A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma
Phase: PHASE2
Conditions: Advanced Head and Neck Squamous Cell Carcinoma
Sponsor: Celldex Therapeutics



Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 4 of 73 
 
Table 7: 
Schedule of CDX-3379 PK Sampling Times ..............................................................42 
Table 8: 
Schedule of CDX-3379 ADA Sampling Times ...........................................................42 
Table 9: 
Schedule of CDX-3379 Blood Biomarker Sampling Times........................................43 
Table 10: Clinical Laboratory Tests to be Performed During Study ...........................................48 
Table 11: Observed ORR and Associated Precision and Power Calculations under Varying 
Cohort Sample Sizes and Underlying Response Rates ................................................49 
Table 12: Overall response: patients with target +/–non-target disease ......................................67 
Table 13. Overall response: patients with non-target disease only ..............................................67 
LIST OF FIGURES 
Figure 1: Study Schema...............................................................................................................14 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 5 of 73 
 
1 STUDY PERSONNEL AND STUDY ADMINISTRATION 
Information regarding key personnel involved in the conduct of the study, including names and 
contact details for the Celldex Medical Monitor, protocol signatory, monitors, and other staff, 
participating investigators, clinical laboratories and other medical and/or technical departments 
and/or institutions, and members of additional study committees, will be found in the study files 
of Celldex. Names and contact details of relevant study staff (including the responsible Medical 
Monitor) will be provided to all participating investigators. 
For multinational studies, Celldex will assign the coordinating investigator responsible for signing 
the Clinical Study Report. 
Note: As used throughout this document, “Celldex” refers to Celldex Therapeutics, Inc. or any 
designee to whom study-related responsibilities have been appropriately delegated. 
 
 
 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 6 of 73 
 
2 GLOSSARY OF ABBREVIATIONS 
Abbreviation 
Definition 
ADA 
Anti-drug antibodies/immunogenicity 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AKT 
Protein kinase B 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration time curve 
CBR 
Clinical benefit response  
CI 
Confidence interval 
Cmax 
Maximum concentration 
CPS 
Combined Positive Score 
CRF 
Case report form 
CR 
Complete response 
CT 
Computed tomography 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response  
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ErbB /EGFR 
Epidermal growth factor receptor  
ErbB1 
Human epidermal growth factor receptor 1; HER1 
ErbB2 
Human epidermal growth factor receptor 2; HER2 
ErbB3 
Human epidermal growth factor receptor 3; HER3 
ErbB4 
Human epidermal growth factor receptor 4; HER4 
EU 
European Union 
FAT1 
FAT Atypical Cadherin 1 
FcRn  
Fragment crystallizable receptor – neonatal 
FDA 
Food and Drug Administration 
FNA 
Fine needle aspirate 
5-FU 
5-Fluorouracil 
GCP 
Good Clinical Practice 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 7 of 73 
 
Abbreviation 
Definition 
GMP 
Good Manufacturing Practice 
HER 
Human epidermal growth factor 
HIPAA 
Health Insurance Portability and Accountability Act 
HNSCC 
Head and neck squamous cell carcinoma 
HPV 
Human papillomavirus 
ICF 
Informed consent form 
IgG1λ 
Immunoglobulin G1 lambda  
ICH 
International Conference on Harmonization 
IHC 
Immunohistochemistry  
IND 
Investigational new drug application 
INR 
International normalized ratio  
IRB 
Institutional review board 
IV 
Intravenous 
kg 
Kilogram 
m2 
Meter squared 
mAb 
Monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
mL 
Milliliters 
MRI 
Magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events  
NOTCH 
NOTCH family of cell-signaling receptors 
NRG 
Neuregulin/heregulin  
OS 
Overall survival 
PCR 
Polymerase chain reaction 
PD-1 
Programmed death receptor-1 
PD-L1 
Programmed death-ligand 1 
pErbB3 
Phosphorylated ErbB3 
PFS 
Progression-free survival 
PI3K 
Phosphoinositide 3-kinase  
PK 
Pharmacokinetics 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 8 of 73 
 
Abbreviation 
Definition 
PR 
Partial response 
PTEN 
Phosphatase and tensin homolog 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
Ribonucleic acid 
RTK 
Receptor tyrosine kinases  
SAE 
Serious adverse event 
SD 
Stable disease 
T1/2 
Half-life 
ULN 
Upper limit of normal 
YAP1 
Yes-associated protein 1 
YTE 
M253Y/S255T/T257E; M252Y/S254T/T256E, according to the EU numbering 
system 
 

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

R
FHWX[LPDE ZLWK WXPRU SURJUHVVLRQ GXULQJ RU ZLWKLQ  PRQWKV DIWHU
FRPSOHWLQJWUHDWPHQWUHJDUGOHVVRIDQ\LQWHUYHQLQJWKHUDSLHV
•
0HDVXUDEOHWDUJHWGLVHDVHE\5(&,67FULWHULD(LVHQKDXHUHWDO$SSHQGL[

•
:LOOLQJQHVVWRFRQVHQWIRUWXPRUELRSV\IURPDQDFFHVVLEOHVLWHSULPDU\RUPHWDVWDWLF
SULRUWRLQLWLDWLQJVWXG\WKHUDS\,QFDVHVZKHUHDIUHVKELRSV\LVQRWIHDVLEOHLHLIDQ
DFFHVVLEOHVLWHFDQQRWEHELRSVLHGZLWKDFFHSWDEOHFOLQLFDOULVNRUXSRQSDWLHQWUHIXVDO
DUFKLYDOWLVVXHPD\EHVXEPLWWHGLQVWHDGDIWHUGLVFXVVLRQZLWKDQGDSSURYDOE\WKH
PHGLFDOPRQLWRU
6HH6HFWLRQIRUFRPSOHWHLQFOXVLRQH[FOXVLRQFULWHULD
(QGSRLQWV
3ULPDU\(QGSRLQW
•
2557KHSHUFHQWDJHRISDWLHQWVZKRDFKLHYHD&5RU35FRQILUPHGDFFRUGLQJWR
5(&,67%HVWUHVSRQVHLVUHFRUGHGEHWZHHQWKHGDWHRIILUVWGRVHDQGWKHGDWHRI
GRFXPHQWHG SURJUHVVLRQ SHU 5(&,67  RU WKH GDWH RI VXEVHTXHQW DQWLFDQFHU
WUHDWPHQW ZKLFKHYHU RFFXUV ILUVW )RU SDWLHQWV ZLWKRXW GRFXPHQWHG SURJUHVVLRQ RU
VXEVHTXHQWDQWLFDQFHUWUHDWPHQWDOODYDLODEOHWXPRUDVVHVVPHQWVZLOOFRQWULEXWHWRWKH
EHVWUHVSRQVHDVVHVVPHQW
6HFRQGDU\(QGSRLQWV
•
&%57KHSHUFHQWDJHRISDWLHQWVZKRDFKLHYHEHVWUHVSRQVHRIFRQILUPHG&5RU35
RUVWDEOHGLVHDVH6'IRUDWOHDVWZHHNV%HVWUHVSRQVHLVDVVHVVHGDVGHVFULEHGIRU
255
•
'257KHLQWHUYDOIURPZKLFKPHDVXUHPHQWFULWHULDDUHILUVWPHWIRU&5RU35XQWLO
WKHILUVWGDWHWKDWSURJUHVVLYHGLVHDVHLVREMHFWLYHO\GRFXPHQWHGRUGHDWKZKLFKHYHU
RFFXUVILUVW3DWLHQWVZKRKDYHQRWSURJUHVVHGRUGLHGZLOOEHFHQVRUHGRQWKHGDWHRI
ODVWHYDOXDEOHWXPRUDVVHVVPHQWSDWLHQWVZKRGLGQRWKDYHDQ\RQVWXG\DVVHVVPHQWV
DQG KDYH QRW GLHG ZLOO EH FHQVRUHG RQ WKH GDWH RI ILUVW GRVH ,I D SDWLHQW UHFHLYHV
VXEVHTXHQWDQWLFDQFHUWUHDWPHQWEHIRUHGRFXPHQWHGSURJUHVVLRQWKHQ'25ZLOOEH
FHQVRUHG RQ WKH ODVW HYDOXDEOH WXPRU DVVHVVPHQW RQ RU EHIRUH WKH VWDUW GDWH RI
VXEVHTXHQWDQWLFDQFHUWUHDWPHQW
•
3)67KHWLPHIURPVWDUWRI&';WRWLPHRISURJUHVVLRQRUGHDWKZKLFKHYHU
RFFXUVILUVW3DWLHQWVZKRKDYHQRWSURJUHVVHGRUGLHGZLOOEHFHQVRUHGRQWKHGDWHRI
ODVWHYDOXDEOHWXPRUDVVHVVPHQWSDWLHQWVZKRGLGQRWKDYHDQ\RQVWXG\DVVHVVPHQWV
DQG KDYH QRW GLHG ZLOO EH FHQVRUHG RQ WKH GDWH RI ILUVW GRVH ,I D SDWLHQW UHFHLYHV
VXEVHTXHQWDQWLFDQFHUWUHDWPHQWEHIRUHGRFXPHQWHGSURJUHVVLRQWKHQ3)6 ZLOOEH
FHQVRUHG RQ WKH ODVW HYDOXDEOH WXPRU DVVHVVPHQW RQ RU EHIRUH WKH VWDUW GDWH RI
VXEVHTXHQWDQWLFDQFHUWUHDWPHQW
•
267KHWLPHIURPVWDUWRI&';WRGHDWK3DWLHQWVZKRKDYHQRWGLHGZLOOEH
FHQVRUHGRQWKHGDWHRIODVWFRQWDFW
•
6DIHW\6DIHW\ZLOOEHDVVHVVHGE\YLWDOVLJQPHDVXUHPHQWVFOLQLFDOODERUDWRU\WHVWV
SK\VLFDO H[DPV (&*V DQG WKH LQFLGHQFH DQG VHYHULW\ RI DGYHUVH HYHQWV JUDGHG
DFFRUGLQJWR1DWLRQDO&DQFHU,QVWLWXWH&RPPRQ7R[LFLW\&ULWHULDIRU$GYHUVH(YHQWV
1&,&7&$(Y
•
3KDUPDFRNLQHWLFV 1RQFRPSDUWPHQWDO 3. SDUDPHWHUV ZLOO EH GHWHUPLQHG XVLQJ
&';VHUXPFRQFHQWUDWLRQGDWDREWDLQHGSULRUWRDWFRPSOHWLRQRIDQGRQHKRXU
DIWHUHDFK&';DGPLQLVWUDWLRQDVZHOODVRQGD\VDQGRIWKHILUVWF\FOHDQG
GD\VSRVWWUHDWPHQW
•
,PPXQRJHQLFLW\ 3DWLHQWV ZLOO EH PRQLWRUHG IRU WKH GHYHORSPHQW RI DQWLGUXJ
DQWLERGLHV$'$WR&';6DPSOHVZLOOEHFROOHFWHGIRUIXWXUHHYDOXDWLRQRIWKH
QHXWUDOL]LQJFDSDFLW\RI$'$

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 13 of 73 
 
Response-evaluable population: All patients who have measurable disease at baseline and 
receive one full dose of both CDX-3379 and cetuximab and have post baseline tumor 
response assessment or discontinue study prematurely for disease progression, symptomatic 
deterioration, or death. Patients who discontinue treatment prior to the first tumor 
assessment for other reasons will be excluded from this population. Sensitivity analyses for 
efficacy endpoints will be performed in this population. 
Analysis Methods 
Best overall response (as defined by RECIST 1.1) will be summarized for the all treated 
population.  The ORR calculated as defined above, and the corresponding 95% exact CI 
will be calculated using the Clopper-Pearson method.  
CBR will be analyzed using the same approach as ORR. 
DOR will be estimated using the Kaplan-Meier (KM) product limit method. The KM 
estimate of the median DOR will be reported along with the two-sided 95% CI using 
Brookmeyer and Crowley’s method (log-log transformation).   
Progression-Free Survival and Overall Survival will be analyzed using the same approach 
as DOR. 
Additional analyses may be conducted including estimating objective response rate and 
other efficacy parameters for the response-evaluable population and within biomarker 
defined subgroups. 
Safety analyses will consist of data summaries for clinical and laboratory parameters, and 
for adverse events (AEs). The number and percentage of patients experiencing one or more 
AEs will be summarized by the relationship to study drug and severity based on NCI 
CTCAE v 5.0. Adverse events will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). Laboratory parameters will be summarized using descriptive 
statistics, by post-treatment shifts relative to baseline, and data listings of clinically 
significant abnormalities. Vital signs and ECG data will be summarized using descriptive 
statistics. 
Serum CDX-3379 concentration data will be tabulated by overall study population together 
with descriptive statistics. Individual and mean serum concentration-time profiles of 
CDX-3379 will be generated. Noncompartmental PK data analysis will be performed and 
descriptive statistics provided. If data allows, descriptive statistics of noncompartmental PK 
parameters (AUC, Cmax, CL, t½) will be provided. A population PK analysis may also be 
performed and various PK compartmental models may be explored to characterize the PK 
of CDX-3379 in patients with HNSCC. Exposure response modeling will be performed to 
examine the relationship between CDX-3379 serum exposure and clinical endpoints. The 
impact of physiologically relevant patient characteristics (covariates) and disease on 
PK/pharmacodynamic parameters (and possibly clinical endpoints) may be tested.  
The number and percentage of patients who develop detectable CDX-3379 ADA will be 
summarized. ADA titers will be reported for confirmed ADA-positive patients, and the 
impact of ADA on PK will be assessed if data allow. 
Biomarker data will be summarized descriptively and any correlation with outcome 
(efficacy) will be investigated. Analyses may include estimating objective response rate and 
other efficacy parameters within biomarker defined subgroups (i.e., defined by degree of 
expression or presence of genetic variation).  
 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 15 of 73 
 
Table 1: Schedule of Assessments 
 
Screening 
  
Treatment Period  
End of 
Treatment3 
Follow-up Period4 
Cycle 1 
Cycle 2 and 
subsequent cycles 
Day 1  
Day 8 
 
Day 15 
 
Day 1 
30-day 
 
Survival  
follow-up 
Visit Window1 
Day –28 to –1 
 
(+/- 1 
day) 
(+/- 1 
day) 
 
 
(+/- 3 days) 
Every 12 (±2) weeks 
until study closure 
Informed consent2 
X 
 
 
 
 
 
 
 
Demographics and Medical 
history5 
X 
X 
 
 
 
 
 
 
Tumor tissue 
X6 
 
 
Pregnancy test7 
X 
X 
 
 
 
 
 
 
Vital signs8 
X 
X 
X 
X 
X 
X 
X 
 
Physical examination9 
X 
X 
X 
X 
X 
X 
X 
 
ECOG Performance Status 
(Appendix 3) 
X 
X 
 
 
X 
X 
 
 
12-Lead Electrocardiogram10 
 
X 
X 
 
 
X 
 
 
Serum chemistry11  
X 
X12 
X 
X 
X 
X 
X 
 
Hematology11 
X 
X12 
X 
X 
X 
X 
X 
 
Urinalysis11  
X 
X12 
 
 
X 
X 
 
 
CDX-3379 PK sample13  
 
X14,15 
X14  
X14  
X14,15 
 
X16 
 
Biomarker blood sample13 
X 
X15 
X 
X 
X15,17 
 
X16 
 
Immunogenicity blood sample13 
 
X15 
 
 
X15 
 
X 
 
Diagnostic Imaging / Response 
Assessment18 
X 
 
 
 
X18 
X18 
 
X18 
Administer CDX-337919 
 
X 
 
 
X 
 
 
 
Administer Cetuximab20 
 
 
 
 
 
Concomitant medication review21 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event monitoring22 
 
X 
X 
X 
X 
X 
X 
X 
Survival follow-up 
 
 
 
 
 
 
 
X 
Footnotes on next page 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 16 of 73 
 
Footnotes for Table 1:   
1. A delay in study treatment or performance of study visits due to holidays, weekends, inclement weather, or other 
unforeseen circumstances will be permitted and not considered a protocol deviation. However, significant delays 
(i.e., greater than one week) due to these reasons should be discussed with the Celldex Medical Monitor to reach 
consensus on subsequent scheduling. See Section 8.2 and Section 8.3 for management of dosing delays due to 
toxicity. 
2. No study-specific procedures will be performed prior to receipt of signed Informed Consent (and, if applicable, 
Health Insurance Portability and Accountability Act [HIPAA] authorization). However, assessments performed 
according to standard of care prior to receipt of Informed Consent may be utilized to fulfill the screening 
requirement, if completed within the required window for screening.  
3. The End-of-Treatment (EOT) visit should be performed as soon as feasible following the decision to discontinue 
study drug dosing and prior to initiation of alternate therapies. This visit may be combined with the 30-day post-
treatment follow-up visit, if the windows overlap, with required assessments completed once for the combined 
visit.   
4. Follow-up visit should occur 30 (±3) days after the last dose of CDX-3379. Thereafter, patients should be 
contacted (may be via telephone) every 12 (±2) weeks until study closure for survival status and subsequent 
therapies. For patients who have discontinued study therapy for reasons other than progression, imaging studies 
to assess response should be obtained every 12 (±2) weeks (relative to last disease assessment) until disease 
progression or until patients are started on subsequent therapy, whichever occurs sooner. For these patients, the 
first survival status may be scheduled to coincide with the first post-treatment disease assessment, rather than 
relative to the 30-day follow-up.   
5. Medical history includes prior/concurrent conditions and cancer history including cancer mutation status and 
HPV status, prior treatments and surgical history. At Day 1, medical history is updated prior to administration of 
study drug. 
6. Unless prior agreement is reached with the Medical Monitor for submission of archival tumor, biopsy is to be 
performed of an accessible site (primary or metastatic) that can be biopsied with acceptable clinical risk (as judged 
by the investigator), obtaining a minimum of 3-5 core biopsies for biomarker analysis. FNAs are not acceptable. 
The biopsy site chosen should not have been previously irradiated and must be distinct from RECIST 1.1 target 
lesions, unless the biopsy is obtained prior to the screening disease assessment. 
7. Pregnancy tests are required only for women of childbearing potential (excluding patients who are post-
menopausal with absence of menses for at least 1 year and/or surgically sterilized). A serum pregnancy test must 
be performed during Screening. If the serum pregnancy test is performed more than 7 days prior to Day 1, then a 
urine or serum pregnancy test must also be performed on Day 1 with results reviewed prior to dosing.  
8. Vital signs should include heart rate, respiratory rate, blood pressure, temperature, and weight. Height should be 
recorded at Screen only, while weight is recorded only once per visit. Patients will be monitored during and after 
infusion of CDX-3379 and cetuximab with assessment of vital signs pre-infusion (within 30 minutes of the start 
of infusion), at 30 (± 5) minutes during the infusion, at the end of the infusion (within 5 minutes), and as clinically 
indicated during the 1-hour post-treatment observation period. When cetuximab is administered over two hours, 
vital signs should additionally be assessed at 60 (± 5) minutes and 90 (± 5) minutes.  
9. Complete physical examination should be performed at screening; thereafter, symptom-directed physical 
examinations are acceptable. 
10. Twelve-lead ECGs will be obtained prior to dosing and at 30-60 minutes following the CDX-3379 infusion on 
day 1 and 8 of cycle 1. A second original copy of the ECG tracing should be retained for possible submission to 
Celldex. 
11. Laboratory assessments to be performed locally, as well as requirements for review prior to CDX-3379 and 
cetuximab dosing, are specified in Section 10.2.5.5. See Section 8 for guidance regarding dosing 
modifications/delays due to laboratory toxicity.  
12. Assessments do not need to be repeated if performed within 24 hours of Cycle 1 dosing as part of the screening 
assessment.  

