease progression and will be discontinued from study to allow for appropriate management. 
3. Patients with a malignancy other than that of epithelial origin   
4. Phase 2a Expansion Cohorts ONLY:   Patients with an active second malignancy or 
history of another malignancy within the last 2 years with the exception of: 
• Treated non-melanoma skin cancers 
• Treated carcinoma in situ (CIS) of the breast, cervix, bladder, colon, 
endometrium, skin (melanoma) provided CR was achieved at least 2 years prior to 
study and no additional therapy is ongoing or required during study period with 
the exception of anti-estrogen/androgen therapy or bisphosphonates 
• Controlled, superficial carcinoma of the bladder 
• T1a carcinoma of the prostate comprising < 5% of resected tissue and prostate 
specific antigen (PSA) within normal limits (WNL) since resection  
5. Patients with any of the following hematologic abnormalities at baseline:   
• Hemoglobin < 9.0 g/dL 


 
 
 
 
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• Absolute neutrophil count (ANC) < 1,500 per mm3 
• Platelet count < 100,000 per mm3 
Note: 
Patients may have received a blood/blood product transfusion prior to study, if clinically 
warranted.   
6. Patients with any of the following serum chemistry abnormalities at baseline: 
• Total bilirubin > 1.5 × the upper limit of normal (ULN) for the institution* 
• AST or ALT > 3 × the ULN for the institution (> 5 × if due to hepatic 
involvement by tumor)  
• Serum creatinine > 1.5 × ULN for the institution  
*Patients with evidence of Gilbert’s Syndrome as the etiology of elevated total bilirubin will be eligible, 
provided all other eligibility criteria are met. 
7. Patients with any of the following coagulation parameter abnormalities at baseline 
(unless on a stable dose of anticoagulant therapy for a prior thrombotic event, as 
determined by the Investigator): 
• PT (or international normalized ratio [INR]) > 1.5 × ULN for the institution (> 3× 
ULN for the institution if anticoagulated) 
• PTT (or aPTT) > 1.5 × ULN for the institution (> 3× ULN for the institution if 
anticoagulated)  
8. Patients with: 
• Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary 
embolism (PE), within 4 weeks prior to first study drug administration, unless 
adequately treated and stable 
• Active uncontrolled bleeding or a known bleeding diathesis  
9. Patients with a significant cardiovascular disease or condition, including: 
• Congestive heart failure (CHF) currently requiring therapy 
• Need for antiarrhythmic medical therapy for a ventricular arrhythmia or other 
uncontrolled arrhythmia (patients with controlled atrial fibrillation (heart rate 
[HR] < 90) for > 30 days prior to study entry are eligible) 
• Severe conduction disturbance (e.g., 3rd degree heart block) 
• Left ventricular ejection fraction (LVEF) known to be below the lower limit of 
normal (LLN)* for the center, or < 50% by multi-gated acquisition MUGA scan 
or echocardiogram (Echo) if no LLN is defined by the site 
• QTc interval > 480 msec  
• Uncontrolled hypertension (per the Investigator’s discretion) 


 
 
 
 
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• Class III or IV cardiovascular disease according to the New York Heart 
Association’s (NYHA) Functional Criteria (see Appendix C) 
• History of acute coronary syndromes (including myocardial infarction [MI] and 
unstable angina), coronary angioplasty, stenting, or bypass grafting within 6 
months prior to first study drug administration 
*Assessment of LVEF will not be performed routinely in all patients.  Patients with a history of CHF 
will have either a MUGA scan or echocardiogram at Screening.  If LLN is not defined for a given 
institution, then LVEF must be ≥ 50% 
10. Patients with a significant ocular disease or condition, including: 
• History of ocular inflammatory disease 
• History of disorders of the cornea, including current evidence of keratitis at 
screening  
11. Patients with a significant pulmonary disease or condition, including: 
• Significant symptomatic chronic obstructive pulmonary disease (COPD), as 
assessed by the Investigator   
• History or any current evidence on imaging studies prior to or during study of 
interstitial lung disease (ILD), pulmonary fibrosis  
• History of pulmonary inflammatory disease, pneumonitis, acute respiratory 
distress syndrome (ARDS) 
12. Patients with a significant gastrointestinal (GI) disease or condition, including but not 
limited to: 
• History of inflammatory bowel disease 
• Diarrhea ≥ Grade 2 within 2 weeks prior to first study drug administration* 
*Patients with recent Grade 2 diarrhea secondary to administration of oral contrast are allowed, provided 
symptoms have resolved prior to first study drug administration. 
13. Patients with non-healing wounds on any part of the body 
14. Patients with a known or suspected hypersensitivity to any of the excipients of AVID100 
15. Patients with any other serious/active/uncontrolled infection, any infection requiring 
parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first study 
drug administration  
16. Patients with unresolved > Grade 1 toxicity* associated with any prior antineoplastic 
therapy with the exception of persistent Grade 2 alopecia, peripheral neuropathy, 
decreased hemoglobin, hypomagnesemia, lymphopenia, and/or end-organ failure being 
adequately managed by hormone replacement therapy  
*AE assessments based on Common Terminology Criteria for Adverse Events [CTCAE Version 5.0] 


 
 
 
 
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17. Patients with inadequate recovery from any prior surgical procedure, or patients having 
undergone any major surgical procedure within 4 weeks prior to first study drug 
administration  
Note:  
Patients having undergone recent placement of a central venous access device will be considered 
eligible for enrollment.  
18. Patients with any other serious, life-threatening, or unstable pre-existing medical 
condition (aside from the underlying malignancy), including significant organ system 
dysfunction, or clinically significant laboratory abnormality (ies), which, in the opinion 
of the Investigator, would either compromise the patient’s safety or interfere with 
obtaining informed consent, compliance with study procedures, or evaluation of the 
safety of the study drug  
19. Patients with a psychiatric disorder or altered mental status that would preclude 
understanding of the informed consent process and/or completion of the necessary study-
related evaluations   
20. Patients with the inability or with foreseeable incapacity, in the opinion of the 
Investigator, to comply with the protocol requirements 
4.3.2 
Drugs and Other Treatments to be Excluded  
1. Any antineoplastic agent for the primary malignancy (standard or investigational), 
without delayed toxicity, within 2 weeks 
Note:  See patients to be excluded for criteria on recovery from prior antineoplastic therapy. 
2. Any other investigational treatments during study.  This includes participation in any 
medical device or other therapeutic intervention clinical trials.    
3. Radiotherapy  
• For target lesions within 4 weeks prior to first study drug administration and 
during study  
• For non-target lesions within 1 week prior to C1/D1 
Note: 
A tumor lesion situated in a previously irradiated area is considered a measurable/target 
lesion only if subsequent disease progression has been documented in the lesion.   
Radiotherapy for pain control against non-target lesions is allowed, as long as it does not 
influence bone marrow function (Section 6.12) 
4. Strong inhibitors and/or inducers of cytochrome P450 (CYP) isoenzyme 3A4 within 2 
weeks prior to first study drug administration and during study 
*See <http://medicine.iupui.edu/clinpharm/ddis/> 
5. Immunosuppressive or systemic hormonal therapy (> 10 mg daily prednisone or 
equivalent) within 2 weeks prior to first study drug administration and during study (for 
exceptions, see Section 6.12)   


 
 
 
 
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6. Prophylactic use of hematopoietic growth factors within 1 week prior to first study drug 
administration and during Cycle 1 of study; thereafter prophylactic use of growth factors 
is allowed as clinically indicated   
Note: 
Interventional/therapeutic use of growth factors is allowed at any time during study, including 
during Cycle 1, if deemed necessary by the Investigator.  Growth factor use must be consistent 
with product package insert instructions.  Transfusions are permitted as needed. 
 
Questions regarding patient eligibility must be addressed and resolved by the Investigator in 
consultation with the Sponsor's Medical Monitor(s) prior to enrollment. 


 
 
 
 
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5. 
INVESTIGATIONAL DRUG 
In advance of study start the Sponsor (or designee) will provide labeled supplies of AVID100 to 
the study center Investigational Pharmacy.  Instructions for handling, administration, and 
disposal will be provided in the Study Pharmacy Manual (or other similar document) and are 
summarized below. 
 
AVID100  
AVID100 injection solution concentrate (AVID100) is formulated as a clear to opalescent, 
colorless to pale yellow liquid for IV infusion.  Formulation excipients include: 
 20 mM sodium succinate 
 10% weight to volume (w/v) trehalose dihydrate 
 0.02% w/v polysorbate 20, pH 5.5 
Each single-use, glass vial contains a total volume of 10 mL.  Each vial contains AVID100 at a 
concentration of 6 mg/mL for a total vial content of 60 mg.   
AVID100 is to be diluted in commercially available 0.9 % sodium chloride (NaCl, normal saline, 
NS) solution for IV infusion.   
 
Storage and Handling of  AVID100 
Unused vials of AVID100 must be stored refrigerated between 2° C to 8° C in an access-
controlled secure location (ACSL).  There is no evidence that  UV light exposure affects 
AVID100 but as a precaution, vials should be stored in the shipping box, at temperatures 
between 2° C to 8° C until use. 
The investigational site will be required to maintain a temperature log documenting AVID100 
storage conditions.  Any deviations from the recommended storage conditions should be 
immediately reported to the Sponsor (or designee) and the use of drug interrupted until 
authorization for its continued use has been given.   
AVID100 may be accessed only by the Investigator, a member of the Investigator’s staff 
specifically authorized by the Investigator, or a pharmacist, as appropriate.  The study center 
must insure that investigational drug is accessible to authorized personnel only.  
Vials of AVID100 are to be allowed to warm to room temperature prior to dilution and use. 
 
Stability of AVID100  
Long term stability of AVID100 is being assessed on an ongoing basis and expiry will be 
updated as data accrues.   The stability of the clinical material will be monitored for at least the 
duration of the proposed clinical trial.   
When diluted in 0.9 % NaCl solution AVID100 has been found to be stable for up to 4 hours at 
room temperature (therefore, once diluted and prepared for delivery study drug should be 
administered within 4 hours; see Section 5.8, Dose Preparation). 


 
 
 
 
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Labeling of AVID100 
Vials of AVID100 will bear the appropriate label text for investigational agents, as required by 
governing regulatory agencies.  This includes but is not limited to the investigational drug name, 
concentration (6 mg/mL), total withdrawal volume (10 mL/vial), a cautionary statement 
indicating that the agent is a new drug and restricted to investigational use, storage information, 
and that it was manufactured for the Sponsor.    
 
Packaging of AVID100 
AVID100 drug product provided as a solution for injection in 10 mL single-use vials will be 
shipped refrigerated or in insulated packaging maintaining the required temperature of 
approximately 2°C to 8°C.  Temperature range indicators or monitors will accompany each 
shipping box. 
Each shipment of study drug will be accompanied by a shipment inventory document describing 
the amount of drug shipped to the site.  The inventory information must be checked against the 
actual amount of drug sent and the Sponsor (or designee) notified of any discrepancies.  The 
Investigator (or designee) will then sign the shipment inventory document and maintain it in the 
study file.   
 
Administration of AVID100 
AVID100 will be administered by IV infusion.  An appropriate dose, based on the patient’s 
cohort assignment, is to be diluted to a total volume of: 
• 100 mL if ≤ 180 mg/m2, or to  
• 200 to 250 mL if > 180 mg/m2.  This may include either: 
o 100 mL × 2 (to be administered sequentially) 
o  Up to 250 mL (using a single flexible IV bag)  
AVID100 is to be diluted with 0.9% NaCl and administered over 2 hours (+ 10 minutes), once 
every 3 weeks (Q3W; 3 weeks [21 days] equals 1 dosing cycle).    
 
Dose Calculation 
The Investigator (or designee) will be responsible for calculating the amount of study drug and 
the appropriate dose to dispense to the patient as determined by the patient’s dose cohort 
assignment.   
The dose level will be multiplied by the patient's body surface area (BSA) in order to arrive at 
the total dose to be delivered.  In situations where this calculation results in a value with an 
unwieldy number of decimal places, it is permissible to round the value to the nearest "tenth", or 
according to standard institutional practice.  As a convention, values > 5 should be "rounded" to 
the next higher number.   
Please note: The Sponsor reserves the right to "round" the dose to be administered with each cohort in a similar 
fashion (to the nearest tenth), and will do so at the time a dose cohort is opened for accrual in those 
situations where deemed practical.   


 
 
 
 
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Dosing information will also be recorded on the Drug Dispensing Inventory or other appropriate 
accountability form in use.  This inventory will be maintained throughout the duration of the trial 
and will be periodically reviewed by a representative of the Sponsor.   
 
Dose Preparation  
The designated dose of study drug must be prepared by the study pharmacist (or designee) and 
should be administered by the study staff as soon as possible following preparation, within 4 
hours and taking into account:  
 The total volume of study drug to be delivered will be withdrawn from the study drug 
vial(s) and added to a prefilled IV bag containing 0.9 % NaCl (following removal of an 
appropriate volume of saline, such that the final volume to be infused equals 100 mL 
(doses ≤ 180 mg/m2) or 200 to 250 mL (doses > 180 mg/m2).  Flexible containers should 
be made of polyvinyl chloride. 
 The IV bag containing the diluted study drug solution to be administered should be gently 
inverted to ensure that the material is well mixed.   
 Infusion sets must be made of di(2-ethylhexyl)phthalate (DEHP)-free material and must 
contain an in-line filter (0.22 micron pore size).   
 
Accountability  
The Investigator acknowledges that the study drug supplies are investigational and, as such, must 
be used strictly in accordance with the protocol and only under the supervision of the Principal 
Investigator.  No study medication will be sent to the study site until all regulatory documents, 
including Institutional Review Board (IRB) approval, are received by the Sponsor or its 
designee. 
The Investigator and investigational site staff are responsible for maintaining an accurate 
inventory and accounting of investigational drug.  Receipt and use of AVID100 will be recorded 
on the Drug Dispensing Inventory or other appropriate accountability form in use.   
 
Disposition of Used Supplies  
After study drug is prepared for delivery and administered, the health care professional will 
maintain an inventory of all used vials of study drug, and if authorized by the Sponsor (or 
designee) such supplies may be destroyed in an appropriate manner according to institutional 
policy.   
Note: 
No other use of AVID100 study drug intended for use in this trial is authorized by the Sponsor.  The 
Investigator (or designee) will be responsible for the appropriate handling and disposition of residual study 
drug in partially used vials.   
 
Inventory of Unused Supplies  
Unused study materials MUST be returned to the Sponsor or designee, unless otherwise 
authorized in writing. 


 
 
 
 
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Destruction of Investigational Supplies 
No study drug materials may be destroyed or discarded at the site without the written 
authorization of the Sponsor (or designee).  The destruction of study drug materials must be 
carefully documented per instructions outlined in the Pharmacy Manual (or other similar 
document).  Disposition records must be available for review by a representative of the Sponsor. 
 
Resupply Requests 
Please refer to the Pharmacy Manual (or other similar document) for initial ordering of AVID100 
and to request resupply of study drug.  Please anticipate resupply needs at least 2 weeks in 
advance.     


 
 
 
 
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6. 
EXPERIMENTAL PLAN 
 
Design Elements 
• Uncontrolled, open-label, non-randomized 
• Enrollment in the order of confirmation of eligibility 
• Escalating doses of study drug in sequential patient cohorts (Phase 1a) 
• Cohort expansion at the MTD or RP2D and in other cohorts based on safety (Phase 1a) 
• Addition of expansion cohorts of defined patient populations TBD (Phase 2a) 
 
Projected Recruitment Period for this Trial 
It is anticipated that enrollment to this study will be completed in approximately 24 months.  
• Anticipated date of enrollment of first Phase 1a patient:   
Q4 2016 
• Anticipated date of enrollment of first Phase 2a patient:   
Q3 2018 
• Anticipated date of enrollment of last Phase 2a patient:    
Q4 2019 
Enrollment to the expansion cohorts in Part 2a of the trial will commence upon investigational 
site approval of a protocol amendment defining the disease indications to be explored. 
The end of trial will be reached at the latest 1 month (30 +7 days) after the last patient has been 
discontinued from study drug.  Patients with SD or an ongoing OR at that time will continue to 
be followed to assess duration of disease stabilization or response. 
 
Cohort Management 
For the purposes of this study, "enrollment" is defined as patient registration to participate in 
this trial; at this time the patient's study identification code and dose cohort will be assigned. 
6.3.1 
Prescreening for EGFR 
The trial site will prescreen patients, utilizing archival tumor tissue, for EGFR Tumor Status 
Determination before entering patients into screening for the treatment portion of the trial. The 
site should use a separate prescreening informed consent form.  Prescreening may be performed 
outside the 28 (+ 2) day screening period to allow adequate turnaround time for receipt of results, 
provided separate informed consent has been obtained (see Section 7.4.1; EGFR Tumor Status 
Determination). 
6.3.2 
Patient Screening and Dose Cohort Assignment 
Once a patient has given written informed consent, screening assessments will be conducted, and  
if the patient  is identified as meeting the study eligibility criteria the Investigator (or designee) 
will contact the Sponsor’s representative for the purpose of authorizing enrollment of the patient 
into the trial. 


 
 
 
 
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Patients will be enrolled into the study in the order of confirmation of their eligibility, and 
assigned to a cohort on a “first-come-first-served” basis.   
6.3.2.1. 
Screening of Potential Patients 
All screening activities must be performed within 14 days prior to the first day of dosing (Cycle 
1/Day 1; [C1/D1]), unless otherwise specified.   
The Sponsor (or designee) will be made aware of potential patients for enrollment in order to 
track such study-related activities.   
Patients who sign informed consent and are subsequently deemed to be screen failures will be 
followed for the occurrence of SAEs/AEs until it is determined that they are will not be 
participating in this trial. 
6.3.2.2. 
Submission of Patient Enrollment Documentation 
Once eligibility has been confirmed in accordance with the protocol-stipulated inclusion and 
exclusion criteria, patient enrollment information must be submitted to the Sponsor (or designee) 
via a Patient Enrollment Form.  This information will serve to confirm patient eligibility and 
initiate the enrollment process.  The following information must be provided by the study site at 
this time:   
• Patient gender  
• Date of birth (or age), as allowed by local regulatory requirements 
• Date written informed consent was obtained 
• Underlying diagnosis 
• Confirmation of compliance with all inclusion/exclusion criteria. 
The following information may be requested of the study site at this time: 
• Patient height and weight or BSA (if required for dose calculation) 
• Date of screening 
• Stage of disease and current performance status 
• Sites of metastases (if applicable) 
• Brief description of the prior therapy for the primary diagnosis, including dates of 
initiation and discontinuation as well as best response 
• Planned date of first dosing 
The Sponsor (or designee) will review the information provided and by signing the form will 
authorize eligible patients for start of treatment.  A copy of the fully executed Patient Enrollment 
Form will be returned to the trial site for archiving. This form will document the allocated dose 
of AVID100, and will serve to assign patients to a dose cohort at the time of enrollment.   


 
 
 
 
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6.3.2.3. 
Patient Identification Code Assignment 
Each patient who completes the study screening assessments and is enrolled for study 
participation will be assigned a unique identification code by the Sponsor (or designee).  
Identification codes will be assigned in chronological order, and will be concatenated to indicate 
relevant study information, including:  the participating study center, the study phase or cohort, 
and the patient’s order of enrollment to the trial. 
6.3.2.4. 
Screening Failures 
A patient found not eligible for the trial after giving informed consent will be considered a 
screening-failure.  A list of patients failing screening and the reason for ineligibility will be 
maintained by the site on a Patient Screening Log or other similar document.   
Re-screening of a patient is allowed, if felt to be justified by the Investigator. 
6.3.3 
Cohort Closure 
The Sponsor (or designee) will be in communication with the sites when the target total 
enrollment for a cohort has been attained.  Once recruitment to a cohort is completed, accrual to 
the cohort will be closed, and sites will be so notified in writing.  Cohorts will remain closed to 
further accrual, unless a decision is later made by the Sponsor (or designee) to further expand 
that cohort, based on protocol-defined criteria. 
 
Requirements for Patient Observation 
Patients will be treated on an outpatient basis, and will be evaluated and discharged from the 
clinic on days of scheduled study visits*, unless hospitalization is required for other reasons or to 
assure patient safety.   
AVID100 must be administered under close supervision in an environment where full 
resuscitation facilities are immediately available.  IV infusions will be carefully monitored to 
assess safety and tolerability by qualified site medical personnel.  Such personnel must be 
available in order to evaluate and treat any AEs, as well as to evaluate whether continued 
participation of the patient in the study is warranted or advisable. 
• Phase 1a Dose-Escalation Cohorts:  Patients will be carefully observed for a minimum of 
4 hours following completion of the first administration of study drug (Day 1) for 
evidence of any treatment-related AE(s), and so that final Day 1 samples for post-dosing 
PK assessments may be obtained**, and a minimum of 1 hour following completion of 
subsequent infusions.     
• Phase 2a Expansion Cohorts:  Patients will be carefully observed for a minimum of 2 
hours following completion of the first administration of study drug (Day 1) for evidence 
of any treatment-related AE(s) **, and a minimum of 1 hour following completion of 
subsequent infusions.  PK samples will only be collected prior to dosing on Day 1 of each 
cycle in the Dose Expansion Cohorts.   
At the end of each infusion, the IV line must remain in place for at least 1 hour to allow 
administration of IV drugs, if necessary. 


 
 
 
 
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Patients will be followed on an outpatient basis during the interval between each scheduled study 
visit.   
*Clinical and laboratory assessments will occur at the frequencies indicated (see Section 7; Study Assessments).  In 
the event of an AE, assessment frequencies may be increased, as clinically indicated.  
**Comprehensive collection of clinical samples is critical to the conduct of this study.  In situations where 
collection of 4h samples is logistically difficult due to clinic staff availability, the observation period may be 
shortened, and an "end of day" sample may be obtained at the latest practical time.  Such an option is available 
ONLY after previous discussion with and approval by the Sponsor. 
 
Drug Treatment Regimen  
6.5.1 
Study Start Day  
All patients will receive the initial dose of study drug on Day 1 of Cycle 1 (C1/D1).   
On the day of the first scheduled study drug infusion, and prior to the start of infusion (SOI), the 
Investigator must assess whether any changes have occurred in the clinical state of the patient 
since Screening, which would exclude the patient from the trial. 
6.5.2 
Patient Availability During Cycle 1 
The site should calculate study assessment days as well as sample collection dates and times in 
advance of scheduling a patient’s first day of study drug administration, so as to plan accordingly 
to avoid assessment or collection requirements during non-routine times such as weekends, 
holidays, etc.   
Given the schedule of study drug administration outlined herein, and the PK sampling schedule 
(see Section 7.5; Pharmacokinetic Assessments), patients must be available: 
 Phase 1a:  on Days 1, 2, 4 (± 1 day), and 8 of Cycle 1, therefore, consideration should be 
given to scheduling Day 1 on a Monday or Tuesday*   
 Phase 2a:  on Days 1, 4 (± 1 day), and 8 of Cycle 1, therefore consideration should be 
given to scheduling Day 1 on a Monday, Tuesday, or Friday* 
*unless the study site has weekend hours of operation 
6.5.3 
Therapy with AVID100 
Based on their cohort assignment patients will receive the assigned dose of study drug as 
described below, by the route and schedule as described below: 
6.5.3.1. 
Doses to be Administered 
6.5.3.1.1. 
Doses to be Evaluated During Phase 1a 
Dose cohorts will be numbered sequentially (i.e., Cohort 1, Cohort 2, etc.).  The number of 
cohorts evaluated and the MAD will depend upon toxicities experienced during Cycle 1.   
The initial dose of AVID100 to be evaluated is calculated based on the highest non-severely 
toxic dose (HNSTD) observed in nonclinical toxicology studies, and will be 20 mg/m2/dose 


 
 
 
 
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(with the maximum dose to be administered in this trial not to exceed 330 mg/m2/dose).  An 
accelerated titration design (1 patient per cohort) will be used for dose-escalation for up to 2 
cohorts or until the occurrence of an event that activates a stopping rule.  Thereafter, dose-
escalation will follow a standard 3+3 design with a target toxicity level of 33.3% or less as 
determined by DLTs.  Doses will be calculated as follows: 
• Dose Part A:  Up to 2 cohorts (until at most Cohort 3) will receive consecutive 100% 
increases in dose (EXAMPLE:  Cohort 1 = 20 mg/m2/dose, Cohort 2 = 40 mg/m2/dose, 
etc.) until the occurrence of:  
o A study drug-associated > Grade 2 toxicity or accrual to Cohort 3, whichever 
occurs first (Part B will commence)  
o A study drug-associated DLT (Part C will commence) 
• Dose Part B:  Cohorts will receive consecutive 50% increases in dose (EXAMPLE: 
Cohort x = 60 mg/m2/dose, Cohort x+1 = 90 mg/m2/dose, etc.) until the occurrence of:   
o A study drug-associated DLT (Part C will commence) 
o > 1 patient with a study drug-associated DLT (dose escalation will stop) 
• Dose Part C:  Cohorts will receive consecutive 25% increases in dose (EXAMPLE: 
Cohort x = 60 mg/m2/dose, Cohort x+1 = 75 mg/m2/dose, etc.) until the occurrence of:   
o > 1 patient with a study drug-associated DLT (dose escalation will stop) 
Note:  
The Investigator(s) and Sponsor's Medical Monitor(s) will review clinical and laboratory safety data on an 
ongoing basis throughout the study and make decisions regarding the advisability of continuing accrual to a 
particular dose cohort, and/or escalating the dose and allowing accrual to a higher dose cohort. 
 
Based on emerging tolerability data the Sponsor may choose to escalate the dose between cohorts at an  
increment less than the percent increase allowed above in an effort to protect patient safety. 
6.5.3.1.2. 
Dose to be Administered During Phase 2a 
Patients entered to the Phase 2a portion of this study will receive study drug at the RP2D 
established during the Phase 1a portion of the study.  The MTD and RP2D has been 
determined to be 220 mg/m2.   
Ongoing safety evaluations will continue during accrual of patients to the Phase 2a expansion 
cohorts to determine whether any newly identified AEs necessitate modifications to the protocol 
or discontinuation of accrual to patients within any cohort (Section 6.6.3.3). 
6.5.3.1.3. 
Changes in Dose to be Administered  
In both Phase 1a and Phase 2a, once assigned to a dose cohort each patient will continue to be 
treated with study drug at that same dose level throughout the duration of their time on study, 
unless dose reduction is necessary due to the occurrence of a DLT or other toxicity warranting 
dose reduction at the Investigator’s discretion.  There will be no intra-patient dose-escalation.  


 
 
 
 
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Dose adjustments should be made in the event of noted weight change (± 10%, less at the site’s 
discretion or if required by institution procedures) at visits that require weight measurement.       
6.5.3.2. 
Route of Administration 
Study drug will be administered by the IV route, via indwelling venous access catheter, utilizing 
a controlled infusion device.  Infusion sets must be made of DEHP-free material and must 
contain an in-line filter (0.22 micron pore size).  Flexible containers of NS should be made of 
polyvinyl chloride.  
The catheter may be placed into a peripheral vein (if accessible); administration via central 
venous catheter or port (if in place) is allowed. 
In those instances when study drug administration is associated with PK sampling, and 
administration is via peripheral IV catheter, infusions will be delivered into the arm contralateral 
to that from which blood samples for PK analysis are being obtained. 
6.5.3.3. 
Duration of Infusion 
Study drug will be administered over 2 hours (+ 10 minutes)* 
*Protocol v5.0:  Extended from 1 hour to 1.5 hours due to Grade 3 IRR observed in Cohort 3 (80 mg/m2); effective 
20Jul2017 and documented in a study Note to File dated 21Jul2017 (see Section 2.3.2.1; AVID100-01: Clinical 
Experience)  
*Protocol v6.0:  Extended from 1.5 hours to 2 hours due to Grade 2 IRRs observed in Cohort 4(120 mg/m2); 
effective 21Dec2017 and documented in a study Note to File dated 28Dec2017 (see Section 2.3.2.1; AVID100-01: 
Clinical Experience) 
Administration should be at a constant rate using a programmable volumetric infusion pump in 
order to assure accuracy of delivery (as well as integrity of PK sampling). The times of infusion 
initiation and completion must be recorded on the appropriate page of the patient’s eCRF. 
Note: 
In the event of an infusion-related reaction (IRR) that does not meet the protocol definition of DLT, the 
Investigator may elect to prolong the infusion duration to extend longer than the initially assigned duration 
(for further instructions see Section 8.3.1; Prolongation of Infusion Duration). 
During Phase 1a, the duration of infusion will be prolonged for all subsequent patients entered to 
the trial in the following situations: 
• In the event of a Grade 2 IRR in ≥ two thirds of the patients entered to a cohort, the 
duration of infusion for subsequent patients entered to the trial will be extended by 30 
minutes (or longer, if indicated). 
• In the event of a Grade 3 or greater IRR in any patient within a cohort, the duration of 
infusion for subsequent patients entered to the trial will be extended by 30 minutes (or 
longer, if indicated). Such a case will also be considered to have met the protocol criteria 
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These same criteria will be applied in the event IRRs occur on the extended infusion schedule. In 
such a case, the duration of infusion for subsequent patients entered to the trial will be extended 
by 30 minutes (or longer, if indicated).  
6.5.3.4. 
Volume of Infusion 
All infusions ≤ 180 mg/m2 will be delivered in a final volume of 100 mL.   
All infusions > 180 mg/m2 will be delivered in a final volume of 200 to 250 mL.  This may 
include either:  
• 100 mL × 2 (dose to be divided between two 100 mL infusion volumes to be 
administered sequentially).   
• Up to 250 mL (using a single flexible IV bag) 
6.5.3.5. 
Diluent  
Commercially available sterile 0.9% NaCl for IV infusion is to be used as the diluent.   
6.5.3.6. 
Schedule  
Study drug is to be administered once every 3 weeks (Q3W) on Day 1 of each cycle (3 weeks 
[21 days] equals 1 dosing cycle).   
 
End of Cycle 1 (EOC1) assessments are to be performed no sooner than C1/D21 (-2 days).  
Subsequent cycles may be administered Q3W (± 2 days), unless further delay is required to 
allow for amelioration of toxicities.   
 
Cycle 1 
A minimum of 1 cycle of AVID100 will be administered, if tolerated.  Any interruptions in 
dosing and the reasons for such interruptions must be documented.  If an AE is the cause for 
dosing interruption, it must be detailed on the Adverse Events page of the eCRF.  Determinations 
regarding cohort escalation, DLTs, and MTD will be based on the toxicities observed during this 
3 week period (Cycle 1) of treatment. 
• Patients completing Cycle 1, in the absence of a DLT, will be considered to have 
tolerated the AVID100 regimen.   
• Patients must receive their full planned dose of AVID100 during Cycle 1 in order to be 
considered evaluable for tolerability unless dose reduction, interruption, or 
discontinuation was the result of a DLT.   
• Dose-Escalation Cohorts:  Patients will be replaced, if necessary (e.g., received < 1 full 
dose of AVID100 plus follow-up through EOC1 [C1/D21 {-2 days]}]) for any reason 
other than a DLT), to allow for a thorough assessment of the tolerability in any dose 
cohort.   
• All enrolled patients will be considered in the assessment of safety and tolerability. 


 
 
 
 
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6.6.1 
Premedication 
6.6.1.1. 
Premedication for Infusion-Related Reactions 
Beginning with the first dose, all patients must be premedicated with standard therapies prior to 
each dose of AVID100 to reduce the risk of IRRs associated with study drug.     
The recommended premedication regimen includes administration of dexamethasone 12 hours 
and 6 hours prior to each dose, as well as administration to begin at minimum 30 minutes prior to 
each infusion of a glucocorticoid (e.g., dexamethasone) as well as an H1 (e.g., diphenhydramine/ 
hydroxyzine) and an H2-blocker (e.g., ranitidine/famotidine) (see Section 8.2; Premedication for 
Study Drug-Related Toxicities).   
6.6.1.2. 
Use of Other Premedications  
In the event of other study-drug associated reactions (e.g., nausea, vomiting, diarrhea, etc.), 
patients may be premedicated with standard therapies in order to reduce the potential for such 
reactions in the future. 
Mandatory premedication will be implemented for all patients should a pattern begin to emerge 
of mild-to-moderate study drug-related reactions that are amenable to prophylaxis with standard 
agents.  
6.6.2 
Phase 1a:  Rules for Accrual 
6.6.2.1. 
Filling of Cohorts in Phase 1a 
Cohorts will be filled sequentially during the Phase 1a dose escalation portion of the study.  
Once assigned to a cohort, each patient will continue to be treated at the same dose level and 
schedule of study drug throughout the course of the study (unless dose reduction is necessary due 
to the occurrence of a DLT).   
6.6.2.2. 
Rules for Dose Escalation and Cohort Expansion in Phase 1a 
Dose escalation of AVID100 is based on demonstrated tolerability during Cycle 1 (i.e., the initial 
3 weeks of dosing) and the occurrence of DLTs* thought to be associated with  (i.e., possibly 
related, probably related, or related to) study drug.  The rules for dose escalation and 
identification of the MTD(s)* in this study are as follows:  
*See Section 6.8.3; Definition of DLT and Section 6.9; Definition of Maximum Tolerated Dose 
6.6.2.2.1. 
Establishment of the MTD   
1. Dose Part A:  A minimum of 1 patient will be entered into dose Cohort 1 and 2 ONLY; 
the dose escalation between cohorts (until at most Cohort 3) will be 100%.   
• If during Cycle 1, a patient experiences a > Grade 2 toxicity considered associated 
with study drug, the cohort will be expanded to 3 patients and Part B will 
commence.  


 
 
 
 
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• If during Cycle 1, a patient experiences a DLT considered associated with study 
drug, the cohort will be expanded to 6 patients and Part C will commence. 
2. Dose Part B:  A minimum of 3 patients will be entered into each dose cohort; the dose 
escalation between cohorts will be 50%.  
• If during Cycle 1, any 1 patient experiences a DLT considered associated with 
study drug, the cohort will be expanded to 6 patients and Part C will commence. 
• If during Cycle 1, > 1 patient experiences a DLT, dose escalation will STOP.  
This will indicate that the MTD has been exceeded. 
3. Dose Part C:  A minimum of 6 patients will be entered into any dose cohort where a 
DLT is observed in any of the first 3 patients, otherwise a minimum of 3 patients will be 
entered into each dose cohort; the dose escalation between cohorts will be 25%. 
• If during Cycle 1, > 1 patient experiences a DLT, dose escalation will STOP.  
This will indicate that the MTD has been exceeded. 
4. If it is determined that a dose level is not tolerated, the previous lower dose cohort will be 
expanded to 6 patients (if this has not already been accomplished) as a total of 6 patients 
must be treated before establishing a dose as the MTD. 
5. Once the MTD (or maximum dose to be studied) is achieved and the RP2D is identified, 
that cohort may be expanded up to 12 patients in order to more fully evaluate safety and 
tolerability at that dose level at the Sponsor’s discretion.   
6. Should the DLT rate equal or exceed 33.3%* in an expanded MTD cohort, it will be 
determined that the dose is not tolerated.  If this occurs, the previous lower dose cohort 
may be expanded as above.  Therefore: 
• There is potential for expansion of lower dose cohort(s) if the initially identified 
MTD is not tolerated (either with single or repeat cycles of therapy), and 
• There is potential to evaluate and expand a previously unexamined intermediate 
dose level(s) between 2 established dose levels in order to more fully characterize 
tolerability. 
Note: 
Such action would be taken by the Sponsor (or designee) in the event of an unacceptably 
high frequency of toxicities observed in patients treated at one dose level, considered to 
be in marked contrast to the tolerability noted in the immediately preceding dose cohort. 
*i.e., > 2 DLTs when 7 to 9 patients have been treated, > 3 DLTs when 10 to 12 patients have been treated, 
etc. 
Note:  Based on emerging tolerability data the Sponsor may choose to escalate the dose between cohorts at 
an  increment less than the percent increase allowed above in an effort to protect patient safety. 


