Phase I/II Study of Pembrolizumab and In-situ Injection of CMP-001 in Patients With Relapsed and Refractory Lymphomas
Phase: PHASE1
Conditions: Lymphoma
Sponsor: Umar Farooq

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SPONSOR: University of Iowa 
TITLE: Phase I/II study of Pembrolizumab and in-situ injection of CMP-001 in 
Patients with Relapsed and Refractory Lymphomas 
Principal Investigator 
Umar Farooq 
Co-Investigators  
George Weiner, Brian Link 
Biostatistician 
Brian J Smith 
SPONSOR 
University of Iowa  
Holden Comprehensive Cancer Center 

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ABBREVIATION  
  
Abbreviation or Acronym  
Definition  
AE  
adverse event  
ALT  
alanine aminotransferase  
ANCA  
Anti-Neutrophil Cytoplasmic Antibodies  
AST  
aspartate aminotransferase  
ATC  
Anatomical Therapeutic Chemical  
BMI  
body mass index  
BOR  
best overall response  
Bpm  
beats per minute (heart rate)  
CFR  
Code of Federal Regulations  
CNS  
central nervous system  
CpG  
cytosine linked to a guanine by a phosphate 
bond  
CR  
complete response  
CRA  
Clinical Research Associate  
CRO  
Contract Research Organization  
CT  
computerized tomography  
CTCAE  
Common Terminology Criteria for Adverse 
Events  
CTL  
cytotoxic T lymphocyte  
CTLA-4  
cytotoxic T-lymphocyte-associated protein 4  
CVA  
cerebrovascular accident  
D  
day  
DLN  
draining lymph node  
DLT  
dose-limiting toxicity  
DOR  
duration of response  
ECG  
electrocardiogram  
ECOG  
Eastern Cooperative Oncology Group  
eCRF  
electronic case report form  
EOT  
end of treatment  
FDA  
Food and Drug Administration  
GCP  
Good Clinical Practice  
HBV  
hepatitis B virus  
HCV  
hepatitis C virus  
HIV  
human immunodeficiency virus  
IB  
Investigator’s Brochure  
ICF  
Informed Consent Form  
ICH  
International Conference on Harmonization  
ID  
identification  
IFN  
interferon  
INR  
international normalized ratio  
IRB  
Institutional Review Board  
irRC  
Immune-Related Response Criteria  
IV  
intravenous  
MI  
myocardial infarction  
MedDRA  
Medical Dictionary for Regulatory Activities  
 
 

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Abbreviation or Acronym  
Definition  
MRI  
magnetic resonance imaging  
MTD  
maximum tolerated dose  
N or n  
number  
OBD  
optimal biologic dose  
ODN  
oligodeoxynucleotide  
ORR  
objective response rate  
PD  
progressive disease  
PD-1  
programmed cell death protein 1  
pDC  
plasmacytoid dendritic cells  
PFS  
progression-free survival  
PR  
partial response  
PTT  
partial thromboplastin time  
QTc  
QT corrected for heart rate  
QTcF  
QT corrected according to Fridericia  
RBC  
red blood cell  
RECIST  
Response Evaluation Criteria in Solid 
Tumors  
RP2D  
recommended Phase 2 dose  
SAE  
serious adverse event  
SAP  
statistical analysis plan  
SD  
Stable disease  
SOC  
System Organ Class  
SOP  
standard operating procedure  
SUSAR  
suspected unexpected serious adverse 
reactions  
TEAE  
treatment-emergent adverse event  
Th1  
T helper cell type 1  
TME  
Tumor microenvironment  
TLR9  
Toll-like receptor 9  
Treg  
Regulatory T cell  
TSH  
thyroid stimulating hormone  
TTR  
time to response  
ULN  
upper limit of normal  
U.S.  
United States  
WBC  
white blood cell  
WHO  
World Health Organization  
WHO-DD  
World Health Organization Drug 
Dictionary  
 
 