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 17 of 73 
 
13. Analyses will be performed centrally. Sample collection, processing and shipping instructions will be provided 
separately.   
14. Blood samples for CDX-3379 PK analysis will be drawn predose, immediately after the end of infusion (within 
5 minutes), and 60 minutes (± 5 minutes) post-infusion on Day 1 of each cycle prior to cetuximab administration. 
PK samples will also be collected prior to cetuximab dosing on Day 8 and 15 of Cycle 1.  
15. Predose blood sample may be collected within 24 hours prior to CDX-3379 administration. 
16. To be collected at 30-day follow-up visit, only if additional anticancer therapy has not been started. 
17. Biomarker blood samples to be collected predose at cycle 2, 3, 5, 7, and 9. 
18. See Section 10.2.1 and Appendix 2. Disease evaluation done at screening, near the end of every 2nd cycle (i.e., 
after day 15 of cycles 2, 4, 6, 8, etc. and prior to dosing for the next cycle), and, for patients who have not 
experienced progression at end of treatment, every 12 (±2) weeks until progression or initiation of alternate cancer 
therapies. Disease evaluation is required at end of treatment only if disease progression is not previously 
document. If a partial or complete response is noted, a follow-up radiographic assessment must be done no sooner 
than 28 days later to confirm response. Prior to any intervention (such as surgical resection, palliative radiation 
or alternate anticancer therapy), every effort should be made to perform a tumor response assessment in order to 
document progression and/or confirm an objective response. 
19. Unless otherwise specified, all study assessments should be performed prior to administration of study treatment 
and may be performed up to 24 hours prior to treatment administration if assessments remain within the specified 
visit window. CDX-3379 should be administered first, with a 1-hour observation period before administration of 
cetuximab. Diarrhea prophylaxis is required in accordance with Section 8.4.1.4 
20. Cetuximab will be administered weekly on Days 1, 8, and 15 of each cycle. On Day 1 of each Cycle, cetuximab 
should be administered approximately 1 hour after the completion of CDX-3379 administration and after 
collection of the 60 minute post-infusion PK blood sample. As a routine precaution, patients should be observed 
for at least 1 hour after the end of the cetuximab infusion. See Section 8.4.2 for guidance on cetuximab 
premedication and diarrhea prophylaxis. See Section 8 for additional details regarding study treatment dosing, 
precautions, monitoring, and management of toxicity.   
21. All concomitant medications will be documented if taken within 28 days prior to Day 1, and either (whichever 
occurs sooner): a) through the 30-day post-treatment follow-up, or b) initiation of alternate anticancer therapy. In 
addition, all anticancer surgeries or medications and response to those medications, as well as any concomitant 
medications required to treat study drug-related serious adverse events (SAEs), should also be recorded 
throughout the duration of study follow-up. See Section 9 for further guidance.   
22. Documentation of AEs will continue until the 30-day post-treatment follow-up, or until the initiation of 
subsequent anticancer treatment, whichever occurs first. For AEs or SAEs with a causal relationship to the 
investigational product, follow-up by the investigator is required until the event or its sequelae resolve to 
≤ grade 1, or stabilize for at least three months after the last administration of study treatment (whichever is 
sooner). In addition, any SAE occurring any time after the reporting period must be promptly reported if a causal 
relationship to study treatment is suspected. See Section 10.2.5.1, Section 10.2.5.2, Section 10.2.5.3 and 
Section 10.2.5.4 for further guidance.  
 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 26 of 73 
 
7 INVESTIGATIONAL PLAN 
7.1 
Overall Design and Plan of the Study 
This is an open-label, multicenter Phase 2 study of CDX-3379 in combination with cetuximab in 
patients with cetuximab-resistant HNSCC. Patients will be treated with CDX-3379 plus cetuximab 
until progressive disease, unacceptable toxicity, or other criteria for discontinuation of study 
treatment (Section 7.4.1) are met.  
The study was initially designed according to a Simon’s 2-stage design in which one tumor 
response (CR or PR) would need to be observed in the first 13 evaluable patients before completion 
of accrual to a total of 27 evaluable patients. Patients who discontinue treatment in the absence of 
progression/symptomatic deterioration/death before the first tumor assessment will be considered 
unevaluable for primary analysis and will be replaced. Following completion of stage 1 of the 
study, where 1 complete response was observed, emerging biomarker data were reviewed to assess 
correlation with efficacy.  In the overall CDX-3379 development program, in a small patient 
dataset, FAT1 and NOTCH1, NOTCH2 and NOTCH3 mutations appeared to be associated with 
clinical activity including objective response and durable stable disease.  Given these findings, the 
study design has been amended to enroll up to approximately 45 total patients, including at least 
15 patients whose tumor harbor a FAT1 mutation based on retrospective gene sequencing.  
Screening tissue samples will be required to be submitted as directed by the Sponsor at the time of 
enrollment to allow for gene sequencing and tracking the number of patients whose tumor harbor 
a FAT1 mutation. 
Tumor assessments will be performed approximately every 6 weeks during treatment. Patients 
who discontinue treatment in the absence of progression will continue to have assessments 
approximately every 12 weeks until documented progression or initiation of alternate anticancer 
therapies. Tumor response will be assessed by the investigator in accordance with RECIST 1.1 
guidelines (Eisenhauer, et al. 2009) (Section 10.2.1 and Appendix 2).  
Continuous evaluation of toxicity will be performed by the investigators and Celldex throughout 
the entire course of patient treatment and through 30 days following the last dose of CDX-3379. 
Subsequently, patients will be followed for survival, with contact every 12 weeks until study 
closure. 
7.2 
Selection of Study Population 
7.2.1 
Number of Patients 
It is anticipated that approximately 45 patients will be accrued. Enrollment will be competitive 
with no maximum per site. 
7.2.2 
Patient Eligibility 
7.2.2.1 
Inclusion Criteria 
Patients may be included in the study only if they meet all of the following inclusion criteria prior 
to receiving study treatment: 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 27 of 73 
 
1. Read, understood, and provided written informed consent, and if applicable, Health Insurance 
Portability and Accountability Act (HIPAA) authorization, after the nature of the study has 
been fully explained, and must be willing to comply with all study requirements and 
procedures.  
2. Male or female patients who are 18 years of age or older. 
3. Histologically or cytologically confirmed HNSCC that is recurrent or metastatic, not curable 
with local treatment modalities (e.g., surgery, radiation), and progressive (based on 
radiographic, clinical or pathologic assessment) during or subsequent to last therapy.  
4. Human papilloma virus (HPV) negative tumor, as established by the local site. Acceptable 
standards include p16 immunohistochemistry (where a tumor is classified as p16-positive 
when showing diffuse nuclear and cytoplasmic staining in at least 70% of tumor cells) and/or 
assessment of HPV deoxyribonucleic acid (DNA).  
5. Prior treatment must include (in any combination or sequence):  
a. check-point inhibitor targeting programmed death receptor-1 axis (PD-1/PDL-1), unless 
not a candidate  
b. cetuximab, with tumor progression during or within 6 months after completing treatment 
(regardless of any intervening therapies) 
6. Measurable (target) disease by RECIST 1.1 criteria (Eisenhauer, et al. 2009) (Appendix 2). 
Target lesions selected for tumor measurements should be those where additional (e.g., 
palliative) treatments are not indicated or anticipated.   
7. Willingness to consent for tumor biopsy from an accessible site (primary or metastatic) prior 
to initiating study therapy. In cases where a fresh biopsy is not feasible (i.e., if an accessible 
site cannot be biopsied with acceptable clinical risk or upon patient refusal), archival tissue 
may be submitted instead, after discussion with and approval by the medical monitor. 
8. All residual toxicity related to prior radiotherapy or anticancer therapies (excluding alopecia, 
grade 2 fatigue, vitiligo or endocrinopathies on stable replacement therapy) must resolve to 
grade 1 severity or less (or returned to baseline) prior to receipt of study treatment.  
9. Adequate electrolytes, liver, renal, and hematology function as defined below: 
a. Hemoglobin ≥ 9 g/dL 
b. Absolute neutrophil count ≥ 1500/mm3 
c. Platelet count ≥ 100,000/mm3 
d. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper 
limit of normal (ULN) (≤ 5 × ULN for cases involving liver metastasis) 
e. Bilirubin ≤ 1.5 × ULN (≤ 5 × ULN for cases of documented or suspected Gilbert's 
disease)  

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 28 of 73 
 
f. Serum creatinine ≤ 1.5 g/dL or calculated creatinine clearance (CrCl) ≥60 mL/min for 
patients with serum creatinine > 1.5 x ULN 
g. Serum magnesium ≤ 1.5 × ULN 
h.  Serum calcium and potassium within normal limits 
10. Life expectancy ≥ 12 weeks 
11. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (Appendix 3) 
12. Both male and female patients enrolled in this trial must agree to use highly effective 
contraception during the course of the trial and for at least for 6 months after the final dose of 
CDX-3379 or cetuximab, whichever is later. Patients and/or partners who are surgically sterile 
or postmenopausal are exempt from this requirement. 
7.2.2.2 
Exclusion Criteria 
Patients will be excluded from the study for any of the following reasons: 
1. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II 
(keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.  
2. Received CDX-3379 or other anti-ErbB3 targeted agents previously. 
3. Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy 
for cancer treatment. Concurrent use of hormones for non-cancer related conditions (e.g., 
insulin for diabetes and hormone replacement therapy) is acceptable.  
4. Other prior malignancy active within 3 years, except for localized prostate cancer, cervical 
carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1 differentiated thyroid 
cancer or ductal carcinoma in situ of the breast that has/have undergone curative surgery or 
radiation. 
5. Known brain metastases, unless previously treated and asymptomatic for 2 months and not 
progressive in size or number for 2 months prior to enrollment. Continued use of 
anticonvulsants (in the absence of any suspicion of progressive brain metastases) is acceptable.   
6. Known HIV, hepatitis B or hepatitis C infection, or active infection requiring systemic 
intravenous therapy   
7. Use of any monoclonal based therapies within 4 weeks (excluding cetuximab which does not 
require a wash-out), and all other immunotherapy (tumor vaccine, cytokine, or growth factor 
given to control the cancer) within 2 weeks, prior to the first dose of study treatment.   
8. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned 
start of study treatment 
9. Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring 
local/epidural anesthesia must be completed at least 72 hours before study drug administration 
and patients should be recovered. 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 29 of 73 
 
10. Use of other investigational drugs within 2 weeks or 5 half-lives (whichever is longer) prior to 
study treatment administration 
11. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc 
interval > 450 ms); additional risk factors for torsades de pointes (TdP) (e.g., a history of heart 
failure, family history of Long QT Syndrome, or active hypokalemia,); the use of concomitant 
medications that prolong the QT/QTc interval; significant cardiovascular disease including 
unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure 
(New York Heart Association Class III or IV) related to primary cardiac disease, uncontrolled 
ischemic or severe valvular heart disease; or any of the following within 6 months prior to the 
first dose of study treatment: myocardial infarction, severe/unstable angina, coronary artery 
bypass graft, congestive heart failure, cerebrovascular accident, transient ischemic attack. 
12. Requirement for chronic immunosuppressive medication including systemic corticosteroids 
above the physiologic dose (defined as 30 mg/day hydrocortisone or the equivalent).  
13. Any other acute or chronic medical or psychiatric condition or laboratory abnormality that 
could increase the risk associated with trial participation or trial drug administration or could 
interfere with the interpretation of trial results and, in the judgment of the investigator, would 
make the patient inappropriate for entry into the trial.  
14. Known alcohol or drug abuse. 
15. Women who are pregnant or nursing. All female patients with reproductive potential must have 
a negative pregnancy test prior to starting treatment 
16. Known allergy or past administration reaction including infusion reactions, anaphylactic, or 
anaphylactoid reactions to any component of the CDX-3379 formulation.  
17. Prior history of clinically significant hypersensitivity reaction or significant intolerance to 
cetuximab; history of allergic reactions attributed to compounds of chemical or biologic 
composition similar to those of cetuximab. 
7.3 
Measures to Minimize Bias  
This is non-randomized open-label study. The analysis of tumor response and progression-free 
survival will be based on tumor response assessments performed by the investigator according to 
standardized, objective response criteria (RECIST 1.1). In addition, in the event of a positive study 
outcome, an additional assessment of tumor response and progression may be performed by an 
independent review committee blinded to investigator assessments.  
7.4 
Withdrawal and Replacement of Patients 
Every effort should be made within the bounds of safety and patient choice to have each patient 
complete the study.  
Patients who discontinue the study for reasons other than disease progression, symptomatic 
deterioration or death prior to the first radiographic assessment will be considered unevaluable for 
primary analysis and will be replaced. 

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

$QH[SODQDWLRQZLOOEHUHFRUGHGIRUHDFKSDWLHQWWDNHQRIIVWXG\WUHDWPHQWRUGLVFRQWLQXLQJWKH
VWXG\

'LVFRQWLQXDWLRQRI6WXG\7UHDWPHQW
5HDVRQVIRUSHUPDQHQWGLVFRQWLQXDWLRQRIVWXG\WUHDWPHQWPD\LQFOXGH
• 3URJUHVVLYHGLVHDVHDVDVVHVVHGE\WKHWUHDWLQJLQYHVWLJDWRULQDFFRUGDQFHZLWK5(&,67
FULWHULD$SSHQGL[
• 6\PSWRPDWLF GHWHULRUDWLRQ FOLQLFDO GHWHULRUDWLRQ VXJJHVWLQJ WKDW QR IXUWKHU EHQHILW IURP
WUHDWPHQWLVOLNHO\
1RWH 7KLV FDWHJRU\ LV DSSOLFDEOH WR SDWLHQWV ZLWK D JOREDO GHWHULRUDWLRQ RI KHDOWK VWDWXV
UHTXLULQJGLVFRQWLQXDWLRQRIWUHDWPHQW+RZHYHUSHU5(&,67V\PSWRPDWLFGHWHULRUDWLRQ
LVQRWDGHVFULSWRURIDQREMHFWLYHUHVSRQVHLWLVDUHDVRQIRUVWRSSLQJVWXG\WKHUDS\7KXV
HYHU\HIIRUWVKRXOGEHPDGHWRFRQWLQXHGLVHDVHDVVHVVPHQWVSHUSURWRFROXQWLOGRFXPHQWHG
REMHFWLYHSURJUHVVLRQRULQLWLDWLRQRIDOWHUQDWHWKHUDS\
• 5HTXHVWRIWKHSDWLHQWRUWKHSDWLHQW¶VOHJDOUHSUHVHQWDWLYH
1RWH :LWKGUDZDO RI FRQVHQW IRU FRQWLQXHG VWXG\ WUHDWPHQW VKRXOG EH GLIIHUHQWLDWHG IURP
ZLWKGUDZDORIFRQVHQWIRUVWXG\IROORZXSDQGHYHU\HIIRUWVKRXOGEHPDGHZLWKLQWKHERXQGV
RIVDIHW\DQGSDWLHQWFKRLFHWRKDYHHDFKSDWLHQWFRPSOHWHWKHVWXG\IROORZXS
• $GYHUVHHYHQW
• 1RQFRPSOLDQFHRIWKHSDWLHQW
• 3K\VLFLDQGHFLVLRQIRUUHDVRQVRWKHUWKDQWKHDERYH
• 3UHJQDQF\
• 'HDWKRWKHUZLVHQRWH[SODLQDEOHE\WKHDERYHRSWLRQVDQG
• 3DWLHQWORVWWRIROORZXS$SDWLHQWVKRXOGEHFRQVLGHUHGORVWWRIROORZXSRQO\DIWHUPXOWLSOH
HIIRUWVKDYHEHHQPDGHWRFRQWDFWWKHSDWLHQWWRDVVHVVKLVKHUKHDOWKVWDWXVDIWHUIDLOXUHRIWKH
SDWLHQWWRDWWHQGVFKHGXOHGYLVLWV,IDIWHUWZRGRFXPHQWHGSKRQHFDOOVWKHLQYHVWLJDWLYHVLWHLV
VWLOOXQDEOHWRFRQWDFWWKHSDWLHQWDFHUWLILHGOHWWHUVKRXOGEHVHQWWRKLVKHUKRPHIRULPPHGLDWH
UHVSRQVH,IWKHUHLVVWLOOQRUHVSRQVHWKHSDWLHQWLVWREHFRQVLGHUHGORVWWRIROORZXS$UHFRUG
RIWKHSDWLHQWEHLQJORVWWRIROORZXSVKRXOGEHQRWHGLQWKHVRXUFHGRFXPHQWVDORQJZLWKWKH
SKRQHFRQWDFWVDQGWKHUHWXUQHGFHUWLILHGPDLOLIVHQWEDFN
3DWLHQWVZKRGLVFRQWLQXH&';VKRXOGEHVHHQIRUDQ(QGRI7UHDWPHQW(279LVLWDQG
VKRXOGXQGHUJRDGGLWLRQDOSRVWWUHDWPHQWIROORZXSIRUVDIHW\GLVHDVHSURJUHVVLRQDQGVXUYLYDO
DVGHVFULEHGLQ6HFWLRQZKHQIHDVLEOH