 
 
 
 
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6.6.2.3. 
Rules for Duration of Exposure Prior to Start of Next Patient and Start of Next 
Cohort in Phase 1a 
Dose escalation and accrual to the next cohort will occur only after the minimum number of 
patients required for tolerability assessment in the current cohort have completed Cycle 1, and 
only after acceptable tolerance has been demonstrated in at least 1 of 1, 3 of 3, or 5 of 6 patients 
treated in the current cohort (depending on cohort size), and after consultation with the Sponsor's 
Medical Monitor(s).     
In cohorts with > 1 patient, enrollment will be staggered between the first and second patient by 
at minimum 24 hours in order to assess for IRRs; thereafter patients within a cohort may be 
added concurrently.  For all patients, EOC1 assessments are to be performed no sooner than 
C1/D21 (-2 days). 
6.6.2.4. 
Rules for Establishing the Recommended Phase 2 Dose 
The MTD (or a dose lower than the MTD) will be identified as the RP2D, provided a minimum 
of 6 patients have been treated at that dose, and provided acceptable tolerance has been 
demonstrated in at least 5 of 6 patients treated.   
The RP2D choice will be based on the MTD evaluation as well as other toxicities observed in the 
study, including observations in later cycles of administration of AVID100, as well as on PK and 
other data. 
6.6.3 
Phase 2a:  Rules for Accrual  
6.6.3.1. 
Filling of Cohorts in Phase 2a  
Once the MTD and/or RP2D have been identified, approximately 60 patients in 3 expansion 
cohorts will be enrolled to the Phase 2a portion of the study to more fully evaluate safety, 
tolerability, and the preliminary antineoplastic effect of study drug at that dose level. 
Accrual to the Phase 2 Cohort may begin once the RP2D has been established and a minimum of 
6 patients have been treated at that dose.  If the Phase 1a MTD Cohort is to be expanded up to 12 
patients to more fully evaluate safety and tolerability at that dose level, accrual to Phase 2a may 
begin concurrent with accrual of the additional up to 6 patients to that cohort.  
6.6.3.2. 
Rules for Patient Population to be Treated in Phase 2a  
Patients will be accrued to 3 expansion cohorts in the Phase 2a portion of the study.  The tumor 
types to be evaluated in these expansion cohorts are mTNBC (~30 patients), SCCHN (~15 
patients), and Sq-NSCLC (~15 patients).   
Criteria for eligibility will be as described above with the additional requirement that patient 
tumors must have been documented to express EGFR by IHC* in a central laboratory.  Further, 
FFPE tumor tissue from either a prior procedure or a recent biopsy must be available for 
submission to a central laboratory for other study-related evaluations as planned per protocol. 
**DAKO EGFRpharmDX IHC kit system technology to be utilized.  For this study, EGFR-positive staining is 
defined as 3+ intensity in ≥ 50% of tumor cells or ≥ 2+ intensity in ≥ 75% of tumor cells for mTNBC; or 3+ 
intensity in ≥ 50% of tumor cells for SSCHN and Sq-NSCLC,, whether it is complete or incomplete circumferential 
staining.      


 
 
 
 
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6.6.3.3. 
Rules for Tolerability in Phase 2a 
The criteria for tolerability during Phase 1a will apply to Phase 2a Expansion Cohorts.  Safety 
will be reviewed on an ongoing basis to determine if the dose and schedule chosen based on the 
Phase 1a dose escalation is safe and well-tolerated in expanded populations of patients with the 
tumor types selected for the expansion cohorts (mTNBC, SCCHN, and Sq-NSCLC).  Should it 
be determined that the dose is not well-tolerated (i.e., > 33.3% of patients in an expansion cohort 
experience a Cycle 1 DLT), the safety of that dose level will be re-evaluated and the next lower 
dose with established tolerability in Phase 1a will be administered to subsequent patients.   
An exception will be the occurrence of toxicity suggesting organ damage (e.g., pulmonary 
fibrosis, drug-induced liver injury) occurring in > 2 patients within an expanded cohort, in which 
case further accrual to that cohort will be discontinued.   
 
Continued Therapy After Cycle 1 
Upon completion of Cycle 1, in the absence of unacceptable toxicity or disease progression, 
patients may continue receive additional cycles of study drug Q3W (± 2 days), unless further 
delay is required to allow for amelioration of toxicities.  Administration of subsequent dosing 
cycles is allowable at the discretion of the Investigator, provided the patient meets the 
retreatment criteria listed below.  Additional cycles should be initiated as soon as possible, but 
not longer than 2 weeks after the completion of the previous cycle, if feasible. 
6.7.1 
Retreatment Guidelines 
Clinical judgment will be used when determining whether it is advisable to continue a patient on 
to the next cycle(s) of dosing.  In order to start any new cycle a patient must meet the following 
criteria: 
 ANC > 1,000 per mm3 
 Platelets  > 75,000 per mm3 
 Any ongoing AEs should NOT meet the criteria for DLT. 
 Any ongoing AEs should have either ameliorated to < Grade 1 severity, returned to 
baseline status, or resolved, with the exceptions of Grade 2 alopecia, clinical events that 
are being adequately controlled with best supportive care (e.g., nausea, vomiting, 
diarrhea, fatigue), and asymptomatic laboratory abnormalities that are considered 
clinically insignificant or that are resolving with medical therapy. 
Should any one of the criteria above not be met, dosing of study drug must be delayed.  
6.7.2 
Doses and Regimens 
For a given patient, subsequent cycles of therapy with AVID100 will be administered at the same 
dose and infusion duration established for that patient during Cycle 1, and on the same schedule, 
unless dose reduction is necessary (or a dose adjustment is necessary due to ± 10% [less at the 
site’s discretion or if required by institution procedures] fluctuation in patient weight). 


 
 
 
 
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6.7.3 
Evaluation Schedules 
The same evaluations required during Cycle 1 of the study will be conducted during subsequent 
cycles, at the frequencies indicated (see Section 7; Study Assessments). 
6.7.4 
Duration of Treatment 
Additional cycles of AVID100 may continue to be administered if tolerated and in the absence of 
documented disease progression, at the Investigator’s discretion, provided retreatment criteria 
have been met (see Section 6.7.1; Retreatment Guidelines).   
Such extended therapy will continue for a period of up to 12 months after achieving the “best 
response,” at which time the Medical Monitor and Investigator will discuss the advisability of 
continued therapy based upon the patient’s ongoing response status and the degree of 
demonstrated tolerability. 
6.7.5 
Retreatment Following a Response 
Treatment with AVID100 may be restarted in a patient who: 
• Previously achieved a documented OR on this study, stopped treatment, and subsequently 
progresses, or   
• Discontinued therapy for a reason other than a DLT or PD, and in whom documented OR 
or prolonged SD is subsequently noted. 
Such action may be taken at the Investigator’s discretion, following discussion with the Medical 
Monitor, provided retreatment criteria are met, no anti-cancer treatment was administered since 
the last dose of AVID100, and the trial is still open.  This option for retreatment does not apply 
to patients who previously experienced an unacceptable toxicity that required permanent 
discontinuation of study drug (see Section 9.1 #1; Criteria for Treatment Discontinuation). 
Retreatment with AVID100 may be initiated at the same dose and infusion duration established 
for that patient during their previous course of treatment, and on the same schedule, unless dose 
reduction is necessary.  
The same evaluations required during previous treatment will be conducted during subsequent 
cycles, at the frequencies indicated. 
Retreatment cycles of AVID100 may continue to be administered if tolerated and in the absence 
of further disease progression, at the Investigator’s discretion, as long as retreatment criteria 
continue to be met. 
 
Toxicity and Dose Limiting Toxicity 
6.8.1 
Toxicity Grading 
The CTCAE Version 5.0*) will be used to grade AEs occurring during this study. 
*See < https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm > 


 
 
 
 
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6.8.2 
Toxicity Management and Dose Modification 
If a significant toxicity thought to be related to study drug is experienced at any point during the 
patient’s participation in the study, the Investigator will determine:   
 Whether that toxicity is dose-limiting (see Section 6.8.3; Definition of DLT), thus 
requiring either dose reduction or discontinuation from study; or  
 Whether the toxicity does not meet the protocol definition of DLT, but nevertheless 
warrants dose modification, in which case the Investigator may elect to either reduce the 
dose of study drug, or temporarily interrupt dosing with study drug, in order to allow for 
amelioration of the toxicity.   
For additional information on toxicity management and dose modification, see Section 8.1; 
Determination of DLT versus Non-DLT, and Section 8.3; Dose Modification Options. 
6.8.3 
Definition of DLT 
Any of the following toxicities, if judged to be associated with study drug (i.e., possibly related, 
probably related, or related), will be considered a DLT for the purposes of this trial.   
1. Evidence of pulmonary fibrosis, any grade (patient must be permanently discontinued) 
2. Grade 3 non-hematologic toxicity regardless of duration, with the exceptions of:  
• Grade 3 nausea, vomiting, diarrhea, or fatigue lasting < 2 days with best 
supportive care  
• Grade 3 asymptomatic electrolyte abnormalities that are not considered clinically 
significant by the Investigator and that are controlled with medical therapy  
3. AST and/or ALT elevation > 3 × ULN (or > 3 × baseline if elevated at study entry as 
allowed by study eligibility criteria; see Section 4.3.1 #7), with total bilirubin > 2 × ULN 
without initial findings of cholestasis (i.e., no elevation in serum alkaline phosphatase 
[ALP]), that cannot be explained by other factors  
4. Any Grade 4 non-hematologic toxicity with the exception of: 
• Grade 4 asymptomatic electrolyte abnormalities lasting < 7 days that are not 
considered clinically significant by the Investigator and that are controlled with 
medical therapy 
5. Neutropenia that is: 
• > Grade 3 and associated with fever (ANC < 1000 per mm3; temperature > 38.3ºC 
[101ºF] or a sustained temperature of > 38 ºC [100.4ºF] for > 1 hour ) (i.e., febrile 
neutropenia) 
• Grade 4 and sustained (ANC < 500 per mm3, duration > 5 days) 
6. Thrombocytopenia that is:  
• Grade 3 with clinically significant hemorrhage or requirement for transfusion 


 
 
 
 
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• Grade 4 (platelets < 25,000 per mm3)  
7. Inability to complete Cycle 1 at the assigned dose (i.e., receipt of < 1 full planned dose of 
study drug plus 3 weeks of follow-up due to > Grade 3 toxicity) 
8. Treatment delays > 2 weeks from the scheduled “next dose” due to > Grade 3 toxicity 
Other toxicities may be considered a DLT as determined by the Investigator in 
conjunction with the Medical Monitor. 
The above criteria will be used to make individual patient determinations regarding dose 
reductions, interruptions, or discontinuation throughout the course of the trial, but only those 
DLTs occurring during Cycle 1 will be used to make decisions regarding cohort dose escalation 
and tolerability.  
Events occurring after Cycle 1 will also be evaluated by the Investigator and Medical Monitor 
and taken into consideration when deciding upon further doses to be assessed as well as to 
establishment of the RP2D. 
 
Definition of Maximum Tolerated Dose 
The clinical endpoint of the Phase 1a portion of this trial is determination of the MTD of study 
drug that can be administered by the specified route, infusion duration, and schedule.  
MTD will be defined as the dose below that which produces, during Cycle 1 of treatment, any of 
the indicated DLTs either in > 1 patient in a 3 to 6 patient cohort, or in > 33.3%* of patients in 
the event of an expanded 7 to 12 patient cohort.  
*i.e., > 2 DLTs when 7 to 9 patients have been treated.   
The MTD will not be established until all patients entered into the cohort under evaluation have 
either completed Cycle 1 or discontinued further participation in the trial (or been dose-reduced) 
due to the occurrence of a DLT.   
Previously established tolerability of a dose level will be reevaluated if DLTs thought to be 
possibly related, probably related, or related to study drug are observed in later cycles. 
 
Review of Safety Data During Study 
The Investigator(s) and Sponsor's Medical Monitor(s) and Medical Representatives will 
comprise a Study Safety Committee, and will review clinical and laboratory safety data on an 
ongoing basis throughout the study and make decisions regarding the advisability of continuing 
accrual to a particular dose cohort, and/or escalating the dose and allowing accrual to a higher 
dose cohort.  In order to do so:   
• The following will be promptly reported to the Sponsor or designee: 
o Serious adverse events (SAEs), within 24 hours of Investigator awareness 
o AEs resulting in permanent discontinuation from study, regardless of seriousness 
or relationship to study drug  
o DLTs 


 
 
 
 
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o Dose modifications (i.e., dose reductions, temporary interruptions) 
• AEs will be recorded on the eCRF in a timely manner following a patient completing (or 
being discontinued from) each dosing cycle.  
• The Investigator will make critical laboratory safety data available a timely manner.    
• Patients will be carefully evaluated for evidence of all AEs, including potential 
cumulative and/or delayed toxicities, throughout the duration of their time on study.  
• During Phase 1a:  Biweekly safety teleconferences will be held between the 
Investigational Site(s) and the Sponsor and/or designee; frequency may fluctuate based 
on accrual and study activity, as indicated.  
• During Phase 2a:  Monthly safety teleconferences will be held between the 
Investigational Site(s) and the Sponsor and/or designee; frequency may fluctuate based 
on accrual and study activity, as indicated. 
Availability of these data also will enable the Sponsor (or designee) to notify regulatory 
authorities, as well as Investigators who may be participating at other sites or in other clinical 
trials of the study drug, of events occurring during the trial.  
 
Duration of Study Follow-Up 
Upon discontinuation of a patient from further treatment with study drug, follow-up assessments 
will be conducted as detailed below. 
• End of Treatment (EOT)* evaluations will be conducted within approximately 10 days 
following the decision to discontinue the patient from further treatment with study drug.   
• 1 Month Follow-up (1M FUP)* evaluations will be conducted approximately 30 days (+7 
days) following the last dose of study drug.  
Note: 
The 1M FUP evaluation should be conducted > 30 days following the last dose of study drug as all 
patients are to be followed for a minimum of 30 days after study drug discontinuation in order to 
monitor for the occurrence of suspected AEs that are both serious and unexpected.  See Section 
10.3; Documenting Adverse Events, Section 10.4; Reporting SAEs (Including Patient Deaths) and 
Unexpected AEs, and Section 10.5; Required Follow-up of all AEs and SAEs.   
 
*Given the Q3W dosing frequency, EOT and 1M FUP evaluations may be combined in those 
situations where scheduling coincides, provided a minimum of 30 days of post-dosing follow-up 
have been observed.   
• If an observed toxicity thought to be associated with study drug has not resolved by the 
1M FUP evaluation, an additional follow-up AE assessment will be conducted 
approximately 3 months following the last dose of study drug, if feasible, in order to 
confirm that the event has either resolved, returned to baseline status, or been adequately 
explained and assessed by the Investigator as chronic and/or stable, and that no longer 


 
 
 
 
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term deleterious effects have become evident.*   Follow-up may be repeated 
approximately 6 months following the last dose of study drug, if indicated.   
Any patient who develops pulmonary fibrosis will be followed at approximately 3 month 
intervals for up to 2 years to assess the course of the disease and evaluate potential 
reversibility of this finding. 
In addition, the occurrence of any significant post-therapy event thought to be associated 
with study drug must be reported to the Sponsor (or designee). 
*To confirm that events have resolved, returned to baseline status, or been adequately explained.  
Investigator discretion may be used with respect to the method of contact for this AE assessment; clinical 
events may be followed in writing or by telephone (and documented in writing); an in-person visit will not 
be required. 
• In the event of an ongoing OR or disease stabilization at the EOT, response assessments* 
based on tumor marker and imaging studies (as indicated by disease type) will continue 
to be performed every 3 months during the first year and every 6 months thereafter, until 
disease progression or another therapeutic intervention is initiated, so that data may be 
collected on the duration of stabilization or response, as well as on the overall time to 
disease progression.   
*To continue at the intervals specified until disease progression or another therapeutic intervention is 
initiated; documentation may be submitted in writing; an in-person visit will not be required. 
 
Concurrent Treatments and Supportive Care 
Therapy for other ongoing medical conditions, as well as palliative and supportive care for the 
underlying malignancy will be provided prior to and during this trial, as clinically indicated, and 
in accordance with the standard practices of the institution, except as stipulated by study 
eligibility criteria (see Section 4.3.2; Drugs and Other Treatments to be Excluded). 
Other therapies allowed during the conduct of this trial include: 
• Prophylaxis for Study Drug-Related Toxicities:  Beginning with the first dose, all patients 
must be premedicated with standard therapies prior to each dose of AVID100 to reduce 
the risk of IRRs.  Patients experiencing other study drug-associated reactions may be 
premedicated with standard therapies in order to reduce the potential for such reactions in 
the future. 
• Treatment of Study Drug-Related Toxicities:   Clinical judgment should be used in the 
treatment of any AE that occurs during the study and follow-up period.  
• Treatment of Concurrent Diseases:  Preexisting/concurrent diseases or conditions should 
be managed and treated as clinically appropriate. 
• Blood Products and Growth Factors:  Prophylactic hematopoietic growth factors should 
not be administered during Cycle 1 of study; thereafter prophylactic use of growth factors 
is allowed as clinically indicated.  Interventional/therapeutic use of growth factors is 
allowed during study, including Cycle 1, if deemed necessary by the Investigator.  
Growth factor use must be consistent with product package insert instructions. 
Transfusions are permitted as needed during study.  


 
 
 
 
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• Radiotherapy:  Radiotherapy for pain control against non-target lesions, as long as it does 
not influence bone marrow function.  Patients requiring radiation therapy during study for 
pain management of non-target lesions may have their participation temporarily 
interrupted, at the Investigator’s discretion.  Such treatment should be discussed with the 
Sponsor’s Medical Monitor(s). Patients with suspected new lesions requiring pain 
management should be treated and evaluated for potential PD.  Patients requiring 
palliative radiotherapy to target lesions during study will be discontinued. 
• Bisphosphonates and denosumab:  Bisphosphonates and denosumab for bone metastases 
and other skeletal conditions are allowed, provided the patient is on a stable dose for at 
least 4 weeks prior to study start and remains on the stable dose while receiving study 
treatment. 
• Immunosuppressive or systemic hormonal therapy not exceeding 10 mg daily prednisone 
or equivalent, as well as: 
o Hormonal therapy for appetite stimulation (e.g., Megace) 
o Nasal, ophthalmic, inhaled, and topical glucocorticoid preparations 
o Oral replacement glucocorticoid therapy for adrenal insufficiency 
o Stable hormonal therapy for prostate carcinoma* 
o Stable hormonal therapy for ovarian suppression* 
o Steroid therapy for contrast reaction prophylaxis 
o Low-dose maintenance steroid therapy for other conditions (e.g., stable steroid 
therapy [excluding tapering dose of steroids] for brain 
edema/metastases/radiation) 
o Hormonal contraceptive therapy (in WOCBP must be combined with non-
hormonal contraceptive equivalent to a double-barrier method) 
o Postmenopausal hormone replacement therapy (HRT) 
o Intra-articular steroid injections 
o Higher dose steroid therapy for treatment of an acute intercurrent illness in 
patients with stable disease or an ongoing response.  In such situations, study drug 
treatment should be interrupted for the duration of immunosuppressive therapy 
*Prior or concomitant therapies are permitted, however, patients must have been on a stable dose for 
at least 6 months prior to study start, and if continuing must remain on the stable dose while receiving 
study treatment (i.e., such treatment will not be considered as systemic hormonal therapy for the 
purpose of study eligibility). 
• Meals and Dietary Requirements:  Patients should maintain a normal diet unless 
modifications are required to manage an AE such as diarrhea, nausea, or vomiting. 
• Surgical Procedures:  Patients requiring a minor surgical procedure (e.g., port placement, 
stent placement, skin abscess drainage) may undergo such a procedure at the 
Investigator’s discretion following discussion with the Sponsor's Medical Monitor(s) or 
designee. A brief interruption in therapy may be considered.  


 
 
 
 
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Patients requiring a more extensive or major surgical procedure (e.g., resection of hepatic 
metastases) should have protocol therapy interrupted, but may resume treatment once 
fully recovered and at a minimum 2 weeks after the procedure.  Protocol retreatment 
criteria must be met. 
• Allowed Dosing Delays:  Following Cycle 1 and completion of the DLT assessment 
period, and only if indicated, dosing may be briefly interrupted for situations other than 
treatment-related AEs such as medical (or surgical events) or logistical reasons not 
related to study therapy. Participants should be placed back on study therapy within 2 to 3 
weeks of the scheduled interruption, unless otherwise discussed with the Sponsor. 
 
Information on all concomitant therapies administered, as well as other interventions or 
procedures occurring during the trial period, must be recorded on the appropriate page of the 
patient’s eCRF. 
 


 
 
 
 
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7. 
STUDY ASSESSMENTS   
All patients will be assessed by scheduled clinical, laboratory, and other diagnostic assessments 
throughout the study.   
All efforts should be made to perform assessments as close as possible to the scheduled time 
points. The projection of visit days within each cycle should be made from Day 1 of the 
respective cycle.  Visit windows are provided below.  Study assessments are to be performed as 
follows: 
• Screening evaluations are to be performed within 14 days prior to first study drug dose, 
unless otherwise specified (for exceptions see Section 7.2.11; Pregnancy Testing, Section 
7.4; Disease Assessments).   
• The day of first administration of study drug will be considered Day 1 of study.   
• Cycle 1/Day 4 evaluations may be conducted ± 1 day 
• Dosing and on-study evaluations (including laboratory assessments) are to be performed 
on or about the indicated study day (i.e., ± 2 working days) (a slightly longer allowance 
for routine assessments is permissible in the event of scheduling difficulties associated 
with weekends, holidays, etc.).   
• End of Cycle assessments may be conducted at any time during the week prior to Day 1 
of the next cycle, including on Day 1 of the next cycle, prior to dosing. 
• End of Treatment (EOT)* evaluations are to be performed within approximately 10 days 
following the decision to discontinue treatment, or before initiation of a new treatment, 
whichever occurs first.   
• 1 Month Follow-up (1M FUP)* evaluations are to be performed approximately 30 days 
(+7 days) following the last dose of study drug (i.e., as all patients are to be followed for 
a minimum of 30 days after study drug discontinuation in order to monitor for the 
occurrence of AEs). 
*Given the Q3W dosing frequency, EOT and 1M FUP evaluations may be combined in those situations 
where scheduling coincides, provided a minimum of 30 days of post-dosing follow-up have been observed.   
Note:  
When a patient discontinues treatment with study drug, for any reason, every effort will be made 
to collect routine EOT evaluations as well as subsequent 1M FUP evaluations, per protocol, until 
all protocol-specified assessments have been conducted.   
If, during the course of the study, significant changes from baseline are noted, additional 
monitoring or on-study assessments may be undertaken by the Investigator, or requested by the 
Sponsor (or designee), in order to determine both the relevance of the finding(s) and the duration 
of the event(s).   


 
 
 
 
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Consent and Medical History 
7.1.1 
Signing of Informed Consent/Assessment of Eligibility 
• Screening 
Note:  
All patients must sign an IRB-approved informed consent form (ICF) prior to 
enrollment and prior to submitting to any protocol-related procedure, unless such 
testing was performed previously as part of the routine clinical management of the 
patient.  Disease evaluations [e.g., CT scan, MRI] performed as part of standard of 
care and obtained prior to patient consent for this trial may be allowed as screening 
evaluations if conducted within 28 days (+2d) prior to the first study drug dose.  A 
copy of the fully executed ICF will be given to the patient.   
7.1.2 
Past Medical History  
(To include demographic information, prior and ongoing medical illnesses 
and conditions, prior surgical procedures [not related to the primary 
diagnosis], smoking history) 
• Screening 
7.1.3 
History of the Primary Malignancy  
(To include details of the primary malignancy, including:  
histological/cytological classification; stage of disease at diagnosis and at 
entry;  prior surgical procedures for the malignancy;  prior antineoplastic 
therapy, prior radiation therapy, as well as dates of treatments, numbers of 
cycles, and best response to each therapy.) 
• Screening 
 
Safety Assessments (1)  
(To be performed within 14 days prior to first dose of study drug unless otherwise specified) 
7.2.1 
Medication Survey  
(To include indication for use; corresponding illness or condition must appear 
on the Medical History pages of the eCRF) 
• Prior Medication Survey 
o Screening (to assess eligibility) 
o For a period of 14 days prior to first study drug dose  
• Concomitant Medication Survey (excluding study drug) 
o Throughout the study 
o For a period of 30 days following last study drug dose 


 
 
 
 
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7.2.2 
Adverse Event Assessment  
• Prior to first study drug dose*  
• Throughout the study 
• For the period of 30 days following last study drug dose  
• For the period of 3 to 6 months following last study drug dose, if events 
associated with study drug persist**   
• For the period of up to 2 years in the event of pulmonary fibrosis*** 
• As clinically indicated 
*To detail any symptoms that may be present prior to first study drug dose beginning from 
date of enrollment 
**To confirm that events have resolved, returned to baseline status, or been adequately 
explained.  Investigator discretion may be used with respect to the method of contact for this 
AE assessment; clinical events may be followed in writing or by telephone (and documented 
in writing); an in-person visit will not be required. 
***Any patient who develops pulmonary fibrosis will be followed at approximately 3 month 
intervals for up to 2 years to assess the course of the disease and evaluate potential 
reversibility of this finding. 
7.2.3 
Performance Status Evaluation 
(To be assessed by ECOG score; see Appendix B; Performance Status 
Evaluation) 
• Screening 
• Cycle 1 
o Day 1* 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
• EOT  
• 1M FUP 
• As clinically indicated 
*Need not be assessed prior to Cycle 1 if ≤ 7 days since screening 
7.2.4 
Vital Signs  
(Vital signs [VS] to include temperature, pulse, respiratory rate, blood 
pressure[BP], and oxygen saturation by pulse oximetry) 
Phase 1a Dose-Escalation Cohorts 
• Screening 
• Cycle 1 
o Day 1 
 Prior to SOI 
 EOI (± 5 min)  


 
 
 
 
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 2 and 4 hours after EOI (± 15 min)  
o Day 2 
o Day 4 (± 1 day) 
• Each cycle thereafter 
o Day 1  
• EOT  
• 1M FUP 
• As clinically indicated 
Phase 2a Expansion Cohorts  
• Screening 
• Cycle 1 
o Day 1 
 Prior to SOI 
 EOI (± 5 min) 
• Each cycle thereafter 
o Day 1  
 EOT  
 1M FUP 
 As clinically indicated 
*SOI-Start of Infusion; EOI-End of Infusion 
**Comprehensive assessment of vital signs is critical to the conduct of this study.  In 
situations where an assessment at 4h after EOI is logistically difficult due to clinic staff 
availability, the observation period may be shortened, and an "end of day" assessment may be 
obtained at the latest practical time.  Such an option is available ONLY after previous 
discussion with and approval by the Sponsor. 
7.2.5 
Physical Examination  
(Complete at screening including height, weight, general appearance, skin, 
ears, eyes, nose, throat, neck/thyroid, chest, heart, abdomen, musculoskeletal 
system, peripheral pulses, lymph nodes, neurologic and mental status; 
directed thereafter, must include weight** and pulmonary assessment*** at 
each visit) 
• Screening 
• Cycle 1 
o Day 1* 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
• EOT  


 
 
 
 
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• 1M FUP 
• As clinically indicated 
* Need not be assessed prior to Cycle 1 if  ≤ 7 days since screening 
** Dose adjustments may be made in the event of noted weight change (± 10% [less at the 
site’s discretion or if required by institution procedures]).   
*** Pulmonary findings will be evaluated in detail at each visit by the PI (or physician 
designee); evaluation to include review of pulmonary symptoms including but not limited to: 
cough, sputum production, hemoptysis, wheezing, dyspnea, dyspnea on exertion, chest pain, 
and/or chest pain associated with respirations. 
Note:  See Appendix H (Recommendations for Management of Keratitis and Rash) for dose 
modification instructions for rash 
7.2.6 
Hematology Panel  
(To include complete blood count [CBC] with differential, ANC, and platelet 
count) 
• Screening 
• Cycle 1 
o Day 1* 
o Day 4 (± 1 day) 
o Day 8 
• Each cycle thereafter 
o 
Day 1 (prior to dosing) 
o 
Day 8 
• EOT  
• 1M FUP 
• As clinically indicated**   
*Need not be performed prior to the first dose of Cycle 1 if  ≤ 7 days since screening 
**In the event of hematologic toxicity, the evaluation frequency should be increased to 
include additional evaluations between the scheduled assessments, as clinically indicated. 
7.2.7 
Serum Chemistry Panel  
(To include Na, K, Cl, bicarbonate or carbon dioxide, BUN, creatinine, 
glucose, bilirubin [total and direct], AST, ALT,  alkaline phosphatase, Ca, 
Mg, phosphorus, albumin, total protein, uric acid, amylase, lipase, and 
creatine kinase[CK]***) 
• Screening 
• Cycle 1 
o Day 1* 
o Day 4 (± 1 day) 


 
 
 
 
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o Day 8 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
o Day 8 
• EOT  
• 1M FUP 
• As clinically indicated**   
*Need not be performed prior to the first dose of Cycle 1 if  ≤ 7 days since screening 
**In the event of significant serum chemistry abnormalities, the evaluation frequency should 
be increased to include additional evaluations between the scheduled assessments, as 
clinically indicated. Clinically significant electrolyte abnormalities should be corrected prior 
to dosing. 
***In the event of CK abnormalities while on study, please perform isoenzyme analysis 
7.2.8 
Coagulation Panel 
(To include PTT [or aPTT], PT and/or INR) 
• Screening 
• Cycle 1 
o Day 1* 
o Day 4 (± 1 day) 
o Day 8 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
o Day 8 
• EOT  
• 1M FUP  
• As clinically indicated   
*Need not be performed prior to the first dose of Cycle 1 if  ≤ 7 days since screening 
7.2.9 
Urinalysis   
(Multipanel chemical test strips are acceptable and should include assessment 
of:  specific gravity, pH, protein, glucose, ketones, leukocyte esterase, nitrite, 
bilirubin, urobilinogen, and occult blood; include microscopic sediment 
evaluation if clinically indicated if gross findings are abnormal, including 
white blood cells [WBC] per high power field [hpf] and RBC per /hpf) 
• Screening 
• Cycle 1 
o Day 1* 
o Day 4 (± 1 day) 


 
 
 
 
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o Day 8 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
o Day 8 
• EOT  
• 1M FUP  
• As clinically indicated   
*Need not be performed prior to the first dose of Cycle 1 if  ≤ 7 days since screening 
7.2.10 
Anti-Drug Antibody (ADA) to AVID100  (Central Lab) 
(To assess the potential immunogenicity of AVID100; serum to be isolated; 
residual sample material may be used for biomarker assessments (Section 
7.6.2)) 
• Cycle 1 
o Day 1 (prior to SOI) 
• Each cycle thereafter 
o Day 1 (prior to dosing) 
• EOT 
• 1M FUP 
• As clinically indicated in the event of an IRR 
Note: 
Whole blood (~ 5 mL) to be collected in serum acquisition tubes at each of the 
indicated timepoints (see also Appendix A; Schedules of Events).  In the event that a 
collected serum sample is inadequate or insufficient for ADA analysis, the analysis 
of ADA can be done using a PK serum sample from the same time point, if 
available. 
Detailed procedures for collection, handling, and shipment of samples will be 
provided by the Sponsor (or designee) in the study Laboratory Manual (or other 
similar document). 
7.2.11 
Pregnancy Testing  
(beta-human chorionic gonadotropin [β-hCG] in WOCBP; serum at 
screening, urine or serum thereafter; negative test must be confirmed within 2 
working days prior to first dose of  study drug) 
• Screening  
• Cycle 1 
o Day 1 (within ≤ 2 working days of dosing) 
• EOT 
• As clinically indicated 


 
 
 
 
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7.2.12 
Electrocardiogram  
(To include standard 12-lead ECG with measurement of PR interval, QRS 
duration, QT interval, and QTc interval [msec], as well as heart rate [BPM]) 
(To be evaluated locally; to be performed after patient has been supine for ≥ 
10 minutes)  (Repeat subsequent time points in triplicate separated by 5 
minutes for 4 cycles in patients with a QTc that is either: a) > 500 msec; b) 
increased by 60 msec over baseline*; or c) decreased by 20 msec under 
baseline*)  
• Screening  
• Cycle 1  
o Day 1 
 Prior to SOI 
 EOI (± 5 min) 
 30 minutes after EOI (± 5 min) 
• Subsequent 4 cycles, if QTc abnormalities are observed during Cycle 1  
o Day 1 
 Prior to SOI (in triplicate) 
 EOI (± 5 min) (in triplicate) 
• EOT 
• As clinically indicated** 
*When evaluating QTc, baseline should be considered the ECG immediate preceding the start 
of study drug infusion on the day of assessment.   
**In the event of significant electrolyte abnormalities, the evaluation frequency should be 
increased to include additional evaluations between the scheduled assessments, as clinically 
indicated.   
 
Safety Assessments (2) 
(To be performed within 28 days [+2 days] prior to first dose of study drug, provided no 
antineoplastic therapy has been delivered between safety assessment and first dose of study 
drug) 
7.3.1 
Ophthalmology Examination 
(To include slit lamp evaluation, tests to evaluate corneal integrity and visual 
acuity assessment) 
• Screening 
• End of Cycle 2*,** 
• EOT** 
• As clinically indicated 
*End of Cycle assessments may be conducted at any time during the week prior to Day 1 of 
the next cycle. 