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TABLE OF CONTENTS 
1.0 
TRIAL SUMMARY.................................................................................................... 8 
2.0 
TRIAL DESIGN.......................................................................................................... 8 
2.1 
Investigational Plan .................................................................................................... 8 
 Overall Study Design ............................................................................................ 8 
 Dose Finding Adaptive Design ............................................................................... 9 
 Dose-Limiting Toxicities .................................................................................... 11 
2.2 
Trial Diagram ............................................................................................................ 13 
3.0 
OBJECTIVE(S) & HYPOTHESIS(ES) .................................................................. 14 
3.1 
Primary Objective ..................................................................................................... 14 
3.2 
Secondary Objective ................................................................................................. 14 
3.3 
Exploratory Objective .............................................................................................. 14 
4.0 
BACKGROUND & RATIONALE .......................................................................... 15 
4.1 
Background ............................................................................................................... 15 
 Preclinical and Clinical Trial Data on CMP-001 ................................................ 15 
4.2 
Rationale .................................................................................................................... 16 
 Rationale for immune checkpoint blockade in lymphoma: ................................ 16 
 Rationale for Combining a TLR-9 Agonist with an Anti-PD-1 Antibody: ........ 17 
 Rationale for Intratumoral Administration of TLR9 Agonist: ............................ 18 
 Rationale for combining anti-PD1 and CMP-001 in lymphoma: ....................... 18 
4.3 
Justification for Dose ................................................................................................ 19 
 Justification for CMP-001 dosing: ...................................................................... 19 
 Justification for Pembrolizumab dose: ................................................................ 20 
4.4 
Safety Endpoints ....................................................................................................... 21 
4.5 
Efficacy Endpoints .................................................................................................... 21 

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4.6 
Biomarker Research ................................................................................................. 21 
5.0 
Study Population ....................................................................................................... 21 
5.1 
Participant Inclusion Criteria .................................................................................. 21 
5.2 
Participant Exclusion Criteria ................................................................................. 22 
5.3 
Lifestyle Restrictions ................................................................................................ 25 
 Meals and Dietary Restrictions ........................................................................... 25 
 Contraception ...................................................................................................... 25 
 Pregnancy ............................................................................................................ 25 
 Use in Nursing Women ....................................................................................... 26 
5.4 
Concomitant Medications/Vaccinations (allowed & prohibited) ......................... 26 
 Acceptable Concomitant Medications ................................................................ 26 
 Prohibited Concomitant Medications.................................................................. 26 
 Rescue Medications & Supportive Care ............................................................. 27 
5.5 
Participant Withdrawal/Discontinuation Criteria................................................. 28 
5.6 
Clinical Criteria for Early Trial Termination........................................................ 29 
6.0 
TREATMENT OF SUBJECTS ................................................................................ 29 
6.1 
Study Drug Administration ...................................................................................... 29 
 Recommended Prophylaxis Before and After CMP001 Dosing ........................ 29 
 Administration of CMP-001 ............................................................................... 30 
 Administration of Pembrolizumab ...................................................................... 34 
6.2 
Dose Modifications and Management of Study-Drug Associated Adverse Events34 
 CMP-001 Associated Adverse Events (see Table 2) .......................................... 34 
 Pembrolizumab-Associated Adverse Events ...................................................... 37 
7.0 
TRIAL FLOW CHART ........................................................................................... 44 
8.0 
TRIAL PROCEDURES ........................................................................................... 46 

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8.1 
Trial Procedures........................................................................................................ 46 
 Administrative Procedures .................................................................................. 46 
 Clinical Procedures/Assessments ........................................................................ 48 
 Response/Efficacy Assessments ......................................................................... 49 
 Laboratory Procedures/Assessments .................................................................. 49 
 Exploratory Biomarker Sampling ........................................................................ 51 
 Other Procedures ................................................................................................. 52 
 Visit Requirements .............................................................................................. 52 
8.2 
Assessing and Recording Adverse Events............................................................... 53 
 Definition of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor and to Merck ......................................................................................... 54 
 Reporting of Pregnancy and Lactation to the Sponsor and to Merck ................. 54 
 Immediate Reporting of Adverse Events to the Sponsor and to Merck.............. 55 
 Evaluating Adverse Events ................................................................................. 56 
 Sponsor Responsibility for Reporting Adverse Events ...................................... 60 
9.0 
STATISTICAL ANALYSIS PLAN ........................................................................ 60 
9.1 
Statistical Analysis Plan Summary.......................................................................... 60 
9.2 
Efficacy and Toxicity Analysis ................................................................................. 60 
9.3 
Analysis Populations ................................................................................................. 60 
9.4 
Disposition ................................................................................................................. 61 
9.5 
Demographics and Other Baseline Characteristics ............................................... 61 
9.6 
Protocol Deviations ................................................................................................... 61 
10.0 
LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL 
SUPPLIES ................................................................................................................. 61 
10.1 
Investigational Product ............................................................................................ 61 
10.2 
Packaging and Labeling Information ..................................................................... 62 