'LVFRQWLQXDWLRQIURP6WXG\
5HDVRQVIRUSDWLHQWUHPRYDOIURPWKHVWXG\IROORZXSLQFOXGH

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

+RZHYHUZKLOHRQVWXG\ZKHQFOLQLFDOO\DSSURSULDWHSDWLHQWVVKRXOGVWULFWO\IROORZWKHVWXG\
SUHVFULEHGWUHDWPHQWUHJLPHQ7KHIROORZLQJDUHSURKLELWHGWKURXJKRXWWKHWUHDWPHQWSHULRG
• &RQFXUUHQWDGPLQLVWUDWLRQRIDQ\DQWLFDQFHUWKHUDSLHVLQFOXGLQJFKHPRWKHUDS\UDGLRWKHUDS\
LPPXQRWKHUDS\ ELRORJLF RU KRUPRQDO WKHUDS\ DQGRU RWKHU LQYHVWLJDWLRQDO DJHQWV 1RWH
FRQFXUUHQWXVHRIKRUPRQHVIRUFRQGLWLRQVXQUHODWHGWRFDQFHU>HJLQVXOLQIRUGLDEHWHVDQG
KRUPRQHUHSODFHPHQWWKHUDS\@LVDFFHSWDEOH
ż )ROORZLQJWUHDWPHQWSDWLHQWVPD\UHFHLYHDQ\DSSURSULDWHDOWHUQDWHWKHUDSLHV
7KH0HGLFDO0RQLWRUPXVWEHQRWLILHGLIDSDWLHQWUHFHLYHVDQ\SURKLELWHGPHGLFDWLRQGXULQJWKH
WUHDWPHQWSHULRG
$OOFRQFRPLWDQWPHGLFDWLRQZLOOEHGRFXPHQWHGLQWKHSDWLHQW¶VPHGLFDOUHFRUGDQG&5)LIWDNHQ
ZLWKLQGD\VSULRUWRUDQGRPL]DWLRQHQUROOPHQWDQGHLWKHUZKLFKHYHURFFXUVVRRQHUDGD\V
DIWHUODVWGRVHRIVWXG\WUHDWPHQWHLWKHU&';RUFHWX[LPDERUELQLWLDWLRQRIDOWHUQDWH
DQWLFDQFHUWKHUDS\$OODQWLFDQFHUPHGLFDWLRQVWDNHQWKURXJKRXWWKHVWXG\LQFOXGLQJIROORZXS
VKRXOGDOVREHUHFRUGHGDVVKRXOGFRQFRPLWDQWPHGLFDWLRQVUHTXLUHGWRWUHDWVWXG\GUXJUHODWHG
VHULRXVDGYHUVHHYHQWV6$(V
 678'<352&('85(6

6FKHGXOHRI,QYHVWLJDWLRQVDQG'DWD&ROOHFWLRQ
7KHVWXG\LVGLYLGHGLQWRWKUHHSKDVHV6FUHHQLQJ7UHDWPHQWDQG3RVW7UHDWPHQW)ROORZXS(DFK
SKDVHKDVDVVRFLDWHGHYDOXDWLRQVDQGSURFHGXUHVWKDWPXVWEHSHUIRUPHGDWVSHFLILFWLPHSRLQWVDV
GHVFULEHGLQ WKH IROORZLQJ VHFWLRQV 7DEOHVXPPDUL]HVWKHIUHTXHQF\DQGWLPLQJRIYDULRXV
DFWLYLWLHVVDIHW\DQGRWKHUPHDVXUHPHQWV

6FUHHQLQJ3KDVH
3ULRUWRWKHSHUIRUPDQFHRIDQ\VWXG\VSHFLILFSURFHGXUHVWKHSDWLHQWZLOOKDYHWKHQDWXUHRIWKH
VWXG\H[SODLQHGWRKLPKHUDQGZLOOEHDVNHGWRJLYHZULWWHQLQIRUPHGFRQVHQWDQGLIDSSOLFDEOH
+,3$$ DXWKRUL]DWLRQ ,QIRUPHG FRQVHQW+,3$$ DXWKRUL]DWLRQ PXVW EH REWDLQHG SULRU WR DQ\
VWXG\VSHFLILF SURFHGXUHV WKDW GR QRW IRUP D SDUW RI WKH SDWLHQW¶V QRUPDO FDUH +RZHYHU
DVVHVVPHQWVSHUIRUPHGDFFRUGLQJWRVWDQGDUGRIFDUHSULRUWRUHFHLSWRILQIRUPHGFRQVHQWPD\EH
XWLOL]HGWRIXOILOOWKHVFUHHQLQJUHTXLUHPHQWLIFRPSOHWHGZLWKLQWKHUHTXLUHGZLQGRZIRUVFUHHQLQJ
7KHDVVHVVPHQWVRXWOLQHGLQIRUWKH6FUHHQLQJ9LVLWLQWKH6FKHGXOHRI$VVHVVPHQWV7DEOHZLOO
EHFRPSOHWHGIRUHDFKSDWLHQWSULRUWRLQFOXVLRQLQWKHVWXG\7KHVFUHHQLQJHYDOXDWLRQVPD\EH
FDUULHGRXWRYHUPRUHWKDQRQHYLVLW
3DWLHQWVZKRDUHVFUHHQHGEXWGRQRWPHHWDOOHQWU\FULWHULDLHVFUHHQIDLOXUHVZLOOQRWEHHQWHUHG
LQWKHFOLQLFDOGDWDEDVH,QVWHDGDORJRISDWLHQWVVFUHHQHGIRUWKHVWXG\LQFOXGLQJWKHUHDVRQIRU
VWXG\LQHOLJLELOLW\ZLOOEHPDLQWDLQHGDWWKHVWXG\FHQWHU2QFHDVVLJQHGSDWLHQWQXPEHUVIRUDQ\
VFUHHQLQJIDLOXUHVQRQWUHDWHGXQHYDOXDEOHRUGLVFRQWLQXHGSDWLHQWVZLOOQRWEHUHXVHG
6WXG\HQUROOPHQWZLOORFFXURQO\DIWHUFRQILUPLQJDOOLQFOXVLRQFULWHULDDQGQRQHRIWKHH[FOXVLRQ
FULWHULDKDYHEHHQPHWDQGLQDFFRUGDQFHZLWKLQVWUXFWLRQVSURYLGHGE\&HOOGH[

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI


7UHDWPHQW3KDVH
6WXG\WUHDWPHQWDGPLQLVWUDWLRQLVGLVFXVVHGLQ6HFWLRQ6SHFLILFSURFHGXUHVWREHSHUIRUPHGDW
HDFKYLVLWGXULQJWKHWUHDWPHQWSKDVHDUHOLVWHGLQ7DEOH
7KH(279LVLWVKRXOGEHSHUIRUPHGDVVRRQDVIHDVLEOHIROORZLQJWKHGHFLVLRQWRGLVFRQWLQXHVWXG\
GUXJGRVLQJDQGSULRUWRLQLWLDWLRQRIDOWHUQDWHWKHUDSLHV7KLVYLVLWPD\EHFRPELQHGZLWKWKH
GD\SRVWWUHDWPHQWIROORZXSYLVLWLIWKHZLQGRZVRYHUODSZLWKUHTXLUHGDVVHVVPHQWVFRPSOHWHG
RQFHIRUWKHFRPELQHGYLVLW6SHFLILFSURFHGXUHVWREHSHUIRUPHGDWWKLVYLVLWDUHLOOXVWUDWHGLQ
7DEOH

3RVW7UHDWPHQW)ROORZXS3KDVH
$IROORZXSYLVLWLVWREHFRPSOHWHGRQ'D\GD\VIROORZLQJWKHODVWGRVHRI&';
6XEVHTXHQWO\SDWLHQWVVKRXOGEHIROORZHGRQVWXG\IRUVXUYLYDOZLWKYLVLWVRUWHOHSKRQHFRQWDFW
HYHU\ZHHNVXQWLOWKHVWXG\LVFORVHG
$GGLWLRQDOO\GXULQJWKHSRVWWUHDWPHQWIROORZXS
• 3DWLHQWV ZKR KDYH GLVFRQWLQXHG VWXG\ WKHUDS\ IRU UHDVRQV RWKHU WKDQ SURJUHVVLRQ VKRXOG
XQGHUJRLPDJLQJVWXGLHVWRDVVHVVUHVSRQVHDSSUR[LPDWHO\HYHU\ZHHNVXQWLOGLVHDVH
SURJUHVVLRQRUXQWLOLQLWLDWLRQRIVXEVHTXHQWDQWLFDQFHUWKHUDS\ZKLFKHYHURFFXUVVRRQHU
• 7KURXJKRXW WKH IROORZXS SKDVH GRFXPHQWDWLRQ DQG IROORZXS RI $(V DQG FRQFRPLWDQW
PHGLFDWLRQVVKRXOGFRQWLQXHLQDFFRUGDQFHZLWK6HFWLRQDQG6HFWLRQ
6SHFLILFSURFHGXUHVWREHSHUIRUPHGWKURXJKRXWWKHIROORZXSSKDVHDUHLOOXVWUDWHGLQ7DEOH

0HWKRGVRI$VVHVVPHQW

$FWLYLW\
7XPRUUHVSRQVHDQGSURJUHVVLRQIUHHVXUYLYDOZLOOEHDVVHVVHGYLDLPDJLQJEDVHGHYDOXDWLRQSHU
5(&,67$SSHQGL[
&RQWUDVWHQKDQFHGFRPSXWHGWRPRJUDSK\&7RIWKHFKHVWDEGRPHQDQGSHOYLVDVZHOODVDOO
RWKHUVXVSHFWHGGLVHDVHVLWHVLVUHTXLUHG0DJQHWLFUHVRQDQFHLPDJLQJ05,H[DPVRIWKHEUDLQ
DEGRPHQDQGSHOYLVFDQEHSHUIRUPHGLQOLHXRID&7KRZHYHU05,H[DPVRIWKHFKHVWDUHQRW
UHFRPPHQGHG,QWKHHYHQWWKDWDFKHVW05,LVSHUIRUPHGDQRQFRQWUDVWFKHVW&7LVVWURQJO\
UHFRPPHQGHGWRHYDOXDWHWKHOXQJSDUHQFK\PD%UDLQDQGRUERQHVFDQVDUHUHTXLUHGIRUDQ\
SDWLHQWVZLWKDKLVWRU\RIPHWDVWDVHVWRERQHDQGRUEUDLQRUZKHUHV\PSWRPDWRORJ\UDLVHVWKH
VXVSLFLRQIRUERQHDQGRUEUDLQPHWDVWDVHV/HVLRQVLGHQWLILHGRQERQHVFDQVVKRXOGEHFRQILUPHG
E\D&7RU05,DWEDVHOLQHDQGLILGHQWLILHGDVWDUJHWOHVLRQVGXHWRVRIWWLVVXHFRPSRQHQWWKH\
VKRXOGFRQWLQXHWREHIROORZHGE\WKHVDPHPHWKRGRORJ\LH&7RU05,VFDQ+RZHYHUERQH
OHVLRQVIROORZHGDVQRQWDUJHWGLVHDVHPD\EHVXEVHTXHQWO\IROORZHGE\ERQHVFDQVRQO\/HVLRQV
WKDWFDQQRWEHLPDJHGEXWDUHDVVHVVDEOHE\FOLQLFDOH[DPPD\EHDVVHVVHGE\FRORUSKRWRJUDSK\
LQFOXGLQJDUXOHUSUHIHUUHGPHWKRGRUPHDVXUHGZLWKFDOLSHUV
1RUPDOO\DOOWDUJHWDQGQRQWDUJHWGLVHDVHVLWHVVKRXOGEHHYDOXDWHGDWHDFKDVVHVVPHQW+RZHYHU
IRU SDWLHQWV ZLWK QRQWDUJHW ERQH GLVHDVH ERQH VFDQV QHHG RQO\ EH UHSHDWHG HYHU\ WZHOYH WR

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 42 of 73 
 
eighteen weeks, or more frequently if clinically indicated. 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.  
Target lesions selected for tumor measurements should be those where surgical resection or 
radiation are not indicated or anticipated. 
10.2.2 
Pharmacokinetic Evaluation  
Table 7 details the PK sample collection schedule. Details will be provided separately in a 
laboratory manual to include procedures for collection, processing, storage, and shipment of 
samples, as well as laboratory contact information.   
 
Table 7: Schedule of CDX-3379 PK Sampling Times 
Day 
Time 
Day 1 for all Cycles 
Predose (within 24 hours of CDX-3379 infusion) 
Immediately after the end of CDX-3379 infusion (within 5 minutes) 
Post CDX-3379 dose at 60 minutes after end of CDX-3379 infusion (+ 5 minutes) and 
prior to cetuximab administration 
Cycle 1, Day 8 
During visit prior to cetuximab administration 
Cycle 1, Day 15  
During visit prior to cetuximab administration 
30-Day Follow-up 
During visit, in cases where new anticancer therapy hasn’t yet been started 
10.2.3 
Immunogenicity of CDX-3379 
Table 8 details the immunogenicity sample collection schedule. Details will be provided separately 
in a laboratory manual to include procedures for collection, processing, storage, and shipment of 
samples, as well as laboratory contact information.   
The ADA titer will be reported for samples confirmed positive for the presence of anti-CDX-3379 
antibodies. Tiered analysis will be performed to include screening, confirmatory and titer assay 
components and Positive-Negative cut points will be employed that were statistically determined 
from CDX-3379-naïve validation samples.  
Samples will be collected for assessing the neutralization capacity in the future.  
 
Table 8: Schedule of CDX-3379 ADA Sampling Times  
Cycle and Day 
Time 
Day 1 of each Cycle 
Predose (within 24 hours prior to CDX-3379 infusion) 
30-Day Follow-up 
During visit 
10.2.4 
Biomarker Evaluation and Methods 
Pre-treatment biopsy tumor samples (fresh preferred, archival upon approval by the Medical 
Monitor) are planned to be evaluated for biomarkers that may enrich for patient benefit to 
CDX-3379. Details on performing the core or excisional biopsies (a minimum 3-5 core or 
excisional biopsies preferred, FNAs are not acceptable), preparing the samples and shipping 
instructions can be found in the laboratory manual.  

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

• $Q\$(V6$(VUHVXOWLQJLQGHDWKVKRXOGEHUHFRUGHGZLWKDQHQGGDWHHTXDOWRWKHGHDWKGDWH
ZKLOH RWKHU HYHQWV RQJRLQJ DW WKH WLPH RI GHDWK VKRXOG EH UHFRUGHG ZLWK DQ RXWFRPH RI
³RQJRLQJ´,IUHTXHVWHGDVXPPDU\RIDYDLODEOHDXWRSV\ILQGLQJVVKRXOGEHVXEPLWWHGDVVRRQ
DVSRVVLEOHWR&HOOGH[

6HULRXV$GYHUVH(YHQWV'HILQLWLRQ
$6$(LVDQ\$(IURPWKLVVWXG\WKDWUHVXOWVLQRQHRIWKHIROORZLQJRXWFRPHV
• 'HDWKDQ\$(WKDWKDVDIDWDORXWFRPHPXVWEHDVVLJQHG1&,&7&$(JUDGH
• 5HTXLUHVLQLWLDORUSURORQJHGLQSDWLHQWKRVSLWDOL]DWLRQH[FHHGLQJKRXUV$VZHOODQ\HYHQW
RFFXUULQJZKLOHWKHSDWLHQWLVKRVSLWDOL]HGZKLFKZRXOGRWKHUZLVHUHTXLUHKRVSLWDOL]DWLRQRU
UHTXLUHVWUDQVIHUZLWKLQWKHKRVSLWDOWRDQDFXWHLQWHQVLYHFDUHXQLWVKRXOGDOVREHUHSRUWHG
XQGHU WKLV FULWHULRQ 7KLV FULWHULRQ ZRXOG H[FOXGH KRVSLWDOL]DWLRQ LQ WKH DEVHQFH RI D
SUHFLSLWDWLQJ$(VXFKDVDGPLVVLRQIRUWUHDWPHQWRIDSUHH[LVWLQJFRQGLWLRQQRWDVVRFLDWHG
ZLWK D QHZZRUVHQLQJ $( RU DGPLVVLRQ IRU HOHFWLYH VXUJHU\ $V ZHOO DGPLVVLRQ WR
UHKDELOLWDWLRQKRVSLFHQXUVLQJIDFLOLWLHVDQGRXWSDWLHQWDGPLVVLRQIRUVDPHGD\VXUJHULHVDUH
QRWFRQVLGHUHG³KRVSLWDOL]DWLRQV´IRUWKHSXUSRVHRIWKLVFULWHULRQ
• ,V OLIHWKUHDWHQLQJ $Q $( LV FRQVLGHUHG OLIHWKUHDWHQLQJ LI LQ WKH YLHZ RI HLWKHU WKH
LQYHVWLJDWRURU&HOOGH[LWVRFFXUUHQFHSODFHVWKHSDWLHQWDWLPPHGLDWHULVNRIGHDWK,WGRHVQRW
LQFOXGHDQ$(RUVXVSHFWHGDGYHUVHUHDFWLRQWKDWKDGLWRFFXUUHGLQDPRUHVHYHUHIRUPPLJKW
KDYHFDXVHGGHDWK
• ,VDSHUVLVWHQWRUVLJQLILFDQWGLVDELOLW\LQFDSDFLW\RUVXEVWDQWLDOGLVUXSWLRQRIWKHDELOLW\WR
FRQGXFWQRUPDOOLIHIXQFWLRQV
• &RQJHQLWDODQRPDO\ELUWKGHIHFW
• 2WKHU VLJQLILFDQW PHGLFDO KD]DUG 0HGLFDO DQG VFLHQWLILF MXGJPHQW VKRXOG EH H[HUFLVHG LQ
GHWHUPLQLQJZKHWKHUDQHYHQWLVDQLPSRUWDQWPHGLFDOHYHQW$QLPSRUWDQWPHGLFDOHYHQWPD\
QRWEHLPPHGLDWHO\OLIHWKUHDWHQLQJDQGRUUHVXOWLQGHDWKRUKRVSLWDOL]DWLRQ+RZHYHULILWLV
GHWHUPLQHGWKDWWKHHYHQWPD\MHRSDUGL]HWKHSDWLHQWDQGRUPD\UHTXLUHLQWHUYHQWLRQWRSUHYHQW
RQHRIWKHRWKHU6$(RXWFRPHVWKHLPSRUWDQWPHGLFDOHYHQWVKRXOGEHUHSRUWHGDVVHULRXV
([DPSOHVRIVXFKHYHQWVDUHLQWHQVLYHWUHDWPHQWLQDQHPHUJHQF\URRPRUDWKRPHIRUDOOHUJLF
EURQFKRVSDVP EORRG G\VFUDVLDV RU FRQYXOVLRQV WKDW GR QRW UHVXOW LQ KRVSLWDOL]DWLRQ RU
GHYHORSPHQWRIGUXJGHSHQGHQF\RUGUXJDEXVH

$GYHUVH(YHQW6HULRXV$GYHUVH(YHQW5HSRUWLQJ
7KHLQYHVWLJDWRULVWRUHSRUWDOOGLUHFWO\REVHUYHG$(VDQGDOO$(VVSRQWDQHRXVO\UHSRUWHGE\WKH
VWXG\SDWLHQW,QDGGLWLRQHDFKVWXG\SDWLHQWZLOOEHTXHVWLRQHGDERXW$(V
$GYHUVHHYHQWVDQG6$(VVKRXOGEHUHFRUGHGRQWKH&5)IURPWKHWLPHWKHSDWLHQWKDVUHFHLYHG
DWOHDVWRQHGRVHRIVWXG\WUHDWPHQWWKURXJKZKLFKHYHURFFXUVILUVWHLWKHUDWKHGD\SRVW
WUHDWPHQWIROORZXSYLVLWRUELQLWLDWLRQRIDOWHUQDWHDQWLFDQFHUWKHUDS\