 
 
 
 
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**May be combined if patient discontinues treatment at End of Cycle 2 
Note:  See Appendix H (Recommendations for Management of Keratitis and Rash) for dose 
modification instructions for keratitis (corneal inflammation/ulceration) 
7.3.2 
MUGA Scan or Echocardiogram 
(For measurement of LVEF; to be performed ONLY in patients with a history 
of CHF; individual patients should be followed with the same testing 
procedure throughout the study)    
• Screening 
• EOT 
• As clinically indicated 
Note:  
Assessment of LVEF will not be performed routinely in all patients.  Patients with a 
history of CHF will have either a MUGA scan or echocardiogram at Screening. 
7.3.3 
Pulmonary Function Testing 
(PTF to include spirometry and diffusing capacity [DLCO] to assess for 
evidence of pulmonary fibrosis.  Spirometry assessments are to include but 
are not limited to:  forced vital capacity [FVC], forced expiratory volume in 1 
second [FEV1], forced expiratory flow 25% to 75% [FEF25-75], functional 
residual capacity [FRC], residual volume [RV], and total lung capacity 
[TLC].) 
• Screening 
• EOT 
• As clinically indicated 
7.3.4 
Chest Radiography 
(To include posterior to anterior[PA] and lateral views of the chest to assess 
for evidence of pulmonary fibrosis)    
• Screening 
• EOT 
• As clinically indicated 
Note:  
Diagnostic imaging (CT/MRI) being conducted to for Assessment of Disease will be 
utilized to assess for evidence of pulmonary fibrosis while patients are on (see 
Section 7.4.3; Diagnostic Imaging for Assessment of Disease (and Pulmonary 
Status).     
 
Disease Assessments  
(Screening assessments to be performed within 28 days (+ 2 days) prior to first study drug dose)  


 
 
 
 
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7.4.1 
EGFR Tumor Status Determination   
(To include assessment of FFPE tumor tissue; by local or central evaluation 
of archival tissue or verification by previous pathology report during Phase 
1a and by central evaluation of tumor tissue [archival or from a recent 
biopsy] during Phase 2a) 
Phase 1a Dose-Escalation Cohorts:  Optional (Local or Central Lab)   
Phase 2a Expansion Cohorts:  Required (Central Lab); tumor must be EGFR-
positive by IHC as specified* for patient to be eligible for enrollment.  If 
archival tissue is not available patient must be willing to undergo pre-dosing 
biopsy from a primary or metastatic tumor site** 
• Screening*** 
• Post-dosing: Upon request of the Sponsor based on other study findings, 
after discussion with the Investigator; if available a request may be made 
for collection of additional archival tissue for exploratory biomarker 
assessments (Section 7.6.1):  Optional 
* DAKO EGFRpharmDX IHC kit system technology to be utilized.  For this study, EGFR-
positive staining is defined as ≥ 3+ intensity in ≥ 50% of tumor cells or ≥ 2+ intensity in ≥ 
75% of tumor cells for mTNBC; or 3+ intensity in ≥ 50% of tumor cells for SSCHN and Sq-
NSCLC, whether it is complete or incomplete circumferential staining.   
**Sufficient  FFPE tissue must also be available for submission to a central analytical 
laboratory for other study-related evaluations (see Section7.6.1; Exploratory EGFR Studies 
in Tumor Tissue). 
***The trial will prescreen patients for EGFR Tumor Status Determination before entering 
patients into screening for the treatment portion of the trial.  The site should use a separate 
prescreening informed consent form.  Prescreening may be performed outside the 28 (+ 2) 
day screening period to allow adequate turnaround time for receipt of results, provided 
separate informed consent has been obtained. 
7.4.2 
Tumor Marker Measurement (Phase 1a only) 
(As indicated by tumor type) 
• Screening 
• End of Cycle 2 (and every even-numbered cycle thereafter)* 
• At least 4 weeks following documentation of an OR 
• EOT (if > 6 weeks since previous assessment) 
• 1M FUP (if PD was not documented before or at EOT) 
• Extended Follow-up** (in the event of an ongoing OR or SD at EOT) 
o Every 3 months during the first year of follow-up 
o Every 6 months thereafter 
*End of Cycle assessments may be conducted at any time during the week prior to Day 1 of 
the next cycle. 


 
 
 
 
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**To continue at the intervals specified until disease progression or another therapeutic 
intervention is initiated; documentation may be submitted in writing, an in-person visit will 
not be required. 
7.4.3 
Diagnostic Imaging for Assessment of Disease (and Pulmonary Status)  
(To include diagnostic imaging by computerized tomography [CT] or 
magnetic resonance imaging [MRI] of the chest with each evaluation (for 
disease evaluation where indicated, and to assess for evidence of pulmonary 
fibrosis) plus abdomen and pelvis, and other sites as indicated based on tumor 
type and clinical judgment in order to assess the status of the underlying 
malignancy.  Use of contrast is preferred but is at the discretion of the 
Investigator, as medically indicated.   
The same method(s) of disease evaluation and the same technique should be 
used throughout the study. The location and dimensions of “marker” lesions, 
where such information is available, will be documented on the patient’s 
eCRF.     Standard response criteria will be applied for disease assessments 
and response evaluations [see Appendix F; Measurement of Effect]). 
• Screening 
• End of Cycle 2 (and every even-numbered cycle thereafter)* 
• At least 4 weeks following documentation of an OR 
• EOT (if > 6 weeks since previous assessment) 
• 1M FUP (if PD was not documented before or at EOT) 
• Extended Follow-up** (in the event of an ongoing OR or SD at EOT) 
o Every 3 months during the first year of follow-up 
o Every 6 months thereafter 
*End of Cycle assessments may be conducted at any time during the week prior to Day 1 of 
the next cycle. 
**To continue at the intervals specified until disease progression or another therapeutic 
intervention is initiated; documentation may be submitted in writing, an in-person visit will 
not be required. 
If PD is documented at any time no further disease assessments will be 
required.  Patients with documented PD will be discontinued from further 
treatment with study drug so that alternative management of their malignancy 
may be considered. 
To be assigned a status of partial response (PR) or complete response (CR), 
changes in disease status must be confirmed by repeat studies performed 4 
weeks (+ 7 days) after the criteria for response are first met.  In the case of 
SD, follow-up measurements must have met the SD criteria at least once after 
study entry at for a minimum duration in general not less than 8 weeks.   


 
 
 
 
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In the event of an ongoing OR or SD at the EOT, data will continue to be 
collected on the duration of OR or SD, as well as on the overall time to PD.   
Imaging data (imaging studies and derived assessments) will be stored 
according to usual practice by the sites and will be available upon request 
for potential review by the Sponsor or an independent radiology reviewer.  
7.4.4 
Response Assessment 
(The anti-tumor activity of study drug will be assessed by the Investigator or 
qualified designee according to RECIST v1.1 at the intervals specified) 
• End of Cycle 2 (and every even-numbered cycle thereafter)* 
• At least 4 weeks following documentation of an OR 
• EOT (if > 6 weeks since previous assessment) 
• Extended Follow-up** (in the event of an ongoing OR or SD at EOT) 
o Every 3 months during the first year of follow-up 
o Every 6 months thereafter 
*End of Cycle assessments may be conducted at any time during the week prior to Day 1 of 
the next cycle. 
**Continue at the intervals specified until disease progression or another therapeutic 
intervention is initiated. 
 
Pharmacokinetic Assessments  
Every effort will be made to collect PK samples at the timepoints specified.  Sampling times may 
be adjusted according to early trial results in order to optimize evaluation.  No additional samples 
will be collected without formal amendment to this protocol.  Residual sample material may be 
used for biomarker assessments (Section 7.6.2). Detailed procedures for collection, handling, 
and shipment of samples will be provided by the Sponsor (or designee) in the study Laboratory 
Manual (or other similar document). (see also Appendix A; Schedules of Events). 
7.5.1 
Peripheral Blood Collection (Central Lab)  
(Samples will be evaluated for concentrations of total antibody [AVID100 
plus MAB100], AVID100, and DM1; to include assessment of PK parameters 
such as Cmax, Tmax, AUC, etc.; serum to be isolated) 
Phase 1a Dose-Escalation Cohorts  
• Cycle 1 
o Day 1 
 Prior to SOI 
 EOI (± 5 min)  
 2 and 4 hours after EOI (± 15 min)  
o Day 2 
 24 hours after EOI (± 1 h) 


 
 
 
 
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o Day 4 (± 1 day) 
 At time of visit 
o Day 8  
  At time of visit 
• Cycle 2 
o Day 1  
 Prior to SOI  
 EOI (± 5 min) 
o Day 8  
 At time of visit 
• Each cycle thereafter 
o Day 1  
 Prior to SOI 
• EOI (± 5 min)EOT 
• 1M FUP 
• As clinically indicated in the event of an IRR 
Phase 2a Expansion Cohorts  
• Cycle 1 and Cycle 5 
o Day 1 
 Prior to SOI 
 EOI (± 5 min) 
o Day 8 
 At time of visit 
• Each other cycle  
o Day 1  
 Prior to SOI 
• EOT 
• 1M FUP 
• As clinically indicated in the event of an IRR 
*Comprehensive collection of clinical samples is critical to the conduct of this study.  In 
situations where collection of a 4h after EOI sample is logistically difficult due to clinic staff 
availability, the observation period may be shortened, and an "end of day" sample may be 
obtained at the latest practical time.  Such an option is available ONLY after previous 
discussion with and approval by the Sponsor. 
Note: 
Whole blood (~ 5 mL) to be collected in serum acquisition tubes at each of the 
indicated timepoints. In the event that a collected serum sample is inadequate or 
insufficient for PK analysis, the analysis of PK can be done using an anti-drug 
antibody (ADA) serum sample from the same time point, if available.  


 
 
 
 
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Biomarker Assessments  
To assess potential biomarkers and response predictors; every effort will be made to collect 
samples as specified.  Detailed procedures for collection, handling, and shipment of samples will 
be provided by the Sponsor (or designee) in the study Laboratory Manual (or other similar 
document) (see also Appendix A; Schedules of Events). 
All analyses will be related to and used only in connection with the data collected in the present 
trial and the identity of the patient will remain confidential.  The analyses will not have any 
medical consequences for the patient or their relatives  
7.6.1 
Exploratory Studies in Tumor Tissue (Central Lab) 
(For assessment of tumor EGFR-expression by FISH (or similar assay) and 
other potential biomarkers in submitted FFPE tumor tissue 
Phase 1a Dose-Escalation Cohorts:  Optional   
Phase 2a Expansion Cohorts:   
• Screening:  Required*; if archival tissue is not available patient must be 
willing to undergo pre-dosing biopsy from a primary or metastatic tumor 
site 
• Post-dosing:  If tumor tissue is available from an interval surgery 
performed during study participation :  Optional 
• Post-dosing:  In the event of a documented objective response if the 
patient has accessible residual tumor; in the event of prolonged disease 
stabilization > 8 weeks:  Optional 
• Post-dosing:  Upon request of the Sponsor based on other study findings, 
after discussion with the Investigator:  Optional 
*To be performed in tumor tissue submitted for eligibility (see Section 7.4.1; 
EGFR Tumor Status Determination by IHC).  It must be ensured that the 
archived tissue is sufficient and can be made available to the central 
analytical laboratory prior to deciding to omit a tumor biopsy procedure at 
the time of screening.  If available a request may be made for collection of 
additional archival tissue for exploratory biomarker assessments; such a 
request would be made post-dosing based on other study findings, after 
discussion with the Investigator. 
Biopsies are permissible in Phase 1a cohorts in consenting patients, on a 
case-by-case basis, if considered safe and following discussion between the 
Investigator and the Sponsor’s Medical Monitor. 
Note:  Archival FFPE material, either block tissue samples of the patient’s primary tumor, or 
slides cut from the paraffin block(s) will be submitted.  Unused portions of paraffin 
blocks will be returned to the referring institution.  Tumor specimens should be 
identified only by the patient’s study identifier, surgical pathology and/or histology 


 
 
 
 
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accession numbers.  Identifiers, such as patient names, and government-issued 
identifiers, such as social security numbers, should not be recorded in order to ensure 
confidentiality.  Samples will be kept until used up, or stored for up to 15 years after 
completion of the trial where after all remaining samples will be destroyed.  Samples 
will be used for Forbius research purposes only. 
If required, pre-dosing biopsy is to be performed on a primary, recurrent, or metastatic 
lesion after eligibility has otherwise been confirmed and prior to the first AVID100 
administration. The tumor biopsy must be conducted with minimal morbidity to the 
patient by a percutaneous core needle biopsy either with or without the aid of an 
imaging modality chosen at the discretion of the physician performing the biopsy. 
Specimens should be obtained using standard sterile surgical techniques and formalin-
fixed, paraffin-embedded according to standard laboratory techniques.  All tumor tissue 
samples should be reviewed by a pathologist to confirm the presence of tumor cells 
before the tissue sample (block or slides) is sent to the central laboratory for analysis. 
 
7.6.2 
Exploratory Studies in Peripheral Blood (Central Lab)  
(For, but not limited to, assessment of EGFR ctDNA for EGFR-ECD mutation 
status and EGFRvIII deletions (SCCHN only), as well as assessment of other 
potential biomarkers of interest (required for all indications); may be 
obtained for submission any time after confirmation of eligibility and study 
enrollment but prior to dosing on C1/D1) 
• Screening 
• EOT 
• As indicated (ONLY if using residual material available from ADA and 
PK samplings; no additional blood to be drawn)  
Note: 
  Whole blood (~ 20 mL) to be collected;  


 
 
 
 
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8. 
MANAGEMENT OF TOXICITY 
Comprehensive assessments of any toxicity experienced by the patient will be performed 
throughout the course of this study.  The Principal Investigator, Subinvestigator, or designated 
health professional must be available throughout the course of the study in order to evaluate and 
treat any AE(s), as well as to evaluate whether continued participation in the trial is warranted or 
advisable.  
Anticipated toxicities are detailed in this protocol (see Section 2.4; Rationale for and Risks of 
Proposed Clinical Study, and Section 11; Precautions when Dosing with AVID100), as well as 
in the IB.  Patients will be evaluated throughout the trial for evidence of acute as well as delayed 
and/or cumulative toxicities. Significant changes in a patient’s clinical status or laboratory 
assessments will be followed until the abnormality either resolves, returns to baseline status, or is 
adequately explained and assessed by the Investigator as chronic and/or stable, and that no 
longer term deleterious effects have become evident.   
Grades of toxicity (CTCAE v5.0), as well as clinical judgment, will be used to determine 
appropriate management of the patient experiencing any AE while participating in this study, 
including determining whether the toxicity warrants premedication (Section 8.2.2, Section 8.2.3) 
or a dose modification option such as infusion prolongation (in the event of an IRR) (Section 
8.3.1), temporary dose delay (Section 8.3.2), or dose reduction (Section 8.3.3).  AEs requiring 
discontinuation from study treatment are detailed in Section 9.1. 
 
Determination of DLT versus Non-DLT 
When an AE occurs, the Investigator will also determine whether the protocol definition of a 
DLT is met (Section 6.8.3).  If so, the patient will be either discontinued from treatment or may 
continue treatment if there is evidence of an OR, SD, or other clinical benefit, but must do so at a 
reduced dose of study drug, and ONLY following discussion with the Sponsor’s Medical 
Monitor(s).  Patients may not be retreated following the occurrence of a DLT until retreatment 
criteria have been met (Section 6.7.1).   
Alternatively, the Investigator may determine that the toxicity does not meet the protocol 
definition for DLT, but nevertheless warrants dose modification, because it is: 
• 
Not controlled by optimal supportive care, or 
• 
Not tolerated due to symptomatology or interference with normal daily activities 
For toxicity that does not meet the protocol definition of DLT, the Investigator may, as described 
below, elect to prolong the infusion duration (for IRRs), reduce the dose of study drug, and/or 
temporarily delay dosing with study drug in order to allow for amelioration of the toxicity. 
 
Premedication for Study Drug-Related Toxicities 
8.2.1 
Infusion-Related Reactions 
An IRR is defined as an AE occurring during the study drug infusion and up to 24 hours after the 
end of infusion (EOI), which is assessed by the Investigator to be related to the infusion. Signs of 


 
 
 
 
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IRRs may include but are not limited to facial flushing and swelling, headache, nausea, 
dizziness, anxiety, diaphoresis, tachycardia, hypotension, fever, chills/rigors, chest and throat 
tightness, shortness of breath, wheezing, bronchospasm, as well as chest, back and/or abdominal 
pain or discomfort. 
If an IRR occurs, it should be classified according to the CTCAE (v5.0). Recommended 
management guidelines are provided (see Appendix G: Grading and Management of Infusion 
Reactions).  
8.2.2 
Premedication for IRRs 
Beginning with the first dose, all patients must be premedicated with standard therapies prior to 
each dose of AVID100 to reduce the risk of infusion-related reactions (IRRs).   
The recommended premedication regimen to be administered prior to each study drug infusion, 
beginning with the dose to be delivered on Day 1 of study, is as follows (TABLE 3): 
 TABLE 3:  RECOMMENDED PREMEDICATION REGIMEN  
 
Medication 
 
Dose and Route 
 
Alternative 
Medication 
Dose and Route 
 
1 
dexamethasone* 
10 mg p.o. (12h prior ± 2h) 
 
 
10 mg p.o. (6 h prior ± 2h) 
 
 
10 mg, i.v. 
 
 
2 
diphenhydramine 
50 mg, i.v. 
hydroxyzine 
25 mg, p.o. 
3 
ranitidine 
50 mg, i.v. 
famotidine 
20 mg, i.v. 
Note: Medications to be delivered at minimum 30 minutes prior to the start of study drug infusion. 
*Use of other IV glucocorticoids is allowed, per institutional practice 
 
8.2.3 
Other Study Drug-Related Toxicities 
Following the first dose, should a patient experience symptoms suggestive of other mild to 
moderate study drug-related reactions (e.g., nausea, vomiting, diarrhea, etc.), that patient may be 
premedicated with standard therapies in order to reduce the potential for such reactions in the 
future.   
Mandatory premedication will be implemented for all patients treated on this study should a 
pattern begin to emerge of other mild-to-moderate study drug-related reactions that are amenable 
to prophylaxis with standard agents.  Such action will occur following discussions between the 
Investigator(s) and the Sponsor's Medical Monitor(s). 
Any medications administered for either prophylaxis or therapy of symptoms considered to be 
associated with study drug will be documented on the appropriate page of the eCRF. 
 
Dose Modification Options 
8.3.1 
Prolongation of Infusion Duration 
All IRRs that result in infusion prolongation must be reported promptly to the Sponsor (or 
designee). 
For IRRs the following infusion prolongation instructions are provided:.   


 
 
 
 
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• For Grade 1 reactions, consider slowing the infusion to 50% of the prior rate.  If the 
infusion is slowed, deliver subsequent infusions at the prolonged rate. 
• For Grade 2 reactions, interrupt the infusion for a minimum of 30 minutes, and at least 
until there is either amelioration to < Grade 1 severity or return to baseline status.  
Administer supportive care as medically indicated. Restart the infusion at 50% of the 
prior rate. Subsequent infusions must be administered at the prolonged rate. 
• For Grade 3 reactions, STOP the infusion.  Administer supportive care. The occurrence 
will be considered a DLT and the patient will be either discontinued from treatment, or 
will receive subsequent treatments at a reduced dose and at 50% of the prior rate or 
longer. 
• For Grade 4 reactions, STOP the infusion.  Administer supportive care.  The patient will 
be permanently discontinued from treatment.  
Guidelines for the grading and management of IRRs of all severities are provided (see Appendix 
G: Grading and Management of Infusion Reactions).In all cases the Investigator should use best 
clinical judgment in managing such reactions.   
Should an increased incidence begin to occur of mild-to-moderate IRRs that are managed by 
prolongation of infusion, consideration will be given to extending the infusion duration in this 
study.  Such action will occur following discussions between the Investigator(s) and the 
Sponsor's Medical Monitor(s). 
All infusion interruptions and subsequent prolongations, including modified infusion times, as 
well as the toxicity that necessitated them, will be clearly documented on the appropriate page of 
the patient’s eCRF. 
Note: 
Any assessments to be performed or samples to be collected (e.g., vital signs, PK) at the end of or 
following the EOI will still be performed or collected beginning at the delayed EOI timepoint.  In situations 
where collection of late day samples, in particular the 4h sample, is logistically difficult due to clinic staff 
availability, an "end of day" sample may be obtained at the latest practical time on the day of the reaction. 
To enhance patient safety following an infusion prolongation, subsequent infusions will be 
administered at the prolonged rate.  Rechallenge with a shorter duration of infusion (no less than 
2 hours) may be attempted at the Investigator's discretion, after a minimum of 2 doses with no 
evidence of infusion-related toxicity.   
8.3.2 
Temporary Dose Interruption (Delay) 
All dose interruptions of AVID100 must be reported promptly to the Sponsor (or designee).  
8.3.2.1. 
Delay Between Dosing 
If indicated, the period between any 2 scheduled doses may be extended to allow for 
amelioration of the toxicity.  However, if any observed Grade 3 or Grade 4 toxicity thought to be 
associated with study drug results in delay of dosing beyond 2 weeks of the next scheduled dose, 
regardless of whether the criteria for DLT are met, the event will be considered a DLT, 
necessitating that the patient either have their dose of study drug reduced or be discontinued 
from further treatment with study drug.   


 
 
 
 
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For toxicities not meeting the protocol definition of DLT that are to be managed by dose 
interruption, dosing may be restarted at the same or a reduced dose(s), as clinically indicated.  
However, for a DLT that is managed by dose interruption, administration of study drug MUST 
be restarted at a reduced dose once retreatment criteria have been met (see Section 6.7.1; 
Retreatment Guidelines).  
8.3.3 
Dose Reduction  
All dose reductions of AVID100 must be reported promptly to the Sponsor (or designee).   
In the event that toxicity is to be managed by dose reduction, the study drug dose will be 
decreased as indicated in the following table (TABLE 4).   
TABLE 4:  DOSE REDUCTION SCHEDULE FOR AVID100 
Starting Dose 
First Reduction 
Second Reduction 
Dose Level 1 
½ of Dose Level 1 
¼ of Dose Level 1 
Dose Level 2 
Dose Level 1 
½ of Dose Level 1 
Dose Level 3 
Dose Level 2 
Dose Level 1 
Dose Level 4 
Dose Level 3 
Dose Level 2 
Continue as above 
next lower tolerated dose 
next lower tolerated dose 
Note:  
In the event that an intermediate dose is explored in this study, dose reductions in such cases will be to the next lower 
established tolerated dose level(s). 
 
Patients may have a maximum of 2 dose reductions for study drug-related toxicity, after which 
they will be generally be discontinued from further treatment with study drug.  If indicated, 
further dose reduction in patients with an ongoing OR or SD may be considered after discussion 
with the Sponsor’s Medical Monitor(s). 
Once a patient has undergone a dose reduction, the patient will continue to be treated at the 
reduced dose throughout the remainder of their time on study treatment.  There is no provision in 
this study for either re-escalation or rechallenge with a higher dose of AVID100.  
8.3.4 
Schedule Alterations 
Altered schedules of study drug (i.e., reduced number of treatment days, longer interval between 
treatment days) may be explored as a means of dose reduction, only after discussion with the 
Sponsor (or designee), and only during subsequent cycles of treatment (Cycle 2 and beyond).   
Patients requiring such schedule alterations during Cycle 1 of the study will be considered to 
have met the criteria for DLT due to the inability to complete Cycle 1 of study drug treatment.    
Note: 
Any modification of AVID100 administration, and the reason for such action, must be clearly noted on the 
patient’s eCRF.  If such a modification impacts upon a PK sampling interval, the details of such action 
must also be documented on the appropriate page of the eCRF (to aid in the interpretation of PK findings). 


 
 
 
 
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9. 
REMOVING PATIENTS FROM STUDY TREATMENT 
Every reasonable effort will be made to keep patients in the study; however, in the event that a 
patient is discontinued from study treatment, every effort will be made by the Investigator to 
complete and report the reasons for treatment discontinuation as thoroughly as possible.  This 
evaluation should include EOT observations, as required by the protocol at the time of treatment 
discontinuation (see Section 7; Study Assessments), as well as 1M FUP evaluations.  The 
reason(s) for treatment discontinuation must be clearly documented on the appropriate page of 
the eCRF.  An eCRF must be completed for any patient who receives any amount of study drug.  
 
Criteria for Treatment Discontinuation 
Patients will be discontinued from further treatment with study drug in the event of any of the 
following:  
1. Patient must be permanently discontinued in the event of any major, potentially irreversible 
organ system DLT , including: 
• Pulmonary toxicity defined as: 
o 
Evidence of pulmonary fibrosis, any grade  
o 
Reduction of forced vital capacity (FVC) or DLCO > Grade 3  
• Neurotoxicity defined as peripheral neuropathy > Grade 3 
• Any ocular toxicity  > Grade 3  
• Nephrotoxicity defined as: 
o 
Acute kidney disease > Grade 3 (i.e., creatinine > 3 × baseline or > 4.0 
mg/dL) 
o 
Chronic kidney disease > Grade 3 (i.e., estimated glomerular filtration rate 
[eGFR] or creatinine clearance [CrCl] 29-15 mL/min/1.73 m2) 
o 
Proteinuria > Grade 3 (i.e., > 3.5 g/24 hours) 
• Hepatotoxicity suggestive of drug-induced liver injury, as characterized by the 
following 3 criteria: 
o 
AST and/or ALT elevation > 3 × ULN (or > 3 × baseline if elevated at study 
entry as allowed by study eligibility criteria; see Section 4.3.1 #7)  
o 
Total bilirubin > 2 × ULN without initial findings of cholestasis (i.e., no 
elevation in serum ALP) 
o 
No explanation for the above findings, such as:  viral hepatitis A, B, or C; 
preexisting or acute liver disease; or another drug capable of causing the 
observed injury 
Adapted from:  Hy’s Law. Drug–induced liver injury: premarketing clinical evaluation. Guidance 
for Industry. U.S. Department of HHS, FDA, CDER, CBER, 2009. 


 
 
 
 
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2. Any other DLT (see Section 6.8.3; Definition of DLT) considered by the Investigator to 
require treatment discontinuation. 
Note: 
Patients experiencing a DLT not listed in #1 above may continue at a reduced dose if there is 
evidence of an OR, SD, or other clinical benefit, provided protocol stipulated retreatment criteria 
delineated in Section  6.7.1 (Retreatment Guidelines) have been met, and ONLY following 
discussion with the Sponsor’s Medical Monitor(s)).    
3. Another AE not meeting the criteria for a DLT, yet considered by the Investigator to require 
treatment discontinuation. 
Note: 
AEs resulting in a patient’s permanent discontinuation from study treatment, regardless of 
seriousness or relationship to study drug, MUST be reported promptly to the Sponsor (or 
designee). 
4. Documented progressive disease at any time during the study 
5. Treatment failure not meeting the criteria for progressive disease, but considered by the 
Investigator to require treatment discontinuation. 
6. Requirement for a significant surgical procedure  
Note: 
Patients requiring a minor surgical procedure (e.g., port placement, skin abscess drainage) may 
continue at the Investigator’s discretion following discussion with the Sponsor's Medical 
Monitor(s).  A brief interruption in therapy may be considered.  
7. An intercurrent illness which, in the opinion of the Investigator, would prevent completion of 
study-related evaluations 
8. Significant deviation from the protocol or eligibility criteria.  Such patients will be 
considered protocol violations and will be discontinued from treatment 
9. Pregnancy 
10. Noncompliance with study or follow-up procedures 
11. Patient withdrawal of consent and election to discontinue treatment with study drug. (Patients 
may leave the study at any time for any reason if they wish to do so, without any 
consequence.) 
12. Termination of the study by the Sponsor 
13. Any other reason which, in the opinion of the Investigator, would justify treatment 
discontinuation.  In such a case, the Investigator’s reason for treatment discontinuation must 
be recorded on the appropriate page of the eCRF. 
 
Replacements 
Phase 1a:  Dose-Escalation:  Should a patient discontinue treatment with study drug for reasons 
other than the occurrence of a study drug-induced toxicity prior to completing Cycle 1 a 
replacement patient will be obtained using the original eligibility criteria.  Patients discontinued 
due to study drug-associated toxicity will not be replaced. 


 
 
 
 
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Note:  
Patients must receive their full planned dose of AVID100 during Cycle 1 in order to be considered 
evaluable for tolerability, unless dose reduction, interruption, or discontinuation is the result of a DLT.  
Patients receiving < 1 full planned study drug dose plus 3 weeks of follow-up during Cycle 1 for reasons 
other than toxicity will be replaced. 
Phase 2a Dose-Expansion:  It is not planned to replace any patients in the 3 dose-expansion 
cohorts. 
 


 
 
 
 
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10. 
ADVERSE EVENTS 
 
Definitions 
10.1.1 
Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug-related. 
This includes any unintended or undesirable, noxious, or pathological change, compared to pre-
existing conditions, experienced by a patient during a clinical study or the follow-up period, 
regardless of relationship to study drug.   
AEs include: 
• Suspected adverse drug reactions 
• Reactions from drug overdose, abuse, withdrawal, sensitivity, or toxicity 
• Significant changes or abnormalities, when compared to baseline, in structure (sign), 
function (symptom), clinical laboratory results, or physiological testing.  This includes 
any worsening of a pre-existing condition temporally associated with the use of study 
drug.  
• Other medical events, regardless of their relationship to the study drug, such as injury, 
surgery, accidents, extensions of symptoms, or apparently unrelated illnesses. 
10.1.2 
Suspected Adverse Reaction 
A suspected adverse reaction (SAR) is any AE for which there is a reasonable possibility that the 
study drug caused the AE.  For the purposes of IND safety reporting, "reasonable possibility" 
means there is evidence to suggest a causal relationship between the drug and the AE.  SAR 
implies a lesser degree of certainty about causality than adverse reaction, which means any AE 
caused by a drug.   
Note: 
By definition, all SARs, are AEs, however the converse is not the case as all AEs are not SARs.    
 
Evaluating Adverse Events 
The Investigator will determine the seriousness, intensity, and causality of an AE based on the 
following definitions: 
10.2.1 
“Serious” Adverse Events and Suspected Adverse Reactions 
(Notify Sponsor or designee within 24 hours of Investigator awareness; document on eCRF) 
An AE or SAR is considered "serious" if, in the view of either the Investigator or Sponsor (or 
designee), it results in any of the following outcomes:    
1. Death:  This includes any death that occurs while the patient is “on study” as well as any 
death that occurs within 30 days after study drug administration.  If an autopsy is 
performed, results may be requested by the Sponsor (or designee).  Possible evidence of 


 
 
 
 
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organ toxicity (e.g., radiation damage) and the potential relationship of the toxicity to the 
study treatment will be of particular interest. 
2. A life-threatening AE:  This includes any occurrence that places the patient at 
immediate risk of death from the reaction as it occurred.  It does not include an AE or 
SAR that, had it occurred in a more severe form, might have caused death.  
3. Inpatient hospitalization or prolongation of existing hospitalization 
4. A persistent or significant disability/ incapacity:  A disability is defined as any 
substantial disruption of a person’s ability to conduct normal life functions.   
5. A congenital anomaly/birth defect 
6. Requirement for intervention to prevent permanent impairment or damage:  
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.  Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.  
The term “severe” is often used to describe the intensity (severity) of an event; the event itself 
may be of relatively minor medical significance (such as a severe headache).  This is not the 
same as “serious,” which is based on patient/event outcome or action criteria usually associated 
with events that pose a threat to a patient’s life or functioning.  
Planned or elective hospitalizations, or hospitalizations for the administration of protocol 
therapy, should not be considered SAEs. 
10.2.2 
“Unexpected” Serious Adverse Events and Suspected Unexpected Serious 
Adverse Reactions 
 (Notify Sponsor or designee within 24 hours of Investigator awareness; document on eCRF) 
All AEs or SARs that are both unexpected and serious (i.e., suspected unexpected serious 
adverse reactions; SUSARs) are subject to expedited reporting.   An AE or SAR is considered 
“unexpected” if it is not listed in the IB or protocol (see Section 2.4; Rationale for and Risks of 
Proposed Clinical Study, and Section 11; Precautions when Dosing with AVID100) , or is not 
listed at the specificity or severity that has been observed; or, if an IB is not required or available, 
is not consistent with the risk information described in the general investigational plan or 
elsewhere in the current application, as amended.     
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis.  Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the IB listed only cerebral vascular accidents.  "Unexpected," as used in this definition, also 
refers to AEs or SARs that are mentioned in the IB as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not specifically mentioned 
as occurring with the particular drug under investigation. 


 
 
 
 
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10.2.3 
Non-Serious Adverse Events  
(Document on eCRF) 
All other AEs not fulfilling the previous definitions are classified as non-serious. 
10.2.4 
Protocol-Related Adverse Events 
AEs that are not study drug-related may nevertheless be considered by the Investigator or the 
Sponsor (or designee) to be related to the conduct of the clinical study.  That is, the event may be 
related to the fact that a patient is participating in the study.  For example, a protocol-related AE 
may be an event that occurs during a washout period or that is related to a procedure required by 
the protocol. 
 
Documenting Adverse Events  
Information regarding the occurrence of AEs should be elicited through open-ended questioning 
of the patient, review of physical examination findings, and review of laboratory results.  
All AEs (including SAEs) are to be detailed in the source documents and accurately recorded on 
the Adverse Event page of the patient’s eCRF.  All new events, as well as those that worsen in 
intensity or frequency relative to baseline, which occur from signing of informed consent* 
through the period of protocol-specified follow-up, must be captured.  AEs occurring within 30 
days after the last dose of study drug must be reported. SAEs, thought by the Investigator to be 
related to study drug, however, must be reported any time the Investigator becomes aware of 
such an event, even if this occurrence is more than 30 days after the last dose of study drug. 
AE terms should be recorded concisely, using acceptable medical terms, and, when possible, a 
diagnosis (i.e., disease or syndrome) rather than the component signs and symptoms (e.g., record 
congestive heart failure rather than dyspnea, rales, and cyanosis). However, signs and symptoms 
that are considered unrelated or atypical to encountered syndromes or diseases are to be recorded 
as individual AEs on the eCRF (e.g., if congestive heart failure and severe headache are observed 
at the same time, each event is to be recorded as an individual AE).  The AE should not be 
recorded as a procedure or clinical measurement (i.e., a laboratory or vital sign), but should 
reflect the reason for the procedure or diagnosis.  For fatal AEs, death is considered to be an 
outcome of the AE. The cause of death (rather than the term “death”) should be recorded as the 
AE in the eCRFs.  AEs terms will be classified using the Medical Dictionary for Regulatory 
Activities (MedDRA) classification system.   
*Patients who sign informed consent and are subsequently deemed to be screen failures will be followed for the 
occurrence of SAEs/AEs until it is determined that they are will not be participating in this trial. 
10.3.1 
Information to be Provided for each AE 
The following information will be provided for each AE term reported: 
• Each event will be graded according to the CTCAE (v5.0) as to severity.  For events not 
listed in the  CTCAE, severity will be graded on a 5-point scale as mild, moderate, 
severe, life threatening, or fatal, which correspond to Grades 1, 2, 3, 4, and 5, 
respectively on the CTCAE (see Appendix D; Adverse Event Grading Scale).    