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10.3 
Clinical Supplies Disclosure ..................................................................................... 62 
10.4 
Storage and Handling Requirements ...................................................................... 62 
10.5 
Returns and Reconciliation ...................................................................................... 62 
 
ECOG Performance Status ................................................................ 63 
 
Common Terminology Criteria for Adverse Events V4.0 (CTCAE) 
AND LEE 2014 CRS criteria ................................................................................... 64 
 
Contraceptive Guidance and Pregnancy Testing ............................ 65 
 
Description of the Cheson 2007 Criteria for Assessment of Disease 
Response 
68 
 
DATA AND SAFETY MONITORING PLAN ................................ 70 
 
BOIN12 Trial Design Characteristics ............................................... 75 
REFERENCES: .................................................................................................................... 78 
 
 

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1.0 TRIAL SUMMARY 
Abbreviated Title 
Pembrolizumab and in-situ injection of CMP-001 for 
Relapsed and Refractory Lymphomas 
Trial Phase 
Phase I/II 
Clinical Indication 
Relapsed and Refractory Lymphomas 
Trial Type 
Single arm  
Type of control 
No control arm  
Route of administration 
Pembrolizumab intravenous injection and CMP-001 in-situ 
injection  
Trial Blinding 
No blinding  
Treatment Groups  
Adaptive dose-finding based on efficacy and toxicity 
Number of trial 
participants 
Maximum of 21 evaluable patients  
Estimated enrollment 
period 
3-4 years  
Duration of Participation 
Patient responding to treatment will be followed for 2 years. 
Patient progressing on treatment will come off study.  
Estimated average length 
of treatment per patient 
6 months 
 
 
 
 
2.0 TRIAL DESIGN 
2.1 
Investigational Plan 
 Overall Study Design 
This is a single center, open-label, combined Phase I/II clinical study of intratumoral 
administration of CMP-001 and intravenous administration of pembrolizumab in selected 
subjects with lymphoma. The key study objective is to find a CMP-001 dose (vidutolimod) 
that in combination with pembrolizumab has optimal clinical efficacy and acceptable 
toxicity.  Dose-finding will be performed with an adaptive clinical trial design.  Secondary 
study objectives include characterization of safety, pharmacodynamics, and assessment of 
anti-lymphoma activity. 
Each treatment cycle is 3 weeks in duration.  The first CMP-001 injection stimulates antibody 
formation to the VLP of CMP-001 and will be given subcutaneously.  Subsequently, CMP-
001 will be administered by intratumoral injection every week for seven doses. The seventh 
dose, which is to be administered on Week 7 Day 1 (W7D1), represents the start of dosing at 
3-week intervals (ie, with subsequent CMP-001 doses to be administered on Week 10 Day 1 
[W10D1] and Week 13 Day 1 [W13D1]). Subjects enrolled into this study will continue study 
treatment so long as they do not experience unacceptable toxicities and in the Investigator’s 

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opinion continued treatment is in the subject’s best interest. Patient will be evaluated for 
treatment efficacy and toxicity up to 30 days after end of treatment and followed for long term 
survival for 2 years.  
 
 
 Dose Finding Adaptive Design  
The Bayesian optimal interval design (BOIN12) of Lin et al. (Lin, Zhou, Yan, Li, & Yuan, 
2020). will be used to conduct dose finding for CMP-001 across the levels summarized in 
Table 1b.  Pembrolizumab dose will be fixed at 200 mg IV every 3 weeks.   In the design, 
patients will be assigned adaptively to CMP-001 dosing cohorts to find a dose with 
biologically optimal efficacy and toxicity. 
 