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

+RZHYHU
• $Q\6$(RFFXUULQJDQ\WLPHDIWHUWKHUHSRUWLQJSHULRGPXVWEHSURPSWO\UHSRUWHGLIDFDXVDO
UHODWLRQVKLSWRVWXG\WUHDWPHQWLVVXVSHFWHG
• )RU$(VRU6$(VZLWKDFDXVDOUHODWLRQVKLSWRWKHLQYHVWLJDWLRQDOSURGXFWIROORZXSE\WKH
LQYHVWLJDWRULVUHTXLUHGXQWLOWKHHYHQWRULWVVHTXHODHUHVROYHWRJUDGHRUVWDELOL]HIRUDW
OHDVWWKUHHPRQWKVDIWHUWKHODVWDGPLQLVWUDWLRQRIVWXG\WUHDWPHQWZKLFKHYHULVVRRQHU
$OO$(VZLOOEHUHSRUWHGRQWKH$(SDJHVRIWKH&5)ZKLOH6$(VZLOODOVREHUHSRUWHGLQDQ
H[SHGLWHGIDVKLRQXVLQJWKH6$(UHSRUW7KH$(&5)VDQG6$(UHSRUWVPXVWEHFRPSOHWHGLQD
FRQVLVWHQWPDQQHUIRUH[DPSOHWKHVDPH$(WHUPFDXVDOLW\VHYHULW\DQGRQVHWUHVROXWLRQGDWHV
VKRXOGEHXVHGRQERWKIRUPV
,QFDVHRIDQ6$(UHJDUGOHVVRIFDXVDOLW\DQ6$(UHSRUWPXVWEHFRPSOHWHGDQGVXEPLWWHGWR
&HOOGH[ZLWKLQKRXUVRIWKHVLWH¶VQRWLILFDWLRQRIWKHHYHQWLUUHVSHFWLYHRIWKHH[WHQWRIDYDLODEOH
$( LQIRUPDWLRQ 7KLV WLPHIUDPH DOVR DSSOLHV WR DGGLWLRQDO QHZ LQIRUPDWLRQ IROORZXS RQ
SUHYLRXVO\IRUZDUGHG6$(UHSRUWV7KHLQYHVWLJDWRULVREOLJDWHGWRSXUVXHDGGLWLRQDOLQIRUPDWLRQ
UHTXLUHGIRUWKRURXJKHYDOXDWLRQRIHDFK6$(DVPD\EHUHTXHVWHGE\&HOOGH[
6HULRXVDGYHUVHHYHQWUHSRUWLQJWRUHJXODWRU\DXWKRULWLHVDQGDOOSDUWLFLSDWLQJLQYHVWLJDWRUVZLOOEH
FRQGXFWHG E\ &HOOGH[ LQ DFFRUGDQFH ZLWK &RGH RI )HGHUDO 5HJXODWLRQV &)5 DQG
LQWHUQDWLRQDOUHJXODWLRQVDVDSSURSULDWH

5DSLG1RWLILFDWLRQRI$GYHUVH(YHQWVRI,QWHUHVW
,QDGGLWLRQWRVHULRXVDGYHUVHHYHQWVWKHIROORZLQJDGYHUVHHYHQWVZLOOEHUHSRUWHGZLWKLQKRXUV
XVLQJWKHVDPHUDSLGQRWLILFDWLRQSURFHGXUHVWKDWDUHXVHGIRUVHULRXVDGYHUVHHYHQWVHYHQLIWKH
QDWXUHRIWKHDGYHUVHHYHQWLVQRWGHHPHGVHULRXV
• $Q\RYHUGRVHGHILQHGDVWKHDFFLGHQWDORULQWHQWLRQDODGPLQLVWUDWLRQRIDQ\GRVHRIDSURGXFW
WKDWLVFRQVLGHUHGERWKH[FHVVLYHDQGPHGLFDOO\LPSRUWDQW
• $Q\VXVSHFWHGWUDQVPLVVLRQRIDQLQIHFWLRXVDJHQWYLDVWXG\WUHDWPHQW$QLQIHFWLRXVDJHQWLV
GHILQHGDVDQ\RUJDQLVPYLUXVRULQIHFWLRXVSDUWLFOHSDWKRJHQLFRUQRQSDWKRJHQLF
• 3RWHQWLDO'UXJLQGXFHGOLYHULQMXU\',/,GHILQHGDV
R $ODQLQHDPLQRWUDQVIHUDVH$/7RUDVSDUWDWHDPLQRWUDQVIHUDVH$67HOHYDWLRQ!WLPHV
XSSHUOLPLWRIQRUPDO8/1
$1'
R 7RWDO ELOLUXELQ !  WLPHV 8/1 ZLWKRXW LQLWLDO ILQGLQJV RI FKROHVWDVLV HOHYDWHG VHUXP
DONDOLQHSKRVSKDWDVH
$1'
R 1RRWKHULPPHGLDWHO\DSSDUHQWSRVVLEOHFDXVHVRI$7HOHYDWLRQDQGK\SHUELOLUXELQHPLD
LQFOXGLQJEXWQRWOLPLWHGWRYLUDOKHSDWLWLVSUHH[LVWLQJFKURQLFRUDFXWHOLYHUGLVHDVHRU
WKHDGPLQLVWUDWLRQRIRWKHUGUXJVNQRZQWREHKHSDWRWR[LF

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

• 'HDWKGXHWRGLVHDVHSURJUHVVLRQRFFXUULQJZLWKLQGD\VRIVWXG\WUHDWPHQWKRZHYHUWKHVH
HYHQWVVKRXOGQRWEHGRFXPHQWHGDV$(VRU6$(V,IWKHUHLVDQ\XQFHUWDLQW\DERXWWKHFDXVH
RIGHDWKWKHHYHQWVKRXOGEHUHSRUWHGDVDVHULRXVDGYHUVHHYHQW
• ,IDIHPDOHEHFRPHVRULVIRXQGWREHSUHJQDQWZLWKLQPRQWKVRIH[SRVXUHWRWKHVWXG\
WUHDWPHQWVPDWHUQDOH[SRVXUHRULIDPDOHKDVEHHQH[SRVHGWRWKHVWXG\WUHDWPHQWVZLWKLQ
PRQWKVSULRUWRFRQWUDFHSWLRQSDWHUQDOH[SRVXUH
• $Q\ IROORZXS WR WKH DERYHUHIHUHQFHG HYHQWV LQFOXGLQJ RXWFRPH RI SUHJQDQF\ )XUWKHU
IROORZXSRIELUWKRXWFRPHVZLOOEHKDQGOHGRQDFDVHE\FDVHEDVLV,QWKHFDVHRISDWHUQDO
H[SRVXUHWKHLQYHVWLJDWRUPXVWREWDLQSHUPLVVLRQIURPWKHSDWLHQW¶VSDUWQHULQRUGHUWRFRQGXFW
DQ\IROORZXSRUFROOHFWDQ\LQIRUPDWLRQ

/DERUDWRU\6DIHW\'DWD
7KHIROORZLQJFOLQLFDOODERUDWRU\WHVWVZLOOEHSHUIRUPHGDWWKHVWXG\YLVLWVRXWOLQHGLQ7DEOH


&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

7DEOH &OLQLFDO/DERUDWRU\7HVWVWREH3HUIRUPHG'XULQJ6WXG\
+HPDWRORJ\
&OLQLFDO&KHPLVWU\
8ULQDO\VLV
+HPRJORELQ
6RGLXP
3URWHLQ
+HPDWRFULW
3RWDVVLXP
*OXFRVH
0HDQFRUSXVFXODUYROXPH0&9
&KORULGH
6SHFLILFJUDYLW\
(U\WKURF\WHFRXQW5%&
%LFDUERQDWH
%ORRG
/HXNRF\WHV:%&
*OXFRVHQRQIDVWLQJ

3ODWHOHWV
%ORRGXUHDQLWURJHQ%81
0LFURVFRSLFH[DPLQDWLRQZLOO
EHSHUIRUPHGLILQGLFDWHG
'LIIHUHQWLDO
&UHDWLQLQH
1HXWURSKLOV
&DOFLXP
/\PSKRF\WHV
0DJQHVLXP
7K\URLG)XQFWLRQ
0RQRF\WHV
3KRVSKDWH
7K\URLGVWLPXODWLQJKRUPRQH
76+
(RVLQRSKLOV
$ONDOLQHSKRVSKDWDVH
)UHH7
%DVRSKLOV
$ODQLQHWUDQVDPLQDVH
$/76*37
)UHH7

$VSDUWDWHWUDQVDPLQDVH
$676*27

'LIIHUHQWLDOVKRXOGEHUHSRUWHG
FRQVLVWHQWO\WKURXJKRXWWKH
VWXG\DVHLWKHUDQDEVROXWH
FRXQWSUHIHUUHGRUDV
DSHUFHQWDJH

&RDJXODWLRQ3DQHO
3URWKURPELQWLPH37
3DUWLDOWKURPERSODVWLQWLPH377
,QWHUQDWLRQDOQRUPDOL]HGUDWLR,15

7KHFRDJXODWLRQSDQHOVKRXOGEHGRQHDW
VFUHHQLQJ
7RWDOSURWHLQ
)UHH7DQGIUHH7
SHUIRUPHGDWVFUHHQLQJDQG
WKHQRQO\LI76+LVDEQRUPDODW
VXEVHTXHQWYLVLWV

,IWK\URLGIXQFWLRQWHVWVDUH
DEQRUPDODWHQGRIWUHDWPHQW
FRQWLQXHPRQLWRULQJWR
UHVROXWLRQRUFOLQLFDO
VWDELOL]DWLRQ
$OEXPLQ
/DFWDWH'HK\GURJHQDVH/'+
7RWDO%LOLUXELQ
8ULFDFLG
$P\ODVH
/LSDVH
2QVWXG\WUHDWPHQWGD\VWHVWVPXVWEHSHUIRUPHGZLWKLQKRXUVSULRUWRGRVLQJDQGUHVXOWVPXVWEHUHYLHZHG
SULRUWRVWXG\WUHDWPHQWDGPLQLVWUDWLRQ)RUDOORWKHUODERUDWRU\WHVWVUHVXOWVIURPWKHSULRUYLVLWPXVWEHUHYLHZHG
EHIRUHWKHDGPLQLVWUDWLRQRIVWXG\WUHDWPHQW6HH6HFWLRQIRUJXLGDQFHUHJDUGLQJGRVLQJPRGLILFDWLRQVGHOD\V
GXHWRWR[LFLW\LQFOXGLQJODERUDWRU\DEQRUPDOLWLHV
,QYHVWLJDWRUVPXVWGRFXPHQWWKHLUUHYLHZRIHDFKODERUDWRU\UHSRUWE\VLJQLQJRULQLWLDOLQJDQG
GDWLQJHDFKUHSRUWDVZHOODVDGGUHVVLQJWKHFOLQLFDOVLJQLILFDQFHDQGFDXVDOLW\IRUVLJQLILFDQW
DEQRUPDOLWLHV&OLQLFDOO\VLJQLILFDQWDEQRUPDOODERUDWRU\UHVXOWVVKRXOGEHUHSHDWHGDVVRRQDV
SRVVLEOHSUHIHUDEO\ZLWKLQWRKRXUV6HFWLRQSURYLGHVIXUWKHUJXLGDQFHDVWRZKHQ
DEQRUPDOODERUDWRU\UHVXOWVDUHWREHUHSRUWHGDVDGYHUVHHYHQWV

2WKHU6DIHW\'DWD
7KH IROORZLQJ HYDOXDWLRQV ZLOO DOVR EHSHUIRUPHGGXULQJWKH VWXG\WR PHDVXUH WKH VDIHW\ DQG
WROHUDELOLW\RIVWXG\WUHDWPHQW
• (&*V
• 9LWDOVLJQPHDVXUHPHQWV
• 3K\VLFDOH[DPLQDWLRQV

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 49 of 73 
 
11 SAFETY MONITORING 
As this study is a single-arm, Phase 2 design, an IDMC will not be utilized. To ensure both study 
integrity and patient safety, processes are in place within Celldex for regular review and 
monitoring of emerging safety data. Celldex will regularly communicate study conduct and safety 
information to participating investigators. 
12 STATISTICAL CONSIDERATIONS 
Detailed methodology for summary and statistical analyses of the data collected in this trial will 
be documented in a Statistical Analysis Plan (SAP), which will be developed and maintained by 
Celldex. 
The SAP may modify the plans outlined in the protocol; however, any major modifications of the 
primary endpoint definition and/or its analysis will also be reflected in a protocol amendment. 
12.1 
Sample Size and Power Calculation 
The original sample size for the study was based on Simon’s 2-stage MinMax design. The first 
stage was completed, and the futility stopping rule was not met. The current amendment will 
increase the total sample size from 30 to approximately 45 treated patients, including at least 15 
patients whose tumors harbor a FAT1 mutation based on retrospective gene sequencing.  
Table 11 shows confidence intervals associated with a range of observed ORRs in all treated 
patients (n=45) and in those who are FAT1 mutation-positive (n=15) that would provide sufficient 
precision to rule out < 10%, < 15%, and< 20% ORR based on the lower 95% confidence bound 
for different underlying true response rates (true p). The table also shows the likelihood of 
observing at least the number of responses associated with each of these thresholds (power).  
If the true response rate is ≥ 30%, a sample size of 45 treated patients provides sufficient power to 
rule out < 10% ORR; if the true response rate is ≥ 40%, then the study is adequately powered to 
rule out < 20% ORR. 
A cohort size of 15 treated patients in the FAT1 mutation-positive cohort provides ≥ 70% power 
to rule out < 10% ORR if the true response is ≥ 30%; ≥ 78% power to rule out < 15% ORR if the 
true ORR is ≥ 40%; and ≥ 70% power to rule out < 20% ORR if the true ORR is ≥ 50%. 
Table 11: Observed ORR and Associated Precision and Power Calculations under Varying 
Cohort Sample Sizes and Underlying Response Rates 
Cohort  
Observed 
No. Responses 
r (ORR) 
95% CI a  
of ORR 
(%) 
Power: P (No. observed responses ≥ r | true p)*100 
true p = 50% 
true p = 40% 
true p = 30% 
true p = 20% 
All 
Treated 
Patients 
n=45 
9/45 (20.0%) 
(9.6, 34.6) 
> 99% 
> 99% 
95% 
56% 
12/45 (26.7%) 
(14.6, 41.9) 
> 99% 
98% 
74% 
17% 
15/45 (33.3%) 
(20.0, 49.0) 
> 99% 
86% 
37% 
2% 
FAT1 
mutation 
positive 
n=15 
4/15 (26.7%) 
(7.8, 55.1) 
98% 
91% 
70% 
35% 
5/15 (33.3%) 
(11.8, 61.6) 
94% 
78% 
48% 
16% 
7/15 (46.7%) 
(21.3, 73.4) 
70% 
39% 
13% 
2% 
a Clopper-Pearson 

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI


$QDO\VLV(QGSRLQWV
3ULPDU\(QGSRLQW
• 255 7KH SHUFHQWDJH RI SDWLHQWV ZKR DFKLHYH D EHVW UHVSRQVH RI &5 RU 35 FRQILUPHG
DFFRUGLQJWR5(&,67%HVWUHVSRQVHLVUHFRUGHGEHWZHHQWKHGDWHRIILUVWGRVHDQGWKHGDWH
RIGRFXPHQWHGSURJUHVVLRQSHU5(&,67RUWKHGDWHRIVXEVHTXHQWDQWLFDQFHUWUHDWPHQW
ZKLFKHYHURFFXUVILUVW)RUSDWLHQWVZLWKRXWGRFXPHQWHGSURJUHVVLRQRUVXEVHTXHQWDQWLFDQFHU
WUHDWPHQWDOODYDLODEOHWXPRUDVVHVVPHQWVZLOOFRQWULEXWHWRWKHEHVWUHVSRQVHDVVHVVPHQW
6HFRQGDU\(QGSRLQWV
• &%57KHSHUFHQWDJHRISDWLHQWVZKRDFKLHYHEHVWUHVSRQVHRIFRQILUPHG&5RU35RUVWDEOH
GLVHDVH6'IRUDWOHDVWZHHNV%HVWUHVSRQVHLVDVVHVVHGDVGHVFULEHGIRU255
• '257KHLQWHUYDOIURPZKLFKPHDVXUHPHQWFULWHULDDUHILUVWPHWIRU&5RU35XQWLOWKHILUVW
GDWH WKDW SURJUHVVLYH GLVHDVH LV REMHFWLYHO\ GRFXPHQWHG RU GHDWK ZKLFKHYHU RFFXUV ILUVW
3DWLHQWVZKRKDYHQRWSURJUHVVHGRUGLHGZLOOEHFHQVRUHGRQWKHGDWHRIODVWHYDOXDEOHWXPRU
DVVHVVPHQWSDWLHQWVZKRGLGQRWKDYHDQ\RQVWXG\DVVHVVPHQWVDQGKDYHQRWGLHGZLOOEH
FHQVRUHGRQWKHGDWHRIILUVWGRVH,IDSDWLHQWUHFHLYHVVXEVHTXHQWDQWLFDQFHUWUHDWPHQWEHIRUH
GRFXPHQWHGSURJUHVVLRQWKHQ'25ZLOOEHFHQVRUHGRQWKHODVWHYDOXDEOHWXPRUDVVHVVPHQW
RQRUEHIRUHWKHVWDUWGDWHRIVXEVHTXHQWDQWLFDQFHUWUHDWPHQW
• 3)67KHWLPHIURPVWDUWRI&';WRWLPHRISURJUHVVLRQRUGHDWKZKLFKHYHURFFXUVILUVW
3DWLHQWVZKRKDYHQRWSURJUHVVHGRUGLHGZLOOEHFHQVRUHGRQWKHGDWHRIODVWHYDOXDEOHWXPRU
DVVHVVPHQW SDWLHQWV ZKR GLG QRW KDYH DQ\ RQVWXG\ DVVHVVPHQWV DQG GLG QRW GLH ZLOO EH
FHQVRUHGRQWKHGDWHRIILUVWGRVH,IDSDWLHQWUHFHLYHVVXEVHTXHQWDQWLFDQFHUWUHDWPHQWEHIRUH
GRFXPHQWHGSURJUHVVLRQWKHQ3)6ZLOOEHFHQVRUHGRQWKHODVWHYDOXDEOHWXPRUDVVHVVPHQWRQ
RUEHIRUHWKHVWDUWGDWHRIVXEVHTXHQWDQWLFDQFHUWUHDWPHQW
• 267KHWLPHIURPVWDUWRI&';WRGHDWK3DWLHQWVZKRKDYHQRWGLHGZLOOEHFHQVRUHG
RQWKHGDWHRIODVWFRQWDFW
• 6DIHW\6DIHW\ZLOOEHDVVHVVHGE\YLWDOVLJQPHDVXUHPHQWVFOLQLFDOODERUDWRU\WHVWVSK\VLFDO
H[DPV(&*VDQGWKHLQFLGHQFHDQGVHYHULW\RIDGYHUVHHYHQWVJUDGHG DFFRUGLQJWR1&,
&7&$(Y
• 3KDUPDFRNLQHWLFV1RQFRPSDUWPHQWDO3.SDUDPHWHUVZLOOEHGHWHUPLQHGXVLQJ&';
VHUXP FRQFHQWUDWLRQ GDWD REWDLQHG SULRU WR DW FRPSOHWLRQ RI DQG RQH KRXU DIWHU HDFK
&';DGPLQLVWUDWLRQDVZHOODVRQGD\VDQGRIWKHILUVWF\FOHDQGGD\VSRVW
WUHDWPHQW
• ,PPXQRJHQLFLW\ 3DWLHQWV ZLOO EH PRQLWRUHG IRU WKH GHYHORSPHQW RI $'$ WR &';
6DPSOHVZLOOEHFROOHFWHGIRUIXWXUHHYDOXDWLRQRIWKHQHXWUDOL]LQJFDSDFLW\RI$'$
• %LRPDUNHUV'1$VHTXHQFLQJZLOOEHFRQGXFWHGRQWXPRUVDPSOHVWRDVVHVVIRUPXWDWLRQVLQ
FDQFHUUHODWHGJHQHVVXFKDV)$7127&+127&+127&+$.73,.SKRVSKDWDVH
DQGWHQVLQKRPRORJ37(1RU(UE%IDPLO\PHPEHUV