 
 
 
 
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• The date of onset as well as the duration of the event will be recorded (i.e., date of 
resolution).   
• The method used to treat the AE, specifically, the action taken regarding the study drug 
will be provided (e.g., none, infusion temporarily interrupted, infusion prolonged, 
infusion stopped, dose reduced, dose schedule altered, dosing permanently discontinued). 
• The outcome of the AE (e.g., ongoing, resolved, resolved with sequelae, fatal) will also 
be noted.   
• The Investigator will attempt to assess the relationship of the event to study drug. 
Investigators are required to assess whether there is a reasonable possibility that the 
investigational drug caused or contributed to an AE.  Determination of whether there is a 
reasonable possibility includes assessing temporal relationships, biologic plausibility, 
dechallenge/rechallenge information (if available), association (or lack of association) 
with underlying disease, and presence (or absence) of a more likely cause.  The 
Investigator must attempt to determine if an AE is in some way related to the use of the 
study drug using a 5-point causality scale  (i.e., unrelated, unlikely-related, possibly 
related, probably related, related) (see Appendix E; Clinical Adverse Events:  
Determining Relationship to Study Drug).    
Preexisting condition (i.e., disorders present before the AE reporting period started and noted 
during the Screening period) should not be reported as an AE unless the condition worsens or 
episodes increase in frequency during the AE reporting period. 
Diagnostic and therapeutic procedures, such as surgery, should not be reported as AEs. 
However, the medical condition for which the procedure was performed should be reported if it 
meets the definition of an AE.  For example, acute appendicitis that begins during the AE 
reporting period should be reported as the AE and the resulting appendectomy should be noted as 
the intervention for the AE. 
Abnormal laboratory values or abnormalities in other physiological testing (such as ECGs) per 
se need not be reported as AEs unless the Investigator feels they are clinically significant (CS), 
they are an SAE, they require an intervention, they result in a change to protocol therapy, or they 
result in a patient discontinuing protocol therapy.  Laboratory abnormalities associated with a 
diagnosis (e.g., elevated hepatic enzymes in a patient with hepatitis) need not be listed as a 
separate AE.  If a patient with elevated hepatic enzymes has jaundice but no clinical diagnosis or 
syndrome has been established, then both jaundice and elevated hepatic enzymes should be 
reported as AEs. 
AEs of CTCAE Grade 4 or 5 generally qualify for SAE reporting to the Sponsor or designee, 
however the definition of CTCAE Grade 4 does not necessarily always meet the regulatory 
definition of  “life-threatening”.  As example, a laboratory abnormality of CTCAE Grade 4 does 
not need to be reported as an SAE, unless it meets one of the seriousness criteria.  
 
Progressive neoplastic disease should not be reported as an AE, as this will be recorded as part 
of the patient’s efficacy evaluation.  Progressive disease may be reported as an AE in the case of 
patient death, with death being the outcome of the event. 


 
 
 
 
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10.3.2 
Timeframe for Recording AEs 
The AEs pages of the eCRF will be completed in a timely manner following a patient completing 
(or being discontinued from) each dosing cycle.  
This will enable the Sponsor (or designee) to tabulate the occurrence of AEs, and make decisions 
regarding the advisability of continuing accrual to a particular dose cohort, and/or escalating the 
dose and allowing accrual to a higher dose cohort.  Availability of these data will also enable the 
Sponsor (or designee) to notify any other Investigator participating in clinical studies of the study 
drug of events occurring during the trial, where indicated. 
10.3.3 
Required Follow-up for AEs 
Appropriate consultation and follow-up evaluations should be carried out until the event either 
resolves, returns to baseline status, or has been adequately explained and assessed by the 
Investigator as chronic and/or stable, and that no longer term deleterious effects have become 
evident.  This follow-up may extend up to 6 months after the end of study if indicated, if the 
event has not resolved or been adequately explained.   
 
Reporting SAEs (Including Patient Deaths) and Unexpected SAEs 
10.4.1 
24-Hour Requirement for Reporting to the Sponsor 
All SAEs, including SUSARs and patient deaths, experienced by the patient from signing of 
informed consent until 30 days after receiving the final dose of study drug, or any SAE that 
occurs after 30 days of receiving the final dose of study drug and is believed to be study drug-
related, must be promptly reported (within 24 hours of Investigator awareness) even if the 
experience does not appear to be associated with the study drug or the protocol.  Reports will be 
made by telephone, telefax, or e-mail transmission to the Sponsor or the Sponsor’s designee.     
Where SAE submissions are made to the Sponsor’s Safety Designee, such submissions must then 
be transmitted by to the Sponsor's Medical Monitor(s).  The SAE Form must be transmitted to 
the Medical Monitor(s) whether full information regarding the event is known or not. 
*Patients who sign informed consent and are subsequently deemed to be screen failures will be followed for the 
occurrence of SAEs/AEs until it is determined that they are will not be participating in this trial. 
10.4.2 
Governing Regulatory Requirements Regarding Sponsor Review 
Under ICH Guidelines for Clinical Safety Data Management Definitions and Standards for 
Expedited Reporting, and per Food and Drug Association (FDA) ruling (U.S. Code of Federal 
Regulations, Title 21 CFR Part 312.32), the Sponsor (or designee) must promptly review all 
information relevant to the safety of the study drug obtained or otherwise received by the 
Sponsor (or designee) from foreign or domestic sources, including information derived from any 
clinical or epidemiological investigations, animal or in vitro studies, reports in the scientific 
literature, and unpublished scientific papers, as well as reports from foreign regulatory 
authorities and reports of foreign commercial marketing experience for drugs that are not 
marketed in the United States.   


 
 
 
 
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Prompt reporting by the Investigator to the Sponsor (or designee) facilitates the Sponsor’s ability 
to remain compliant with this ruling.  
10.4.3 
Governing Regulatory Requirements Regarding Sponsor Reporting 
Compliance with this requirement for prompt reporting to the Sponsor (or designee) is essential 
also in that the Sponsor is obligated to, and will be responsible for subsequently informing the 
FDA and local governing Health Authorities, as well as all other participating Clinical 
Investigators (i.e., all Investigators to whom the Sponsor or designee is providing drug under its 
INDs or under any Investigator’s IND) of potential serious risks from clinical trials or any other 
source, of events that meet reporting criteria. 
10.4.3.1. 
Reporting Criteria  
Under ICH Guidelines and FDA ruling the Sponsor (or designee) is required to submit written 
documentation detailing: 
• Any SAR that is both serious and unexpected.  Reporting is required only if there is 
evidence to suggest a causal relationship between the drug and the AE, such as: 
o A single occurrence of an event that is uncommon and known to be strongly 
associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson 
Syndrome) 
o One or more occurrences of an event that is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug (e.g., 
tendon rupture) 
o An aggregate analysis of specific events observed in a clinical trial (such as 
known consequences of the underlying disease or condition under investigation or 
other events that commonly occur in the study population independent of drug 
therapy) that indicates those events occur more frequently in the drug treatment 
group than in a concurrent or historical control group   
• Any findings from epidemiological studies, pooled analysis of multiple studies, or 
clinical studies, whether or not conducted under an IND and whether or not conducted by 
the Sponsor, that suggest a significant risk in humans exposed to the drug.  
• Any findings from laboratory animals or in vitro testing, whether or not conducted by the 
Sponsor, that suggest a significant risk in humans exposed to the drug, such as reports of 
mutagenicity, teratogenicity, or carcinogenicity, or reports of significant organ toxicity at 
or near the expected human exposure dose. 
• Any clinically important increase in the rate of a serious SAR over that listed in the 
protocol or IB. 
10.4.3.2. 
Reporting Format 
Written submission of such reactions or findings, from the Sponsor (or designee) to FDA must 
be in the form of an IND Safety Report presented in a narrative format, or on FDA Form 3500A 
(MedWatch form).  For international trials a Council for International Organizations of Medical 


 
 
 
 
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Sciences (CIOMS) I form may be used for U.S. FDA reporting as well as ex-U.S. reporting to 
relevant local governing Health Authorities. 
10.4.3.3. 
Reporting Timeframes 
Written submission must be made by the Sponsor (or designee) to FDA and other relevant local 
governing Health Authorities and Investigators as soon as possible, but in no case later than 15 
calendar days after the Sponsor (or designee) determines that the information qualifies for 
reporting (i.e., usually after initial notification of the reaction or finding). 
In addition, the Sponsor (or designee) is further required to report, by either telephone or 
facsimile transmission or in writing to the FDA, the occurrence of any unexpected fatal or life-
threatening SAR as soon as possible, but in no case later than 7 calendar days after the Sponsor 
(or designee’s) initial receipt of the information. 
10.4.4 
Information to be Provided by the Investigator to the Sponsor  
10.4.4.1. 
Initial Information on an SAE 
At the time of the initial contact(s), the Investigator must transmit information to the Sponsor (or 
designee) sufficient for completion of an IND Safety Report or similar document.  The Sponsor 
(or designee) will request the following information about the patient and the event: 
• Patient identification number, gender, date of birth (or age) 
• Height, weight or body surface area (only where required for dose calculation) 
• Primary disease under treatment  
• Lot number and expiration date of study drug (if available) 
• Dose, schedule, and route of study drug administered 
• Date of most recent study drug administration 
• Date of event onset (Start Date) and duration (Stop Date) indicating the period during 
which the event met the serious criteria. 
• Description of event 
• Date of death (if applicable) 
• Action take regarding study drug (e.g., none, infusion temporarily interrupted, infusion 
prolonged, infusion stopped, dose reduced, dose schedule altered, dosing permanently 
discontinued)  
• Intervention(s) required (e.g., none, drug treatment required, non-drug treatment or 
procedure required) 
• Concomitant therapy (including regimen(s) and indication) 
• Pertinent laboratory data/diagnostic study (including dates) 
• Pertinent medical history 


 
 
 
 
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• Did event abate after interruption of study drug administration  
(if applicable)? 
• Did event recur after study drug was reintroduced (if applicable)? 
In addition to the above information, the Sponsor (or designee) will require the Investigator’s 
assessment of the following: 
• Severity of the AE 
• Relationship of the AE to study treatment 
• Outcome of the AE (e.g., resolved, recovery with sequelae, event ongoing, patient died) 
10.4.4.2. 
Follow-up Information on an SAE 
Information not available at the time of the initial report (e.g., resolution date for the SAE, 
laboratory and diagnostic test reports, physician's summaries, etc.) must be submitted to the 
Sponsor (or designee), as it becomes available, in the form of a follow-up SAE report.  The same 
timelines governing initial reports apply to follow-up reporting. 
10.4.4.3. 
SAE Review and Potential Impact On Trial Conduct 
The Investigator will review each SAE report and evaluate further the relationship of the AE to 
study drug and to the patient’s underlying disease. 
Based on the Investigator’s assessment of causality of the AE and discussions with the Medical 
Monitor(s), a decision will be made by the Sponsor (or designee) concerning the need for further 
action with respect to the future conduct of this trial.  The primary consideration governing 
further action is whether new findings affect the safety of other patients participating in the 
clinical study.  If the discovery of a new AE related to study drug raises concern over the safety 
of its continued administration to patients, the Sponsor (or designee) will take immediate steps to 
notify FDA, other local governing Health Authorities, and all Investigators participating in 
clinical studies of the study drug. 
Further action required may include any of the following: 
• Alteration of the existing research program by modification of the protocol 
• Discontinuation or suspension of the study 
• Alteration of the informed consent process by modification of the existing consent form 
and informing current study participants of new findings 
• Modification of previously identified expected AE lists, including those included in the 
IB, to include AEs newly identified as study drug-related 
 
Required Follow-up for All AEs and SAEs 
Appropriate consultation and follow-up evaluations should be carried out until the event has 
resolved, returned to baseline, or is otherwise explained by the Investigator. 


 
 
 
 
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All SAEs should be promptly reported by the Investigator to his/her Institutional Review Board 
(IRB) or Ethics Committee (EC) according to their IRB/EC submission requirements.  Should 
the FDA or other governing Health Authorities require that the Sponsor submit additional data 
on the event, the Investigator will be asked to provide those data to the Sponsor (or designee) in 
a timely fashion. 
Note: 
All patients are to be followed for a minimum of 30 days after study drug discontinuation in order to 
monitor for the occurrence of SARs that are both serious and unexpected.  A longer period of time may be 
specified by the Sponsor (or designee) if required to assure the safety of the patient. 


 
 
 
 
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11. 
PRECAUTIONS WHEN DOSING WITH AVID100 
 
Precautions Regarding Procreation 
11.1.1 
Reproduction 
No studies specifically evaluating the effects of AVID100 on reproductive function in animals 
are available. Thus, patients receiving study drug must be informed that there could be potential 
risks relating to reproductive outcomes as a result its administration. 
11.1.2 
Contraception 
AVID100 has not been evaluated in human studies of embryo fetal development. For this reason 
women of childbearing potential (WOCBP), and fertile men with a partner of childbearing 
potential, should only be administered study drug when highly effective contraceptive measures 
have been taken, and in potential women participants when predosing pregnancy tests are 
negative. 
• Women are considered of childbearing potential if they have experienced menarche, and 
they have not undergone surgical sterilization (hysterectomy, bilateral tubal ligation, or 
bilateral oophorectomy), or are not post-menopausal. Post-menopause is defined as: 1) 
amenorrhea for > 12 months with no other cause, or 2) irregular menstrual periods, on 
HRT, with a documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL. 
In women under 55 years of age who have not been surgically sterilized, post-
menopausal status should be confirmed by evaluation of serum FSH.  
Women who are using oral contraceptives, other hormonal contraceptives (vaginal 
products, transdermal patches, or implanted or injectable products), or mechanical 
products such as an intrauterine device or barrier methods (diaphragm, condoms, 
spermicides) to prevent pregnancy, or are practicing abstinence, or where their partner is 
surgically sterile (e.g., vasectomy), should be still be considered of childbearing potential 
and must agree to true abstinence or to use a highly effective method of contraception 
during the study and for 3 months after the last dose of study drug. 
• Men are considered fertile unless they have undergone surgical sterilization (bilateral 
vasectomy or a bilateral orchiectomy), and must with their partner of childbearing 
potential agree true abstinence or to to use a highly effective method of contraception 
during the study and for 3 months after the last dose of study drug, and refrain from 
sperm donation during this period.  
• A highly effective method of contraception is defined as true abstinence or non-hormonal 
contraception equivalent to a double-barrier method (includes a single-barrier method in 
combination with a spermicide) or intrauterine device. 
   


 
 
 
 
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11.1.3 
Pregnancy 
Female subjects cannot be pregnant at the time of study entry, must be removed from study 
therapy if they do become pregnant during treatment, and should not become pregnant within 3 
months following the last dose of study drug. Male subjects must avoid procreating during study 
or within 3 months following the last dose of study drug.    
A pregnancy test must be performed on, and the results reviewed for, on each WOCBP prior to 
first study drug administration.  A negative pregnancy test performed within ≤ 2 working days 
prior to first study drug administration must be documented on the patient’s CRF. 
If it is confirmed that a study participant has become pregnant while participating in this trial, 
study drug administration will be discontinued immediately.  Any pregnancy occurring during 
this study will be reported immediately to the Sponsor (or designee).  The Investigator will then 
report follow-up information to the Sponsor (or designee) regarding the course of the pregnancy, 
including perinatal and neonatal outcome, regardless of the fact that the patient has discontinued 
treatment with study drug.  Once the newborn is determined to be healthy, as defined by and 
agreed upon by the Sponsor (or designee) and Investigator, additional follow-up will no longer 
be required.  A female partner of a male patient on the trial who becomes pregnant will be 
approached for permission to have the pregnancy followed until term and reported upon to the 
Sponsor (or designee). 
11.1.4 
Breastfeeding 
There is no information regarding presence or absence of study drug in breastmilk. There is also 
no information regarding the effects of study drug on maternal milk production or on suckling 
neonates. For these reasons, women who are nursing are not eligible to participate in this study. 
Lactating women who do participate in this study must discontinue nursing during study and 
until 3 months after the last dose of study drug. 
 
Additional Precautions 
There are no known contraindications to the administration of AVID100, however the following 
additional precautions are provided.   
In studies of other monoclonal antibodies and ADCs: 
• IRRs have been observed, therefore safety in patients with previous presumed 
formulation-related infusion reactions should be carefully evaluated prior to 
administration of AVID100.  Premedication to prevent infusion reactions should be 
administered to all patients with a history of such reactions, and facilities and personnel 
to treat such reactions, if they occur, should be available.  In the event of an IRR, the 
infusion should be slowed/interrupted so that appropriate measures may be taken.  
In nonclinical toxicology studies of AVID100: 
• Changes in the skin that were related to AVID100 were observed including: 
hyperkeratosis, dryness,  flaking, erythema, hyperpigmentation, lesions, fragile skin, scab 
formation, abrasions and ulcerations.  Skin findings  worsened over time with continued 
dosing and resolved over a period of 10 days in a recovery study.  Skin findings led to 


 
 
 
 
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excessive scratching in severely affected animals.  Severe skin rash accompanied by 
other findings led to early sacrifice of animals treated at the highest dose (25 mg/kg) on a 
weekly schedule.   Histopathological changes in the skin considered to be related to 
AVID100 included single cell necrosis, fibrosis, and lymphocytic infiltrates. These 
findings were consistent with those observed with other anti-EGFR antibodies (i.e., 
cetuximab, panitumumab). 
• Diarrhea, dehydration, decreases in food consumption and weight loss were observed in 
some animals. Mild hyperplasia was observed in the colon and jejunum of some animals.  
Mild lymphocytosis was observed in the colon of some animals.  As with the skin 
toxicity detailed above, these findings were treatment-related and believed to be  
consistent with the toxicity profile of cetuximab. 
• Mild to moderate increases of  ALT and ALP were observed in all studies.  Levels of 
both of these enzymes returned to near baseline levels before the next dose on a weekly 
schedule or by the end of the study. Minimal to mild hepatocellular hypertrophy and 
minimal hepatocellular vacuolation as well as hepatic single cell necrosis and increased 
mitosis were observed microscopically. Hepatoxicity has been identified as a major 
toxicity of an approved ADC conjugated to DM1, ado-trastuzumab emtansine.  
• Decreases in platelet counts which were reversible were observed and considered to be 
treatment related.  Platelet counts recovered  between weekly doses suggesting that this 
toxicity is reversible. Similar effects on platelets have been observed with ado-
trastuzumab emtansine and are consistent with the effects of the cytotoxic moiety DM1. 
Slight reductions in red cell parameters were also observed. Minimal to moderated bone 
marrow reduced cellularity has been observed. 
• Minimal to marked lymphoid depletion was observed in lymphoid organs in repeat dose 
studies although enlarged lymph nodes and lymphoid hyperplasia has also been observed 
in the single dose GLP study in 5 of 6 animals.  In this same study thymic atrophy and 
lymphoid hypoplasia were observed. 
• Cardiac effects were not prominent in these studies, although sinus tachycardia and sinus 
bradycardia were observed in some animals but these findings were not considered to be 
related to AVID100 administration.  All of the electrocardiograms were qualitatively and 
quantitatively within normal limits.  The QTc interval was longer in animals treated with 
10 mg/kg AVID100 but these changes were minor and there was no evidence of a dose 
response effect.  In the heart there was AVID100-related minimal to moderate 
myocardial degeneration and increased incidence of minimal mononuclear cell 
inflammation.  This finding was only observed in 1 of 6 animals receiving 10 mg/kg and 
this dose level was declared the HNSTD in the 4 week study. 
• There were no AVID100-related ocular changes during the course of the 4 week GLP 
study in animals receiving 10 mg/kg.  AVID100-related epithelial changes in the eye 
consisted of single cell necrosis/increased mitosis in the cornea and conjunctiva. 
• Increased single cell necrosis/increased mitosis was observed in a wide variety of organs 
and tissues, although only the findings in the skin were considered to have contributed to 
the toxicity seen in animals receiving 25 mg/kg in the GLP weekly dosing study.  In 


 
 
 
 
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addition to these changes seen in skin, similar findings were observed in the kidney, 
reproductive tract, mammary gland, trachea, and other tissues. 
• Toxicity to the ovaries, including degradation of corpora lutea, was observed in 
nonclinical toxicology studies. Severe sperm depletion was also noted in repeat dose 
studies.  
In addition to findings in toxicology studies a number of other potential risks of AVID100 
administration have been identified. 
• The use of AVID100 in lactating women or in children has not been evaluated.  These 
patients will be excluded from study entry.   
• No formal drug interaction studies have been performed, therefore no specific guidance 
can be provided about use of concomitant medications.  Use of strong inhibitors or 
inducers of CYP3A4 is not permitted in patients treated with AVID100. 
• There is no experience with clinical overdose of AVID100.  Higher doses of AVID100 in 
animals have resulted in skin and other toxicities including lethality in animals receiving 
repeated doses of 25 mg/kg.  If severe reactions occur in patients receiving AVID100  it 
should be discontinued and all appropriate supportive medical care should be instituted to 
ameliorate these potential adverse effects. 
 


 
 
 
 
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12. 
REGULATORY AND ETHICAL CONSIDERATIONS 
 
Conditions of Testing 
In sponsoring this study, it is the intention of the Sponsor to obtain patient safety data for 
submission to regulatory authorities.  In agreeing to conduct this investigation, the investigative 
facility agrees to follow all requirements stipulated in this protocol as well as regulations 
described in the U.S. Code of Federal Regulations (CFR) and by local governing Health 
Authorities concerning: 
• Responsibilities of Investigators (in the U.S. Title 21CFR, Part 312) 
• Informed Consent of Human Subjects (in the U.S. Title 21 CFR, Part 50) 
• Institutional Review Boards (in the U.S. Title 21 CFR, Part 56) 
In addition, , this trial will be conducted in compliance with, and the Investigator agrees to 
perform the study in accordance with,  the International Council on Harmonization of Technical 
Requirements for Pharmaceuticals for Human Use (ICH E6(R2) GCP) 
(EMA/CHMP/ICH/135/1995) Guideline for Good Clinical Practice (GCP), the Declaration of 
Helsinki, and applicable regulations. 
 
Institutional Review 
The Investigator will submit this protocol, any protocol modifications, and the patient consent 
form to be utilized in this study, to the appropriate Institutional Review Board or Ethics 
Committee for review and approval.  This committee must operate in accordance with ICH 
E6(R2) GCP, the U.S. Code of Federal Regulations, Title 21 CFR Part 56, and/or local 
governing Health Authorities, as appropriate.  A letter confirming approval of the protocol, and 
the informed consent document, must be forwarded to the Sponsor (or designee) prior to 
initiation of this study.  The Investigator will not start the study, nor will study drug be shipped 
to the investigational site, before providing the Sponsor (or designee) with evidence of this 
approval.  
The Investigator is responsible for assuring continuing review and approval of the clinical study.  
The Investigator must also promptly report all changes in the research activity and all 
unanticipated problems involving risk to the patients or others to his/her IRB or EC.  The 
Investigator will not make any changes in the protocol without IRB or EC approval, except 
where necessary to eliminate apparent immediate hazards to the patients.  The Investigator will 
provide progress reports to the IRB or EC as required by the IRB or EC.  If the study remains in 
progress for more than one year, the Investigator must obtain annual renewal and re-approval 
from the IRB or EC where appropriate.  Documentation of renewal must be submitted to the 
Sponsor (or designee).  The Investigator will provide notice to the IRB or EC of completion of 
participation in the study. 
 


 
 
 
 
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Informed Consent 
The Investigator agrees to protect the rights, safety, and welfare of the patients entered into the 
study, including obtaining written informed consent prior to performing any study-related 
procedures, and informing each patient that the study drugs are being used for investigational 
purposes.   
Prior to study start, the Sponsor will provide a sample informed consent form (ICF) for 
modification, as appropriate, by each Investigator.  The sample ICF must include all elements 
required by ICH Good Clinical Practices and must adhere to the IRB/EC requirements and 
ethical principles that have their origin in the Declaration of Helsinki.   
The Investigator's revision to the Sponsor's sample ICF, along with any other written study 
information to be provided to the patient, must then be reviewed and approved by the 
investigational site's IRB or EC.  A copy of the investigational site's IRB-approved or EC-
approved consent form document to be utilized during the study then must be submitted to the 
Sponsor (or designee) for review prior to study initiation. 
Prior to each patient's entry to the study, the Investigator or his/her staff will explain the nature 
of the study, its purpose and associated procedures, its expected duration, and the potential risks 
associated with participation.  All questions about the trial will be answered to the satisfaction of 
the patient or the patient’s legal representative.  The patient will be informed of the right to 
withdraw from the study at any time without consequence, and without having to provide a 
reason for this decision.  Following the discussion, the patient will be asked if they are willing to 
personally sign and date the statement of informed consent.  Only if the patient voluntarily 
agrees to sign the informed consent statement and has done so, may he/she enter the study.   
It is the responsibility of the Investigator to obtain written informed consent from each patient, 
thereby attesting that consent was freely given freely, in accordance with ICH E6(R2) GCP, the 
U.S. Code of Federal Regulations, Title 21 CFR Part 50, or local governing Health Authorities, 
as appropriate.  An Investigator listed on Form FDA 1572 (or similar document for ex-U.S sites) 
will then co-sign the informed consent document.  A copy of the signed and dated informed 
consent document will be provided to the patient.  The original executed version must remain in 
the Investigator's file, per local requirements, and must be available for verification by a 
representative of the Sponsor (or designee). 
 
Conditions for Modifying or Terminating the Study 
12.4.1 
Modification of the Study Protocol 
In the event that modifications in the experimental design, dosages, assessments, patient 
selection, etc., of the protocol are indicated or required, such changes will only be instituted 
following consultation between the Sponsor (or designee) and Investigator and will be 
accomplished through formal amendment(s) to this protocol and approval by the appropriate 
review committees, except where necessary to immediately eliminate apparent hazards to 
patients.  Protocol changes to eliminate an apparent hazard to a trial patient may be implemented 
by the Investigator immediately. The Investigator must then, without delay, inform the local IRB 
and the Sponsor (or designee), who will immediately notify local governing Health Authorities.  


 
 
 
 
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A modification to the protocol will not be made without the express written approval of the 
Sponsor (or designee).  Any amendment prepared by the Sponsor (or designee) will be 
implemented according to the Sponsor (or designee’s) standard operation procedures (SOPs) and 
will be reported to the appropriate regulatory body, the appropriate IRB(s) or EC(s), and made a 
formal component of the protocol document. 
12.4.2 
Modification of the Informed Consent Document 
In the event that modifications in the experimental design, dosages, assessments, patient 
selection, etc., of the protocol are indicated or required, and in the event that such modifications 
substantially alter the study design or increase the potential risk to patients, the Investigator will 
prepare a revision to the existing Informed Consent document.  Such a revision will be reviewed 
and approved by the appropriate IRB(s) or EC(s), and documentation of this approval will be 
forwarded to the Sponsor (or designee) for submission to the appropriate regulatory body.  
In addition, all current study participants, as well as subsequent study candidates, will be 
informed of the study design modification or increase in potential risk, and written informed 
consent for the modification/risk will be obtained as outlined above (see Section 12.3; Informed 
Consent). 
12.4.3 
Conditions for Termination of the Study 
The Sponsor reserves the right to terminate the study, or terminate a clinical trial site's 
participation in the study, at any time.  Should the Sponsor, the Sponsor’s designee, and/or the 
Investigator(s) discover conditions, during the course of the study, that indicate that it should be 
discontinued, an appropriate procedure for termination will be instituted.  Reasons for study 
termination may include, but are not limited to, the following: 
• Investigator non-compliance with the protocol, GCP, or regulatory requirements 
• Unsatisfactory enrollment with respect to quantity or quality 
• Incomplete data collection; inaccurate or knowingly false data submission 
• Safety concerns; incidence and/or severity of AEs in the study that indicate a potential 
health hazard or unexpected, serious, or unacceptable risk caused by the study treatment 
• Drug supply or manufacturing issues 
• The Sponsor’s decision to modify or discontinue development of the study drug 
• A request to discontinue the study by a regulatory or health authority 
If terminating the study, the Sponsor and Investigator(s) will assure that adequate consideration 
is given to the protection of patients' interests. 
 
Deviation from the Protocol 
The study is to be conducted as described in this protocol.  Under no circumstances should the 
protocol be modified for any patient without the prior consent of the Sponsor, and, if necessary 
the IRB or Ethics Committee responsible for patients at the investigative site. 


 
 
 
 
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Departures from either the protocol eligibility criteria or the experimental plan, as outlined 
herein, will be determined as allowable only in extremely rare instances, and only on a case-by-
case basis.  The Investigator, or other health professional in attendance, must prospectively 
contact the Sponsor's Medical Monitor(s) to discuss the associated circumstances.  Based on the 
information provided, a decision will be made as to the patient’s continued eligibility status.   
Authorization granted for any departure from the protocol applies only to the specific individual 
patient being discussed.   
 
Documents to be Submitted to the Sponsor 
The following documents must be submitted to the Sponsor (or designee) prior to study 
initiation: 
1. Local health authority permission to conduct the study and local import licenses (copy) 
(ex-U.S. sites, where applicable) 
2. Signed and dated Form FDA 1572* (original) (or similar document confirming trial 
responsibility for ex-U.S. sites) 
*In conducting this study the Investigator agrees to comply with commitments listed under Section 9 of 
Form FDA 1572. 
3. Signed and dated curriculum vitae (CV) of the Principal Investigator and each 
Subinvestigator* named on Form FDA 1572 (copies).  Physician CVs should be current 
(updated within 2 years) and accompanied by a copy of the current medical license.   
*A Subinvestigator is defined as a clinician responsible for study-related medical decisions, diagnoses, and 
treatment. 
4. Written, signed notification of IRB or EC approval of the study protocol (copy) 
5. Written, signed notification of IRB or EC approval of the informed consent document to 
be used during the study (copy) 
6. Written, signed notification of IRB or EC approval of any other material provided to 
potential trial participants with information about the trial (e.g., advertisements) (copy) 
7. IRB-approved or EC-approved informed consent document to be used during the study 
(copy)   
8. A current IRB or EC membership list for the reviewing committee, or the multiple 
project assurance number from the Federal-Wide Assurance (FWA) program 
(www.ohrp.osophs.dhhs.gov) 
9. Laboratory normal ranges for the reference laboratories to be utilized (protocol-specific 
analytes only)  
10. Name, location, and current laboratory certification (with date), for the reference 
laboratories to be utilized; curriculum vitae of the laboratory director 
11. Signed and dated Investigator Protocol Agreement Statement; statement is included as 
part of this protocol (original) 


 
 
 
 
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12. Fully executed clinical trial agreement 
13. Financial disclosure information for the Investigator and each Subinvestigator(s) 
 
Data Review During this Study 
Data obtained as a result of the study will be reviewed in a timely manner throughout by the 
Sponsor (or designee) and Sponsor's Medical Monitor(s) in order to assess safety and the 
progress of the project. 
 
Trial Registration 
The trial will be registered in one or more public trial registries (e.g., ClinicalTrials.gov). The 
trial results will be posted in the same clinical trial registries as the initial registration in 
accordance with the latest International Committee of Medical Journal Editors (ICMJE) 
recommendations (URL: www.icmje.org). 


 
 
 
 
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13. 
INVESTIGATOR RESPONSIBILITIES 
 
Medical Supervision 
An Investigator conducting a clinical study with an investigational agent is required to comply 
with regulations described in U.S. Code of Federal Regulations, Title 21 CFR Part 312 and ICH 
Good Clinical Practices. 
Medical supervision for the conduct of this protocol is the responsibility of the Principal 
Investigator.  The Principal Investigator must name all Subinvestigators and may delegate certain 
day-to-day activities to such Subinvestigators, but, retains overall responsibility for ensuring that 
the study is conducted properly and in accordance with the design and intent herein.  A 
memorandum outlining the specifics of the delegation will be maintained at the investigational 
site, in the study files, and will be updated as appropriate.   
The Principal Investigator is responsible for ensuring that drugs and devices are available for 
treating possible medical emergencies.  The Principal Investigator is required to ensure 
compliance with respect to the investigational drug schedule, visit schedule and procedures 
required by the protocol.  The Principal Investigator is responsible for ensuring that the study is 
conducted according to sound medical practices. 
 
Confidentiality 
All goods, materials, information (oral or written) and unpublished documentation provided to 
the Investigator (or any company acting on their behalf), inclusive of this protocol, the patient 
electronic Case Report Forms and the IB are the exclusive property of the Sponsor.  Documents 
and information provided to the Investigator by the Sponsor may not be given or disclosed by the 
Investigator or by any person within his authority either in part or in totality to any unauthorized 
person without the prior written formal consent of the Sponsor. 
It is specified that the submission of this protocol and other necessary documentation to the IRB 
or Ethics Committee is expressly permitted, the IRB or Ethics Committee members having the 
same obligation of confidentiality. 
The Investigator shall consider as confidential and shall take all necessary measures to ensure 
that there is no breach of confidentiality in respect of all information accumulated, acquired or 
deduced in the course of the trial, other than that information to be disclosed to a third party 
mandated by applicable law. 
Note: 
Any language relating to these issues appearing in the clinical trial agreement will supersede that which is 
outlined in this section. 
 
Use of Information and Publication 
Publication of a summary of the results of the study is permissible according to the Sponsor and 
is not inconsistent with the preceding affirmation.  Scientific dissemination of the results of this 
study is encouraged.   Any formal publication of data collected as a result of the study will be 
considered a joint publication by the Investigator and the appropriate personnel of Forbius or 
their designees.  Authorship will be determined by mutual agreement.   


 
 
 
 
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In the event of a publication describing multicenter trial results, the Investigator with the largest 
number of evaluable patients enrolled into the study will be named as first author.  The second 
highest enroller will be named as second author, and so forth.  However, the Sponsor retains the 
right to designate one of the authors or someone else involved to be named as the primary author.  
In such an event, the Sponsor will strive to ensure that all Investigators who actively participated 
in the study are given appropriate credit in the publication.   
For any publication or presentation, a manuscript of the paper or abstract must be received and 
approved by the Sponsor prior to outside submission.  Whether or not there is a Forbius author of 
the publications or presentations, a manuscript will be forwarded to Forbius for review and 
approval at least 30 days prior to submission of a journal publication, or at least 10 days prior to 
submission of an abstract. 
Note:   Any language relating to these issues appearing in the clinical trial agreement will supersede that which is 
outlined in this section. 
 
Patient Screening Log 
A record listing all patients entered into the study, as well as those considered for entry into the 
study and subsequently excluded, must be maintained by the Investigator.  Patients excluded 
from the study will have the reason for exclusion recorded on the Patient Screening Log (or other 
similar document).  
 
Drug Dispensing Inventory 
Study center personnel will maintain adequate records of the receipt, dispensing, and disposition 
of all study drug that the Sponsor ships to the site.  Records will be maintained, either on a form 
to be provided by the Sponsor or on a reasonable facsimile authorized for use by the Sponsor, 
and should include appropriate dates, quantities received, quantities dispensed, lot number (or kit 
number), disposition details, and the identification code of the patient who received the study 
drug. 
The Investigator agrees to administer study drug only to patients under his/her personal 
supervision.  The Investigator will not supply study drug to any person not authorized to receive 
it. 
 
Handling and Disposal of Investigational Drug 
Study drug should be stored in a secure location, under the indicated conditions (see Section 5; 
Investigational Drug). After study drug is prepared for delivery and administered, the health care 
professional will maintain an inventory of all used vials of study drug, after which, with 
authorization from the Sponsor, all such supplies may be destroyed in an appropriate manner 
according to institutional policy.  Destruction of such supplies will be documented.  Information 
regarding the number of vials utilized for each patient, as well as the dose of study drug 
administered to the patient, will be recorded on the appropriate drug inventory form. 
Periodically throughout and at the conclusion of the study, unused vials of study drug will be 
inventoried by a representative of the Sponsor (or designee).  At the completion of this trial, all 


 
 
 
 
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unused study materials MUST be returned to the Sponsor (or designee), unless otherwise 
authorized in writing. 
 