Table 1a: Dose Levels in the Adaptive Design  
Dose 
Level 
Pembrolizumab 
Dose 
CMP-001 Dose 
(mg) 
1* 
Per Product Label 
7.5 
2 
Per Product Label 
10 
* Starting dose 
 
Table 1b. Decision table to choose Case A, B, or C to determine the dose assignment for new 
patients 
 
 

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A maximum of 21 patients will be treated sequentially in up to 7 cohorts of three patients 
each.  Treatment will start in the first cohort at a CMP-001 dose of 7.5 mg.  After a cohort is 
evaluable for efficacy and dose-limiting toxicity (DLT), the next cohort will be treated at the 
admissible dose with highest mean utility.  Admissible dose levels (𝑗𝑗) are determined according 
to the following posterior probability criteria for their true rates of DLT (𝜋𝜋𝑇𝑇,𝑗𝑗) and efficacy (𝜋𝜋𝐸𝐸,𝑗𝑗): 
Pr൫𝜋𝜋𝑇𝑇,𝑗𝑗> 0.3ห𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑൯< 0.925 
Pr൫𝜋𝜋𝐸𝐸,𝑗𝑗< 0.5ห𝑑𝑑𝑑𝑑𝑑𝑑𝑑𝑑൯< 0.90. 
Desirable tradeoff between treatment benefit and risk is quantified with a utility function defined 
by the investigators to be Pr൫𝜋𝜋𝐸𝐸,𝑗𝑗൯−0.3 Pr൫𝜋𝜋𝑇𝑇,𝑗𝑗൯.  If a dose is found to not meet the admissibility 
criteria during the trial, it will be eliminated from further enrollment.  If the number of patients at 
the current dose reaches 12, the trial will be stopped.  Specifically, dose selection in the BOIN12 
design proceeds according to the following 3 steps.  
1. Treat the first cohort at dose level 𝑗𝑗= 1.  
2. Suppose that the current dose level is 𝑗𝑗, use decision Table 1a to choose one of the 
following three cases to determine the dose for treating the next cohort of patients. 
Case A:  Determine the desirability of dose levels 𝑗𝑗−1, 𝑗𝑗, and 𝑗𝑗+ 1 using the rank-based 
desirability scores (RDS) given in Table A of APPENDIX F, and choose the one that has 
the highest desirability to treat the next cohort.  If the RDS of all three doses are “E,” stop 
the trial and no dose should be selected.  In the case that dose level 𝑗𝑗−1 or 𝑗𝑗+ 1 does not 
exist, then apply the above rule to dose levels 𝑗𝑗 and 𝑗𝑗+ 1 (or 𝑗𝑗 and 𝑗𝑗−1).  
Case B:  Determine the desirability of dose levels 𝑗𝑗 and 𝑗𝑗−1 using the RDS given in Table 
A of APPENDIX F, and choose the one that has the higher desirability to treat the next 
cohort.  If the RDS of the two doses are “E,” stop the trial and no dose should be selected.  
If the current dose level 𝑗𝑗 is the lowest dose, treat the next cohort of patients at the lowest 
dose unless the RDS of the lowest dose is “E,” at which point terminate the trial. 
Case C:  Determine the desirability of dose levels 𝑗𝑗 and 𝑗𝑗−1 using the RDS given in Table 
A of APPENDIX F.  
o If the current dose level 𝑗𝑗 is the lowest dose, treat the new patients at the lowest 
dose unless the RDS of the lowest dose is “E,” at which point terminate the trial. 
o If the current dose level 𝑗𝑗 is not the lowest dose and the RDS of dose level 𝑗𝑗−1 is 
not “E,” de-escalate the dose to level 𝑗𝑗−1 to treat the next cohort of patients. 
o If the current dose level 𝑗𝑗 is not the lowest dose and the RDS of dose level 𝑗𝑗−1 is 
“E,” stay at the current dose level 𝑗𝑗 to treat the next cohort of patients unless the 
RDS of dose level 𝑗𝑗 is “E,” at which point terminate the trial. 