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 52 of 73 
 
Progression-Free Survival and Overall Survival will be analyzed using the same approach as DOR.  
Additional analyses may be conducted including estimating objective response rate and other 
efficacy parameters for the response-evaluable population and within biomarker defined 
subgroups. 
12.5.2 
Safety Analyses 
Safety analyses will consist of data summaries for clinical and laboratory parameters, and for AEs. 
The number and percentage of patients experiencing one or more AEs will be summarized by the 
relationship to study drug and severity based on NCI CTCAE v 5.0. Adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Laboratory parameters will be 
summarized using descriptive statistics, by post-treatment shifts relative to baseline, and data 
listings of clinically significant abnormalities. Vital signs and ECG data will be summarized using 
descriptive statistics. 
12.5.3 
Pharmacokinetic Analyses 
Serum CDX-3379 concentration data will be tabulated by overall study population together with 
descriptive statistics. Individual and mean serum concentration-time profiles of CDX-3379 will be 
generated. Noncompartmental PK data analysis will be performed and descriptive statistics 
provided. If data allows, descriptive statistics of noncompartmental PK parameters (AUC, Cmax, 
CL, t½) will be provided. A population PK analysis may also be performed and various PK 
compartmental models may be explored to characterize the PK of CDX-3379 in patients with 
HNSCC. Exposure-response modeling will be performed to examine the relationship between 
CDX-3379 serum exposure and clinical endpoints. The impact of physiologically relevant patient 
characteristics (covariates) and disease on PK/pharmacodynamic parameters (and possibly clinical 
endpoints) may be tested.  
12.5.4 
Immunogenicity Analyses 
The number and percentage of patients who develop detectable CDX-3379 ADA will be 
summarized.  ADA will be reported for confirmed ADA-positive patients, and the impact of ADA 
on PK will be assessed if data allow. 
12.5.5 
Biomarker Analyses 
Biomarker data will be summarized descriptively and any correlation with outcome (efficacy) will 
be investigated.  Analyses may include estimating objective response rate and other efficacy 
parameters within biomarker defined subgroups (i.e., defined by degree of expression or presence 
of genetic variation).  
12.5.6 
Study Treatment and Medications 
The duration of treatment, total number of doses and total dose administered will be tabulated for 
study treatments. The primary reason for treatment modifications will be tabulated. 
All medications will be coded using WHO Drug Dictionary, and they will be listed and 
summarized by anatomical therapeutic class and preferred name. 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 53 of 73 
 
13 DATA HANDLING AND RECORD KEEPING 
13.1 
Data Quality Assurance 
Monitoring and auditing procedures defined by Celldex will be followed in order to comply with 
Good Clinical Practice (GCP) guidelines. Each center will be visited at regular intervals by a 
monitor to ensure compliance with the study protocol, GCP and legal aspects.  
To ensure the safety of participants in the study and to ensure accurate, complete, and reliable data, 
the investigator will keep records of laboratory tests, clinical notes, and patient medical records in 
the patient files as original source documents for the study. All the information required by the 
protocol should be provided; any omissions require explanation. 
Celldex will provide CRFs for the recording and collection of data. The CRF will either be in paper 
or via an electronic data capture (EDC) system. Entries made in the CRF must be either verifiable 
against source documents, or have been directly entered into the CRF, in which case the entry in 
the CRF will be considered as the source data. The source data parameter to be verified and the 
identification of the source document must be documented. Corrections to CRFs and source data 
will be made only by authorized members of the study staff, clearly entered, initialed and dated. 
The investigator will sign the CRFs to indicate that, to his/her knowledge, they are complete and 
accurate. If further changes are made after this, the investigator will be made aware of the 
corrections and his/her approval will be documented by re-signing. In cases where an EDC system 
is utilized, an electronic audit trail is maintained. 
The investigator will permit Celldex direct access to source data/documents for trial-related 
monitoring, audits, review, and inspection(s). Through ongoing monitoring visits at the 
investigational sites, Celldex will periodically check the patient data recorded in the CRF’s against 
source documents, to ensure accuracy, completeness, and adherence to the protocol, regulatory 
compliance, and the maintenance of comprehensive clinical records.  
The study may be audited by Celldex and/or regulatory agencies at any time. If requested, the 
investigator will provide Celldex, applicable regulatory agencies, and/or applicable ethical review 
boards with direct access to original source documents, which may include applicable electronic 
medical record system(s). 
13.2 
Archiving of Study Documentation 
To enable evaluations and/or audits by regulatory authorities or Celldex, the investigator agrees to 
keep records, including the identity of all participating patients (sufficient information to link 
records, e.g., CRFs and hospital records), all original signed informed consent forms (ICFs), copies 
of all CRFs, SAE forms, source documents, and detailed records of treatment disposition, and 
adequate documentation of relevant correspondence (e.g., letters, meeting minutes, telephone calls 
reports). The duration of record retention by the investigator should be according to International 
Conference on Harmonisation (ICH), local regulations, or as specified in the Clinical Trial 
Agreement, whichever is longer. 
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), Celldex should be prospectively notified. The study 
records must be transferred to a designee acceptable to Celldex, such as another investigator, 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 54 of 73 
 
another institution, or to an independent third party arranged by Celldex. The investigator must 
obtain written permission from Celldex before disposing of any records, even if retention 
requirements have been met. 
14 ETHICAL CONSIDERATIONS 
14.1 
Institutional Review Board or Ethics Committee 
International Conference on Harmonisation GCP guidelines require that all investigational drug 
studies be conducted under the auspices of an Institutional Review Board/Ethics Committee 
(IRB/EC). This committee, the makeup of which must conform to national, state, and local 
guidelines regarding such, will approve all aspects of the study, including the protocol and 
informed consent to be used and any modifications made to the protocol or informed consent. The 
investigator will provide Celldex with a copy of the communication from the IRB/EC to the 
investigator indicating approval/favorable opinion of the protocol and consent form. All changes 
to the protocol or consent form must be reviewed and approved prior to implementation, except 
where necessary to eliminate apparent immediate hazards to human patients. 
The investigator will provide Celldex with documentation of ethical review board approval of the 
protocol and the informed consent document before the study may begin at the investigative site(s). 
The investigator will also be responsible for obtaining periodic IRB/EC re-approval throughout 
the duration of the study. Copies of the investigator’s periodic report to the IRB/EC and copies of 
the IRB/EC’s continuance of approval must be retained in the site study files and furnished to 
Celldex. 
The IRB/ECs must supply to Celldex, upon request, a list of the IRB/EC members involved in the 
vote and a statement to confirm that the IRB/EC is organized and operates according to GCP and 
applicable laws and regulations. 
14.2 
Ethical Conduct of the Study 
The procedures set out in this protocol, pertaining to the conduct, evaluation, and documentation 
of this study, are designed to ensure that Celldex and investigator abide by GCP Guidelines and 
under the guiding principles detailed in the Declaration of Helsinki. The study will also be carried 
out in keeping with applicable local law(s) and regulation(s). The investigator is responsible for 
complying with the protocol and all appropriate regulations and guidelines governing global 
clinical research. Additionally, he/she is responsible for ensuring that all participating staff 
members are adequately trained and competent to perform his/her assigned tasks. 
14.3 
Patients Information and Informed Consent  
Sample ICFs will be provided. Prior to the beginning of the study, the investigator must have the 
IRB/EC’s written approval/favorable opinion of the written ICF and any other written information 
to be provided to patients. The written approval of the IRB/EC together with the approved patient 
information/ICFs must be filed in the study files. The ICF must contain all elements required ICH 
GCP Guidelines (E6) in addition to any other elements required by national, state, local or 
institutional policy.  

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 55 of 73 
 
The investigator will be responsible for obtaining an ICF signed by each patient or his/her legally 
authorized representative, prior to his/her participation in the study, in accordance with ICH GCP 
guidelines. Informed Consent will be obtained from a patient or his/her legally authorized 
representative after a full explanation of the purpose of the study, the risks and discomforts 
involved, potential benefits, etc., have been provided by the investigator or designee, both verbally 
and in writing. The investigator is responsible to see that informed consent is obtained from each 
patient or legal representative and to obtain the appropriate signatures and dates on the ICF 
document prior to the performance of any protocol-specific procedures and prior to the 
administration of study drug. Participation in the study and date of informed consent given by the 
patient should be documented appropriately in the patient’s files. The investigator will be 
responsible for communicating in a timely fashion any new findings, including amendments to the 
protocol, that could affect a patient’s willingness to continue in the study. 
The original or copy of the signed copy of the ICF must be maintained in the institution’s records 
and is subject to inspection by Celldex or regulatory agencies. The patient or his/her legally 
authorized representative will also be given a copy of the signed consent form. 
As used in this protocol, the term "informed consent" includes all consent and/or assent given by 
patients or their legal representatives. 
14.4 
Protocol Amendments 
Modifications to the study protocol will not be implemented by either Celldex or the investigator 
without agreement by each party and IRB/EC approval/favorable opinion. However, the 
investigator may implement a deviation from, or a change of, the protocol to eliminate an 
immediate hazard(s) to the trial patients without prior IRB/EC/Celldex approval/favorable 
opinion. In these cases, the implemented deviation or change, the reasons for it, and if appropriate, 
the proposed protocol amendment, should be submitted to the IRB/EC and Celldex as soon as 
practical. Any deviations from the protocol must be fully explained and documented by the 
investigator with notification to the Sponsor and IRB/EC as appropriate.  
14.5 
Confidentiality 
All records identifying the patient will be kept confidential and, to the extent permitted by the 
applicable laws and/or regulations, will not be made publicly available.  
Patient names will not be supplied to Celldex. Only the patient number and patient initials (as 
permissible) will be recorded in the CRF, and if the patient name appears on any other document 
(e.g., pathologist’s report), it must be obliterated before a copy of the document is supplied to 
Celldex. Study findings stored on a computer will be stored in accordance with local data 
protection laws. The patients will be informed in writing that representatives of Celldex, IRB/EC, 
or Regulatory Authorities may inspect their medical records to verify the information collected, 
and that all personal information made available for inspection will be handled in strictest 
confidence and in accordance with local data protection laws. 
If the results of the study are published, the patient’s identity will remain confidential.  
The investigator will maintain a list to enable patients’ records to be identified. 

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

 38%/,&$7,2132/,&<
$OOGDWDDQGUHVXOWVDQGDOOLQWHOOHFWXDOSURSHUW\ULJKWVLQWKHGDWDDQGUHVXOWVGHULYHGIURPWKH
VWXG\ ZLOO EHWKHSURSHUW\RI&HOOGH[ZKRPD\XWLOL]HWKHGDWDLQYDULRXVZD\VVXFKDVIRU
VXEPLVVLRQWRJRYHUQPHQWUHJXODWRU\DXWKRULWLHVRUGLVFORVXUHWRRWKHULQYHVWLJDWRUV
&HOOGH[ VXSSRUWV SXEOLFDWLRQ RI WKH UHVXOWV RI WKLV WULDO LQ DSSURSULDWH VFLHQWLILF MRXUQDOV DQG
PHHWLQJV,QDFFRUGZLWKVWDQGDUGHGLWRULDODQGHWKLFDOSUDFWLFH&HOOGH[HQFRXUDJHVSXEOLFDWLRQRI
PXOWLFHQWHU WULDOVRQO\ LQ WKHLU HQWLUHW\DQGQRW DVLQGLYLGXDOFHQWHUGDWD $Q\SUHVHQWDWLRQRU
SXEOLFDWLRQRIGDWDFROOHFWHGIURPWKLVVWXG\ZLOOEHJHQHUDWHGLQDFFRUGDQFHZLWKWKHIROORZLQJ
SULQFLSOHV
• $XWKRUVKLS LQFOXGLQJ LGHQWLILFDWLRQ RI D OHDG DXWKRU DQG FRUUHVSRQGLQJ DXWKRU ZLOO EH
GHWHUPLQHGE\PXWXDODJUHHPHQWLQDFFRUGDQFHZLWKWKH,QWHUQDWLRQDO&RPPLWWHHRI0HGLFDO
-RXUQDO(GLWRUV,&0-(FULWHULDIRU DXWKRUVKLS DFFRUGLQJWRRYHUDOOFRQWULEXWLRQWRVWXG\
FRQGXFWFKLHIO\E\OHDGHUVKLSLQVWXG\GHVLJQDQGGHFLVLRQPDNLQJDQGWKHQE\FRQWULEXWLRQ
$OOPHDQLQJIXOFRQWULEXWLRQVZLOOEHDFNQRZOHGJHG
• $XWKRUVZLOOIROORZ*RRG3XEOLFDWLRQ3UDFWLFH*33DQGRWKHUUHFRJQL]HGVWDQGDUGVDQGZLOO
ZRUN WRJHWKHU WR GLVFXVV SUDFWLFDO FRQVLGHUDWLRQV HJ FKRLFH RI SRWHQWLDO MRXUQDOV RU
FRQJUHVVHV DYRLG GXSOLFDWH SXEOLFDWLRQ HQVXUH WKDW SXEOLFDWLRQV DUH DFFXUDWH EDODQFHG
WUDQVSDUHQWDQGSURGXFHGLQDWLPHO\PDQQHUDVVXPHUHVSRQVLELOLW\IRUWKHFRQWHQWDFFXUDF\
DQGFRPSOHWHQHVVRIWKHSXEOLFDWLRQHVWDEOLVKDSURFHVVEDVHGRQKRQHVWVFLHQWLILFGHEDWHWR
UHVROYHGLIIHUHQFHVLQLQWHUSUHWDWLRQRIGDWDGLVFORVHDOOSRWHQWLDOFRQIOLFWVRILQWHUHVWGLVFORVH
IXQGLQJVRXUFHVLQFOXGLQJ&HOOGH[VXSSRUWIRUWKHVWXG\IXQGLQJDQGLQNLQGVXSSRUWVXFKDV
PHGLFDOZULWLQJDQGDVVXPHUHVSRQVLELOLW\IRUDOOILQDOGHFLVLRQVRQSXEOLFDWLRQFRQWHQWDQG
IRUILQDODSSURYDORIWKHYHUVLRQIRUVXEPLVVLRQRUSUHVHQWDWLRQ
• &HOOGH[ZLOOSURYLGHDXWKRUVZLWKDFFHVVWRDOOUHOHYDQWVWXG\GRFXPHQWVQHHGHGWRVXSSRUWWKH
SXEOLFDWLRQ LQFOXGLQJ SURWRFROV VWDWLVWLFDO DQDO\VLV SODQV FOLQLFDO VWXG\ UHSRUWV ZKHQ
DYDLODEOHDQGGDWDWDEOHVGHVFULEHHGLWRULDODQGRWKHUVXSSRUWWKDWPD\EHDYDLODEOHWRWKH
DXWKRUVIRUWKHGHYHORSPHQWRIDSXEOLFDWLRQDQGHQVXUHWKDWDOODXWKRUVDJUHHWRDQ\VXSSRUW
WREHSURYLGHGDQGSURYLGHDWLPHO\UHYLHZRIWKHSXEOLFDWLRQRUSUHVHQWDWLRQ
• $GGLWLRQDOO\DXWKRUVDQG&HOOGH[ZLOODYRLGSUHPDWXUHUHOHDVHRIVWXG\LQIRUPDWLRQWKDWFRXOG
MHRSDUGL]HSXEOLFDWLRQDQGUHVSHFWHPEDUJRHVVHWE\MRXUQDOVDQGFRQJUHVVHV



Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 57 of 73 
 
16 REFERENCES 
 
1. 
Alvarado D, Ligon GF, Lillquist JS, et al. ErbB activation signatures as potential 
biomarkers for anti-ErbB3 treatment in HNSCC. PLoS One. 2017;12(7):e0181356. 
2. 
American Cancer Society. Cancer Facts & Figures 2017. Atlanta: American Cancer 
Society. 2017. 
3. 
Amin DN, Campbell MR, Moasser MM. The role of HER3, the unpretentious member of 
the HER family, in cancer biology and cancer therapeutics. Seminars in Cell & 
Developmental Biology. 2010;21(9):944-950. 
4. 
Bauman JE, Saba NF, Wise-Draper TM, et al. CDX3379-04:  Phase II evaluation of CDX-
3379 in combination with cetuximab in patients with advanced head and neck squamous 
cell carcinoma (HNSCC). J Clin Oncol. 2019;37. 
5. 
Burtness B, Anadkat M, Basti S, et al. NCCN Task Force Report: Management of 
dermatologic and other toxicities associated with EGFR inhibition in patients with cancer. 
J Natl Compr Canc Netw. 2009;7 Suppl 1:S5-21; quiz S22-24. 
6. 
Cancer Genome Atlas Network. Comprehensive genomic characterization of head and 
neck squamous cell carcinomas. Nature. 2015;517(7536):576-582. 
7. 
Chiu CG, Masoudi H, Leung S, et al. HER-3 Overexpression Is Prognostic of Reduced 
Breast Cancer Survival. Annals of Surgery. 2010;251(6):1107-1116. 
8. 
Cohen EEW, Licitra LF, Fayette J, et al. Biomarker analysis in recurrent and/or metastatic 
head and neck squamous cell carcinoma (R/M HNSCC) patients (pts) treated with second-
line afatinib versus methotrexate (MTX): LUX-Head & Neck 1 (LUX-H&N1). Journal of 
Clinical Oncology. 2015;33(15_suppl):6023-6023. 
9. 
Dall'Acqua WF, Kiener PA, Wu H. Properties of Human IgG1s Engineered for Enhanced 
Binding to the Neonatal Fc Receptor (FcRn). Journal of Biological Chemistry. 
2006;281(33):23514-23524. 
10. 
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(2):228-247. 
11. 
Engelman JA, Zejnullahu K, Mitsudomi T, et al. MET Amplification Leads to Gefitinib 
Resistance 
in 
Lung 
Cancer 
by 
Activating 
ERBB3 
Signaling. 
Science. 
2007;316(5827):1039-1043. 
12. 
Ferlay J, Shin H-R, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide 
burden of cancer in 2008: GLOBOCAN 2008. International Journal of Cancer. 
2010;127(12):2893-2917. 
13. 
Ferris RL, Blumenschein G, Jr., Fayette J, et al. Nivolumab for Recurrent Squamous-Cell 
Carcinoma of the Head and Neck. N Engl J Med. 2016;375(19):1856-1867. 
14. 
Hayes DN, Van Waes C, Seiwert TY. Genetic Landscape of Human Papillomavirus–
Associated Head and Neck Cancer and Comparison to Tobacco-Related Tumors. Journal 
of Clinical Oncology. 2015;33(29):3227-3234. 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 58 of 73 
 
15. 
He C, Lv X, Hua G, et al. YAP forms autocrine loops with the ERBB pathway to regulate 
ovarian cancer initiation and progression. Oncogene. 2015;34(50):6040-6054. 
16. 
Koyama T, Chen H. Proper inference from Simon's two-stage designs. Stat Med. 
2008;27(16):3145-3154. 
17. 
Martin D, Degese MS, Vitale-Cross L, et al. Assembly and activation of the Hippo 
signalome by FAT1 tumor suppressor. Nat Commun. 2018;9(1):2372. 
18. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 
19. 
Sacco AG, Cohen EE. Current Treatment Options for Recurrent or Metastatic Head and 
Neck Squamous Cell Carcinoma. Journal of Clinical Oncology. 2015;33(29):3305-3313. 
20. 
Shames DS, Carbon J, Walter K, et al. High Heregulin Expression Is Associated with 
Activated HER3 and May Define an Actionable Biomarker in Patients with Squamous Cell 
Carcinomas of the Head and Neck. PLoS ONE. 2013;8(2):e56765. 
21. 
Stein A, Voigt W, Jordan K. Chemotherapy-induced diarrhea: pathophysiology, frequency 
and guideline-based management. Ther Adv Med Oncol. 2010;2(1):51-63. 
22. 
Vermorken JB, Stohlmacher-Williams J, Davidenko I, et al. Cisplatin and fluorouracil with 
or without panitumumab in patients with recurrent or metastatic squamous-cell carcinoma 
of the head and neck (SPECTRUM): an open-label phase 3 randomised trial. Lancet Oncol. 
2013;14(8):697-710. 
23. 
Wang C, Gu C, Jeong KJ, et al. YAP/TAZ-Mediated Upregulation of GAB2 Leads to 
Increased Sensitivity to Growth Factor-Induced Activation of the PI3K Pathway. Cancer 
Res. 2017;77(7):1637-1648. 
24. 
Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: 
role of HER (ErbB) family members. Oncogene. 2008;27(28):3944-3956. 
25. 
Zhang J, Ji JY, Yu M, et al. YAP-dependent induction of amphiregulin identifies a non-
cell-autonomous component of the Hippo pathway. Nat Cell Biol. 2009;11(12):1444-1450. 
 
 
 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 59 of 73 
 
Appendix 1. 
Investigator Signature 
 
Investigator Signature 
Protocol CDX3379-04 
I confirm that I have read this protocol; I understand it; and I will work according to this protocol 
and to the ethical principles stated in the latest version of the Declaration of Helsinki, the applicable 
ICH guidelines for good clinical practices, and the applicable laws and regulations of the country 
of the study site for which I am responsible. I will accept the monitor's overseeing of the study. I 
will abide by the publication plan set forth in the protocol and my agreement with Celldex 
Therapeutics, Inc. I will promptly submit the protocol to applicable ethical review board(s) and 
will not begin the study until regulatory approval has been obtained and all required essential 
documents have been completed. 
 
Instructions to the investigator: Please SIGN and DATE this signature page and PRINT your name.  
Return a completed and signed version to Celldex Therapeutics, Inc., and retain a copy with this 
protocol. 
 
 
 
 
 
Signature of Investigator 
 
Date 
 
 
 
 
 
 
Investigator Name (Please Print) 
 
Investigator Title 
 
 
 
 
 
 
 
Name of Facility 
 
Location of Facility 
 
 
(City, State (if applicable), Country) 
 
 

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

$SSHQGL[
5(&,67&ULWHULD
7RDVVHVVREMHFWLYHUHVSRQVHRUIXWXUHSURJUHVVLRQLWLVQHFHVVDU\WRHVWLPDWHWKHRYHUDOOWXPRU
EXUGHQ DW EDVHOLQH DQG XVH WKLV DV D FRPSDUDWRU IRU VXEVHTXHQW PHDVXUHPHQWV $OO EDVHOLQH
HYDOXDWLRQVVKRXOGEHSHUIRUPHGDVFORVHDVSRVVLEOHWRWKHWUHDWPHQWVWDUWDQGQHYHUPRUHWKDQ
ZHHNV EHIRUH WKH EHJLQQLQJ RI WKH WUHDWPHQW 7KH VDPH PHWKRG RI DVVHVVPHQW DQG WKH VDPH
WHFKQLTXHVKRXOGEHXVHGWRFKDUDFWHUL]HHDFKLGHQWLILHGDQGUHSRUWHGOHVLRQDWEDVHOLQHDQGGXULQJ
IROORZXS ,PDJLQJ EDVHG HYDOXDWLRQ VKRXOG DOZD\V EH GRQH UDWKHU WKDQ FOLQLFDO H[DPLQDWLRQ
XQOHVVWKHOHVLRQVEHLQJIROORZHGFDQQRWEHLPDJHGEXWDUHDVVHVVDEOHE\FOLQLFDOH[DP6HH
³0HWKRGVRI/HVLRQ0HDVXUHPHQW´IRUIXUWKHUJXLGDQFH
$WEDVHOLQHOHVLRQVVKRXOGEHLGHQWLILHGDVHLWKHU³7DUJHW´RU³1RQ7DUJHW´DVIROORZV
7DUJHW/HVLRQV
• 8SWRDPD[LPXPRIILYHPHDVXUDEOHWDUJHWOHVLRQVWRWDOZLWKDPD[LPXPRIWZRWDUJHWOHVLRQV
SHURUJDQVKRXOGEHLGHQWLILHGDVWDUJHWOHVLRQVDQGZLOOEHUHFRUGHGDQGPHDVXUHGDWEDVHOLQH
7KLVPHDQVLQLQVWDQFHVZKHUHSDWLHQWVKDYHRQO\RQHRUWZRRUJDQVLWHVLQYROYHGDPD[LPXP
RIWZRDQGIRXUOHVLRQVUHVSHFWLYHO\ZLOOEHUHFRUGHG
• 7DUJHWOHVLRQVVKRXOGEHVHOHFWHGRQWKHEDVLVRIWKHLUVL]HOHVLRQVZLWKWKHORQJHVWGLDPHWHU
EH UHSUHVHQWDWLYH RI DOO LQYROYHG RUJDQV DQG VKRXOG EH WKRVH WKDW OHQG WKHPVHOYHV WR
UHSURGXFLEOHUHSHDWHGPHDVXUHPHQWV,WPD\EHWKHFDVHWKDWRQRFFDVLRQWKHODUJHVWOHVLRQ
GRHVQRWOHQGLWVHOIWRUHSURGXFLEOHPHDVXUHPHQWLQZKLFKFLUFXPVWDQFHWKHQH[WODUJHVWOHVLRQ
ZKLFKFDQEHPHDVXUHGUHSURGXFLEO\VKRXOGEHVHOHFWHG
• $OO WDUJHW OHVLRQ PHDVXUHPHQWV VKRXOG EH UHFRUGHG LQ PHWULF QRWDWLRQ XVLQJ FDOLSHUV LI
FOLQLFDOO\DVVHVVHG
• $VXPRIWKHGLDPHWHUVORQJHVWIRUQRQQRGDOOHVLRQVVKRUWD[LVIRUQRGDOOHVLRQVIRUDOOWDUJHW
OHVLRQV ZLOO EH FDOFXODWHG DQG UHSRUWHG DV WKH EDVHOLQH VXP GLDPHWHUV 7KH EDVHOLQH VXP
GLDPHWHUVZLOOEHXVHGDVUHIHUHQFHWRIXUWKHUFKDUDFWHUL]HDQ\REMHFWLYHWXPRUUHJUHVVLRQLQ
WKHPHDVXUDEOHGLPHQVLRQRIWKHGLVHDVH6HH³7XPRUUHVSRQVHHYDOXDWLRQ´
1RQ7DUJHW/HVLRQV
• $OORWKHUPHDVXUDEOHQRQPHDVXUDEOHOHVLRQVRUVLWHVRIGLVHDVHLQFOXGLQJSDWKRORJLFDOO\PSK
QRGHVVKRXOGEHLGHQWLILHGDVQRQWDUJHWOHVLRQVDQGVKRXOGDOVREHUHFRUGHGDWEDVHOLQH,WLV
DFFHSWDEOHWRUHFRUGPXOWLSOHQRQWDUJHWOHVLRQVLQYROYLQJWKHVDPHRUJDQDVDVLQJOHLWHPRQ
WKH FDVH UHSRUW IRUP HJ µPXOWLSOH HQODUJHG SHOYLF O\PSK QRGHV¶ RU µPXOWLSOH OLYHU
PHWDVWDVHV¶
• 1RQWDUJHWOHVLRQVVKRXOGEHIROORZHGDVµSUHVHQW¶µDEVHQW¶RULQUDUHFDVHVµXQHTXLYRFDO
SURJUHVVLRQ¶6HH³7XPRUUHVSRQVHHYDOXDWLRQ´:KLOHVRPHQRQWDUJHWOHVLRQVPD\DFWXDOO\
EHPHDVXUDEOHWKH\QHHGQRWEHPHDVXUHGDQGLQVWHDGVKRXOGEHDVVHVVHGRQO\TXDOLWDWLYHO\

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

0($685$%,/,7<2)78025$7%$6(/,1(
• 0HDVXUDEOH7XPRUOHVLRQVPXVWEHDFFXUDWHO\PHDVXUHGLQDWOHDVWRQHGLPHQVLRQORQJHVW
GLDPHWHULQWKHSODQHRIPHDVXUHPHQWLVWREHUHFRUGHGZLWKDPLQLPXPVL]HRI
R PPE\&7VFDQ&7VFDQVOLFHWKLFNQHVVQRJUHDWHUWKDQPP
R PP FDOLSHU PHDVXUHPHQW E\ FOLQLFDO H[DP OHVLRQV ZKLFK FDQQRW EH DFFXUDWHO\
PHDVXUHGZLWKFDOLSHUVVKRXOGEHUHFRUGHGDVQRQPHDVXUDEOH
R PPE\FKHVW;UD\
1RWH7REHFRQVLGHUHGSDWKRORJLFDOO\HQODUJHGDQGPHDVXUDEOHDO\PSKQRGHPXVWEH• PP
LQVKRUWD[LVZKHQDVVHVVHGE\&7VFDQIRUO\PSKQRGHVRQO\WKHVKRUWD[LVLVPHDVXUHGDQG
IROORZHG
• 1RQPHDVXUDEOH $OO RWKHU OHVLRQV LQFOXGLQJ VPDOO OHVLRQV ORQJHVW GLDPHWHU PP RU
SDWKRORJLFDOO\PSKQRGHVZLWK• WRPPVKRUWD[LVDVZHOODVWUXO\QRQPHDVXUDEOH
OHVLRQV /HVLRQV FRQVLGHUHG WUXO\ QRQPHDVXUDEOH LQFOXGH OHSWRPHQLQJHDO GLVHDVH DVFLWHV
SOHXUDORUSHULFDUGLDOHIIXVLRQLQIODPPDWRU\EUHDVWGLVHDVHO\PSKDQJLWLFLQYROYHPHQWRIVNLQ
RUOXQJDQGDEGRPLQDOPDVVHVDEGRPLQDORUJDQRPHJDO\LGHQWLILHGE\SK\VLFDOH[DPWKDWLV
QRWPHDVXUDEOHE\UHSURGXFLEOHLPDJLQJWHFKQLTXHV
6SHFLDOFRQVLGHUDWLRQVUHJDUGLQJOHVLRQPHDVXUDELOLW\
• 0DOLJQDQWO\PSKQRGHV/\PSKQRGHVPHULWVSHFLDOPHQWLRQVLQFHWKH\DUHQRUPDODQDWRPLFDO
VWUXFWXUHVZKLFKPD\EHYLVLEOHE\LPDJLQJHYHQLIQRWLQYROYHGE\WXPRXU1RGDOVL]HLV
QRUPDOO\UHSRUWHGDVWZRGLPHQVLRQVLQWKHSODQHLQZKLFKWKHLPDJHLVREWDLQHGIRU&7VFDQ
WKLVLVDOPRVWDOZD\VWKHD[LDOSODQHIRU05,WKHSODQHRIDFTXLVLWLRQPD\EHD[LDOVDJJLWDO
RUFRURQDO7KHVPDOOHURIWKHVHPHDVXUHVLVWKHVKRUWD[LV$WEDVHOLQHDQGLQIROORZXSRQO\
WKHVKRUWD[LVZLOOEHPHDVXUHGDQGIROORZHG7REHFRQVLGHUHGSDWKRORJLFDOO\HQODUJHGDQG
PHDVXUDEOHDO\PSKQRGHPXVWEH• PPLQVKRUWD[LVZKHQDVVHVVHGE\&7VFDQ&7VFDQ
VOLFHWKLFNQHVVUHFRPPHQGHGWREHQRJUHDWHUWKDQPP$OORWKHUSDWKRORJLFDOQRGHVWKRVH
ZLWKVKRUWD[LV• PPEXWPPVKRXOGEHFRQVLGHUHGQRQWDUJHWOHVLRQV1RGHVWKDWKDYH
DVKRUWD[LVPPDUHFRQVLGHUHGQRQSDWKRORJLFDODQGVKRXOGQRWEHUHFRUGHGRUIROORZHG
• %RQH OHVLRQV %RQH VFDQ 3(7 VFDQ RU SODLQ ILOPV DUH QRW FRQVLGHUHG DGHTXDWH LPDJLQJ
WHFKQLTXHVWRPHDVXUHERQHOHVLRQV+RZHYHUWKHVHWHFKQLTXHVFDQEHXVHGWRFRQILUPWKH
SUHVHQFHRUGLVDSSHDUDQFHRIERQHOHVLRQV/\WLFERQHOHVLRQVRUPL[HGO\WLFEODVWLFOHVLRQV
ZLWKLGHQWLILDEOH VRIW WLVVXH FRPSRQHQWV WKDW FDQ EH HYDOXDWHG E\ FURVV VHFWLRQDO LPDJLQJ
WHFKQLTXHV VXFK DV &7 RU 05, FDQ EH FRQVLGHUHG DV PHDVXUDEOH OHVLRQV LI WKH VRIW WLVVXH
FRPSRQHQWPHHWVWKHGHILQLWLRQRIPHDVXUDELOLW\GHVFULEHGDERYH%ODVWLFERQHOHVLRQVDUHQRQ
PHDVXUDEOH
• &\VWLFOHVLRQV/HVLRQVWKDWPHHWWKHFULWHULDIRUUDGLRJUDSKLFDOO\GHILQHGVLPSOHF\VWVVKRXOG
QRWEHFRQVLGHUHGDVPDOLJQDQWOHVLRQVQHLWKHUPHDVXUDEOHQRUQRQPHDVXUDEOHVLQFHWKH\
DUHE\GHILQLWLRQVLPSOHF\VWVµ&\VWLFOHVLRQV¶WKRXJKWWRUHSUHVHQWF\VWLFPHWDVWDVHVFDQEH
FRQVLGHUHGDVPHDVXUDEOHOHVLRQVLIWKH\PHHWWKHGHILQLWLRQRIPHDVXUDELOLW\GHVFULEHGDERYH
+RZHYHULIQRQF\VWLFOHVLRQVDUHSUHVHQWLQWKHVDPHSDWLHQWWKHVHDUHSUHIHUUHGIRUVHOHFWLRQ
DVWDUJHWOHVLRQV
• /HVLRQVZLWKSULRUORFDOWUHDWPHQW7XPRUOHVLRQVVLWXDWHGLQDSUHYLRXVO\LUUDGLDWHGDUHDRULQ
DQDUHDVXEMHFWHGWRRWKHUORFRUHJLRQDOWKHUDS\DUHXVXDOO\QRWFRQVLGHUHGPHDVXUDEOHXQOHVV
WKHUHKDVEHHQGHPRQVWUDWHGSURJUHVVLRQLQWKHOHVLRQ