Recording and Processing of Data 
Clinical trial data for this study will be captured in an electronic format.  Electronic data capture 
(EDC) services will be provided by a vendor to be determined by the Sponsor.  The Investigator 
agrees to provide all information requested on the electronic case report forms (eCRF) in an 
accurate manner according to instructions provided.   Electronic CRFs are designed for computer 
processing and analysis.  All data must be carefully entered to permit meaningful interpretation.  
Corrections to entered data will be tracked within the EDC system.  Data must be entered onto 
eCRFs in a timely fashion. 
An eCRF is required to be submitted for every patient who receives any amount of study drug.  
This includes submission of retrievable data on patients who withdraw before completion of the 
study.  Prior to submission, eCRFs must be reviewed for completeness and accuracy, and signed 
and dated where indicated, by either the Principal Investigator or a physician Subinvestigator 
whose name is listed on Form FDA 1572 for this study. 
 
Source Document Requirements 
The Investigator will maintain adequate and accurate records for each patient treated with study 
drug.  Source documents such as hospital, clinic or office charts, laboratory reports, radiology 
and pathology reports, pharmacy records, study worksheets, and signed informed consent 
documents, must completely reflect the nature and extent of the patient’s medical care, must be 
included in the Investigator’s files along with patient study records, and must be available for 
source document verification against entries in the eCRF.    
The Sponsor (or designee) will check eCRF entries against source documents according to the 
guidelines of Good Clinical Practice.  The consent form will include a statement by which 
patients allow the Sponsor (or designee), as well as authorized regulatory agencies, to have direct 
access to source data that support data on the eCRF (e.g., patient medical files, appointment 
books, original laboratory records, etc.).  The Sponsor (or designee), bound by confidentiality 
and privacy regulations, will not disclose patient identities or personal medical information. 
 
Laboratory Reports 
Prior to initiation of this study, the Investigator must supply the Sponsor (or designee) with the 
normal laboratory values for the laboratories to be utilized; specifically, the normal laboratory 
values for analytes required to be measured, per protocol, are to be supplied.  The corresponding 
laboratory certification number must also be noted, and a copy of the Director's curriculum vitae 
provided. 
Laboratory safety evaluations must be performed at the intervals specified.  If unexplained 
laboratory abnormalities occur, corroborative tests will be performed until the laboratory 
abnormality has resolved, returned to baseline status, and/or adequate explanation of the 
abnormality has been provided. 


 
 
 
 
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Copies of any additional records pertinent to the study (e.g., laboratory data, radiological reports, 
patient chart summaries, autopsy reports) must be made available to the Sponsor (or designee) or 
governing Health Authorities, if requested, with due precaution taken to ensure patient 
confidentiality. 
 
Record Retention 
Regulatory authorities require that the Investigator retain copies of all files pertaining to the 
study (i.e., records of study article disposition, signed informed consent documents, electronic 
case report forms, all correspondence, dates of monitoring visits, and records which support 
them) for a period of 2 years following the date of marketing application approval of the drug, 
for the indication that is the subject of the study.  If no application is filed, or the application is 
not approved for the indication under study, all files pertaining to the study are to be maintained 
for 2 years after the investigation is discontinued and governing regulatory agencies have been so 
notified.  Study records must be stored in a safe and secure location permitting timely retrieval, if 
necessary.  The Investigator must obtain written permission from the Sponsor prior to disposing 
of any records. 
If the Investigator relocates, retires, or withdraws for any reason from the study, trial records 
may be transferred to an acceptable designee, such as another Investigator within the institution.  
The Sponsor (or designee), as well as the responsible IRB or Ethics Committee, must be notified 
of the identity of the individual assuming responsibility for maintaining the study records and the 
location of their storage.   
 
Monitoring of the Study 
The Sponsor has responsibility to governing regulatory authorities to take all reasonable steps to 
ensure the proper conduct of the study with respect to trial ethics, protocol adherence, and data 
integrity and validity. 
This study will be closely monitored by representatives of the Sponsor (and/or designee) 
throughout its duration.  Monitoring will be in the form of personal visits with the Investigator 
and his/her staff as well as any appropriate communications by telephone, telefax, mail, or e-mail 
transmission.  The purpose of these contacts is to review study progress, Investigator and patient 
adherence to protocol requirements, and any emergent problems associated with the conduct of 
the study.  The following points will be usually assessed during monitoring visits at the site: 
• Required regulatory documentation 
• Signed informed consent documents 
• Patient accrual and follow up 
• Study drug inventory records 
• Investigator and patient compliance to the study protocol 
• Concomitant therapy use 
• AE documentation 
• Data as accurate, complete, and verifiable when compared to source documents 


 
 
 
 
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The Investigator and study staff are expected to cooperate with monitors during such visits and 
provide them with all relevant study documents. 
In addition, the study may be evaluated by Sponsor auditors (and/or designees) and government 
inspectors who must be allowed access to eCRFs, source documents and other study files.  
Sponsor reports will be kept confidential.  The Investigator should promptly notify the Sponsor 
of any audits scheduled by any regulatory authorities, and promptly forward copies of audit 
reports. 
As applicable, in accordance with the Health Insurance Portability and Accountability Act 
(HIPAA) and associated privacy regulations, patient authorization to use personally identifiable 
health information may be required from each patient before research activities. This 
Authorization document must clearly specify what parties will have access to a patient’s personal 
health information, for what purpose, and for how long. 
 
Patient Confidentiality 
Every effort will be made to maintain the anonymity and confidentiality of patients during this 
clinical study.  Coded patient identifiers will be utilized at all times (including in any 
publications) when referring to a particular patient.  However, because of the experimental 
nature of this treatment, the Investigator agrees to allow representatives of the Sponsor, or their 
designee, as well as authorized representatives of the governing regulatory agency, to inspect the 
facilities used in this study and to inspect, for purposes of verification, the hospital or clinic 
records of all patients enrolled into this study.  A statement to this effect should be included in 
the informed consent document. 
 
  Financing and Insurance 
The study will be supported by the Sponsor.  Specifics of the financing and insurance coverage 
will be addressed in the clinical study agreement between the Sponsor and the Investigator or 
Institution. 


 
 
 
 
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14. 
STATISTICAL ANALYSIS AND REPORTING OF DATA 
 
Statistical Considerations 
The primary objectives of the Phase 1a portion of this trial are to assess the safety, tolerability, 
DLTs, and, if feasible, the MTD of AVID100 when administered by 2-hour* IV infusion to 
patients with a histologically-documented, measurable or non-measurable, locally advanced or 
metastatic solid tumor malignancy of epithelial origin that is refractory to standard therapy or for 
which no standard therapy is available.  These effects will be assessed by treating patient cohorts 
with sequentially escalating doses of AVID100.  Other studies to be conducted during this trial 
include characterization of the pharmacokinetic profile of AVID100, and description of the 
preliminary antineoplastic activity of AVID100 in these same patient cohorts.   
In addition, once the MTD is identified, the Phase 2a portion of the trial will enroll patients to 3 
expansion cohorts of patients (approximately 60 patients total) with advanced (unresectable or 
metastatic) malignancies of epithelial origin (tumor types mTNBC, SCCHN, and Sq-NSCLC), 
and confirmed as expressing the EGFR and with measurable disease, will be entered to further 
evaluate tolerability and assess the preliminary antineoplastic activity of AVID100 in this patient 
population. 
Data on safety and preliminary activity collected from additional patients added to the Phase 2a 
expansion cohorts will be summarized with patients treated at that same dose level in the Phase 
1a portion of the trial.  No tests of statistical inference will be performed. 
*Protocol v5.0:  Extended from 1 hour to 1.5 hours due to Grade 3 IRR observed in Cohort 3 (80 mg/m2); effective 
20Jul2017 and documented in a study Note to File dated 21Jul2017 (see Section 2.3.2.1; AVID100-01: Clinical 
Experience) 
*Protocol v6.0: Extended from 1.5 hours to 2 hours due to Grade 2 IRRs observed in Cohort 4(120 mg/m2); 
effective 21Dec2017 and documented in a study Note to File dated 28Dec2017 (see Section 2.3.2.1; AVID100-01: 
Clinical Experience) 
 
Sample Size Considerations 
Sample size for the Phase 1a dose escalation portion of the study will be determined by safety 
observations, occurrence of DLTs, and the number of cohorts required to evaluate safety and 
choose an RP2D.  It is assumed that approximately 4 cohorts will be required to determine the 
MTD, thereby enrolling approximately 14-30 patients during the dose escalation phase of the 
study.  However, the protocol allows for enrollment of > 4 cohorts, should this be necessary to 
identify the MTD. 
Sample size for the Phase 2a Expansion Cohorts will be approximately 60 patients treated at the 
RP2D, with accrual to be divided among up to 3 cohorts (tumor types mTNBC, N=30; SCCHN, 
N=15; and Sq-NSCLC, N=15; all approximations); additional patients may be entered to the 
Phase 2a Expansion Cohorts if fewer than 30 patients are required to establish the RP2D in Phase 
1a.   
  


 
 
 
 
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The current planned initial enrollment of 15 patients per cohort (or cohort subgroup in the case of 
mTNBC) may be expanded based on initial observation of  > 2 objective responses (13% ORR) 
in any of the three indications to be studied. This sample size has a 35.2% power to detect a 40% 
ORR compared to a potential control response of 20% at a two-sided 0.05 level of significance 
(TABLE 5).  In addition, the power is between 45-54% to detect objective response rates between 
20 to 40% in a 15 patient cohort at a two-sided 0.05 level of significance (TABLE 7). 
After evaluation of the initial ORR in each cohort a decision will be made to either continue to 
include patients with treatment-refractory advanced/metastatic malignancies without other 
therapeutic options on an open-label trial(e.g., if the objective response rate is ≥ 20% and 
responses are durable), consider alternative trial designs for further exploration of efficacy in any 
of the indications, or discontinue development if fewer than two (0 or 1) responses are observed 
in any of the three initial fifteen patient cohorts. The durability of objective responses and 
disease stabilization > 8 weeks will also be considered in the decision to expand cohorts or 
pursue other options for further development in any of the three indications (TABLE 4).  See also 
Appendix I.   
TABLE 5:  TEST OF NULL AT 0.05 LEVEL (TWO SIDED) USING NORMAL APPROXIMATION   
Power (%) for specified N (Computed using EAST 6.4) 
Null (π 0) 
True (π) 
N=15 
N=20 
N=34 
N=40 
0.20 
0.30 
13.2 
16.3 
24.6 
28.1 
 
0.40 
35.2 
44.7 
66.3 
73.3 
 
0.50 
64.2 
76.5 
93.8 
96.7 
 
0.60 
88.5 
95.5 
99.7 
99.9 
 
TABLE 6:  SMALLEST VALUE OF P (%) FOR STATISTICAL SIGNIFICANCE  
(Level 0.05, 2-Sided)  
π 0 
N=15 
N=20 
N=34 
N=40 
0.20 
45.2 
41.7 
36.2 
35.0 
0.25 
50.4 
46.9 
41.6 
40.2 
0.30 
55.2 
51.9 
46.8 
45.5 
0.35 
59.9 
56.8 
51.8 
50.5 
0.40 
64.3 
61.4 
56.7 
55.5 
0.45 
68.6 
65.8 
61.4 
60.2 
0.50 
72.6 
70.1 
66.0 
64.9 
 
Statistical Analysis 
Statistical analyses will be carried out using SAS Version 9.3 or higher. The statistical methods 
for this study will be described in a detailed statistical analysis plan (SAP) which will be 
finalized prior to database lock.  Any deviations from the planned analysis will be justified in the 
final study report.  


 
 
 
 
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Patient characteristics including race, ECOG PS, and age will be described using descriptive 
statistics. Frequency tables will summarize the incidence and type of treatment-related AEs by 
severity, experienced by patients who received at least 1 dose of study drug (Safety population). 
Continuous variables, including baseline characteristics, will be summarized by reporting the 
number of observations, mean, standard deviation, median, minimum and maximum.  
Categorical/discrete variables will be summarized using frequency tables showing the number 
and percentage of patients within a particular category.  Time-to-event data will be summarized 
using the Kaplan-Meier method.  Withdrawals of patients from study medication and causes of 
death will also be reported as listings and summary tables. 
Unless indicated otherwise, summary statistics will be reported for observed data only.  Missing 
data will not be imputed.  If a baseline value is missing, no change from baseline will be 
calculated.  Baseline is defined as the last available observation prior to the first administration 
of study drug on Cycle 1/Week 1/Day 1. 
14.3.1 
Analysis Sets 
• Safety analyses will be conducted on patients receiving any amount of a AVID100 dose 
(partial or complete).  Patients completing Cycle 1 in the absence of a DLT, will be 
considered to have tolerated the AVID100 regimen.  Patients must receive their planned 
dose of AVID100 during Cycle 1 plus 2 weeks of follow-up in order to be considered 
evaluable for tolerability, unless dose reduction, interruption, or discontinuation was the 
result of a DLT. 
• PK analyses will be performed in Dose Escalation Cohorts and Expansion Cohorts on 
patients who receive any amount of their assigned dose of AVID100 and have an 
adequate number of concentration determinations to allow for PK calculation.   
• All enrolled* patients will be evaluated for antineoplastic activity.  In addition, patients 
who complete Cycle 2 (6 weeks) of treatment, receive at least 2 planned doses during that 
period, and have a follow-up assessment of disease status will be considered evaluable 
for assessment of antineoplastic activity.  Patients who are withdrawn from the study 
before completion of Cycle 2 because of progressive disease also will be included in 
assessments of antineoplastic activity.   
* For the purposes of this study, "enrollment" is defined as patient registration to participate in this trial; 
at this time the patient's study identification code and dose cohort will be assigned.   
14.3.2 
Safety Analysis 
14.3.2.1. 
Adverse Events 
AEs will be coded by system-organ-class and preferred term using the most current MedDRA.   
Events will be recorded starting at study enrollment through 30 days following the last dose of 
AVID100, and will be tabulated by maximum severity according to the CTCAE (v5.0).   
The calculation of AE incidence will be based on the number of patients per AE category.  For 
each patient who has multiple AEs classified to the same category, that patient will be tabulated 


 
 
 
 
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under the highest toxicity grade for that AE category.  Summary tables will be presented by dose 
level, seriousness, severity, and relatedness. 
During Phase 1a, first-cycle DLTs, AEs leading to death or to discontinuation of study treatment, 
and SAEs will be evaluated with special attention. 
14.3.2.2. 
Laboratory Determinations 
Actual values and change-from-baseline values for continuous data from laboratory 
determinations (serum chemistry, hematology, coagulation studies, and urinalysis) will be 
presented in listings.  Categorical data measurements will be similarly summarized for the actual 
values.  Laboratory measurements will be graded according to CTCAE, when applicable. The 
frequencies of the highest CTCAE grade observed will be displayed for each AE and for each 
starting dose level.  Laboratory determinations categorized as in or out of normal range will be 
summarized in some cases using worst-case shift tables.  Clinically significant (CS) or not 
clinically significant (NCS) criteria may be applied for out-of-range values. 
14.3.2.3. 
Vital Signs, Body Weight, Physical Exam Findings 
Actual values and change-from-baseline values for vital signs and body weights, as well as 
physical examination findings, will be summarized descriptively.  
14.3.2.4. 
ECG Findings 
Descriptive statistics of ECG observations will be presented. The frequency and percentage of 
ECG results will be summarized for the following ECG measurements:  heart rate, PR interval, 
QRS duration, QT interval and QTc interval.  The heart rate-corrected QT interval (QTc), 
indicating repolarization time, will be calculated.  T-wave and ST-segment ECG abnormalities 
will be graded based on definitions in the NCI Common Toxicity Criteria (CTC).  Additional 
details regarding the ECG analyses will be provided in the SAP. 
14.3.2.5. 
Other Safety Data 
Concomitant medications and findings in physical examinations, pulmonary function tests, and 
anti-drug antibody analyses (ADA) will be summarized in text as recorded in the eCRF, and as 
made available from an independent central assay laboratory, in the case of ADA data. 
14.3.2.6. 
Maximum Tolerated Dose 
For Phase 1a, a table will be presented showing the MTD as well as a summary of the dose 
escalation and any subsequent dose reductions. 
14.3.3 
Other Analyses 
14.3.3.1. 
Antineoplastic Activity 
Phase 1a 
As the primary objective in the Phase 1a portion of the study is to determine the MTD and to 
evaluate the safety of the study treatment, all antineoplastic activity analyses will be descriptive 
and exploratory in nature.   Disease status will be summarized by cycle and dose group, 


 
 
 
 
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including changes from baseline.  As a secondary objective, OR, duration of OR, SD, and TTP 
will be assessed and calculated, wherever possible, according to standard response criteria (see 
Appendix F; Measurement of Effect).    
Phase 2a 
As a primary objective of the Phase 2 portion of the trial, OR, duration of OR and SD, as well as 
TTP will be assessed and calculated, wherever possible, according to standard response criteria 
(see Appendix F; Measurement of Effect).  Frequency counts and percentages will be presented 
for an objective response rate (ORR) and disease control rate (DCR).  For analysis of TTP, the 
median time to event and 95% confidence intervals will be calculated using the Kaplan-Meier 
method.   
Response Calculations 
In the event of an OR (CR or PR) the duration of the OR will be determined from the day the 
initial response is observed (using screening/baseline images for comparison) to the day that 
progression is observed.  Duration of SD (minimum duration of not less than 8 weeks) will also 
be assessed using the time from the first dose of AVID100 to the day that PD is documented. 
The ORR will be calculated as the proportion of patients who achieve either a complete response 
or a partial response (CR+PR).  ORR, time to OR, and duration of OR will be determined.   
DCR will be calculated as the proportion of  patients who achieve either a complete response, 
partial response, or disease stabilization for a minimum of 8 weeks (CR+PR+SD). 
TTP will be measured from the treatment start date (date of first dose) to either the date the 
patient is first recorded as having disease progression (even if the patient went off treatment 
because of toxicities), or the date of death if the patient dies due to any cause before progression. 
If a patient is lost to follow-up, the patient will be censored as of the date of last contact.  Patients 
who start a new treatment before they progress will be censored as of the date of start of the new 
treatment. If a patient has not progressed nor died, time to progression is censored at the date of 
last follow-up.  TTP will be analyzed using the method of Kaplan and Meier.  
Imaging Data 
Imaging data (imaging studies and derived assessments) will be stored by the sites and will be 
available upon request for potential review by the Sponsor or an independent radiology reviewer.  
If an independent radiology review is conducted, a charter will be prepared and finalized by the 
Sponsor (or designee) prior to initiating the radiology reviews. 
14.3.3.2. 
Pharmacokinetic Parameters 
The PK profile of total antibody (AVID100  plus MAB100), AVID100, and DM1 will be 
determined by noncompartmental analysis using standard PK software (e.g., Phoenix 
WinNonlin).  Parameters to be determined will include time of maximum observed concentration 
(Tmax), maximum (peak) concentration (Cmax), minimum (trough) concentration (Cmin), and area 
under the concentration curve for the last measurable concentration (AUClast).  When the 
terminal elimination phase can be identified, additional parameters such as elimination half-life 
(T½), clearance (Cl), and volume of distribution (Vd) will be determined. 


 
 
 
 
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Evaluations to delineate dose-response and PK parameter-response relationships will be 
undertaken.   
14.3.3.3. 
Biomarker Parameters 
Biomarker assessments, to include collection of archival or recent biopsy tissue for assessment of 
EGFR-expression and other potential biomarkers, will be conducted in on an optional basis in 
consenting patients in Phase 1a, and in all patients in Phase 2a. 
A summary of the changes in potential biomarker(s) will be presented.   
Biomarker analyses will be performed according to standard methodologies and will examine 
relationships between the biomarker assessments and clinical toxicities observed during the 
study.  These analyses will be described in the SAP. 
 
Clinical Study Report 
Following study completion a final integrated clinical/statistical study report will be prepared.  
Further studies may be planned depending on a review of the data 
 
 
 
 
 
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APPENDIX A 
Study Assessments 
TABLE 7:  STUDY ASSESSMENTS SCHEDULE 
STUDY ASSESSMENTS 
Screen 
CYCLE 1 
CYCLE 2 
SUBSEQUENT CYCLES 
EOT <10d 
after 
decision to 
dis-continue 
1M FUP* 
30 d (+7) 
after last 
dose 
Extended 
Follow Up*     
if OR or SD at 
EOT 
As 
Clinically 
Indicated 
D1 
D2 
D4 
+/- 
1d 
D8 
D1 
D8 
End of 
Cycle 2 
D1 
D8 
End of Even 
Number 
Cyclesd 
CONSENT AND MEDICAL HISTORY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent1/ Eligibility Assessment 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Past Medical History 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
History of Primary Malignancy2 
x 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SAFETY ASSESSMENTS (1) (screening assessments within 14 days prior to first study drug  dose  unless  specified) 
Medication Survey3 
x 
from 14 days prior to 1st dose through 30 days after last dose 
 
 
AE Assessments4 
from enrollment through 30 days after last dose; through 3 months (or 6 months to 2 years)  follow-up if associated AEs persist 
 
 
ECOG PS Evaluation 
x 
xa 
 
 
 
x 
 
 
x 
 
 
x 
x 
 
x 
Phase 1a: Vital Signs5 
x 
SOI; EOI; 
 2, 4h  after 
EOI 
x 
x 
 
x 
 
 
x 
 
 
x 
x 
 
x 
Phase 2a: Vital Signs5 
x 
SOI, EOI 
 
 
 
x 
 
 
x 
 
 
x 
x 
 
x 
Physical Exam/to include weight and 
pulmonary assessment6 
x 
xa 
 
 
 
x 
 
 
x 
 
 
x 
x 
 
x 
Hematology Panel7 
x 
xa 
 
x 
x 
x 
x 
 
x 
x 
 
x 
x 
 
x 
Serum Chemistry Panel8 
x 
xa 
 
x 
x 
x 
x 
 
x 
x 
 
x 
x 
 
x 
Coagulation Panel9 
x 
xa 
 
x 
x 
x 
x 
 
x 
x 
 
x 
x 
 
x 
Urinalysis10 
x 
xa 
 
x 
x 
x 
x 
 
x 
x 
 
x 
x 
 
x 
ADA to AVID10011 
 
x 
 
 
 
x 
 
 
x 
 
 
x 
x 
 
xe 
Pregnancy Testing12 (w/in 2 days of 1st dose) 
x 
x 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
ECG (12-lead)13 
x 
SOI, EOI, 30 
min after EOI 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
SAFETY ASSESSMENTS (2) (screening assessments within 28days  (+/- 2) prior to first study drug  dose provided no antineoplastic therapy has been delivered between assessment and first dose of study drug) 
Ophthalmology Exam14 
x 
 
 
 
 
 
 
 
 
 
End of C2 only 
x 
 
 
x 
MUGA Scan or Echo15 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Pulmonary function tests16 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
Chest radiography (PA and lateral) 
x 
 
 
 
 
 
 
 
 
 
 
x 
 
 
x 
DISEASE ASSESSMENTS (screening assessments within 28 days (+2d) prior to first study drug dose) 
Phase 1a only:  Document EGFR positivity17 
optional 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase 2a only:  Document EGFR positivity17  
required 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase 1a only:  Tumor Marker Measurement18 
x 
 
 
 
 
 
 
x 
 
 
x 
xb 
 
q3m for 1y, 
q6m afterc 
 
Imaging for Disease (and Pulmonary Status)19 
x 
 
 
 
 
 
 
x 
 
 
x 
xb 
 
q3m for 1y, 
q6m afterc 
 
Response Assessment20 
 
 
 
 
 
 
 
x 
 
 
x 
xb 
 
q3m for 1y, 
q6m afterc 
 
ADDITIONAL ASSESSMENTS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Phase 1a:  PK Sampling21 
 
SOI; EOI; 
2,  4h  after 
EOI 
24h  
after 
EOI 
x 
x 
SOI  
EOI 
x 
 
SOI  
EOI 
 
 
x 
x 
 
xe 
Phase 2a:  PK Sampling22 
 
SOI           
EOI 
 
 
x 
SOI 
 
 
SOI, 
EOI-C5 
only 
C5 only 
 
x 
x 
 
xe 
Phase 1a: Archival Tumor for  
EGFR confirmation and biomarker studies22 
 
optional; submit any time after study 
enrollment; if available 
 
 
 
 
 
 
 
 
 
 
Phase 2a: Tumor for exploratory studies22 
required 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
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Phase 2a:  Blood for Exploratory Studies 23 
x 
 
 
 
 
 
 
 
 
 
x 
 
 
 
TRIAL TREATMENT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AVID100 Infusion (2-h) 
 
x 
 
 
 
x 
 
 
x 
 
 
 
 
 
 
Phase 1a: Post-Infusion Monitoring 
 
4h 
 
 
 
x 
 
 
x 
 
 
 
 
 
 
Phase 2a: Post-Infusion Monitoring 
 
2h 
 
 
 
x 
 
 
x 
 
 
 
 
 
 
 
*Given the Q3W dosing frequency, EOT and 1M FUP evaluations may be combined in those situations where scheduling coincides, provided a minimum of 30 days of post-dosing follow-up have 
been observed.   
 
Abbreviations:  SOI-start of infusion; EOI-end of infusion; EOT-end of treatment; 1M FUP-1 month follow-up 
 
a Need not be assessed prior to Cycle 1 if ≤ 7 days since screening;  
b Conduct only if > 6 weeks since the previous assessment;  
c To be conducted in the event of ongoing objective response (OR) or stable disease (SD) at the end of treatment; continue until progressive disease (PD) or another therapeutic intervention is initiated 
d End of Cycle assessments may be conducted at any time during the week prior to Day 1 of the next cycle. 
e Additional ADA and PK sampling to be performed in the event of an IRR, as close as possible to the onset of the event 
  
 
1. Informed Consent:  To be signed prior to enrollment and prior to performing any protocol-related procedure, unless such testing was performed previously as part of the routine clinical management 
of the patient.   
2. History of Primary Malignancy: To include details of the primary malignancy, including:  histological/cytological classification; stage of disease at diagnosis and at entry;  prior surgical procedures 
for the malignancy;  prior antineoplastic therapy, prior radiation therapy, as well as dates of treatments, numbers of cycles, and best response to each therapy.  
3. Medication Survey:  To include period within 14 days prior to first study drug dose and throughout study for a period of 30 days following last study drug dose. 
4. AE Assessments:  To detail symptoms that may be present prior to/at the time of first administration.  AEs to be assessed from enrollment, throughout study and for the 1 month period (30 days) 
following last study drug dose; AEs to continue to be assessed for the 3 month (and if necessary 6 month) period following last study drug dose if events associated with study drug persist (to confirm 
that events have resolved, returned to baseline status, or been adequately explained.  Investigator discretion may be used with respect to the method of contact for this AE assessment; clinical events 
may be followed in writing or by telephone (and documented), an in-person visit will not be required). Any patient who develops pulmonary fibrosis will be followed at approximately 3 month 
intervals for up to 2 years to assess the course of the disease and evaluate potential reversibility of this finding. 
5. Vital Signs:  To include temperature, pulse, respiratory rate, blood pressure, and pulse oximetry.   
6. Physical Examination:  Complete at screening including height, weight, general appearance, skin, ears, eyes, nose, throat, neck/thyroid, chest/breasts, lungs, heart, abdomen, musculoskeletal system, 
pulse, lymph nodes, neurologic and mental status; directed thereafter, must include weight and pulmonary assessment.  Dose adjustments may be made in the event of noted weight change (± 10% 
[less at the site’s discretion or if required by institution procedures]). Pulmonary findings will be evaluated in detail at each visit by the PI (or physician designee); evaluation to include review of 
pulmonary symptoms including but not limited to: cough, sputum production, hemoptysis, wheezing, dyspnea, dyspnea on exertion, chest pain, and/or chest pain associated with respirations. 
7. Hematology Panel:  To include CBC with differential, ANC, and platelet count.  Evaluation frequency should be increased in the event of hematologic toxicity. 
8. Serum Chemistry Panel:  To include Na, K, Cl, bicarbonate or carbon dioxide, BUN, creatinine, glucose, bilirubin [total and direct], AST, ALT,  alkaline phosphatase, Ca, Mg, phosphorous, albumin, 
total protein, uric acid, amylase, lipase, and CK (in the event of abnormalities while on study, please perform isoenzyme analysis).  Evaluation frequency should be increased in the event of 
significant serum chemistry abnormalities.  Clinically significant electrolyte abnormalities should be corrected prior to dosing. 
9. Coagulation Panel:  To include PTT (or aPTT), PT and/or INR 
10. Urinalysis:  Multipanel chemical test strips are acceptable and should include assessment of:  specific gravity, pH, protein, glucose, ketones, leukocyte esterase, nitrite, bilirubin, urobilinogen, and 
occult blood; include microscopic sediment evaluation if clinically indicated if gross findings are abnormal, including WBC/high power field [hpf] and RBC/hpf.   
11. ADA to AVID100 (Central Lab):  To assess immunogenicity; whole blood (~5 mL at each timepoint) will be collected for serum acquisition.  In the event that a collected serum sample is 
inadequate or insufficient for ADA analysis, the analysis of ADA can be done using a PK serum sample from the same time point, if available. Residual sample material may be used for biomarker 
assessments. See Laboratory Manual (or other similar document) for details regarding collection, handling, and shipping.  
12. Pregnancy Testing:  -hCG in WOCBP; serum at Screening, urine or serum thereafter; negative test must be confirmed within 2 working days prior to first dose of study drug 
13. ECG (12-Lead):  To include measurement of PR interval, QRS duration, QT interval, and QTc interval [msec], as well as heart rate [BPM]; to be performed after patient has been supine for > 10 
minutes; repeat subsequent time points in triplicate separated by 5 minutes for 4 cycles (Day 1 at SOI and EOI) in patients with a QTc that is either:  a) > 500 msec; b), increased by 60 msec over 


 
 
 
 
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baseline; or c) decreased by 20 msec under baseline.   
14. Ophthalmology Examination:  To include slit lamp evaluation, tests to evaluate corneal integrity, and visual acuity assessment.  End of C2 and EOT may be combined if patient discontinues treatment 
at End of C2 
15. MUGA Scan or Echocardiogram: For measurement of LVEF; to be performed ONLY in patients with a history of CHF, individual patients should be followed with the same testing procedure 
throughout the study. 
16. Pulmonary Function Tests:  To include spirometry and diffusing capacity (DLCO) to assess for evidence of pulmonary fibrosis (spirometry assessments are to include but are not limited to:  forced 
vital capacity [FVC], forced expiratory volume in 1 second [FEV1], forced expiratory flow 25% to 75% [FEF25-75], functional residual capacity [FRC], residual volume [RV], and total lung capacity 
[TLC]) 
17. EGFR status determination/documentation of EGFR positivity by IHC:   
• Phase 1a: Optional (Local or Central*) 
• Phase 2a: Required (Central Lab*); tumor must be EGFR-positive for patient to be eligible for enrollment 
*The trial site will prescreen patients for EGFR Tumor Status Determination before entering patients into screening for the treatment portion of the trial.  The site should use a separate prescreening 
informed consent form.  Prescreening may be performed outside the 28 (+ 2) day screening period to allow adequate turnaround time for receipt of results, provided separate informed consent has 
been obtained. 
18. Tumor Marker Measurement (Phase 1a only):  As indicated by tumor type. 
19. Imaging for Assessment of Disease (and Pulmonary Status) (e.g., diagnostic imaging / marker lesion measurements, etc.; as indicated by tumor type, imaging of the chest imaging required with each 
evaluation (for disease evaluation where indicated, and to assess for evidence of pulmonary fibrosis):  Follow with the same procedure(s) throughout; no further disease assessments required after 
documented PD and/or initiation of another therapeutic intervention; duration of OR to be measured from date initial response is observed to date PD is observed; for PR or CR, tumor measurement 
changes must be confirmed no less than 4 weeks after criteria for response are met; for SD, follow-up measurements must meet the SD criteria at least once after study entry at a minimal interval of 
not less than 8 weeks.  Imaging studies documenting response must be available for review by the Sponsor (or designee). 
20. Response Assessment:  To be assessed by the Investigator according to RECIST v1.1  
21. PK Sampling (Central Lab): Whole blood (~5 mL at each timepoint) will be collected for serum acquisition.  In the event that a collected serum sample is inadequate or insufficient for PK analysis, 
the analysis of PK can be done using an anti-drug antibody (ADA) serum sample from the same time point, if available.  Residual sample material may be used for biomarker assessments. See 
Laboratory Manual (or other similar document) for details regarding collection, handling, and shipping.  PK sampling times may be adjusted according to early trial results in order to optimize 
evaluation.   
22. Tumor for Exploratory Studies (Central Lab):  For assessment of tumor EGFR-expression by FISH (or similar assay) and other potential biomarkers.  Directions for submitting blocks or pre-cut 
slides to be provided by the Sponsor (or designee) in the Laboratory Manual or other similar document.   
• Phase 1a: To be submitted if available.   
• Phase 2a: Required; to be performed in tumor tissue submitted for eligibility; if archival tissue is not available the patient must have primary or metastatic tumor sites(s) considered safely 
accessible for biopsy, and must be willing to undergo tumor biopsy  
23. Blood for Exploratory Studies (Central Lab):  Phase 2a; may be obtained for submission any time after confirmation of eligibility and study enrollment but prior to dosing on C1/D1 
 
 
 


 
 
 
 
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TABLE 8:  PHARMACOKINETIC SAMPLING SCHEDULE 
See also TABLE 4 
Study Day 
Phase 1a 
Phase 2a 
Allowance   
(+/-) 
Reference 
CYCLE 1 
 
 
 
 
Day 1 
SOI 
SOI 
 
Prior to SOI 
 
EOI 
EOI 
5 min 
EOI 
 
2h 
 
15 min 
 
4h 
 
15 min 
Day 2 
24h 
 
1h 
 
Day 4 
At time of visit 
 
1 day 
 
Day 8 
At time of visit 
At time of visit 
 
 
CYCLE 2 
 
 
 
 
Day 1 
SOI 
SOI 
 
Prior to SOI 
 
EOI 
 
5 min 
EOI 
Day 8 
At time of visit 
 
 
 
POST-TREATMENT 
 
 
 
 
EOT 
At time of visit 
At time of visit 
 
 
1M FUP 
At time of visit 
At time of visit 
 
 
In the event of an IRR 
At time of 
event 
At time of 
event 
 
 
TOTAL SAMPLES  
12 
5 
 
 
 
SOI = Start of Infusion 
EOI = End of Infusion 
 
PK samples for each additional cycle: 
• 
Phase 1a:  Day 1 (SOI, EOI) 
• 
Phase 2a:  Day 1 (SOI)  
Day 1 (SOI, EOI) Cycle 5 only 
Day 8 (at time of visit) Cycle 5 only 
 
Actual collection times are to be recorded on the patient’s eCRF or other equivalent sample collection log as authorized by the Sponsor 
(or designee). 
 
Comprehensive collection of clinical samples is critical to the conduct of this study.  In situations where collection of the 4h sample is 
logistically difficult due to clinic staff availability, an "end of day" sample may be obtained at the latest practical time.  Such an option 
is available ONLY after previous discussion with and approval by the Sponsor. 
 


 
 
 
 
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TABLE 9:  MAXIMUM TOTAL BLOOD COLLECTION VOLUMES 
STUDY 
Vol./ 
sample 
(mL) 
Screening 
Cycle 1 
Cycle 2 
EOT 
1M FUP 
TOTAL 
VOLUME 
ASSESSMENTS 
# of 
Samples 
Vol.  
(mL) 
# of 
Samples 
Vol.   
(mL) 
# of 
Samples 
Vol.  
(mL) 
# of 
Samples 
Vol.  
(mL) 
# of 
Samples 
Vol.  
(mL) 
Phase 1a 
  
  
  
  
  
  
  
  
  
  
  
  
Hematology  
5 
1 
5 
3 
15 
2 
10 
1 
5 
1 
5 
40 
Chemistries  
10 
1 
10 
3 
30 
2 
20 
1 
10 
1 
10 
80 
Coagulation  
5 
1 
5 
3 
15 
2 
10 
1 
5 
1 
5 
40 
Pregnancy Test 
5 
1 
5 
0  
  
0  
  
0  
  
0  
  
5 
ADA Testing 
5 
0  
  
1 
5 
1 
5 
1 
5 
1 
5 
20 
Tumor Markers 
5 
1 
5 
 0 
  
1 (end) 
5 
1 
5 
1 
5 
20 
PK Studies 
5 
0  
  
7 
35 
3 
15 
1 
5 
1 
5 
60 
Total Volume  
  
  
30 
  
100 
  
65 
  
35 
  
35 
265 
Phase 2a 
  
  
  
  
  
  
  
  
  
  
  
  
Hematology 
5 
1 
5 
3 
15 
2 
10 
1 
5 
1 
5 
40 
Chemistries 
10 
1 
10 
3 
30 
2 
20 
1 
10 
1 
10 
80 
Coagulation  
5 
1 
5 
3 
15 
2 
10 
1 
5 
1 
5 
40 
Pregnancy Test 
5 
1 
5 
0  
  
0  
  
0  
  
 0 
  
5 
ADA Testing 
5 
0  
  
1 
5 
1 
5 
1 
5 
1 
5 
20 
PK Studies 
5 
0  
  
3 
15 
1 
5 
1 
5 
1 
5 
30 
Exploratory 
Studies  
20 
1 
20 
0 
 
0 
 
1 
20 
0 
 
40 
Total Volume  
  
  
45 
  
80 
  
50 
  
50 
  
30 
255 
 
Along with Screening, single days not detailed with maximum blood volume requirements > 20 mL: 
• Phase 1a:  Cycle 1/Day 1= 50mL, Day 4=25mL 
• Phase 2a:  Cycle 1/Day 1=35mL (55 mL if biomarker sample is drawn prior to dosing on C1/D1) 
Blood volumes for each additional cycle:  50 mL, 60 mL for Cycle 5 
 
If sites are able to perform hematology, serum chemistry, and coagulation studies with smaller volumes of blood per sample, they are encouraged to do 
so.  Required PK, and ADA volumes are fixed and should not be reduced.   
For the purpose of estimating a patient’s total blood collection volume during study participation, maximum estimates are used. During a patient’s 
study participation, the maximum amounts of venous blood that will be collected are listed above.  Study duration is based on 6 weeks estimated 
average patient participation, i.e., an average of Cycle 1 (3 weeks) plus Cycle 2 (3 weeks).   
An indwelling venous access device is required for PK blood sample collections on Day 1 of Cycle 1.  When an indwelling catheter (or equivalent 
venous access) is utilized, a blood flush discard of up to 3 mL is to be done before drawing the first blood tube collected on the scheduled day/time for 
routine laboratory tests and PK samples. Blood flush discard volumes ARE NOT included in volume calculations in table above and should be 
considered when summarizing actual blood collection volumes. 
 
Given the Q3W dosing frequency, EOT and 1M FUP evaluations may be combined in those situations where scheduling coincides, provided a 
minimum of 30 days of post-dosing follow-up have been observed.   
 
In the event of an IRR: 
If a patient should have an IRR associated with AVID100 administration, all attempts will be made to obtain blood samples as close to the onset of the 
event as possible for assessment of  the presence of ADA and PK (to provide information on the nature of the infusion reaction).  Blood volume for 
such collections is not included on this table; however, it is anticipated that a total of approximately 10 mL would be required; ADA (5 mL), PK (5 
mL). 
 


 
 
 
 
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APPENDIX B 
Performance Status Evaluation 
 
TABLE 10:  MEASURES OF PERFORMANCE STATUS 
 
 
Percent 
 
KARNOFSKY1 Performance 
Status Description 
 
 
 
Level 
 
ECOG2 
 
100 
 
Normal; no complaints, no evidence of 
disease 
 
 
0 
 
 
 
Normal activity 
 
90 
 
Able to carry on normal activity; minor 
signs or symptoms of disease 
 
 
80 
 
Normal activity with effort; some signs or 
symptoms of disease 
 
 
1 
 
 
 
Symptoms but ambulatory 
 
70 
 
Cares for self; unable to carry on normal 
activity or do active work 
 
 
60 
 
Requires occasional assistance but is able to 
care for most needs 
 
 
2 
 
 
 
In bed < 50% of time 
 
50 
 
Requires considerable assistance and 
frequent medical care 
 
 
40 
 
Disabled; requires special care and 
assistance 
 
 
3 
 
 
 
In bed > 50 % of time 
 
30 
 
Severely disabled; hospitalization is 
indicated although death is not imminent 
 
 
20 
 
Very sick; hospitalization is necessary 
 
 
 
4 
 
 
 
100 % bedridden 
 
10 
 
Moribund; fatal processes progressing 
rapidly 
 
 
0 
 
Death 
 
 
 
5 
 
 
1Karnofsky DA, Abelman WH, Craver LF, Burchenal JH. The use of nitrogen mustards in the palliative treatment of carcinoma.  Cancer. 
1948;1:634-656. 
2Oken M, Creech RH, Tormey DC, Horton J, Davis TE, McFadden E, Carbone PP. Toxicity and response criteria of the eastern cooperative 
oncology group.  Am J Clin Oncol. (CCT) 1982; 5:649-655. 


 
 
 
 
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APPENDIX C 
New York Heart Association’s Functional Criteria 
 
TABLE 11:  NEW YORK HEART ASSOCIATION FUNCTIONAL CRITERIA 
 
 
Class I 
 
No limitation of physical activity.  Ordinary physical activity does not cause undue fatigue, 
palpitation, dyspnea, or anginal pain. 
 
 
Class II 
 
Slight limitation of physical activity.  Comfortable at rest, but ordinary physical activity results in 
fatigue, palpitation, dyspnea, or anginal pain. 
 
 
Class III 
 
Marked limitation of physical activity.  Comfortable at rest, but less than ordinary physical activity 
results in fatigue, palpitation, dyspnea, or anginal pain. 
 
 
Class IV 
 
 
Unable to carry on any physical activity without discomfort.  Symptoms of cardiac insufficiency or 
anginal syndrome may be present even at rest.  If any physical activity is undertaken discomfort 
increases. 
 
 
The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 
9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256 
 


 
 
 
 
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APPENDIX D 
Adverse Event Grading Scale 
TABLE 12:  CLINICAL ADVERSE EVENT GRADING 
Severity 
CTCAE* 
Grade 
Definition 
Mild 
1 
Awareness of symptom, but easily tolerated.  Event is usually transient requiring 
no special treatment; does not interfere with usual status or activities 
 
Moderate 
2 
Event may be ameliorated by simple therapeutic measures; may interfere with 
usual activities 
 
Severe 
3 
Event results in temporary disability or incapacity; inability to perform usual 
activities; requires intervention 
 
Life-threatening 
4 
Event requires immediate intervention; need for emergency treatment; patients is at 
risk of death at the time of the event 
 
Fatal 
5 
Event resulting in the subsequent death of the patient 
 
 
Note: 
In those cases where further definition of an event is provided by the NCI Common Terminology Criteria for Adverse 
Events (CTCAE, v5.0), please refer to that document for grading and severity information. 
*< https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm > 


 
 
 
 
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APPENDIX E 
Clinical Adverse Events:  Determining Relationship to Study Drug 
TABLE 13:  CLINICAL ADVERSE EVENTS:  DETERMINING RELATIONSHIP TO STUDY DRUG 
UNRELATED 
This category applies to those AEs which, after careful medical consideration, are clearly felt to be due to extraneous causes 
(disease, environment, etc) that are unrelated to the administration of study drug. 
UNLIKELY RELATED (must have first 2) 
This category applies to those AEs which, after careful medical consideration, are felt unlikely to be related to the 
administration of the study drug.  The relationship of an AE to the study drug can be considered unlikely if: 
• 
It does not follow a reasonable temporal sequence from administration of the drug. 
• 
It could readily have been a result of the patient’s clinical state, environmental or toxic factors, or other modes of 
therapy administered to the patient. 
• 
It does not follow a known response pattern to the suspected drug. 
• 
It does not reappear or worsen when the drug is readministered. 
 
POSSIBLY RELATED (must have first 2) 
This category applies to those AEs which, after careful medical consideration, are felt unlikely to be related to the 
administration of the study drug, but the possibility cannot be ruled out with certainty.  The relationship of an AE to the study 
drug can be considered possible if: 
• 
It follows a reasonable temporal sequence from administration of the drug. 
• 
It could readily have been a result of the patient’s clinical state, environmental or toxic factors, or other modes of 
therapy administered to the patient. 
• 
It follows a known response pattern to the suspected drug. 
 
PROBABLY RELATED (must have first 3) 
This category applies to those AEs which, after careful medical consideration, are felt with a high degree of certainty to be 
related to the administration of the study drug.  The relationship of an AE to the study drug can be considered probable if: 
• 
It follows a reasonable temporal sequence from administration of the drug.  
• 
It could not be reasonably explained by the known characteristics of the patient’s clinical state, environmental or 
toxic factors or other modes of therapy administered to the patient. 
• 
It disappears or decreases upon cessation of drug or reduction in dose.* 
• 
It follows a known response pattern to the suspected drug. 
 
RELATED (must have first 3) 
This category applies to those AEs, which, after careful medical consideration, are felt to be related to the administration of 
the study drug.  The relationship of an AE to the study drug can be considered related if: 
• 
It follows a reasonable temporal sequence from administration of the drug or drug levels have been established in 
body fluids or tissues. 
• 
It could not be reasonably explained by the known characteristics of the patient’s clinical state, environmental or 
toxic factors or other modes of therapy administered to the patient. 
• 
It disappears or decreases upon cessation of drug or reduction on dose and appears upon rechallenge.* 
• 
It follows a known response pattern to the suspected drug. 
 
Adapted from:  Karch FE and Lasagna L. Adverse drug reactions: a critical review. JAMA. 1975 Dec 22; 234 (12):1236-1241.  
 
*There are exceptions when an AE does not disappear upon discontinuation of the drug, yet drug-relatedness clearly exists, e.g., 
1) tardive dyskinesia, 2) fixed drug eruptions. 
 
 


 
 
 
 
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APPENDIX F 
Measurement of Effect   
TABLE 14:  RESPONSE CRITERIA FOR SOLID TUMORS 
Summary of RECIST v1.1 Guidelines 
 
For the purposes of this study, patients should be re-evaluated for response every 8 weeks.  In addition to a baseline scan, 
confirmatory scans should also be obtained > 4 weeks following initial documentation of objective response (OR). 
 
Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response 
Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) [Eur J Ca 45:228-247, 2009].  Changes in the largest 
diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are 
used in the RECIST criteria. 
 
A. DEFINITIONS 
 
Evaluable for Toxicity:  All patients will be evaluable for toxicity from the time of their first treatment with study drug.   
Evaluable for Objective Response:  Only those patients who have measurable disease present at baseline, have received at 
least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.  These patients 
will have their response classified according to the definitions stated below.   
 
Note:        Patients who exhibit objective disease progression prior to the end of cycle 1 will also be considered evaluable.) 
 
Evaluable Non-Target Disease Response:  Patients who have lesions present at baseline that are evaluable but do not meet the 
definitions of measurable disease, have received at least one cycle of therapy, and have had their disease re-evaluated will be 
considered evaluable for non-target disease.  The response assessment is based on the presence, absence, or unequivocal 
progression of the lesions.  
 
B. DISEASE PARAMETERS 
 
Measurable Disease:  Measurable lesions are defined as those that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as > 20 mm by chest x-ray, as >10 mm with CT scan, or as >10 mm with calipers by clinical 
exam.  All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). 
Note:  
Tumor lesions that are situated in a previously irradiated area might or might not be considered measurable.   
If the investigator thinks it appropriate to include them, the conditions under which such lesions should be considered must be 
defined in the protocol. 
Malignant Lymph Nodes:  To be considered pathologically enlarged and measurable, a lymph node must be > 15 mm in short 
axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).  At baseline and at follow-
up, only the short axis will be measured and followed. 
Non-Measurable Disease:  All other lesions (or sites of disease), including small lesions (longest diameter < 10 mm or 
pathological lymph nodes with ≥ 10 to < 15 mm short axis), are considered non-measurable disease.  Bone lesions, 
leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease, and 
abdominal masses (not followed by CT or MRI) are considered as non-measurable. 
 
Note:  
Cystic lesions that meet the criteria for radiographically defined simple cysts should not be considered as malignant lesions (neither 
measurable nor non-measurable) since they are, by definition, simple cysts. 
 
Cystic lesions thought to represent cystic metastases can be considered as measurable lesions, if they meet the definition of 
measurability described above.  However, if non-cystic lesions are present in the same patient, these are preferred for selection as 
target lesions. 
 
Target Lesions:  All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, representative of all 
involved organs, should be identified as target lesions and recorded and measured at baseline.  Target lesions should be 
selected on the basis of their size (lesions with the longest diameter), be representative of all involved organs, but in addition 
should be those that lend themselves to reproducible repeated measurements.  It may be the case that, on occasion, the largest 


 
 
 
 
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lesion does not lend itself to reproducible measurement in which circumstance the next largest lesion which can be measured 
reproducibly should be selected.  A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all 
target lesions will be calculated and reported as the baseline sum diameters.  If lymph nodes are to be included in the sum, then 
only the short axis is added into the sum.  The baseline sum diameters will be used as reference to further characterize any 
objective tumor regression in the measurable dimension of the disease. 
 
Non-Target Lesions:  All other lesions (or sites of disease) including any measurable lesions over and above the 5 target 
lesions should be identified as non-target lesions and should also be recorded at baseline.  Measurements of these lesions are 
not required, but the presence, absence, or in rare cases unequivocal progression of each should be noted throughout follow-up. 
 
C. METHODS FOR EVALUATION OF MEASURABLE DISEASE 
 
All measurements should be taken and recorded in metric notation using a ruler or calipers.  All baseline evaluations should be 
performed as closely as possible to the beginning of treatment and never more than 4 weeks before the beginning of the 
treatment. 
 
Note: 
The same method of assessment and the same technique should be used to characterize each identified and reported lesion at 
baseline and during follow-up.  Imaging-based evaluation is preferred to evaluation by clinical examination unless the lesion(s) 
being followed cannot be imaged but are assessable by clinical exam. 
 
Clinical Lesions:  Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules and 
palpable lymph nodes) and  10 mm diameter as assessed using calipers (e.g., skin nodules).  In the case of skin lesions, 
documentation by color photography, including a ruler to estimate the size of the lesion, is recommended.  
 
Chest X-ray:  Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by 
aerated lung.  However, CT is preferable.  
 
Conventional CT and MRI:  This guideline defines measurability of lesions on CT scan based on the assumption that CT slice 
thickness is 5 mm or less.  If CT scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion should 
be twice the slice thickness.  MRI is also acceptable in certain situations (e.g. for body scans).   
Use of MRI remains a complex issue.  MRI has excellent contrast, spatial, and temporal resolution; however, there are many 
image acquisition variables involved in MRI, which greatly impact image quality, lesion conspicuity, and measurement.  
Furthermore, the availability of MRI is variable globally.  As with CT, if an MRI is performed, the technical specifications of 
the scanning sequences used should be optimized for the evaluation of the type and site of disease.  Furthermore, as with CT, 
the modality used at follow-up should be the same as was used at baseline and the lesions should be measured/assessed on the 
same pulse sequence.  It is beyond the scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters for 
all scanners, body parts, and diseases.  Ideally, the same type of scanner should be used and the image acquisition protocol 
should be followed as closely as possible to prior scans.  Body scans should be performed with breath-hold scanning 
techniques, if possible. 
 
PET-CT:  At present, the low dose or attenuation correction CT portion of a combined PET-CT is not always of optimal 
diagnostic CT quality for use with RECIST measurements.  However, if the site can document that the CT performed as part of 
a PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the CT portion of the PET-CT 
can be used for RECIST measurements and can be used interchangeably with conventional CT in accurately measuring cancer 
lesions over time.  Note, however, that the PET portion of the CT introduces additional data which may bias an Investigator if it 
is not routinely or serially performed.   
 
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be used as a method of measurement.  
Ultrasound examinations cannot be reproduced in their entirety for independent review at a later date and, because they are 
operator dependent, it cannot be guaranteed that the same technique and measurements will be taken from one assessment to the 
next.  If new lesions are identified by ultrasound in the course of the study, confirmation by CT or MRI is advised.  If there is 
concern about radiation exposure at CT, MRI may be used instead of CT in selected instances. 
 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor evaluation is not advised.  However, such 
techniques may be useful to confirm complete pathological response when biopsies are obtained or to determine relapse in trials 
where recurrence following complete response (CR) or surgical resection is an endpoint. 
 
Tumor Markers:  Tumor markers alone cannot be used to assess response.  If markers are initially above the upper normal 


 
 
 
 
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limit, they must normalize for a patient to be considered in complete clinical response.  Specific guidelines for both CA-125 
response (in recurrent ovarian cancer) and PSA response (in recurrent prostate cancer) have been published [JNCI 96:487-488, 
2004; J Clin Oncol 17, 3461-3467, 1999; J Clin Oncol 26:1148-1159, 2008].  In addition, the Gynecologic Cancer Intergroup 
has developed CA-125 progression criteria which are to be integrated with objective tumor assessment for use in first-line trials 
in ovarian cancer [JNCI 92:1534-1535, 2000]. 
 
Cytology, Histology:  These techniques can be used to differentiate between partial responses (PR) and complete responses 
(CR) in rare cases (e.g., residual lesions in tumor types, such as germ cell tumors, where known residual benign tumors can 
remain). 
 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens during treatment when the 
measurable tumor has met criteria for response or stable disease is mandatory to differentiate between response or stable 
disease (an effusion may be a side effect of the treatment) and progressive disease. 
 
 
FDG-PET:  While FDG-PET response assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression (particularly possible 'new' disease).  New lesions 
on the basis of FDG-PET imaging can be identified according to the following algorithm:  
 
a. 
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of PD based on a new lesion. 
b. 
No FDG-PET at baseline and a positive FDG-PET at follow-up:   
• 
If the positive FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD.   
• 
If the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, additional follow-up CT  
scans are needed to determine if there is truly progression occurring at that site (if so, the date of PD will be the 
date of the initial abnormal FDG-PET scan).   
• 
If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that is not progressing 
on the basis of the anatomic images, this is not PD. 
c. 
FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy in cases where a residual 
radiographic abnormality is thought to represent fibrosis or scarring.  The use of FDG-PET in this circumstance should 
be prospectively described in the protocol and supported by disease-specific medical literature for the indication.  
However, it must be acknowledged that both approaches may lead to false positive CR due to limitations of FDG-PET 
and biopsy resolution/sensitivity. 
 
Note: 
A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake greater than twice that of the surrounding 
tissue on the attenuation corrected image. 
D. RESPONSE CRITERIA 
 
1. 
Evaluation of Target Lesions 
 
 Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes (whether target or non-
target) must have reduction in short axis to < 10 mm. 
 
 Partial Response (PR):  At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the 
baseline sum diameters. 
 
 Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target lesions, taking as reference the 
smallest sum on study (this includes the baseline sum if that is the smallest on study).  In addition to the relative increase of 
20%, the sum must also demonstrate an absolute increase of at least 5 mm.   
 
Note:       The appearance of one or more new lesions is also considered progression. 
 
 Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as 
reference the smallest sum diameters while on study. 
 
 
2.  Evaluation of Non-Target Lesions 
 
Complete Response (CR):  Disappearance of all non-target lesions and normalization of tumor marker level.  All lymph 
nodes must be non-pathological in size (< 10 mm short axis). 


 
 
 
 
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Note:  
 If tumor markers are initially above the upper normal limit, they must normalize for a patient to be considered in complete 
clinical response. 
 
 
Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the 
normal limits. 
 
Progressive Disease (PD):  Appearance of one or more new lesions and/or unequivocal progression of existing non-target 
lesions.  Unequivocal progression should not normally trump target lesion status.  It must be representative of overall 
disease status change, not a single lesion increase.     
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating physician should 
prevail in such circumstances, and the progression status should be confirmed at a later time by the review panel (or 
Principal Investigator). 
 
3.  
Evaluation of Best Overall Response 
 
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence 
(taking as reference for progressive disease the smallest measurements recorded since the treatment started).  The patient's 
best response assignment will depend on the achievement of both measurement and confirmation criteria. 
 
For Patients with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response when 
Confirmation is Required* 
CR 
CR 
No 
CR 
> 4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
 
> 4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-PD/Not evaluated 
No 
PR 
SD 
Non-CR/Non-PD/Not evaluated 
No 
SD 
Documented at least once  
> 4 wks. from baseline** 
PD 
Any 
Yes or No 
PD 
 
no prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
*      See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
**    Only for non-randomized trials with response as primary endpoint. 
***  In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease 
progression. 
 
Note:  Patients with a global deterioration of health status requiring discontinuation of treatment without objective 
evidence of disease progression at that time should be reported as “symptomatic deterioration.”  Every effort 
should be made to document the objective progression even after discontinuation of treatment. 
 
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/Non-PD* 
Not all evaluated 
No 
Not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*   Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as an 
endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is not 
advised. 
 
 
 
E. DURATION OF RESPONSE 
 
Duration of Overall Response:  The duration of overall response is measured from the time measurement criteria are met for 
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as reference for progressive disease the smallest measurements recorded since the treatment started). 
 
The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that 
progressive disease is objectively documented. 
 
 
Duration of Stable Disease:  Stable disease is measured from the start of the treatment until the criteria for progression are 
met, taking as reference the smallest measurements recorded since the treatment started, including the baseline measurements.  
 
F. PROGRESSION-FREE SURVIVAL 
 
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. 
 
Adapted from: Eisenhauer EA, Therasse P, Bogaerts J, et. al.  New response evaluation criteria in solid tumours: revised 
RECIST guideline (version 1.1). Eur. J. Cancer. 2009; 45:229-247. 
 
 
<http://www.eortc.be/recist/documents/RECISTGuidelines.pdf >  
 
 
 
 


 
 
 
 
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APPENDIX G 
Grading and Management of Infusion Reactions 
 
Grading of Infusion Reactions 
 
The CTCAE v5.0* definition of infusion-related reactions (General Disorders and Administration Site Conditions) is 
shown below. Symptoms occurring during or following infusion of investigational therapy may also be defined 
according to AE categories such as allergic reaction, anaphylaxis, or cytokine release syndrome.  In the setting of 
symptoms occurring during or following infusion of investigational therapy, investigators are encouraged to use the AE 
term “Infusion-related Reaction” and any additional terms (including those not listed here) that best describe the event.  
Those described should be graded as follows: 
 
TABLE 15:  GRADING OF INFUSION REACTIONS 
Adverse 
Event 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Infusion 
related 
reaction 
Mild transient 
reaction; infusion 
interruption not 
indicated; 
intervention not 
indicated 
Therapy or infusion 
interruption indicated but 
responds promptly to 
symptomatic treatment 
(e.g., antihistamines, 
NSAIDS, narcotics, IV 
fluids); prophylactic 
medications indicated for 
<=24 hrs 
Prolonged (e.g., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial improvement; 
hospitalization indicated for 
clinical sequelae 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Death 
Definition: A disorder characterized by adverse reaction to the infusion of pharmacological or biological substances. 
Allergic 
reaction 
Systemic  
intervention not 
indicated 
Oral intervention indicated  
Bronchospasm; hospitalization 
indicated for clinical sequelae 
intravenous intervention 
indicated 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Death 
Definition: A disorder characterized by an adverse local or general response from exposure to an allergen. 
Anaphylaxis 
- 
- 
Symptomatic bronchospasm, 
with or without urticaria; 
parenteral intervention indicated; 
allergy-related 
edema/angioedema; hypotension 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Death 
Definition: A disorder characterized by an acute inflammatory reaction resulting from the release of histamine and histamine-like substances from 
mast cells, causing a hypersensitivity immune response. Clinically, it presents with breathing difficulty, dizziness, hypotension, cyanosis and loss of 
consciousness and may lead to death. 
Cytokine 
release 
syndrome 
Fever with or 
without 
constitutional 
symptoms 
Hypotension responding 
to fluids; hypoxia 
responding to < 40% O2 
Hypotension managed with one 
pressor; hypoxia requiring ≥ 
40% O2 
Life-threatening 
consequences; 
urgent intervention 
indicated 
Death 
Definition: A disorder characterized by fever, tachypnea, headache, tachycardia, hypotension, rash, and/or hypoxia  is caused by the release of 
cytokines from the cells. 
*See < https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm > 
 
 
 
Guidelines for Management of Infusion Reactions 
 
Consistent with usual medical practice, selected parenteral medications may be utilized for Grade > 2 
allergic/hypersensitivity reactions.  The Sponsor should be contracted immediately if questions arise concerning the 
grade of the reaction.  The following are recommended management guidelines for infusion reactions associated 
with AVID100 administration.  In all cases the Investigator should use best clinical judgment in managing such 
reactions. 
 


 
 
 
 
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TABLE 16:  MANAGEMENT OF INFUSION REACTIONS 
Grade 1 
• Consider slowing the infusion to 50% of the prior rate 
• Monitor the patient for worsening condition 
• If the infusion is extended, administer subsequent infusions at the prolonged rate 
Grade 2 
 
• Interrupt the infusion for a minimum of 30 minutes 
• Administer additional pharmacologic therapy (e.g., diphenhydramine, acetaminophen) and appropriate 
supportive care (e.g., oxygen), as medically indicated  
• Resume the infusion at 50% of the prior rate once the infusion reaction has resolved or decreased to Grade 1 
• Monitor the patient for worsening condition 
• Administer subsequent infusions at the prolonged rate 
> Grade 3 
 
• Stop the infusion  
• Administer additional pharmacologic therapy (diphenhydramine, dexamethasone) and appropriate 
supportive care (e.g., oxygen) for the infusion reaction, as medically indicated  
• Administer epinephrine or bronchodilators as medically indicated 
• Hospital admission for observation may be indicated 
• Do not resume infusion after a > Grade 3 reaction 
• Patients who have a  Grade 3 infusion reaction will be considered to have had a DLT and will be either 
discontinued from treatment, or receive subsequent treatments with a reduced dose of AVID100 (see 
Section 8.3.2; Dose Reduction) 
• Patients who have a > Grade 3 infusion-related reaction will be considered to have had a DLT and will be 
discontinued from treatment 
• Administer subsequent infusions at the prolonged rate 
 
 
In the Event of Infusion Prolongation 
 
Any assessments to be performed or samples to be collected (e.g., vital signs, PK) at the end of or following EOI 
will still be performed or collected beginning at the delayed EOI timepoint.  In situations where collection of late 
day samples, in particular the 4h sample, is logistically difficult due to clinic staff availability, an "end of day" 
sample may be obtained at the latest practical time on the day of the reaction.  
 
Rechallenge with a shorter duration of infusion (no less than 2 hours) may be attempted at the Investigator's 
discretion, after a minimum of 2 doses with no evidence of infusion-related toxicity.   
All infusion interruptions and subsequent prolongations, including modified infusion times, as well as the toxicity 
that necessitated them, will be clearly documented on the appropriate page of the patient’s eCRF. 
 
 
Modification of Infusion Duration for the Trial 
 
During Phase 1a, the duration of infusion will be prolonged for all subsequent patients entered to the trial in the 
following situations: 
• 
In the event of a Grade 2 IRR in ≥ two thirds of the patients entered to a cohort, the duration of infusion for 
subsequent patients entered to the trial will be extended by 30 minutes (or longer, if indicated). 
• 
In the event of a Grade 3 or greater IRR in any patient within a cohort, the duration of infusion for 
subsequent patients entered to the trial will be extended by 30 minutes (or longer, if indicated). Such a case 
will also be considered to have met the protocol criteria for a DLT, thus requiring expansion of the cohort 
 
These same criteria will be applied in the event IRRs occur on the extended infusion schedule. In such a case, the 
duration of infusion for subsequent patients entered to the trial will be extended by 30 minutes (or longer, if 
indicated). 


 
 
 
 
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APPENDIX H 
Recommendations for Management of Keratitis and Rash 
 
Management of Keratitis 
Any symptoms of keratitis (corneal inflammation/corneal ulceration) should prompt a follow-up ophthalmologic 
evaluation as soon as possible. 
• Grade 1 Keratitis  
Will result in treatment with preservative-free artificial tears, ointments, and/or other therapies as clinically 
indicated, with a follow-up examination within 2 weeks. 
• Grade 2 Keratitis 
Will be managed as described above, with continuation of study drug  dosing at the discretion of the 
investigator.  Persistence of Grade 2 keratitis (> 2 weeks), while on therapy will result in immediate interruption 
of dosing with study drug.  Patients may be retreated at the discretion of the investigator, at a reduced dose, 
after resolution or amelioration of findings to ≤ Grade 1 severity.   
• Grade 3 Keratitis 
Will result in immediate interruption of study drug  dosing.  Patients may be retreated at the discretion of the 
investigator, at a reduced dose, after resolution or amelioration of findings to ≤ Grade 1 severity.   
Patients with persistent ≥ Grade 2 keratitis after 7 days of interrupted dosing will be discontinued from further 
participation in the trial, with scheduled follow-up ophthalmologic assessments at a frequency deemed 
medically appropriate. 
 
 
Management of Rash 
Several different treatment options have been utilized in order to relieve symptoms and improve the rash associated 
with study drug  therapy.  When possible, topical therapy is preferred.  Although no single approach has emerged 
as superior, recommendations for management are as follows: 
• 
Grade 1Rash  
 
Mild, grade 1 rash has been observed to resolve without intervention.   
• 
Grade 2 Rash 
 
May be treated according to current standard of care 
 
• 
Grade 3 (or greater) Rash (or intolerable Grade 2 Rash) 
 
Will result in dose reduction of study drug and treatment. 
 


 
 
 
 
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APPENDIX I 
Sample Size Considerations 
 
The sample size considerations are presented for estimation and testing with respect to the response rate for efficacy, 
i.e., inference regarding the true probability of response. The normal approximation to the binomial distribution is 
used, unless otherwise specified.  
Let π denote the true unknown probability of interest. The goal is to conclude that this probability exceeds a 
specified value (π0). 
Testing the null hypothesis H0: π = π0 against the one-sided alternative hypothesis H1: π > π0 can be used to 
achieve this goal. This test is performed at the 2.5% level, which is equivalent to testing the two-sided alternative at 
the 5% level. 
The test procedure is to conclude that the observed result is statistically significant if: 
 
n1/2 (p- π0)/(p(1-p))1/2 >1.96, 
where p is the observed proportion of responses from n subjects. 
The smallest value of p required to have statistical significance for specified values of π0 and n is the solution to this 
inequality, but a “closed expression” is not possible. This value of p is determined by evaluating n1/2 (p- π0)/(p(1-
p))1/2 and then comparing this value to 1.96, and is given in the following table. 
 
SMALLEST VALUE OF P (%) FOR STATISTICAL SIGNIFICANCE  
(Level 0.05, 2-Sided)  
π 0 
N=15 
N=20 
N=34 
N=40 
0.20 
45.2 
41.7 
36.2 
35.0 
0.25 
50.4 
46.9 
41.6 
40.2 
0.30 
55.2 
51.9 
46.8 
45.5 
0.35 
59.9 
56.8 
51.8 
50.5 
0.40 
64.3 
61.4 
56.7 
55.5 
0.45 
68.6 
65.8 
61.4 
60.2 
0.50 
72.6 
70.1 
66.0 
64.9 
 
Other alternatives for this examination are power considerations: (1) determination of power for specified n and 
assumed true value of π, (2) determination of n required to have power 80% or 90% for assumed true value of π, and 
(3) determination of π for specified n and power. The latter is related to a confidence interval (CI) because it is 
estimation of π, so the 95% CI is presented for specified values of the observed proportion of responses from n 
subjects (p); this is also related to the values given in the first Table. In addition to the 95% CI using the normal 
approximation, the 95% CI using the exact binomial method is also presented as these are presented in the protocol 
for p=15% and 25%. 
Power (%) for specified n and sample size (n) required for power 80% or 90% for assumed true value of the true 
probability of response (π) are given in the following table. 
 