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

0(7+2'62)/(6,210($685(0(17
• &OLQLFDOH[DP&OLQLFDOOHVLRQVZLOORQO\EHFRQVLGHUHGPHDVXUDEOHZKHQWKH\DUHVXSHUILFLDO
DQG• PPGLDPHWHUDVDVVHVVHGXVLQJFDOLSHUVHJVNLQQRGXOHV)RUWKHFDVHRIVNLQOHVLRQV
GRFXPHQWDWLRQE\FRORUSKRWRJUDSK\LQFOXGLQJDUXOHUWRHVWLPDWHWKHVL]HRIWKHOHVLRQLV
VXJJHVWHG$VQRWHGDERYHZKHQOHVLRQVFDQEHHYDOXDWHGE\ERWKFOLQLFDOH[DPDQGLPDJLQJ
LPDJLQJHYDOXDWLRQVKRXOGEHXQGHUWDNHQVLQFHLWLVPRUHREMHFWLYHDQGPD\DOVREHUHYLHZHG
DWWKHHQGRIWKHVWXG\
• &KHVW;UD\ &KHVW &7 LV SUHIHUUHG RYHU FKHVW ;UD\ SDUWLFXODUO\ZKHQSURJUHVVLRQLVDQ
LPSRUWDQWHQGSRLQWVLQFH&7LVPRUHVHQVLWLYHWKDQ;UD\SDUWLFXODUO\LQLGHQWLI\LQJQHZ
OHVLRQV+RZHYHUOHVLRQVRQFKHVW;UD\PD\EHFRQVLGHUHGPHDVXUDEOHLIWKH\DUHFOHDUO\
GHILQHGDQGVXUURXQGHGE\DHUDWHGOXQJ
• &7 05, &7 LV WKH EHVW FXUUHQWO\ DYDLODEOH DQG UHSURGXFLEOH PHWKRG WR PHDVXUH OHVLRQV
VHOHFWHGIRUUHVSRQVHDVVHVVPHQW7KLVJXLGHOLQHKDVGHILQHGPHDVXUDELOLW\RIOHVLRQVRQ&7
VFDQEDVHGRQWKHDVVXPSWLRQWKDW&7VOLFHWKLFNQHVVLVPPRUOHVV:KHQ&7VFDQVKDYH
VOLFHWKLFNQHVVJUHDWHUWKDQPPWKHPLQLPXPVL]HIRUDPHDVXUDEOHOHVLRQVKRXOGEHWZLFH
WKHVOLFHWKLFNQHVV05,LVDOVRDFFHSWDEOHLQFHUWDLQVLWXDWLRQVHJIRUERG\VFDQV,IWKHUHLV
FRQFHUQDERXWUDGLDWLRQH[SRVXUHDW&705,PD\EHXVHGLQVWHDGRI&7LQVHOHFWHGLQVWDQFHV
• )'*3(7 :KLOH )'*3(7 UHVSRQVH DVVHVVPHQWV QHHG DGGLWLRQDO VWXG\ LW LV VRPHWLPHV
UHDVRQDEOH WR LQFRUSRUDWH WKH XVH RI )'*3(7 VFDQQLQJ WR FRPSOHPHQW &7 VFDQQLQJ LQ
DVVHVVPHQWRISURJUHVVLRQ6HH³7XPRU5HVSRQVH(YDOXDWLRQ´
• 8OWUDVRXQG8OWUDVRXQGLVQRWXVHIXOLQDVVHVVPHQWRIOHVLRQVL]HDQGVKRXOGQRWEHXVHGDVD
PHWKRGRIPHDVXUHPHQW8OWUDVRXQGH[DPLQDWLRQVFDQQRWEHUHSURGXFHGLQWKHLUHQWLUHW\IRU
LQGHSHQGHQW UHYLHZ DW D ODWHU GDWH DQG EHFDXVHWKH\ DUH RSHUDWRUGHSHQGHQWLWFDQQRW EH
JXDUDQWHHGWKDWWKHVDPHWHFKQLTXHDQGPHDVXUHPHQWVZLOOEHWDNHQIURPRQHDVVHVVPHQWWR
WKHQH[W,IQHZOHVLRQVDUHLGHQWLILHGE\XOWUDVRXQGLQWKHFRXUVHRIWKHVWXG\FRQILUPDWLRQE\
&7RU05,LVDGYLVHG
• (QGRVFRS\ODSDURVFRS\7KHXWLOL]DWLRQRIWKHVHWHFKQLTXHVIRUREMHFWLYHWXPRUHYDOXDWLRQLV
QRWDGYLVHG+RZHYHUWKH\FDQEHXVHIXOWRFRQILUPFRPSOHWHSDWKRORJLFDOUHVSRQVHZKHQ
ELRSVLHVDUHREWDLQHGRUWRGHWHUPLQHUHODSVHLQWULDOVZKHUHUHFXUUHQFHIROORZLQJFRPSOHWH
UHVSRQVHRUVXUJLFDOUHVHFWLRQLVDQHQGSRLQW
• 7XPRUPDUNHUV7XPRUPDUNHUVDORQHFDQQRWEHXVHGWRDVVHVVREMHFWLYHWXPRUUHVSRQVH,I
PDUNHUVDUHLQLWLDOO\DERYHWKHXSSHUQRUPDOOLPLWKRZHYHUWKH\PXVWQRUPDOL]HIRUDSDWLHQW
WREHFRQVLGHUHGLQFRPSOHWHUHVSRQVH
• &\WRORJ\KLVWRORJ\7KHVHWHFKQLTXHVFDQEHXVHGWRGLIIHUHQWLDWHEHWZHHQ35DQG&5LQUDUH
FDVHVLIUHTXLUHGE\SURWRFROIRUH[DPSOHUHVLGXDOOHVLRQVLQWXPRUW\SHVVXFKDVJHUPFHOO
WXPRUVZKHUHNQRZQUHVLGXDOEHQLJQWXPRUVFDQUHPDLQ:KHQHIIXVLRQVDUHNQRZQWREHD
SRWHQWLDO DGYHUVH HIIHFW RI WUHDWPHQW HJ ZLWK FHUWDLQ WD[DQH FRPSRXQGV RU DQJLRJHQHVLV
LQKLELWRUVWKHF\WRORJLFDOFRQILUPDWLRQRIWKHQHRSODVWLFRULJLQRIDQ\HIIXVLRQWKDWDSSHDUV
RUZRUVHQVGXULQJWUHDWPHQWFDQEHFRQVLGHUHGLIWKHPHDVXUDEOHWXPRUKDVPHWFULWHULDIRU
UHVSRQVHRUVWDEOHGLVHDVHLQRUGHUWRGLIIHUHQWLDWHEHWZHHQUHVSRQVHRUVWDEOHGLVHDVHDQG
SURJUHVVLYHGLVHDVH

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

780255(63216((9$/8$7,21
(YDOXDWLRQRIWDUJHWOHVLRQV
7DUJHW OHVLRQV ZLOO EH DVVLJQHG DQ RYHUDOO UHVSRQVH DVVHVVPHQW DW HDFK HYDOXDWLRQ WLPH SRLQW
DFFRUGLQJWRWKHIROORZLQJGHILQLWLRQV
• &RPSOHWH5HVSRQVH&5'LVDSSHDUDQFHRIDOOWDUJHWOHVLRQV$Q\SDWKRORJLFDOO\PSKQRGHV
ZKHWKHUWDUJHWRUQRQWDUJHWPXVWKDYHUHGXFWLRQLQVKRUWD[LVWRPP
• 3DUWLDO5HVSRQVH35$WOHDVWDGHFUHDVHLQWKHVXPRIGLDPHWHUVRIWDUJHWOHVLRQVWDNLQJ
DVUHIHUHQFHWKHEDVHOLQHVXPGLDPHWHUV
• 3URJUHVVLYH'LVHDVH3'$WOHDVWDLQFUHDVHLQWKHVXPRIGLDPHWHUVRIWDUJHWOHVLRQV
WDNLQJDVUHIHUHQFHWKHVPDOOHVWVXPRQVWXG\WKLVLQFOXGHVWKHEDVHOLQHVXPLIWKDWLVWKH
VPDOOHVWRQVWXG\,QDGGLWLRQWRWKHUHODWLYHLQFUHDVHRIWKHVXPPXVWDOVRGHPRQVWUDWH
DQDEVROXWHLQFUHDVHRIDWOHDVWPP1RWHWKHDSSHDUDQFHRIRQHRUPRUHQHZOHVLRQVLVDOVR
FRQVLGHUHGSURJUHVVLRQ
• 6WDEOH'LVHDVH6'1HLWKHUVXIILFLHQWVKULQNDJHWRTXDOLI\IRU35QRUVXIILFLHQWLQFUHDVHWR
TXDOLI\IRU3'WDNLQJDVUHIHUHQFHWKHVPDOOHVWVXPGLDPHWHUVZKLOHRQVWXG\
6SHFLDOQRWHVRQWKHDVVHVVPHQWRIWDUJHWOHVLRQV
• /\PSKQRGHV/\PSKQRGHVLGHQWLILHGDVWDUJHWOHVLRQVVKRXOGDOZD\VKDYHWKHDFWXDOVKRUW
D[LV PHDVXUHPHQW UHFRUGHG PHDVXUHG LQ WKH VDPH DQDWRPLFDO SODQH DV WKH EDVHOLQH
H[DPLQDWLRQHYHQLIWKHQRGHVUHJUHVVWREHORZPPRQVWXG\7KLVPHDQVWKDWZKHQO\PSK
QRGHVDUHLQFOXGHGDVWDUJHWOHVLRQVWKHµVXP¶RIOHVLRQVPD\QRWEH]HURHYHQLIFRPSOHWH
UHVSRQVHFULWHULD DUHPHWVLQFHDQRUPDOO\PSK QRGHLVGHILQHGDVKDYLQJDVKRUWD[LVRI
PP)RU356'DQG3'WKHDFWXDOVKRUWD[LVPHDVXUHPHQWRIWKHQRGHVLVWREHLQFOXGHG
LQWKHVXPRIWDUJHWOHVLRQV
• 7DUJHWOHVLRQVWKDWEHFRPHµWRRVPDOOWRPHDVXUH¶:KLOHRQVWXG\DOOOHVLRQVQRGDODQGQRQ
QRGDOUHFRUGHGDWEDVHOLQHVKRXOGKDYHWKHLUDFWXDOPHDVXUHPHQWVUHFRUGHGDWHDFKVXEVHTXHQW
HYDOXDWLRQHYHQZKHQYHU\VPDOOHJPP+RZHYHUVRPHWLPHVOHVLRQVRUO\PSKQRGHV
ZKLFKDUHUHFRUGHGDVWDUJHWOHVLRQVDWEDVHOLQHEHFRPHVRIDLQWRQ&7VFDQWKDWWKHUDGLRORJLVW
PD\QRWIHHOFRPIRUWDEOHDVVLJQLQJDQH[DFWPHDVXUHDQGPD\UHSRUWWKHPDVEHLQJµWRRVPDOO
WRPHDVXUH¶:KHQWKLVRFFXUVLWLVLPSRUWDQWWKDWDYDOXHEHUHFRUGHGRQWKHFDVHUHSRUWIRUP
,ILWLVWKHRSLQLRQRIWKHUDGLRORJLVWWKDWWKHOHVLRQKDVOLNHO\GLVDSSHDUHGWKHPHDVXUHPHQW
VKRXOGEHUHFRUGHGDVPP,IWKHOHVLRQLVEHOLHYHGWREHSUHVHQWDQGLVIDLQWO\VHHQEXWWRR
VPDOOWRPHDVXUHDGHIDXOWYDOXHRIPPVKRXOGEHDVVLJQHG1RWH,WLVOHVVOLNHO\WKDWWKLV
UXOHZLOOEHXVHGIRUO\PSKQRGHVVLQFHWKH\XVXDOO\KDYHDGHILQDEOHVL]HZKHQQRUPDODQG
DUHIUHTXHQWO\VXUURXQGHGE\IDWVXFKDVLQWKHUHWURSHULWRQHXPKRZHYHULIDO\PSKQRGHLV
EHOLHYHGWREHSUHVHQWDQGLVIDLQWO\VHHQEXWWRRVPDOOWRPHDVXUHDGHIDXOWYDOXHRIPP
VKRXOGEHDVVLJQHGLQWKLVFLUFXPVWDQFHDVZHOO7KLVGHIDXOWYDOXHLVGHULYHGIURPWKHPP
&7 VOLFH WKLFNQHVV EXW VKRXOG QRW EH FKDQJHG ZLWK YDU\LQJ &7 VOLFH WKLFNQHVV 7KH
PHDVXUHPHQWRIWKHVHOHVLRQVLVSRWHQWLDOO\QRQUHSURGXFLEOHWKHUHIRUHSURYLGLQJWKLVGHIDXOW
YDOXHZLOOSUHYHQWIDOVHUHVSRQVHVRUSURJUHVVLRQVEDVHGXSRQPHDVXUHPHQWHUURU7RUHLWHUDWH
KRZHYHULIWKHUDGLRORJLVWLVDEOHWRSURYLGHDQDFWXDOPHDVXUHWKDWVKRXOGEHUHFRUGHGHYHQ
LILWLVEHORZPP

&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

• /HVLRQVWKDWVSOLWRUFRDOHVFHRQWUHDWPHQW:KHQQRQQRGDOOHVLRQVµIUDJPHQW¶WKHORQJHVW
GLDPHWHUVRIWKHIUDJPHQWHGSRUWLRQVVKRXOGEHDGGHGWRJHWKHUWRFDOFXODWHWKHWDUJHWOHVLRQ
VXP6LPLODUO\DVOHVLRQVFRDOHVFHDSODQHEHWZHHQWKHPPD\EHPDLQWDLQHGWKDWZRXOGDLG
LQREWDLQLQJPD[LPDOGLDPHWHUPHDVXUHPHQWVRIHDFKLQGLYLGXDOOHVLRQ,IWKHOHVLRQVKDYH
WUXO\FRDOHVFHGVXFKWKDWWKH\DUHQRORQJHUVHSDUDEOHWKHYHFWRURIWKHORQJHVWGLDPHWHULQWKLV
LQVWDQFHVKRXOGEHWKHPD[LPDOORQJHVWGLDPHWHUIRUWKHµFRDOHVFHGOHVLRQ¶
(YDOXDWLRQRIQRQWDUJHWOHVLRQV
1RQWDUJHWOHVLRQVZLOOEHDVVLJQHGDQRYHUDOOUHVSRQVHDVVHVVPHQWDWHDFKHYDOXDWLRQWLPHSRLQW
DFFRUGLQJWRWKHIROORZLQJGHILQLWLRQV
• &RPSOHWH5HVSRQVH&5'LVDSSHDUDQFHRIDOOQRQWDUJHWOHVLRQVDQGQRUPDOL]DWLRQRIWXPRU
PDUNHUOHYHO$OOO\PSKQRGHVPXVWEHQRQSDWKRORJLFDOLQVL]HPPVKRUWD[LV
• 1RQ&51RQ3'3HUVLVWHQFHRIRQHRUPRUHQRQWDUJHWOHVLRQVDQGRUPDLQWHQDQFHRIWXPRU
PDUNHUOHYHODERYHWKHQRUPDOOLPLWV
• 3URJUHVVLYH'LVHDVH3'8QHTXLYRFDOSURJUHVVLRQVHHFRPPHQWVEHORZRIH[LVWLQJQRQ
WDUJHW OHVLRQV 1RWH WKH DSSHDUDQFH RI RQH RU PRUH QHZ OHVLRQV LV DOVR FRQVLGHUHG
SURJUHVVLRQ
6SHFLDOQRWHVRQDVVHVVPHQWRISURJUHVVLRQRIQRQWDUJHWGLVHDVH
• :KHQ WKH SDWLHQW DOVR KDV PHDVXUDEOH GLVHDVH ,Q WKLV VHWWLQJ WR DFKLHYH µXQHTXLYRFDO
SURJUHVVLRQ¶RQWKHEDVLVRIWKHQRQWDUJHWGLVHDVHWKHUHPXVWEHDQRYHUDOOOHYHORIVXEVWDQWLDO
ZRUVHQLQJLQQRQWDUJHWGLVHDVHVXFKWKDWHYHQLQSUHVHQFHRI6'RU35LQWDUJHWGLVHDVHWKH
RYHUDOOWXPRUEXUGHQKDVLQFUHDVHGVXIILFLHQWO\WRPHULWGLVFRQWLQXDWLRQRIWKHUDS\VHHIXUWKHU
GHWDLOVEHORZ$PRGHVWµLQFUHDVH¶LQWKHVL]HRIRQHRUPRUHQRQWDUJHWOHVLRQVLVXVXDOO\QRW
VXIILFLHQWWRTXDOLW\IRUXQHTXLYRFDOSURJUHVVLRQVWDWXV7KHGHVLJQDWLRQRIRYHUDOOSURJUHVVLRQ
VROHO\RQWKHEDVLVRIFKDQJHLQQRQWDUJHWGLVHDVHLQWKHIDFHRI6'RU35RIWDUJHWGLVHDVH
ZLOOWKHUHIRUHEHH[WUHPHO\UDUH
• :KHQWKHSDWLHQWKDVRQO\QRQPHDVXUDEOHGLVHDVH7KHVDPHJHQHUDOFRQFHSWVDSSO\KHUHDV
QRWHGDERYHKRZHYHULQWKLVLQVWDQFHWKHUHLVQRPHDVXUDEOHGLVHDVHDVVHVVPHQWWRIDFWRULQWR
WKHLQWHUSUHWDWLRQRIDQLQFUHDVHLQQRQPHDVXUDEOHGLVHDVHEXUGHQ%HFDXVHZRUVHQLQJLQQRQ
WDUJHWGLVHDVHFDQQRWEHHDVLO\TXDQWLILHGE\GHILQLWLRQLIDOOOHVLRQVDUHWUXO\QRQPHDVXUDEOH
DXVHIXOWHVWWKDWFDQEHDSSOLHGZKHQDVVHVVLQJSDWLHQWVIRUXQHTXLYRFDOSURJUHVVLRQLVWR
FRQVLGHU LI WKH LQFUHDVH LQ RYHUDOO GLVHDVH EXUGHQ EDVHG RQ WKH FKDQJH LQ QRQPHDVXUDEOH
GLVHDVHLVFRPSDUDEOHLQPDJQLWXGHWRWKHLQFUHDVHWKDWZRXOGEHUHTXLUHGWRGHFODUH3'IRU
PHDVXUDEOHGLVHDVHLHDQLQFUHDVHLQWXPRUEXUGHQUHSUHVHQWLQJDQDGGLWLRQDOLQFUHDVH
LQµYROXPH¶ZKLFKLVHTXLYDOHQWWRDLQFUHDVHGLDPHWHULQDPHDVXUDEOHOHVLRQ([DPSOHV
LQFOXGHDQLQFUHDVHLQDSOHXUDOHIIXVLRQIURPµWUDFH¶WRµODUJH¶DQLQFUHDVHLQO\PSKDQJLWLF
GLVHDVHIURPORFDOL]HGWRZLGHVSUHDGRUPD\EHGHVFULEHGLQSURWRFROVDVµVXIILFLHQWWRUHTXLUH
DFKDQJHLQWKHUDS\¶,IµXQHTXLYRFDOSURJUHVVLRQ¶LVVHHQWKHSDWLHQWVKRXOGEHFRQVLGHUHGWR
KDYHKDGRYHUDOO3'DWWKDWSRLQW:KLOHLWZRXOGEHLGHDOWRKDYHREMHFWLYHFULWHULDWRDSSO\WR
QRQPHDVXUDEOHGLVHDVHWKHYHU\QDWXUHRIWKDWGLVHDVHPDNHVLWLPSRVVLEOHWRGRVRWKHUHIRUH
WKHLQFUHDVHPXVWEHVXEVWDQWLDO