 
 
 
 
 


 
 
 
 
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POWER (%) FOR SPECIFIED N 
SAMPLE SIZE REQUIRED 
FOR SPECIFIED POWER 
Null (π0) 
True (π) 
N=15 
N=20 
N= 34 
N=40 
Power=80% 
Power=90% 
0.20 
0.30 
13.2 
16.3 
24.6 
28.1 
165 
221 
 
0.35 
22.9 
29.0 
45.0 
51.2 
80 
107 
 
0.40 
35.2 
44.7 
66.3 
73.3 
48 
64 
 
0.45 
49.5 
61.3 
83.4 
88.8 
32 
42 
 
0.50 
64.2 
76.5 
93.8 
96.7 
22 
30 
 
0.55 
77.8 
88.2 
98.4 
99.4 
16 
22 
 
0.60 
88.5 
95.5 
99.7 
99.9 
12 
16 
0.25 
0.45 
34.3 
43.6 
65.0 
72.0 
49 
66 
 
0.50 
0.491 
60.9 
83.0 
88.5 
32 
43 
 
0.55 
0.646 
76.9 
94.0 
96.8 
22 
29 
 
0.60 
0.790 
89.2 
98.6 
99.5 
16 
21 
0.30 
0.50 
0.341 
43.2 
64.5 
71.6 
50 
66 
 
0.55 
0.495 
61.3 
83.4 
88.8 
32 
42 
 
0.60 
0.660 
78.2 
94.6 
97.2 
21 
29 
 
0.65 
0.811 
90.7 
99.0 
99.6 
15 
20 
0.35 
0.55 
0.343 
43.6 
65.0 
72.0 
49 
66 
 
0.60 
0.507 
62.6 
84.5 
89.8 
31 
41 
 
0.65 
0.683 
80.3 
95.6 
97.8 
20 
27 
0.40 
0.60 
0.352 
44.7 
66.3 
73.3 
48 
64 
 
0.65 
0.528 
65.0 
86.4 
91.2 
29 
39 
 
* Computed using EAST 6.4 
 
 
95% CI FOR PROBABILITY OF RESPONSE (Π;% ) 
p 
Normal Approximation to Binomial 
Exact Binomial 
N=15** 
N=20 
N=34** 
N=40 
N=15 
N=20 
N=40 
10% 
(0, 25.2)* 
(0, 23.1)* 
(0, 20.1)* 
(0.7, 19.3) 
 
(1.2, 31.7) 
(2.8, 23.7) 
15% 
(0, 33.1)* 
(0, 30.6)* 
(3.0, 27.0) 
(3.9, 26.1) 
 
(3.2, 37.9) 
(5.7, 29.8) 
20% 
(0, 40.2)* 
(2.5, 37.5) 
(6.6, 33.4) 
(7.6, 32.4) 
(4.3, 48.1) 
(5.7, 43.7) 
(9.1, 35.6) 
25% 
(3.1, 46.9) 
(6.0, 44.0) 
(10.4, 39.6) 
(11.6, 38.4) 
 
(8.7, 49.1) 
(12.7, 41.2) 
30% 
(6.8, 53.2) 
(9.9, 50.1) 
(14.6, 45.4) 
(15.8, 44.2) 
 
(11.9, 54.3) 
(16.6, 46.5) 
35% 
(10.9, 59.1) 
(14.1, 55.9) 
(19.0, 51.0) 
(20.2, 49.8) 
 
(15.4, 59.2) 
(20.6, 51.7) 
40% 
(15.2, 64.8) 
(18.5, 61.5) 
(23.5, 56.5) 
(24.8, 55.2) 
(16.3, 67.7) 
(19.1, 63.9) 
(24.9, 56.7) 
p= Observed Proportion 
From epitools.ausvet.com.au 
* Computed lower limit is negative. 
** Not all observed proportions given above are possible for n=15 and n=34 
 
The overall sample size for the Phase 2a Expansion Cohorts will be approximately 60 patients treated at the RP2D, 
with accrual to be divided among up to 3 cohorts (tumor types mTNBC, SCCHN, and Sq-NSCLC); additional 
patients may be entered to the Phase 2a Expansion Cohorts if fewer than 30 patients are required to establish the 
RP2D in Phase 1a.   
The current planned initial enrollment of 15 patients per cohort (or in each subcohort in the case of TNBC) may be 
expanded based on initial observation of  > 2 objective responses (13% ORR) in any of the three indications (two 
separate cohorts in TNBC) to be studied. This sample size has a 35.2% power to detect a 40% ORR compared to a 
potential control response of 20% at a two-sided 0.05 level of significance.  In addition, the power is between 45-
54% to detect objective response rates between 20 to 40% in a 15 patient cohort at a two-sided 0.05 level of 
significance.   After evaluation of the initial ORR in each cohort a decision will be made to either continue to 
include patients with treatment-refractory advanced/metastatic malignancies without other therapeutic options on an 
open-label trial (e.g., if the objective response rate ≥ 20% and responses are durable), consider alternative trial 
designs for further exploration of efficacy in any of the indications, or discontinue development if fewer than two (0 
or 1) responses are observed in any of the three initial fifteen patient cohorts. The durability of objective responses 


 
 
 
 
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and disease stabilization > 8 weeks will also be considered in the decision to expand cohorts or pursue other options 
for further development in any of the three indications. 
TEST OF NULL AT 0.05 LEVEL (TWO SIDED) USING NORMAL APPROXIMATION   
Power (%) for specified N (Computed using EAST 6.4) 
Null (π 0) 
True (π) 
N=15 
N=20 
N=34 
N=40 
0.20 
0.30 
13.2 
16.3 
24.6 
28.1 
 
0.40 
35.2 
44.7 
66.3 
73.3 
 
0.50 
64.2 
76.5 
93.8 
96.7 
 
0.60 
88.5 
95.5 
99.7 
99.9 
 
 


 
 
 
 
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cancers to therapeutic target in human neoplasia. J Clin Oncol. 2001; 19(18 Suppl): 32S-40S. 
 
77. Roberts RB, Arteaga CL, and Threadgil DW. Modeling the cancer patient with genetically 
engineered mice: Prediction of toxicity from molecule-targeted therapies. Cancer Cell. 2004; 
5: 115-120. 
 
78. Vectibi® (panitumumab) [package insert]. Amgen, Inc., Thousand Oaks, CA. 2015. 
 
79. Portrazza® (necitumumab) [package insert]. Eli Lilly and Company, Indianapolis, IN. 2015. 
 
80. Adcetris® (brentuximab vedotin) [package insert]. Seattle Genetics, Bothell, WA. 2016. 
 
 
 
 

ICF_001.pdf: 
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Protocol Number: AVID100-01 
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MODEL INFORMED CONSENT DOCUMENT 
AGREEMENT TO BE IN A RESEARCH STUDY 
 
NAME OF SPONSOR COMPANY: FORBIUS (FORMATION BIOLOGICS, CORP. 
CITY AND STATE: 
 
Austin, Texas, USA 
 
STUDY NAME: 
 
A Phase 1a/2a Cohort Dose Escalation Trial to Determine the 
Safety, Tolerance, Maximum Tolerated Dose, and Preliminary 
Antineoplastic Activity of AVID100, an Anti-Human Epidermal 
Growth Factor Receptor (EGFR) Monoclonal Antibody Linked 
to the Maytansinoid DM1, in Patients with Advanced or 
Metastatic Solid Tumors of Epithelial Origin 
 
STUDY NUMBER: 
 
AVID100-01 (Version 11; 30May2020) 
 
 
Model Informed Consent (Version 5; 30May2020) 
 
NAME OF STUDY DOCTOR: 
(to be completed) 
TELEPHONE NUMBER(S): 
(to be completed) 
PATIENT: 
 
(to be completed) 
 
INTRODUCTION 
You are being invited to take part in a research study.  The doctors at __    site______ study the nature of 
cancer in an attempt to develop improved methods of diagnosis and treatment. They are conducting this 
study to assist Formation Biologics, Inc. (also known as Forbius, and hereafter referred to as the Sponsor) 
in studying an investigational drug called AVID100 (hereafter referred to as the study medication or study 
drug).   
AVID100 is referred to as an investigational drug because it is in the early stages of development and has 
not been approved by any regulatory authority, which means that it is not available to be prescribed or 
sold.  It is being tested as a possible treatment for your disease.  You are being asked to take part in this 
study because you have a particular type of solid tumor cancer (either breast cancer, cancer of the head 
and neck, or lung cancer) that the study hopes to evaluate, and your disease has not responded to 
conventional treatment. 
It is important for you to know that the doctors involved in the study have no financial interest in either 
Formation Biologics or the results of this study.  In addition, it is important for you to know that 
Formation Biologics is providing the funding to cover the costs of conducting this study. 
Before you decide if you want to join this study, it is important for you to know why the research is being 
done, how your information will be used, what the study will involve, and the possible benefits, risks, and 
discomforts, so that you can make an informed decision about whether you wish to participate.  This 
process is known as “informed consent.”  This document that you are reading is referred to as a “consent 


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form” and it gives detailed information about the study, as well as how your confidentiality will be 
maintained.  No further tests or procedures will be required of you for this study other than those 
that are described in this form.   
Please take as much time as you need to carefully read this consent form.  Some words may be new to 
you, and you may find some of the language difficult to understand.  If so, please ask questions. The 
information it contains will be discussed with you.  If there is anything you do not understand, or if you 
would like more information, please ask the study doctor or study staff.  You may also discuss the study 
with your family, friends, and your own physician if you wish.   
If you decide that you want to join this study, you will be asked to sign this consent form before having 
any assessments or tests performed.  The study staff will give you a copy to take home with you to review 
prior to signing if you wish, and if you sign it, you will be given a copy of the signed version for your 
records. You will not be able to begin the study until you have read and signed this form.  
Please know that you are free to refuse to participate in this study, and if you agree to join, you are free to 
leave the study at any time without having to give a reason. A decision not to take part in this study, or to 
withdraw at any time, will not affect your health care in any way. 
1. 
BACKGROUND AND PURPOSE OF THE STUDY 
Cancer is a destructive process caused by abnormal, out of control growth of cells.  Cancers (or 
malignancies) fall into two categories.  Blood (or hematologic) cancers are the result of an abnormal 
growth of cells in the blood, bone marrow or lymph cells of the body.  Solid tumor cancers consist of an 
abnormal growth of cells in other body tissues such as the lung, breast, colon, prostate, ovary, stomach, or 
liver.  In advanced stages of disease, solid tumors may spread from the organ where they began to other 
organs of the body, a process called metastasis, and as a result cause far-reaching damage. Epithelial 
malignancies are a particular group of solid tumor cancers that come from tissues lining the external 
(skin) and internal (mucus membrane) surfaces of the body, and are the types of cancers this study will 
evaluate.   
You are being invited to take part in this research study because you have an “epithelial” solid tumor 
cancer, one of the types to be tested in this study (either breast cancer, cancer of the head and neck, or 
lung cancer), and standard treatments have either failed to control your disease, you are unable to tolerate 
the side effects, or no effective therapy is available. Before agreeing to join this study, you should discuss 
with your study doctor whether all standard therapies that are available for your cancer have been tried.  
Once such drug to discuss, if you have a cancer of the head and neck, is cetuximab which is approved by 
the U.S. Food and Drug Administration (FDA) for use in patients with advanced forms of head and neck 
cancer after a therapy that contains a platinum-based drug has been shown not to work or not be tolerated.  
As a potential drug for the treatment of cancer, AVID100, the study medication, is a combination of an 
antibody that is known to target the surface of certain types of cancer cells, joined by a chemical linker to 
a drug that is known to kill certain types of cancer cells (a cancer chemotherapy drug).  As a result, 
AVID100 is thought to work by reaching cancer cells, and then damaging or killing them, thereby 
affecting how cancer cells grow and spread.  This is the first study to test AVID100 in humans.  
AVID100 is not known to be a cure, but it is being tested to see if it can stop or control your illness.   


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At this point, we neither know whether the study medication will provide any benefit for cancer patients, 
nor do we know all of the side effects that may occur when patients receive the study medication.  Studies 
performed with AVID100 in monkeys have shown how the drug is handled in these animals, and have 
provided early information about the possible side effects.  These animal studies have allowed us to 
choose the starting dose level for studies in humans, and identify a range of higher dose levels that we 
believe may be safe to give to patients.  Extensive research has shown that with higher doses of cancer 
medication there is generally a greater likelihood of patients responding to treatment.  However, there is 
also a higher chance of side effects.   
If you decide to participate, you will be monitored carefully throughout the study.  At the first sign of an 
unacceptable side effect your doctor will decide how best to take care of you, including removing you 
from the study if your doctor feels this is in your best interest. 
This study will be conducted in two parts, Part 1 and Part 2 (or Phase 1 and Phase 2).   
• 
Part 1 has been completed.  The main goal of Part 1 was to determine the highest dose of the 
study medication that can be given safely and with the least harmful side effects to patients with 
epithelial solid tumor cancers.  
• 
Part 2 is ongoing.  The main goals of Part 2 will be to test further the safety and effects of that 
highest safe dose in additional patients who have specific types of epithelial solid tumor cancers.  
The specific types of tumors to be tested are:  1) advanced breast cancer; 2) cancers of the head 
and neck; and 3) lung cancer.  
You are being invited to participate in Part 2 of the trial. Your study doctor will explain the 
requirements of this part when he or she discusses this study with you. 
2. 
DESCRIPTION OF THE STUDY 
What kind of study is this? 
• 
Part 2 is an open-label study.  “Open-label” means that the study doctor knows exactly what 
treatment is being given to each patient.  The highest dose determined to be safe in Part 1 is being 
given to all patients in Part 2.   
What doses of study medication will be tested, and what dose will I receive? 
In Part 1 increasingly higher doses of study medication were tested in small groups of patients.  Doses 
tested were based on a calculation of a patient’s height and body weight (referred to as “body surface 
area”).  The highest safe dose tested was the dose of 220 milligrams per meter squared per dose (220 
mg/m2).    
This is the dose you will receive, unless the study doctor decides a lower dose will be safer for you.  
How will the study medication be given to me? 
The study medication will be given intravenously (in the vein).  Before you are given study medication, a 
needle will be used to insert a thin, flexible tube (catheter) into one of your veins, usually in your arm.  
You will receive the study medication into your vein through this flexible tube, a procedure referred to as 
an intravenous infusion, or an IV infusion.  If you already have a catheter or a port that allows doctors to 


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give you medication into one of your veins, consideration will be given to using this to deliver your study 
medication.   
Your infusions will be given using an infusion pump and an inline filter. An infusion pump is a device 
that delivers medications into your body at a controlled rate.  An inline filter is a small filter in the plastic 
tubing used to prevent bacteria and other unnecessary or unwanted materials from getting into your body. 
Each IV infusion of study medication will take about 2 hours.  If you have side effects that appear to be 
related to how quickly the study medication is being infused, it may be given to you more slowly, about 
30 minutes or 1 to 1½ hours longer, depending on what your study doctor thinks is most safe.     
How often will the study medication be given to me? 
Study medication will be given once every 3 weeks.  This means that study medication will be given on 
Day 1 of each 21-day period.  Each of these 21-day (or 3 week) periods is referred to as one “cycle” of 
dosing.   
Will I need to stay in the hospital during this study? 
No, it is not expected that you will need to stay in the hospital during this study.  Administration of study 
medication, and all the tests and procedures associated with this study can be done on an outpatient basis, 
meaning you will need to come to the clinic to be seen by the study doctors and study team, but you will 
not need to stay overnight, unless you have a side effect and the study doctors think staying in the hospital 
will be safer for you.   
How will the study doctor know if I have side effects?  
The first time you are given the study medication (on Cycle 1/Day1), you will be observed for a minimum 
of 2 hours after the end of infusion.  For all later doses (Cycle 2 and beyond) you will be observed for a 
minimum of 1 hour following the infusion. 
During Cycle 1, which will be the first 3 weeks you are on study, and throughout your participation in this 
trial, your doctor will ask questions about how you are feeling and whether you are having any side 
effects.  In addition, throughout the study your doctor will carefully monitor your condition by physical 
exams, lab tests to check your blood and urine, as well as ECGs to check your heart, pulmonary function 
tests (also called PFTs) to check your lungs, imaging studies such as chest X-rays to check your lungs, as 
well as CT scans or MRI scans to further check your lungs and to check the overall status of your disease.  
Will I receive any medications to prevent side effects? 
Yes, you will.  Beginning with your first dose of study drug, you will receive standard medications before 
each dose to reduce the risk of a side effect called an “infusion reaction.”  You will be given these 
medications also referred to as "premedication", to take by mouth before each infusion.  You will need to 
take a dose by mouth about 12 hours and another dose about 6 hours before your scheduled infusion of 
study drug.  In addition, when you arrive at the study center the morning of your infusion, you will be 
given premedications by IV and perhaps also by mouth beginning at least 30 minutes before each infusion 
of study drug.  There are more details about infusion reactions later in this consent form.   


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What will happen if I have other side effects? 
At the first sign of unacceptable side effects, your doctor may decide to prescribe additional medications 
to treat or attempt to prevent the side effects.   
In addition, study medication dosing may be interrupted (stopped temporarily), dosing may be slowed 
(your 2 hour infusion may be stretched to a longer period), the dose may be lowered, or the dosing may be 
stopped completely at any time if you experience any side effects during the treatment periods that 
suggest such actions may help you.  If necessary, your doctor may decide to remove you from the study.   
How many cycles of study medication will I receive? 
At the end of the first cycle, if you are experiencing no significant side effects, you will go on to receive 
an additional cycle.  Your doctor will monitor your condition carefully throughout this period.   
As the study progresses, the number of cycles you will receive will also depend on the results of imaging 
studies (scans) performed to assess the status of your disease.  
• 
At the end of 2 cycles (after receiving 2 doses [after 6 weeks]), and every 2 cycles (6 weeks) 
thereafter, you will have imaging studies performed. 
At these points, if you agree, and if there is evidence that the study treatment may be improving or 
stabilizing your disease, your doctor may recommend that you continue to receive additional cycles.  You 
may continue receiving cycles of study medication as long as your doctor recommends, as long as you 
consent to participate, and as long as your disease is not progressing and requiring alternative therapy, 
provided you are tolerating any side effects from the study medication.   
How many hospitals and how many patients will take part in this study? 
 
It is expected that about 90 patients in total will participate in this study. 
• 
Part 1:  The initial part of this study took place at 2 different clinics in the United States (U.S.).  
24 patients participated in this part of the study.   
• 
Part 2:  This part of the study will take place at approximately 6 to 12 clinics in the U.S. and 
Canada.  Approximately 60 patients will participate in this part of the study.   
3. 
TAKING PART IN THE STUDY  
It is up to you to decide whether or not to take part in the study. You are free to refuse to participate. Even 
if you refuse to participate in this study, you will not be disadvantaged in any way.  Your refusal will not 
affect the medical treatment and care you are entitled to receive. If you decide to participate, you may 
change your mind and decide to withdraw from the study at any time and for any reason. You are not 
required to explain your reasons for withdrawing. If you withdraw, you will not suffer any penalty or loss 
of benefits regarding your future care.  
Your study doctor can also withdraw you from the study at any time if he or she feels it is in your best 
interest, or if you cannot comply with study requirements.  
In addition, your participation in the study may be stopped by the Sponsor, by regulatory authorities, or 
by your hospital’s independent Institutional Review Board (IRB) or independent research Ethics 


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Committee (EC) (The IRB or EC is responsible for reviewing the design and approving the ethical 
conduct of this study in order to assure that patient safety is maintained and patients’ rights are not 
violated) at any time without your consent.  If this were to happen, it would occur after the reason(s) for 
doing so has been explained to you, and after you have been given advice about continued care for your 
condition, if this is appropriate.  
Also, the Sponsor has the right to stop the study for medical or business reasons. If this happens, all 
patients participating in the study will be withdrawn. 
If you withdraw (or are withdrawn) from the study, you will be asked to go through End of Treatment and 
One Month Follow-up procedures detailed later in this consent form. 
4. 
STUDY PROCEDURES  
What tests and procedures will I undergo as part of this study? 
If you agree to participate in this study, first you will have several tests and procedures done to see if you 
qualify for the study, and if it is safe for you to participate.  This is called the “Screening” process.  
During Screening for this study, your doctor will ask you many detailed questions about your medical 
history, about your disease and other treatments you may have received for it, and about other 
medications you have taken or are now taking.   
During Screening, as well as throughout the study, your doctor will carefully monitor your condition by 
asking you questions about how you are feeling.  You will also have the following tests and procedures 
performed at Screening and at different times during the study (times that will be detailed later in this 
consent form):   
• 
Your doctor will measure your height, weight, check your vital signs (temperature, blood 
pressure, heart rate, and oxygen content in your blood), perform physical exams always including 
an assessment of your lungs, an eye exam, and lab tests to check your blood and urine.   
• 
If you are a woman who is capable of getting pregnant, you will have pregnancy tests done. 
These tests must be done on a blood sample at screening, but may be done on a blood or urine 
sample when repeated later in the study.  If you are a woman capable of getting pregnant, or a 
man in a relationship with a woman capable of getting pregnant, the doctors will explain to you 
how important it is for a pregnancy not to occur during the study and for a period of at least 3 
months after you have taken your last dose of study medication.  The doctors will then counsel 
you on how best to avoid pregnancy during this period.   
• 
The condition of your heart will be checked by measuring the electrical traces of your heart, a 
painless procedure called an electrocardiogram (ECG).  In addition, you may have another heart 
test, either an echocardiogram (“Echo”) or a multigated acquisition (MUGA) scan, to further 
check the condition of your heart and to assess how well your heart is working as a pump.  These 
tests will be described in more detail later in this consent form.     
• 
The condition of your lungs and how well they are working will be checked by pulmonary 
function tests (PFTs).  These tests will be described in more detail later in this consent form.  You 
will also have chest X-rays to check the status of your lungs. 
• 
Your study doctor will perform tests to check the status of your disease.  You will have imaging 
tests (such as a CT scan or MRI scan) to check the location and size of your cancer.  Whatever 


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test your doctors use to check your disease at the beginning of the study will most likely be the 
same test that will be used later during the study.  The choice of test will depend on your disease 
type because different tests are better for checking different diseases.  These tests will also be 
used to check the status of your lungs. 
• 
Your doctor will ask to evaluate a left-over sample of your tumor that has been stored (archived) 
after a previous biopsy or surgery to determine whether your tumor cells are positive for the 
target of this study medication.  In addition, other tests called “biomarker tests” will be done to 
learn more about the tumor.  Your study doctor will talk to you about arranging to get a small 
portion of that sample sent in so these tests can be done.       
o Tumor testing is required because your tumor must be positive for the target of this 
study medication in order for you to participate.  Tumor samples will be sent to a central 
lab for this testing. 
If a sample of your tumor is not available, or if there is not enough tumor tissue to do all 
the required testing, you will be asked to have a biopsy of your tumor performed.  If this 
is the case, you must be willing to undergo this biopsy in order to determine whether you 
will be eligible to participate in the study.  If such a biopsy is necessary, the study doctor 
will discuss this with you.   
A tumor biopsy is a procedure in which a small sample of your tumor is removed with a 
thin needle. You will be asked to agree to this procedure only if your doctor thinks 
your tumor is safely accessible for biopsy and it is thought that such procedure can 
be done with minimal risk to you. You will receive a painkiller prior to the biopsy 
and/or some anaesthesia to numb the area where the needle will pass. This procedure will 
be described in more detail later in this consent form. 
The following tests and procedures will also be performed during the study, but only after it is determined 
that you qualify for the study and it is considered safe for you to participate: 
• 
You will undergo blood tests that will help the doctors determine how the study medication is 
absorbed by your body and how long it stays in your blood.  These are called “pharmacokinetic 
studies”, or “PK studies.”  Blood samples will be sent to a central lab for this testing.  If there is 
blood left over from these tests, the blood may be used to do some of the “biomarker tests” 
mentioned above.  
• 
You will have blood tests to check whether your body has made antibodies (proteins made by the 
immune system) to the study medication.  These are referred to as “anti-drug-antibody (ADA) 
tests.”  Blood samples will be sent to a central lab for this testing.  Once again, if there is blood 
left over from these tests, the blood may be used to do some of the “biomarker tests” mentioned 
above. 
• 
Your study doctor will ask for a blood sample to do “biomarker tests” on tumor cells that may be 
circulating in your blood.  If you have a cancer of the head or neck, additional tests will be done 
on this sample. 


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Will all patients participating in the study undergo the same tests and procedures? 
All of the tests listed are required, meaning if you participate in this study you must agree to have all of 
them performed. 
Are there other tests that may be performed that are not required, but are considered optional? 
Yes, there is optional testing that may be requested of you.  This testing involves collection of tumor 
tissue for “biomarker tests.”  You may refused these tests and still be eligible to participate in this 
study.  The conditions for this optional testing are as follows:  
• 
Should you require surgery on an area of tumor while you are on this study, the doctors will ask 
your permission to submit a small portion of the tumor tissue for testing.   
• 
Should you have a response to the study medication while you are on this study, or should you 
have a period of no growth of your tumor for more than 8 weeks, the doctors will ask your 
permission to biopsy an area of tumor that remains in order to submit the tumor tissue for testing. 
• 
Should other study findings suggest that more could be learned about the study medication if your 
tumor could be tested after dosing, the doctors will ask your permission to biopsy an area of 
tumor in order to submit the tumor tissue for testing.  
How much blood will be taken from me during this study? 
Routine blood tests require a little more than 1 tablespoon of blood.  One tablespoon of blood is equal to 
about 15 milliliters (mL), and routine blood tests require about 20 mL, although efforts will be made to 
collect smaller amounts of blood for these studies where possible.   
In addition, each PK test requires a teaspoon (5 mL), and a pregnancy test (if you should need one), and 
the anti-drug antibody test each require about 1 teaspoon each (about 5 mL).   
Throughout the study, blood will be taken on all study visit days, but the most blood that will be taken 
from you on any day will be as follows:  
• 
Screening: a little less than 2 tablespoons (about 25 mL)  
• 
Cycle 1 
o Day1: When PK samples will be taken, a little more than 2 tablespoons (about 35 mL)* 
o Day 4: A little more than 1 tablespoon (about 20 mL) 
o Day 8: A little less than 2 tablespoon (about 25 mL) 
• 
Cycles that Follow  
o Day 1:  About 3 tablespoons (about 45 mL) 
o Day 8:  A little more than 1 tablespoon (about 20mL) 
• 
Cycles that Follow except Cycle 5 
o Day 1:  A little more than 3 tablespoons (about 50 mL) 
o Day 8:  A little less than 2 tablespoons (about 25 mL) 
• 
End of treatment visit: about 2 tablespoons (about 30 mL)* 
• 
One month follow-up visit:  about 2 tablespoons (about 30 mL) 


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• 
In addition, if you should have an infusion reaction a little more than a teaspoon of blood will be 
taken (about 10 mL for PK and ADA studies) to be tested so that more can be learned about the 
study medication during these reactions. 
*Patients with cancer of the head or neck will have a little more than 1 tablespoon extra taken on these days 
The total amount of blood taken from you will depend upon how long you remain on the study; cycles 
after Cycle 1 require a little less blood to be taken.    
5. 
SCHEDULE OF TESTING DURING THE STUDY 
You must agree to come to the study center on the days specified by your study doctor, so that the 
necessary tests can be done.  Your study doctor and his or her staff will give you a schedule that lets you 
know when you need to come to the center and will explain what tests will be performed at each visit.   
Most of the tests that will be done throughout the study are routine tests that are part of the normal care of 
patients with your condition.  What you can expect at each point of the study is described below. 
SCREENING  
If you decide to participate, and after you sign this informed consent form, the following tests and 
procedures will be done to make sure it is safe for you to take part in the study.  Most of these tests will be 
done within 14 days before you receive the first dose of study medication, some may be done within 28 
days before you receive the first dose.  The screening process may take more than one day to complete.   
• 
Review of your past medical history:  You will be asked several basic questions (for example, 
your gender, age, and ethnicity).  You will be asked about your past and current health problems 
and about any prior surgical procedures you have had that are not related to your disease. 
• 
Review of your cancer history:  You will be asked about the prior surgical procedures you have 
had that are related to your disease and about the cancer therapies you have received for your 
disease. 
• 
Review of your current medications:  You will be asked about the medications you use currently 
as of the day of screening, including vitamins, nutritional supplements, or herbal medications not 
prescribed by your doctor. 
• 
Performance status:  You will be asked to rate how well you can carry out your normal daily 
activities (this is called performance status). 
• 
Vital signs:  You will have your temperature and vital signs (including your pulse, breathing rate, 
blood pressure, and oxygen concentration in your blood) measured to check your overall health. 
• 
Physical exam:  You will have a complete physical examination including an assessment of your 
general appearance and measurement of your height and weight.  
• 
Eye exam:  You will have an exam of your eyes, including an evaluation of your corneas, which 
are the transparent layers that form the front of the eyes.   
• 
Routine blood and urine tests:  Blood and urine will be collected for routine laboratory tests. 
• 
Pregnancy test:  If you are a woman who may be able to get pregnant, a pregnancy test will be 
done. The results of this test must show that you are not pregnant in order for you to take part in 


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this study.  This test must be done on a blood sample at screening, but may be done on a blood or 
urine sample when repeated later in the study 
• 
ECG:  You will have an electrocardiogram done; this is an electrical tracing of your heartbeat.  
• 
Echo or MUGA:  Either you will have an Echo or a MUGA scan to check the activity and 
function of your heart, but only if you have a history of heart problems. 
• 
Pulmonary function tests:  You will have a group of tests that measure how well your lungs work.  
This includes how well you are able to breathe, and how well your lungs are able to bring oxygen 
to the rest of your body.   
• 
Chest X-ray:  A chest x-ray will be done to check the condition of your lungs. 
• 
CT scan or MRI:  You will have either a CT scan or an MRI to check the status of your disease 
(unless you have had one of these scans within 28 days of the screening visit and the results are 
made available to the study doctor).  
• 
Stored (archival) tumor sample or tumor biopsy:  A request will be made to obtain a sample of 
your tumor tissue from a previous biopsy or surgery to determine whether your tumor is positive 
for the target of this study medication and to do biomarker studies. 
o Providing a sample of tumor tissue is required, and if not available, you will need to 
undergo a biopsy to collect tumor tissue for testing.  The test performed must show that 
your tumor is positive for the target of this study medication for you to be eligible for the 
study, and there must be enough tumor tissue to perform the other required biomarker 
studies.   
Once it is confirmed that you are eligible for the study, and it is safe for you to take part, the following 
will be done: 
• 
A blood sample will be taken to do tests on tumor cells that may be circulating in your blood   
STUDY MEDICATION SCHEDULE 
If your Screening tests show that you can take part in this study, you will receive the study medication into 
your vein (IV) on Day 1 of each 21-day (3-week) cycle. Your study doctor will also provide you with 
premedications to take by mouth.  You will take these medications at home about 12 hours and about 6 
hours before each of your scheduled infusions of study drug.        
STUDY VISIT SCHEDULE 
Cycle 1 
Day 1:  On the first day of dosing, you will need to remain at the clinic, until about 2 hours after your 
study medication infusion is completed.  
Several blood samples will be taken on this day, so a member of the study team will insert a catheter (a 
thin, flexible tube also called “an IV”) into one of the veins (probably in your arm) so you won’t need to 
be stuck with a needle many times to take the samples.   
During this visit premedication will be administered and the following will be done:   


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Items that are italicized: may not need to be repeated if you had your Screening visit within 7 days before 
starting the study medication 
• 
Review of your medications and review of any symptoms that you may be experiencing or have 
been experiencing since the last visit 
• 
Vital signs  
• 
Physical exam including body weight and lung assessment, and assessment of your performance 
status  
• 
Routine blood and urine sample collections to check your overall health  
• 
Pregnancy test if you are a woman who may be able to get pregnant – required within 2 working 
days of receiving your first dose 
• 
PK blood sample collection  – one sample before getting your study medication dose, and one at 
the end of infusion 
• 
ADA blood sample collection to compare to samples that will be taken later in the study to check 
whether your body has made antibodies to the study medication 
• 
Premedication administration  
• 
Study medication administration 
Day 4:  During this visit the following will be done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
Routine blood and urine sample collections to check your overall health 
  
Day 8:  During this visit the following will be done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
Routine blood and urine sample collections to check your overall health  
• 
PK blood sample collection – one sample 
Subsequent Cycles 
If you tolerated the first cycle and remain on the study, you will continue to receive the study medication 
on Day 1 of each 21-day (3 week) cycle.  During each cycle, you will also need to have the following 
tests and procedures. 
Day 1:  During this visit premedication will be administered and the following will be done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
Vital signs  
• 
Physical exam including body weight and lung assessment, and assessment of your performance 
status 
• 
Routine blood and urine sample collections to check your overall health  


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• 
PK blood sample collection – one sample before getting your study medication; one sample at the 
end of infusion during Cycle 5 only  
• 
ADA blood sample collection  
• 
Premedication administration  
• 
Study medication administration   
Day 8:  During this visit the following will be done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
Routine blood and urine sample collections to check your overall health  
• 
PK blood sample collection – one sample during Cycle 5 only 
End of Even-Numbered Cycles (Cycle 2, 4, 6, etc.) 
During the week prior to Day 1 of the next cycle:  During this visit, the following will be done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
CT scan or MRI to assess your disease and check your lung status    
• 
End of Cycle 2 only: Ophthalmology Exam 
End of Treatment Visit  
You will need to return to the clinic within 10 days following the decision for you to discontinue 
participation in the study to have the following done: 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have experienced since the last visit 
• 
Vital signs  
• 
Physical exam including body weight and lung assessment, and assessment of your performance 
status  
• 
Eye exam 
• 
Routine blood and urine sample collections to check your overall health  
• 
ADA blood sample collection 
• 
Pregnancy test if you are a woman who may be able to get pregnant 
• 
ECG to check your heart 
• 
ECHO or MUGA to check your heart (only if you have a history of heart problems) 
• 
Pulmonary function tests to check your lungs 
• 
Chest X-ray to check your lungs 
• 
CT scan or MRI to assess your disease and check your lung status (only if it has been more than 6 
weeks since the previous CT or MRI)    
• 
PK blood sample collection – one sample during visit 


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• 
Patients with a cancer of the head or neck:  a blood sample will be taken to do tests on tumor cells 
that may be circulating in your blood 
One Month Follow-Up Visit  
You will need to return to the clinic about 1 month (30 days) after your last dose of study medication to 
have the following done: 
Note:  Depending on scheduling and when the decision is made for you to leave the study, the End of Treatment Visit and the 
One Month Follow-up Visit may be done on the same day.  If this is the case, the assessments listed to be performed at 
the End of Treatment Visit will be the assessments to be conducted. 
• 
Review of your medications and review of any symptoms or side effects that you may be 
experiencing or have been experiencing since the last visit 
• 
Vital signs  
• 
Physical exam including body weight and lung assessment, and assessment of your performance 
status  
• 
Routine blood and urine sample collections to check your overall health  
• 
ADA blood sample collection 
• 
CT scan or MRI to assess your disease and check your lung status (only if disease progression 
was not shown on a previous CT or MRI)   
• 
PK blood sample collection – one sample during visit  
6. 
POSSIBLE RISKS OF PARTICIPATING IN THIS STUDY 
As with all research studies, the study medication and study procedures may involve unknown risks. Any 
medication can have temporary and/or permanent side effects and can cause unforeseen adverse reactions.  
What are the risks associated with AVID100? 
Little is known about potential side effects of AVID100 since this is the first study in which it is being 
tested in humans.  Based on animal studies conducted in which monkeys were given AVID100, as well as  
side effects known to occur with drugs similar to AVID100, including antibodies linked to cancer 
chemotherapy agents, the following side effects have been observed suggesting that some of  these effects 
may be seen in patients treated with AVID100: 
Side effects of AVID100 in animal studies and of side effects of drugs similar to AVID100: 
• 
Skin changes including: 
o 
Generalized rash, acne-type rash, or red/bumpy rash  
o 
Skin thickening, redness, increased pigment 
o 
Dryness, flaking, and/or cracking 
o 
Itching and eczema 
o 
Skin and nail infections  
o 
Sores, scabs, bruises, ulcers, changes in healing 
• 
Fatigue, weakness 
• 
Headache 
• 
Diarrhea, constipation, abdominal pain 


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• 
Dehydration 
• 
Loss of appetite, weight loss 
• 
Rapid heartbeat, slowed heartbeat, irregular heartbeat 
• 
Unusual taste in the mouth 
• 
Swelling of the face 
• 
Inflamed lips and membranes of the mouth causing sores and pain  
• 
Inflamed membranes of the eye causing redness and pain 
• 
Blistering and swelling of the hands and feet 
• 
Changes in blood tests, particularly: 
o 
Decreases in red blood cells which could cause anemia, the symptoms of which are tiredness/fatigue, and 
shortness of breath 
o 
Decreases in platelets (which help the body with blood clotting), which could result in increased bruising 
and longer bleeding from a cut or injury, including excessive bleeding (hemorrhage) 
o 
Decreases in blood salts (called electrolytes) such as magnesium, calcium, and potassium 
o 
Increases in tests that measure how the liver is working 
• 
Damage to the nervous system resulting in numbness, tingling, and weakness in the arms, hands, legs, and feet (also 
known as peripheral neuropathy) 
• 
Damage to the liver, including liver failure 
• 
Damage to the lungs, including scaring and stiffness of the lungs (a condition called pulmonary fibrosis) 
• 
Abnormalities in tissues when looked at under a microscope, including changes to the: 
o 
Eyes, particularly the layers that cover the front of the eye (the cornea and the conjunctiva) , which could 
mean the eyes are being damaged  
o 
Bone marrow, where there could be a decrease in cells that make the blood  
o 
Thymus and lymph nodes, where there could be fewer cells to help the immune system  
o 
Ovaries (in women), which could result in changes in fertility 
o 
Sperm (in man) where there could be a decrease in number   
o 
Skin, liver, heart, GI tract changes suggesting inflammation and damage  
What other risks can be anticipated with AVID100? 
Along with the side effects listed above, because you will be receiving the study medication by 
intravenous (IV) infusion, there is a risk of experiencing what is called an infusion reaction.  
Infusion reactions have been seen with other drugs that are similar to AVID100, and even though the risk 
of these reactions does not appear to be as great with AVID100, having such side effects is still possible.  
You will be given medications to try to decrease or prevent these reactions before receiving an AVID100 
dose.  Infusion reactions may include:  
Side effects of infusion reactions: 


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• 
Facial flushing and/or swelling 
• 
Rash 
• 
Fever 
• 
Shortness of breath 
• 
Wheezing 
• 
Headache 
• 
Nausea 
• 
Dizziness 
• 
Sweating 
• 
Feeling anxious 
• 
Fast heart rate 
• 
Low blood pressure 
• 
Chills and/or cold sweats 
• 
Chest and throat tightness 
• 
Airway spasm 
• 
Chest, back, and/or abdominal discomfort/pain  
What is the experience thus far with AVID100 in this study? 
Thus far, a limited number of patients have been treated with AVID100 in this study, so a limited amount 
of information is available.  The side effects that have been seen thus far are listed below.   
Side effects of AVID100 seen in this study (mostly mild to moderate in severity) 
Side effects seen most often have included (in 20% or more of patients): 
• 
Rash and acne-like rash  
• 
Fatigue 
• 
Nausea 
• 
Decrease in platelets (which help the body with blood clotting), which could result in increased bruising and longer 
bleeding from a cut or injury, including excessive bleeding (hemorrhage) 
Side effects seen less frequently have included (in 5% to up to 20% of patients): 
• 
Infusion reactions 
• 
Headache 
• 
Vomiting 
• 
Diarrhea 
• 
Not feeling hungry 
• 
Mouth sores 
• 
Dry skin 
• 
Itching 
• 
Redness/itchiness of the eyes 
• 
Irritation of the cornea, which is the transparent layer forming the front of the eye 
• 
Watery eyes 
• 
Cough 
• 
Decrease in red blood cells which carry oxygen to tissues and may result in tiredness and shortness of breath 
• 
Increase in blood chemicals that are measures of how your liver is doing 
• 
Increase in blood lipase, a chemical involved in digestion and a measure of how your pancreas is doing 
• 
Decreases in electrolytes, which are the salts in the blood 
• 
Protein in the urine which could be due to kidney injury 
Side effects seen rarely have included (in less than 5% of patients):  
• 
Dry eyes 
• 
Eye pain 
• 
Eyes sensitive to light 
• 
Inflammation of the cornea and deeper layers of the eyes  
• 
Bloody nose 


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Side effects of AVID100 seen in this study (mostly mild to moderate in severity) 
• 
Increased sweating 
• 
Feeling of discomfort 
• 
Abdominal pain 
• 
Dehydration 
• 
Altered sense of taste 
• 
Weight loss 
• 
Hair loss 
• 
Muscle aches 
• 
Restless legs 
• 
Numbness and tingling in the hands and feet 
• 
Lung inflammation 
• 
Shortness of breath 
• 
Decreased amount of air breathed out during breathing tests 
• 
Worsening asthma symptoms 
• 
Irritation of the sinuses 
• 
Cold-like symptoms 
• 
Flu-like symptoms 
• 
Poor wound healing 
• 
Infection of the mouth  
• 
Dry mouth 
• 
Fungal infection of the skin 
• 
Bladder infection 
• 
Decrease in white blood cells called lymphocyte which help the body fight infection 
• 
Change in a blood test that measures how long it takes blood to clot 
• 
Increase in blood amylase, a chemical involved in digestion and a measure of how your pancreas is doing 
• 
Increase in blood uric acid, a measure of how your kidney is doing 
• 
Decrease in blood albumin, a protein made in the liver that helps keep body fluids in balance  
More severe side effects have been rare and have included (in less than 5% of patients): 
• 
Vomiting (at a dose higher than is being given in the Phase 2 part of this study) 
• 
Decrease in lymphocytes with no symptoms  
• 
Decrease in platelets with no symptoms 
• 
Increase in blood chemicals of liver function with no symptoms 
• 
Increase in blood lipase with no symptoms 
• 
Protein in the urine with no symptoms 
• 
One patient experienced sores in the mouth that were considered severe.  When healed the patient continued on 
study at a lower dose. 
• 
Two patients experienced pneumonitis, which is an inflammation of the lungs.  It was considered severe in both 
cases.  In one patient it was accompanied by shortness of breath, cough, wheezing, painful breathing, and decreased 
oxygen levels in the blood.  The patient was taken off study, treated with steroids, and was reported to improve. In 
the second patient it was accompanied by shortness of breath, anxiety, extreme fatigue, and decreased oxygen levels 
in the blood.  Symptoms began after the patient was off study and were reported to be resolving. 
• 
One patient experienced a decrease in platelets, which help the body with blood clotting.  The patient then had a fall 
hitting his head which resulted in bleeding in his head.  The patient recovered and continued on study at a lower 
dose.   
• 
One patient experienced an infusion reaction that was considered severe, with shortness of breath, chest tightness, 
chest pain, and rapid heartbeat reported.  The infusion was stopped; the patient was given medications and watched 
carefully at the clinic and briefly at the ER until the symptoms went away.  The patient was taken off the study.  
This patient received study drug by a shorter infusion time (1 hour) than is used now (2 hours); and was treated at a 
point in the study when premedications were not required to be given 
• 
One patient experienced an infusion reaction that was considered life-threatening, with shortness of breath, and 
difficulty breathing.  The infusion was stopped; the patient was given medications, taken to the hospital, and 
required a breathing tube.  The patient was taken off the study and recovered from the reaction.   
 


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Side effects of AVID100 seen in this study (mostly mild to moderate in severity) 
If you should have an infusion reaction, 2 blood samples will be taken (about 1½ teaspoons) so that PK and ADA 
tests can be done in an effort to better understand these reactions. 
What will be done to prevent or lessen side effects from the study medication and what should I do if I 
have side effects? 
All care will be taken to minimize side effects, but they can be unpredictable both in nature and severity.  
In order to ensure that your treatment is as safe as possible, you will be watched carefully throughout each 
infusion of study medication, and for a period of time following each infusion until it is considered safe 
for you to leave the clinic.  After your first infusion, you will be monitored for at least 2 hours after the 
end of your infusion. For each subsequent infusion, you will be monitored for at least 1 hour after the end 
of your infusion.  Throughout the study, your doctor will ask questions about how you are feeling and 
whether you are having any side effects.  In addition, your study doctor will carefully monitor your 
condition by physical exams, frequent blood tests will be done, and special attention will be paid to the 
workings of your eyes, heart, lungs, kidneys, liver, and digestive system. 
Medicines or supplements you might be taking could cause side effects if you use them while you are 
receiving AVID100.  Because of this, you must tell your study doctor or a member of the study staff 
about all your past and present illnesses and allergies.  You must also tell them about all vitamins, 
supplements, and medicines you are taking. 
For your own safety and for the safety of other participants in the study, you must inform the study doctor 
or study staff about any side effects or other health problems you experience during the study.  This 
should be done, no matter how minor the changes might seem to you, whether or not you think they might 
be caused by the study medication.   
Any side effects that may occur during treatment need to be carefully monitored by your study doctors so 
that they can give you the care that you need.  You will be given premedications before your dose(s) of 
study medication to decrease or prevent these side effects; however, if the doctors see a pattern in any 
other side effects that you experience during this study, they may give you additional medications before 
you receive your dose(s) in an effort to lessen the side effects or prevent them from occurring.   
At the first sign of any unacceptable side effect, you will be given medication to treat your symptoms.  In 
addition, your doctor may decide to interrupt, slow, lower, or stop your dose, or it may be necessary to 
remove you from the study.  If stopped and restarted, your infusion may be given to you at a slower rate. 
What are the risks associated with pregnancy during this study? 
If you become pregnant, or if your partner becomes pregnant, there may be unknown risks to the embryo 
or fetus.  If you are a woman who is able to have children (unless you have had a hysterectomy, tubal 
ligation, or you have been postmenopausal for at least one year) you will have a pregnancy test at 
screening, and if the result is positive, you will not be able to be in the study.  
If you are a sexually-active man or woman, you must use a medically effective form of birth control as 
per institutional standards throughout the study and for 3 months after the last dose of study medication. 
The study doctor will discuss methods of birth control with you, if needed.  


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If you become pregnant or think you may be pregnant during the study, contact the study doctor’s office 
immediately. You will be withdrawn from the study. If your partner becomes pregnant or thinks she may 
be pregnant during the study, contact the study doctor’s office immediately.  
The study doctor must follow up and document the course and the outcome of all pregnancies, even if you 
withdraw from the study or if the study has finished. If you or your partner becomes pregnant during the 
study, the study doctor or his/her staff will ask to contact you/your partner and your/your partner’s 
physician for information about the pregnancy and the child until at least 3 months after the birth.  
You must not be breast-feeding during the study. 
Are there other risks associated with taking part in this trial? 
A possible concern is that there may be a risk associated with other medications you might be taking while 
on this trial.  Since there is no way to predict whether the study medication might interact in some way with 
other drugs or medications, it is very important that you tell your study doctor all the medications you take 
throughout the entire time you are on the study.  Your study doctor will ask you questions about this at each 
visit.   
In particular, there is a concern about taking herbal medications or preparations for your cancer, such as 
those that are available at health food stores to treat disease and improve well-being.  These medications 
and preparations should not be taken while you are on this study because there is no way to determine 
how they will affect you or the way the study medication is handled by your body. 
What are the risks associated with study procedures? 
Blood sampling:  Blood will be taken from a vein in your arm during the study.  The taking of a blood 
sample may cause some discomfort and bruising, and there is a potential for infection. Other risks, 
although rare, include dizziness and fainting.  
IV catheter placement:  On days of multiple PK sampling, an IV catheter may be placed in order to reduce 
the number of times you would need to be stuck with a needle.  If you have a catheter or port in place, 
consideration may be given to using this for IV access to deliver the study medication. 
Blood pressure:  An inflatable cuff will be placed on your arm, and a machine will measure your blood 
pressure and heart rate.  You may experience mild discomfort in your arm while the cuff is inflated. 
Electrocardiogram (ECG):  This is a painless, non-invasive test that shows how your heart is working by 
making a tracing of the electrical activity of your heart.  To have an ECG, you will lie on a bed/couch for 
several minutes. Small sticky pads called electrodes will be stuck to your chest, shoulders and hips (or 
ankles) and a machine will measure the electrical activity of your heart. Small patches of your hair may 
need to be clipped in these areas.  The sticky pads may cause some local irritation and may be 
uncomfortable to remove.  
Echocardiogram (ECHO) (only in patients with a history of certain heart problems): An Echo is an 
ultrasound of your heart.  Gel will be spread on your chest and then a device known as a transducer will 
be pressed firmly against your skin, aiming an ultrasound beam through your chest to your heart. The 
transducer records the sound wave echoes from your heart. A computer converts the echoes into moving 
images on a monitor.  You may feel uncomfortable from lying still or from the transducer pressing on 
your chest. 


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Multigated acquisition (MUGA) scan (only in patients with a history of certain heart problems):  A 
MUGA scan creates video images of the heart to see how it is working.  A special camera will be used to 
monitor your heart’s activity during the test. Electrodes will be placed on your chest to monitor your 
heart’s electrical activity during the test. A small amount of radioactive material, called a tracer, will be 
injected into a vein in your arm. Sometimes a small amount of blood from your arm will be withdrawn 
and mixed with the tracer. Then the mixture will be put back into your body through the vein.  Similar to 
taking a blood sample, there may be some discomfort and bruising where the needle was inserted, and 
there is a potential for infection.  Other risks, although rare, include dizziness and fainting.  There is also a 
slight risk of allergic reaction to the radioactive tracer. 
Pulmonary function tests (PFTs):  These tests determine how much air your lungs can hold, how quickly 
you can move air in and out of your lungs, and how well your lungs put oxygen into and remove carbon 
dioxide from your blood.  You will need to breathe into a mouthpiece attached to a recording device 
(spirometer).  You will also need to take a breath of air containing a very small amount of carbon 
monoxide while measurements are taken from the breath you exhale. There should be no pain or 
discomfort involved in these tests.   
Computerized tomography (CT) scan:  A CT scan is a series of cross-sectional X-rays of your body.  CT 
scans do expose you to more radiation than a standard X-ray, but the risk is small. Some people have a 
reaction to the contrast dye that is injected into a vein before the scan, as it contains iodine, so you will 
have to tell your doctor if such a reaction has ever happened to you in the past.  Allergy to iodine may 
cause nausea, vomiting, sneezing, itching or hives. A severe allergic reaction (called anaphylaxis) that 
results in difficulty breathing can occur, but it is rare.  
Magnetic resonance imaging (MRI):  An MRI scan is painless and will not expose you to X-ray radiation.  
Before this scan, contrast medium may be injected into one of your veins; this is like a dye and will 
spread through your body and will help give clearer images. The injection of contrast medium may cause 
some discomfort and bruising. There is a risk of potentially serious reactions in some individuals who 
receive contrast medium.  Some people may feel frightened by the cramped space inside the machine or 
by the loud, repeated sounds the machine makes.  The greatest risk of having an MRI is the chance of 
metal objects moving rapidly toward the magnet and hitting you. To reduce this risk, all people giving 
and getting the MRI scan will be asked to remove all metal from their clothing and all metal objects from 
their pockets.  Please inform the study doctor if you have metal in your body from an operation, since you 
may not be able to have a MRI scan.  Also, if you have a pacemaker you should not have a MRI scan.  
Tumor biopsy:  A tumor biopsy is a procedure in which a small sample of your tumor is removed with a 
thin needle. You may be asked to agree to this if samples of your tumor are not available from a previous 
biopsy or surgical procedure, but only if the study doctor thinks your tumor is safely accessible for 
biopsy.  A tumor biopsy is done to diagnose and gather information on a tumor or potential tumor. You 
will receive a pain-killer prior to the biopsy and/or some local anesthesia to numb the area where the 
needle will pass to help control any discomfort or pain. You may also be given medications to make you 
sleep during the procedure. 
There are general risks that are part of any surgery procedure, no matter how minor, such as: excessive 
bleeding; infection; damage to nearby organs; discomfort or pain at the biopsy site; delayed healing at the 
biopsy site; reactions from pain medications which may include constipation, sluggishness and fatigue, or 
dry mouth; reactions from anesthesia which may include drowsiness, dizziness, confusion, shakiness, 


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ringing in the ears, nausea, tingling or numbness, visual changes, slurred speech, muscle twitching, 
changes in heartbeat, decreased blood pressure, and extremely rarely seizures or severe and dangerous 
blood pressure changes; more serious reactions, may occur rarely. 
7. 
POSSIBLE BENEFITS OF PARTICIPATING IN THIS STUDY 
You may not get any direct benefit from taking part in this study. You will be given close attention from 
the study staff during the time you are involved in the study. You may receive information about your 
health from physical examinations and medical tests done in this study. 
This study is expected to benefit the Sponsor by providing information on whether the study medication 
might be a useful treatment for patients with certain epithelial solid tumor cancers. 
If the results of this study are favorable, and, along with additional studies that lead to approval by 
regulatory authorities of AVID100 for use in humans, there may be benefits for patients in the future. 
8. 
ALTERNATIVE TREATMENTS 
You do not have to be in this study to get treatment for your cancer. Instead of taking part in this study, 
your doctor will explain the other options available to you.  These options may include:   
• Receiving other treatments for your cancer, if such treatments are available.   
• Taking part in another research study 
• Getting no treatment for your cancer, or 
• Receiving "comfort care only" where treatments are directed only at reducing symptoms, relieving 
suffering and maximizing comfort, dignity, and control.  In comfort care only, treatment is not 
directed at curing, slowing, or reversing your disease.   
If you have any questions concerning alternative treatments, please ask your study doctor.  Your study 
doctor can discuss your treatment options with you.  If you decide not to take part in this study, your 
decision will not affect your care at this hospital.   
9. 
COSTS RELATED TO THE STUDY 
Study medication will be provided at no cost to you.  In addition, there will be no cost to you for the 
additional blood and urine tests, hospital stays, doctor visits, and other procedures related to this study.  
You, your insurance company, or government program, are responsible for the costs of the usual tests and 
procedures done in the routine care for your cancer.  This includes the cost of routine blood and urine 
tests, x-rays, scans, surgeries, other treatments, and physician’s charges that are not related to this study. 
10. 
COMPENSATION RELATED TO THE STUDY 
You will not receive any financial compensation for taking part in this study.   
This study is part of the development of a potential new drug.  If the results of the study are successful, 
and the study medication is eventually sold commercially, you will not be compensated for taking part in 
this study.   


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11. 
INJURY OR COMPLICATIONS 
If you suspect illness or injury you should contact your study doctor immediately.  In the event of illness 
or injury resulting from your participation in this trial, necessary medical treatment will be provided.   
If not covered by your insurance, government program, or by any other third party, the Sponsor will pay 
for such emergency medical treatment and will provide payment for reasonable medical expenses, 
including hospitalization, subject to the treatment being required as a direct result of the study 
medication or its administration in accordance with the Protocol, as determined by the Sponsor and the 
study doctor.  No other type of compensation such as lost wages or other damages will be paid to you as a 
result of your taking part in this study. 
The Sponsor will not provide payment for expenses that are in any way attributable to the negligence or 
misconduct of any person employed by or acting on behalf of the Investigator or the Site.  The Sponsor 
will not pay for medical expenses for injuries unrelated to the study medication or which are in any way 
attributable to known or expected side effects or to the natural course of any underlying disease or 
treatment process. 
If you have any questions concerning the availability of medical care or if you think you have 
experienced a research-related illness, injury or emergency, contact:  
 
(insert name and telephone number of appropriate contact) 
 
Contact Name:  
 
________________________________ 
Telephone Number:  
________________________________ 
12. 
NEW INFORMATION 
If any new information about the study medication becomes available which may influence your decision 
to continue in the study, you will be told in a timely manner so that you can decide whether to withdraw 
from the study. 
13. 
REMOVAL OR WITHDRAWAL FROM THE STUDY 
You may be removed from the study without your consent if you experience a side effect or develop a 
medical condition during the study that your doctor thinks may put you at serious risk.  You may be 
removed from the study without your consent if your doctor decides that your disease has worsened and 
the treatment is not providing benefit.   
You have the right to withdraw from the study at any time.  If you are removed or decide to withdraw 
from the study, you are entitled to receive treatment according to the standard of care for your medical 
condition as determined by your doctor.  Should you be removed from the study, or if you decide to stop 
taking part in the study, you will be asked to make a final visit to receive physical examinations and to 
have final laboratory tests performed.   


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CONFIDENTIAL 
 
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14. 
TERMINATION OF THE STUDY 
In addition to previously mentioned reasons for withdrawal from the study, your participation in this study 
may be ended without your consent for the following reasons, including: 
• 
If the study doctor believes, for any reason, that it is in your best interest 
• 
If you refuse to have tests that are needed to determine whether this treatment is safe 
• 
If you refuse to have treatment or do not return for follow-up as recommended by your study doctor, 
or do not follow the study doctor’s instructions 
• 
If you require treatment with medications that are not allowed in this study 
• 
If you become pregnant 
• 
If other causes prevent you from continuing in this study 
• 
If the Sponsor decides to end the study or your participation at any time 
15. 
USE OF SAMPLES COLLECTED 
The samples that you donate, and related information gathered from the samples, may be provided to the 
Sponsor and/or its representatives, collaborators, contractors and service providers for analysis in 
connection with the Study and the development of AVID100 .  Your samples will not bear your name or 
any personal information about you, only your study code number will be displayed.  During the testing 
process, any blood or tissue samples collected from you as part of this study will not be used for any other 
research or genetic tests without your written permission, except for tests specified by the study protocol.  
In the future, people who do research with your samples may need to know more about your health.  
While the doctors coordinating this study may provide reports about your health, they will not provide 
your name or any other information that will let the researchers know who you are. 
The samples collected during this study will be kept until they are used up, or they will be stored for a 
number of years (possibly up to 15 years) after the end of the study, and will then be destroyed by the 
laboratory, whichever comes first (the end of the study occurs when a final study report is completed by 
the Sponsor).  The samples will be used for research purposes only and will not be sold. 
16. 
CONFIDENTIALITY AND AUTHORIZATION FOR DISCLOSURE 
By signing this form, you consent to the study doctor and his or her staff collecting and using your 
personal data for the study. This includes: your date of birth (day, month and/or year as allowed by local 
regulations), your sex, your ethnic origin and information on your physical or mental health or condition.  
The information shared with the Sponsor is protected by the use of a code, which is a number specifically 
assigned to you. The study doctor is in control of the code needed to connect your data to you. The 
Sponsor will not be given your name, but will only know of your code number. 
All medical records and research materials that identify you by name will be held confidential 
(confidential data) so far as permitted by law.  However the study doctor, the Sponsor and its 
representatives, the study monitor (who checks how the study is going and makes sure that the 
information is being collected properly) and, under certain circumstances, the regulatory authorities and  
the IRB or EC will be able to inspect confidential data that identify you by name.  


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All personal data from this study will be treated in accordance with national and local data protection 
laws. 
By signing this consent form, you grant permission for medical information about you obtained during 
this study (your study data) to be made available to authorized representatives of the regulatory 
authorities and other government agencies.  You also grant permission for your study data to be made 
available to the Sponsor, the study monitor, other study personnel, and the IRB or EC.  The Sponsor may 
transfer your study data in or outside ___ insert country  where study is being conducted___ for the 
purposes described in this document.  Please be aware that the laws in other countries may not provide the 
same level of data protection and may not stop your study data from being shared with others. The study 
doctor, the regulatory authorities, and the Sponsor may keep the study data indefinitely. 
You have the right to request information about your study data held by the study doctor and the Sponsor.  
You also have the right to request that any inaccuracies in such data be corrected.  If you wish to make a 
request, then please contact the study doctor, who can help you contact the Sponsor if necessary. 
If you withdraw your consent for participating in this study, your study data that were collected before 
you withdrew your consent may still be used as described above.  Once you have withdrawn your consent 
for participating in the study, no further data will be collected about you for the purposes of this study 
unless you agree otherwise, for example, you agree to have further tests and examinations.  If you do 
agree to have further data collected after you have withdrawn your consent, these study data may also be 
used as described above. 
The results of this study may be published in a medical journal and shown at medical meetings. You will 
not be identified (by name or any other means, e.g., photo) in any of these publications. 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law, or in one or more other public trial registries. Such Web sites or registries will not include 
information that can identify you.  At most, they will in include a summary of the trial design and/or a 
summary of results. You can search these Web sites at any time.  
Your health information cannot be used or disclosed (made known) by your study doctor for research 
purposes unless you sign this consent form.  By signing this consent form, you authorize the study doctor 
and his/her staff to use this information in conducting the study and to disclose and provide access to or 
copies of this information to the following: 
1. Sponsor (Formation Biologics)  
2. MedSource (contract research organization overseeing the study on the Sponsor’s behalf), and 
other organizations working with the Sponsor to monitor the progress of the study or analyse the 
study data 
3. (insert lab name) (local laboratory)  
4. The U.S. Food and Drug Administration (FDA) or similar, national regulatory authorities 
5. The (insert IRB/EC name) (IRB/EC) to ensure that patient safety and rights are protected  
Access to this information is necessary to ensure that the study is being done correctly, and to collect and 
analyse data about the safety and effectiveness of the study medication. 
You should know that once information is disclosed under this consent form to someone who is not a 
health care provider, the information is no longer protected.  The Sponsor and those working with the 


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CONFIDENTIAL 
 
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Sponsor on this study will only use and disclose your information as described in this consent form.  If 
reports or articles are written about the study, your name will not appear on any report or publication. 
You agree that, while the study is still in progress, you may not be given access to health information 
about you that is related to the study. While a request for access to health information can be denied, the 
study doctor and staff will consider whether it is medically appropriate under the circumstances to allow 
access. Your agreement that you may be denied access to your study-related health information during the 
study will not be used to deny you access to that information after the study is completed at all locations 
and study results are analysed. 
You can only participate in the study if you authorize the use and disclosure of the information as 
described above. If you decide not to sign this consent form, you will not be enrolled in the study. If you 
sign this consent form and decide later to withdraw your consent, you will not be permitted to continue 
your participation in the study.  Information collected up to the time that you withdraw your consent may 
continue to be used and disclosed as described above, but only as necessary to protect the integrity of the 
research study.  
This authorization to use or disclose the information as described above is not time limited (that is, will 
not automatically expire). 
You may decide not to sign this consent form, or you may revoke (withdraw) this authorization at any 
time. You can do this by giving written notice to your study doctor, informing him or her that you are 
revoking your consent to use and disclose your health information.  The contact information for your 
study doctor is provided below. 
(insert name and telephone number of appropriate contact) 
 
Study Doctor:     
 
________________________________ 
 
Address:  
 
 
________________________________ 
 
 


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CONFIDENTIAL 
 
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17. 
YOUR RIGHTS AS A PARTICIPANT 
Taking part in this study is voluntary.  If you choose not to participate in this study, your care will not be 
affected.  You may choose not to participate at any time during the study.  Leaving the study will not affect 
your care. 
We will tell you, in a timely manner, about significant new information that may affect your willingness to 
stay in this study.  
You will be given a signed copy of this document.  This consent form/authorization document does not 
have an expiration date. 
Someone other than the study doctor that you can call for information about the consent process, the rights 
of research subjects, or research-related injury is:   
(insert name and telephone number of appropriate contact) 
Contact Name:  
 
________________________________ 
Telephone Number:  
________________________________ 
This study has been reviewed by an Institutional Review Board (IRB) or an Ethics Committee (EC).  The 
IRB or EC is responsible for assuring that the patients’ safety, rights, and welfare are protected.  If you have 
questions concerning your rights in connection with this study, you can contact the IRB or EC.   You may 
reach the Committee office at the following address and telephone number. 
(insert name of IRB chairperson and/or name of IRB, address, and telephone number) 
IRB/EC contact:    
________________________________ 
Address: 
 
 
________________________________ 
Telephone Number   
________________________________ 
18. 
WHOM TO CONTACT IF YOU HAVE QUESTIONS OR PROBLEMS 
If you have questions about the study, or need more information about the study before you decide 
whether to take part, or if you have a problem related to the study, you may contact the study doctor or 
his/her staff at the number listed on the first page of this consent form. 
If you take part in this study and have any side effects during the study, call the study doctor at the 
number listed on the first page of this consent form.  If you are calling after hours or on a weekend, you 
may contact. 
(insert name and telephone number of appropriate contact) 
Contact Name:  
 
________________________________ 
Telephone Number:  
________________________________ 
 


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Protocol Number: AVID100-01 
CONFIDENTIAL 
 
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19. 
CONSENT FOR STORED TUMOR TISSUE SCREENING FOR ELIGIBILITY AND 
BIOMARKER STUDIES  
I understand that I am being asked to allow testing of my tumor at screening to determine if it is positive 
for the target of the study medication.   
Because tumor tissue for testing is available from a prior biopsy or surgery I have undergone, I 
understand that I am being asked to consent to collection and testing of this tissue.      
I also understand that I am being asked to consent to additional biomarker testing of my tumor for 
research purposes.  
Based on study findings, and how I do on this study (if I participate), a request may be made for 
collection of additional stored tumor tissue after I begin treatment.  I understand that agreement to 
collection of this additional tissue is optional. 
Patients asked to participate in Part 2: 
  Yes, I give permission to collect and test a stored sample of my tumor to determine if my 
tumor is positive for the target of the study medication, and for other research purposes.  I 
understand that if my tumor is not positive for the target of the study medication, I will not be 
eligible to participate in this study. 
  Yes, I give permission to collect and test additional stored sample of my tumor at a later date, 
should such a request be made. 
  No, I do not give permission to collect and test a stored sample of my tumor. 
 
    
 
Signature of Patient 
Date (mm/dd/yyyy) 
Printed Name of Patient 
 
 
 
 
Signature of Witness (relationship  
to patient, if any) 
Date (mm/dd/yyyy) 
Printed Name of Witness 
 
 


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Protocol Number: AVID100-01 
CONFIDENTIAL 
 
AVID100-01: Model ICF: Version 5.0 30May2020 (P2 stand-alone)        
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20. 
CONSENT FOR TUMOR BIOPSY FOR ELIGIBILITY AND BIOMARKER STUDIES  
I understand that I am being asked to allow testing of my tumor at screening to determine if it is positive 
for the target of the study medication.  
Because sufficient tumor tissue for testing is not available from a prior biopsy or surgery I have 
undergone, I understand that I am being asked to consent to a tumor biopsy to be performed    
I also understand that I am being asked to consent to additional biomarker testing of my tumor for 
research purposes.  
A tumor biopsy is a procedure in which a small sample of tumor is removed with a thin 
needle.  Tumor biopsies will only be done if tumor tissue from the original site of the 
tumor, or from a site in your body where the tumor has spread, is thought to be easily 
accessible.  Tumor sampling will only be attempted if a small sample can be taken with 
very little risk to you, and only if you agree to the procedure. 
Patients asked to participate in Part 2   
   
Yes, I give permission to collect and test a biopsy sample of my tumor to determine if my tumor 
is positive for the target of the study medication, and for other for research purposes.  I 
understand that if my tumor is not positive for the target of the study medication, I will not be 
eligible to participate in this study. 
  
No, I do not give permission to collect and test a biopsy sample of my tumor 
 
    
 
Signature of Patient 
Date (mm/dd/yyyy) 
Printed Name of Patient 
 
 
 
 
Signature of Witness (relationship  
to patient, if any) 
Date (mm/dd/yyyy) 
Printed Name of Witness 
 
 


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Protocol Number: AVID100-01 
CONFIDENTIAL 
 
AVID100-01: Model ICF: Version 5.0 30May2020 (P2 stand-alone)        
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21. 
CONSENT FOR OPTIONAL COLLECTION OF TUMOR TISSUE FOR BIOMARKER 
STUDIES  
I understand that I am being asked to allow additional testing of my tumor during the treatment portion of 
the study (after I have received study medication).  I understand that this testing is optional, and if I 
refuse I may still participate in this study. 
I understand that I am being asked to consent to the following: 
• 
Release of a small portion of my tumor for testing, should I require surgery on an area of tumor 
while I am in the study 
• 
A biopsy on an area of remaining tumor, should I have a response to study medication or a 
period of stable disease for more than 8 weeks 
• 
A biopsy of my tumor, should study other findings suggest that more could be learned about the 
study medication if tumor tissue could be tested after dosing.     
A tumor biopsy is a procedure in which a small sample of tumor is removed with a thin 
needle.  Tumor biopsies will only be done if tumor tissue from the original site of the tumor, 
or from a site in your body where the tumor has spread, is thought to be easily accessible.  
Tumor sampling will only be attempted if a small sample can be taken with very little risk to 
you, and only if you agree to the procedure. 
I also understand that I am being asked to consent to this additional optional biomarker testing of my 
tumor for research purposes.  
Patients asked to participate in Part 2   
   
Yes, I give permission to collect and test a biopsy sample of my tumor for research purposes.  I 
understand that I may change my mind at a later time, if I choose to do so. 
  
No, I do not give permission to collect and test a biopsy sample of my tumor 
 
    
 
Signature of Patient 
Date (mm/dd/yyyy) 
Printed Name of Patient 
 
 
 
 
Signature of Witness (relationship  
to patient, if any) 
Date (mm/dd/yyyy) 
Printed Name of Witness 
 
 


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Protocol Number: AVID100-01 
CONFIDENTIAL 
 
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22. 
AGREEMENT TO CONSENT:  PATIENT’S STATEMENT  
The research project and treatment procedures associated with it have been fully explained to me.  In 
addition, I have read the description of the clinical research study, or have had it translated into a 
language I understand.  All experimental procedures have been identified and no guarantee has been 
given about the possible results.  I have had the opportunity to ask questions concerning any and all 
aspects of the project and any procedures involved.  I am aware that my primary doctor may be informed 
of my participation in this study, and that my primary doctor may be asked to provide information about 
my medical history.  I am aware that participation is voluntary.  I know that I may withdraw my consent 
at any time.  I am aware that my decision not to take part, or to withdraw, will not restrict my access to 
health care services, and that I have not waived any of the legal rights that I would have if I were not a 
participant in a medical research study.   
It has been explained to me that my personal data, including data relating to health or condition, and 
ethnic origin, may be used as described in this consent form, but that confidentiality of medical records 
concerning my involvement in this project will be maintained in an appropriate manner.  When required 
by law, the records of this research may be reviewed by applicable government agencies, including the 
U.S. Food and Drug Administration (FDA) and Formation Biologics, or their representatives. 
I, the undersigned, hereby voluntarily consent to participate as a patient in the above described research 
project.  I will receive a copy of this consent for my records.  I understand that if I have any questions 
concerning this research, or my rights in connection with the research, including if a research related 
injury occurs, I can contact the doctor(s) listed above.  If I have questions concerning my rights in 
connection with the research, I can contact the Institutional Review Board or Ethics Committee, and that 
contact number has been provided to me. 
 
 
 
Signature of Patient  
Date (mm/dd/yyyy) 
Printed Name of Patient  
 
 
 
 
Signature of Witness (relationship  
to patient, if any) 
Date (mm/dd/yyyy) 
Printed Name of Witness 
23. 
STATEMENT OF PERSON CONDUCTING INFORMED CONSENT DISCUSSION 
I, the undersigned, certify that to the best of my knowledge, the patient signing this consent form had the 
study fully and carefully explained and clearly understands the nature, risks, and benefits of participation 
in this research study. 
 
 
 
Signature of Investigator  (or 
Person Obtaining Consent) 
Date (mm/dd/yyyy) 
Printed Name of Person Obtaining 
Consent