&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

1HZOHVLRQV
7KHDSSHDUDQFHRIQHZPDOLJQDQWOHVLRQVGHQRWHVGLVHDVHSURJUHVVLRQWKHUHIRUHVRPHFRPPHQWV
RQGHWHFWLRQRIQHZOHVLRQVDUHLPSRUWDQW
• 7KHUHDUHQRVSHFLILFFULWHULDIRUWKHLGHQWLILFDWLRQRIQHZUDGLRJUDSKLFOHVLRQVKRZHYHUWKH
ILQGLQJRIDQHZOHVLRQVKRXOGEHXQHTXLYRFDOLHQRWDWWULEXWDEOHWRGLIIHUHQFHVLQVFDQQLQJ
WHFKQLTXHFKDQJHLQLPDJLQJPRGDOLW\RUILQGLQJVWKRXJKWWRUHSUHVHQWVRPHWKLQJRWKHUWKDQ
WXPRUIRUH[DPSOHVRPHµQHZ¶ERQHOHVLRQVPD\EHVLPSO\KHDOLQJRUIODUHRISUHH[LVWLQJ
OHVLRQV7KLVLVSDUWLFXODUO\LPSRUWDQWZKHQWKHSDWLHQW¶VEDVHOLQH OHVLRQVVKRZ SDUWLDORU
FRPSOHWHUHVSRQVH)RUH[DPSOHQHFURVLVRIDOLYHUOHVLRQPD\EHUHSRUWHGRQD&7VFDQUHSRUW
DVDµQHZ¶F\VWLFOHVLRQZKLFKLWLVQRW
• $OHVLRQLGHQWLILHGRQDIROORZXSVWXG\LQDQDQDWRPLFDOORFDWLRQWKDWZDVQRWVFDQQHGDW
EDVHOLQHLVFRQVLGHUHGDQHZOHVLRQDQGZLOOLQGLFDWHGLVHDVHSURJUHVVLRQ$QH[DPSOHRIWKLV
LVWKHSDWLHQWZKRKDVYLVFHUDOGLVHDVHDWEDVHOLQHDQGZKLOHRQVWXG\KDVD&7RU05,EUDLQ
RUGHUHGZKLFKUHYHDOVPHWDVWDVHV7KHSDWLHQW¶VEUDLQPHWDVWDVHVDUHFRQVLGHUHGWREHHYLGHQFH
RI3'HYHQLIKHVKHGLGQRWKDYHEUDLQLPDJLQJDWEDVHOLQH
• ,IDQHZOHVLRQLVHTXLYRFDOIRUH[DPSOHEHFDXVHRILWVVPDOOVL]HFRQWLQXHGWKHUDS\DQG
IROORZXSHYDOXDWLRQZLOOFODULI\LILWUHSUHVHQWVWUXO\QHZGLVHDVH,IUHSHDWVFDQVFRQILUPWKHUH
LVGHILQLWHO\DQHZOHVLRQWKHQSURJUHVVLRQVKRXOGEHGHFODUHGXVLQJWKHGDWHRIWKHLQLWLDOVFDQ
• :KLOH)'*3(7UHVSRQVHDVVHVVPHQWVQHHGDGGLWLRQDOVWXG\LWLVVRPHWLPHVUHDVRQDEOHWR
LQFRUSRUDWH WKH XVH RI )'*3(7 VFDQQLQJ WR FRPSOHPHQW &7 VFDQQLQJ LQ DVVHVVPHQW RI
SURJUHVVLRQ SDUWLFXODUO\ SRVVLEOH µQHZ¶ GLVHDVH 1HZ OHVLRQV RQ WKH EDVLV RI )'*3(7
LPDJLQJFDQEHLGHQWLILHGDFFRUGLQJWRWKHIROORZLQJDOJRULWKP
R 1HJDWLYH)'*3(7DWEDVHOLQHZLWKDSRVLWLYH)'*3(7DWIROORZXSLVDVLJQRI3'
EDVHGRQDQHZOHVLRQ$µSRVLWLYH¶)'*3(7VFDQOHVLRQPHDQVRQHZKLFKLV)'*DYLG
ZLWKDQXSWDNHJUHDWHUWKDQWZLFHWKDWRIWKHVXUURXQGLQJWLVVXHRQWKHDWWHQXDWLRQFRUUHFWHG
LPDJH
R 1R)'*3(7DWEDVHOLQHDQGDSRVLWLYH)'*3(7DWIROORZXS,IWKHSRVLWLYH)'*3(7
DWIROORZXS FRUUHVSRQGV WR DQHZ VLWH RI GLVHDVH FRQILUPHG E\&7 WKLV LV 3' ,IWKH
SRVLWLYH)'*3(7DWIROORZXSLVQRWFRQILUPHGDVDQHZVLWHRIGLVHDVHRQ&7DGGLWLRQDO
IROORZXS&7VFDQVDUHQHHGHGWRGHWHUPLQHLIWKHUHLVWUXO\SURJUHVVLRQRFFXUULQJDWWKDW
VLWHLIVRWKHGDWHRI3'ZLOOEHWKHGDWHRIWKHLQLWLDODEQRUPDO)'*3(7VFDQ,IWKH
SRVLWLYH)'*3(7DWIROORZXSFRUUHVSRQGVWRDSUHH[LVWLQJVLWHRIGLVHDVHRQ&7WKDWLV
QRWSURJUHVVLQJRQWKHEDVLVRIWKHDQDWRPLFLPDJHVWKLVLVQRW3'



&OLQLFDO3URWRFRO&';
&HOOGH[7KHUDSHXWLFV,QF
$PHQGPHQW-XQ
&';


&RQILGHQWLDO
3DJHRI

(YDOXDWLRQRIRYHUDOOUHVSRQVH
,WLVDVVXPHGWKDWDWHDFKSURWRFROVSHFLILHGWLPHSRLQWDQRYHUDOOUHVSRQVHDVVHVVPHQWRFFXUV7KH
SDWLHQW¶VRYHUDOOUHVSRQVHDVVLJQPHQWZLOOGHSHQGRQWKHILQGLQJVRIERWKWDUJHWDQGQRQWDUJHW
GLVHDVHDQGZLOODOVRWDNHLQWRFRQVLGHUDWLRQWKHDSSHDUDQFHRIQHZOHVLRQV
7DEOHSURYLGHVDVXPPDU\RIWKHRYHUDOOUHVSRQVHVWDWXVFDOFXODWLRQDWHDFKWLPHSRLQWIRU
SDWLHQWVZKRKDYHPHDVXUDEOHGLVHDVHDWEDVHOLQH:KHQSDWLHQWVKDYHQRQPHDVXUDEOHWKHUHIRUH
QRQWDUJHWGLVHDVHRQO\7DEOHLVWREHXVHG
6SHFLDOQRWHVRQHYDOXDWLRQRIRYHUDOOUHVSRQVH
• 0LVVLQJDVVHVVPHQWVDQGLQHYDOXDEOHGHVLJQDWLRQ
R :KHQQRLPDJLQJPHDVXUHPHQWLVGRQHDWDOODWDSDUWLFXODUWLPHSRLQWWKHSDWLHQWLVQRW
HYDOXDEOH1(DWWKDWWLPHSRLQW
R ,IRQO\DVXEVHWRIOHVLRQPHDVXUHPHQWVDUHPDGHDWDQDVVHVVPHQWXVXDOO\WKHFDVHLVDOVR
FRQVLGHUHG 1( DW WKDW WLPH SRLQWXQOHVVDFRQYLQFLQJ DUJXPHQW FDQ EH PDGH WKDWWKH
FRQWULEXWLRQRIWKHLQGLYLGXDOPLVVLQJOHVLRQVZRXOGQRWFKDQJHWKHDVVLJQHGWLPHSRLQW
UHVSRQVH7KLVZRXOGEHPRVWOLNHO\WRKDSSHQLQWKHFDVHRI3')RUH[DPSOHLIDSDWLHQW
KDGDEDVHOLQHVXPRIPPZLWKWKUHHPHDVXUHGOHVLRQVDQGDWIROORZXSRQO\WZROHVLRQV
ZHUHDVVHVVHGEXWWKRVHJDYHDVXPRIPPWKHSDWLHQWZLOOKDYHDFKLHYHG3'VWDWXV
UHJDUGOHVVRIWKHFRQWULEXWLRQRIWKHPLVVLQJOHVLRQ
• µ6\PSWRPDWLFGHWHULRUDWLRQ¶3DWLHQWVZLWKDJOREDOGHWHULRUDWLRQRIKHDOWKVWDWXVUHTXLULQJ
GLVFRQWLQXDWLRQRIWUHDWPHQWZLWKRXWREMHFWLYHHYLGHQFHRIGLVHDVHSURJUHVVLRQDWWKDWWLPH
VKRXOGEHUHSRUWHGDVµV\PSWRPDWLFGHWHULRUDWLRQ¶(YHU\HIIRUWVKRXOGEHPDGHWRGRFXPHQW
REMHFWLYHSURJUHVVLRQHYHQDIWHUGLVFRQWLQXDWLRQRIWUHDWPHQW6\PSWRPDWLFGHWHULRUDWLRQLVQRW
DGHVFULSWRURIDQREMHFWLYHUHVSRQVHLWLVDUHDVRQIRUVWRSSLQJVWXG\WKHUDS\7KHREMHFWLYH
UHVSRQVHVWDWXVRIVXFKSDWLHQWVLVWREHGHWHUPLQHGE\HYDOXDWLRQRIWDUJHWDQGQRQWDUJHW
GLVHDVHDVVKRZQLQ7DEOHDQG7DEOH
• ,QVRPHFLUFXPVWDQFHVLWPD\EHGLIILFXOWWRGLVWLQJXLVKUHVLGXDOGLVHDVHIURPQRUPDOWLVVXH
:KHQWKHHYDOXDWLRQRIFRPSOHWHUHVSRQVHGHSHQGVXSRQWKLVGHWHUPLQDWLRQLWLVUHFRPPHQGHG
WKDWWKHUHVLGXDOOHVLRQEHLQYHVWLJDWHGILQHQHHGOHDVSLUDWHELRSV\EHIRUHDVVLJQLQJDVWDWXV
RIFRPSOHWHUHVSRQVH)'*3(7PD\EHXVHGWRXSJUDGHDUHVSRQVHWRD&5LQDPDQQHU
VLPLODUWRDELRSV\LQFDVHVZKHUHDUHVLGXDOUDGLRJUDSKLFDEQRUPDOLW\LVWKRXJKWWRUHSUHVHQW
ILEURVLVRUVFDUULQJ
• )RU HTXLYRFDO ILQGLQJV RI SURJUHVVLRQ HJ YHU\ VPDOO DQG XQFHUWDLQ QHZ OHVLRQV F\VWLF
FKDQJHV RU QHFURVLV LQ H[LVWLQJ OHVLRQV WUHDWPHQW PD\ FRQWLQXH XQWLO WKH QH[W VFKHGXOHG
DVVHVVPHQW ,I DW WKH QH[W VFKHGXOHG DVVHVVPHQW SURJUHVVLRQ LV FRQILUPHG WKH GDWH RI
SURJUHVVLRQVKRXOGEHWKHHDUOLHUGDWHZKHQSURJUHVVLRQZDVVXVSHFWHG
• &RQILUPDWLRQRIUHVSRQVH,QWKHHYHQWRIFRPSOHWHRUSDUWLDOUHVSRQVHVHIIRUWVVKRXOGEHPDGH
WRREWDLQDFRQILUPDWRU\VFDQQRVRRQHUWKDQGD\VODWHU



Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 67 of 73 
 
Table 12: Overall response: patients with target +/–non-target disease 
Target lesions   
Non-target lesions  
New lesions  
Overall response 
CR  
CR  
No  
CR 
CR  
Non-CR/non-PD  
No  
PR 
CR  
Not evaluated  
No  
PR 
PR  
Non-PD or not all evaluated 
No  
PR 
SD  
Non-PD or not all evaluated 
No  
SD 
Not all evaluated 
Non-PD  
No  
NE 
PD  
Any  
Yes or No  
PD 
Any  
PD  
Yes or No  
PD 
Any  
Any  
Yes  
PD 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and NE = 
inevaluable. 
 
Table 13. Overall response: patients with non-target disease only 
Non-target lesions 
New lesions  
Overall response 
CR  
No  
CR 
Non-CR/non-PD  
No  
Non-CR/non-PD a 
Not all evaluated  
No  
NE 
Unequivocal PD  
Yes or No  
PD 
Any  
Yes  
PD 
CR = complete response, PD = progressive disease, and NE = inevaluable. 
a ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as 
endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured 
is not advised. 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 68 of 73 
 
FREQUENTLY ASKED QUESTIONS 
What should be done if several unique lesions at baseline become confluent at a follow-up 
evaluation? 
Measure the longest diameter of the confluent mass and record to add into the sum of the longest 
diameters. 
How large does a new lesion have to be to count as progression? Does any small sub-
centimeter lesion qualify, or should the lesion be at least measurable? 
New lesions do not need to meet ‘measurability criteria’ to be considered valid. If it is clear on 
previous images (with the same technique) that a lesion was absent then its definitive appearance 
implies progression. If there is any doubt (because of the techniques or conditions) then it is 
suggested that treatment continue until next scheduled assessment when, generally, all should be 
clear. Either it gets bigger and the date of progression is the date of the first suspicion, or it 
disappears and one may then consider it an artefact with the support of the radiologists. 
How should one lesion be measured if on subsequent exams it is split into two? 
Measure the longest diameter of each lesion and add this into the sum.  
Does the definition of progression depend on the status of all target lesions or only one? 
As per the RECIST 1.1 guideline, progression requires a 20% increase in the sum of diameters of 
all target lesions AND a minimum absolute increase of 5 mm in the sum.  
What is the criterion for a measurable lesion if the CT slice thickness is >5 mm? 
RECIST 1.1 recommends that CT scans have a maximum slice thickness of 5 mm and the 
minimum size for a measurable lesion is twice that: 10 mm (even if slice thickness is <5 mm). If 
scanners with slice thickness >5 mm are used, the minimum lesion size must have a longest 
diameter twice the actual slice thickness. 
What should we record when target lesions become so small they are below the 10 mm 
‘measurable’ size? 
Target lesion measurability is defined at baseline. Thereafter, actual measurements, even if <10 
mm, should be recorded. If lesions become very small, some radiologists indicate they are ‘too 
small to measure’. This guideline advises that when this occurs, if the lesion is actually still present, 
a default measurement of 5 mm should be applied. If in fact the radiologist believes the lesion has 
gone, a default measurement of 0 mm should be recorded 
If a patient has several lesions which have decreased in size to meet PR criteria and one has 
actually disappeared, does that patient have PD if the ‘disappeared’ lesion reappears? 
Unless the sum meets the PD criteria, the reappearance of a lesion in the setting of PR (or SD) is 
not PD. The lesion should simply be added into the sum. If the patients had had a CR, clearly 
reappearance of an absent lesion would qualify for PD. 
When measuring the longest diameter of target lesions in response to treatment, is the same 
axis that was used initially used subsequently, even if there is a shape change to the lesion 
that may have produced a new longest diameter? 
The longest diameter of the lesion should always be measured even if the actual axis is different 
from the one used to measure the lesion initially (or at different time point during follow-up). The 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 69 of 73 
 
only exception to this is lymph nodes: as per RECIST 1.1 the short axis should always be followed 
and as in the case of target lesions, the vector of the short axis may change on follow-up. 
Target lesions have been selected at baseline and followed but then one of these target lesions 
then becomes non-evaluable (i.e. different technique used). What is the effect this has on the 
other target lesions and the overall response? 
What may be done in such cases is one of the following:  
(a) If the patient is still being treated, call the center to be sure that future evaluations are done 
with the baseline technique so at least SOME courses are fully evaluable 
(b) If that is not possible, check if there IS a baseline exam by the same technique which was used 
to follow patients...in which case if you retrieve the baseline measures from that technique you 
retrieve the lesion evaluability 
(c) If neither (a) nor (b) is possible then it is a judgement call about whether you delete the lesion 
from all forms or consider the impact of the lesion overall is so important that its being non-
evaluable makes the overall response interpretation inevaluable without it. Such a decision should 
be discussed in a review panel.  
It is NOT recommended that the lesion be included in baseline sums and then excluded from 
follow-up sums since this biases in favor of a response. 
What if a single non-target lesion cannot be reviewed, for whatever reason; does this negate 
the overall assessment? 
Sometimes the major contribution of a single non-target lesion may be in the setting of CR having 
otherwise been achieved: failure to examine one non-target in that setting will leave you unable to 
claim CR. It is also possible that the non-target lesion has undergone such substantial progression 
that it would override the target disease and render patient PD. However, this is very unlikely, 
especially if the rest of the measurable disease is stable or responding. 
A patient has a 32% decrease in sum cycle 2, a 28% decrease cycle 4 and a 33% decrease 
cycle 6. Does confirmation of PR have to take place in sequential scans or is a case like this 
confirmed PR? 
It is not infrequent that tumor shrinkage hovers around the 30% mark. In this case, most would 
consider PR to have been confirmed looking at this overall case. Had there been two or three non-
PR observations between the two time point PR responses, the most conservative approach would 
be to consider this case SD. 
A patient has a lesion measurable by clinical exam and by CT scan. Which should be 
followed? 
CT scan. Always follow by imaging if that option exists since it can be reviewed and verified. 
A lesion which was solid at baseline has become necrotic in the center. How should this be 
measured? 
The longest diameter of the entire lesion should be followed. Eventually, necrotic lesions which 
are responding to treatment decrease in size. In reporting the results of trials, you may wish to 
report on this phenomenon if it is seen frequently since some agents (e.g. angiogenesis inhibitors) 
may produce this effect.  

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 70 of 73 
 
If I am going to use MRI to follow disease, what is minimum size for measurability? 
MRI may be substituted for contrast enhanced CT for some sites, but not lung. The minimum size 
for measurability is the same as for CT (10 mm) as long as the scans are performed with slice 
thickness of 5mm and no gap. In the event the MRI is performed with thicker slices, the size of a 
measurable lesion at baseline should be two times the slice thickness. In the event there are inter-
slice gaps, this also needs to be considered in determining the size of measurable lesions at 
baseline. 
Can PET–CT be used with RECIST?  
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 your site has 
documented that the CT performed as part of a PET–CT is of the same diagnostic quality as a 
diagnostic CT (with IV and oral contrast) then the PET–CT can be used for RECIST 
measurements. 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. 
 
Adapted from Eisenhower 2009 (Eisenhauer, et al. 2009) 
 
 

Clinical Protocol CDX3379-04 
Celldex Therapeutics, Inc. 
Amendment 1 (28-Jun-2019) 
CDX-3379 
 
 
Confidential 
Page 71 of 73 
 
Appendix 3. 
ECOG Performance Status 
 
ECOG PERFORMANCE STATUS* 
 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours. 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair. 
5 
Dead 
* As published in Am. J. Clin. Oncol (Oken, et al. 1982)