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3. Repeat step 2 until the maximum sample size of 21 is reached or if the number of patients 
treated on any dose reaches 12.  Then, use the isotonic estimation method described in 
Lin et al. (Lin et al., 2020) to select the (biologically optimal) dose that is admissible and 
that has the highest estimated utility. 
We have treated 6 patients on the study so far. The first 3 patients were treated at the dose 
level of 5 mg and the next 2 patients at dose level 7.5 mg. The three patients treated at 7.5 mg 
CMP001 dose will be included to the maximum accrual goal of 21 with this updated protocol. 
(Previous version had target accrual of 39 patients). This means additional 18 patients are 
needed to complete the study. Patients treated at 5 mg included 2 patients with recent anti-
B cell therapy (Rituximab, CAR T cells) and did not develop antiQbeta antibody important 
for CMP001 function. We updated the exclusion criteria to account for this observation.  
 
 Dose-Limiting Toxicities 
The DLT observation period is 15 days from date of first (W1D1) CMP-001 injection (i.e., 
following 3 doses of CMP-001; W1D1, W2D1, W3D1).  Subjects who have received at least one 
dose of CMP-001 and pembrolizumab are evaluable for DLT assessments.  
DLTs are defined below and only include AEs that are considered possibly, probably, or definitely 
related to the CMP-001 plus pembrolizumab combination. Attribution of AEs specifically to either 
CMP-001 or pembrolizumab is challenging, therefore, the relationship to CMP-001 should be 
based on attribution to the combination of the two study drugs (CMP-001 + pembrolizumab).  
The following AEs will be considered DLTs if deemed related to study drug combination: 
• Hematologic 
o Grade 4 neutropenia 
o Febrile neutropenia, defined as absolute neutrophil count (ANC) <1000/mm3 
with a temperature of ≥ 38.3 degrees C 
o Grade ≥ 3 neutropenic infection 
o Grade ≥ 3 thrombocytopenia with clinically significant bleeding seeking medical 
intervention 
o Grade 4 thrombocytopenia 
• Non-hematologic: 
o Grade ≥ 3 toxicities (non-laboratory); excluding: 
  Grade 3 fatigue lasting <7 days 
 
Grade 3 arthralgia or myalgia that downgrades to less or equal to grade 2 
within 3 days of supportive care 
 
Grade 3 pain at injection site that downgrades to less than or equal to 
Grade 2 within 3 days of supportive care 

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 Grade 3 electrolyte abnormalities that are asymptomatic and reversed with 
medical intervention within 3 days 
o Grade ≥ 3 nausea, vomiting or diarrhea despite maximal medical intervention 
o Grade 4 aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 
unless alternate explanations such as viral hepatitis or disease progression in the 
liver 
• Other (non- AST/ALT) non-hematologic Grade ≥ 3 laboratory value if the abnormality 
leads to overnight hospitalization  
 
IMPORTANT: CMP-001 activates plasmacytoid dendritic cells (pDC) through agonism of 
TLR9. Upon activation by CMP-001, pDCs will induce large amounts of interferon and TH1-
promoting cytokines. Therefore, it is expected that toxicities associated with CMP-001 dosing 
may resemble interferon-related toxicities as well as symptoms associated with cytokine release 
such as chills, rigors, fever, nausea/vomiting, flu-like symptoms and/or hypotension which may 
present hours after CMP-001 injection. Therefore, AEs such as headache, chills, rigors, fever, 
nausea/vomiting, flu-like symptoms and/or hypotension that are Grade 3 and below AND 
resolved to  Grade 1 or below within 24 hours with standard supportive care will not be 
considered a DLT.  All toxicities regardless of grade should be managed according to standards 
of care and reported as AEs. 
 
An AE believed by the Investigator to be caused by tumor flare or pseudoprogression does not 
necessarily need to be considered a DLT.  Any such cases that would otherwise meet DLT 
criteria must be discussed immediately with the Medical Monitor.  If the Investigator, Medical 
Monitor, and Sponsor agree that tumor flare is a likely explanation for the AE, treatment with 
CMP-001 may continue as long as the subject is closely monitored by the Investigator or study 
staff while on study. 
 
Subjects who experience a DLT will have CMP-001 and pembrolizumab dosing withheld until 
the toxicity has returned to ≤ Grade 1.  If the Investigator determines that continued treatment 
with CMP-001 is in the subject’s best interest, treatment of CMP-001 may resume at a reduced 
dose, one dose level lower than the subject’s current dose at the same schedule after consultation 
with the Sponsor. Only one dose reduction is allowed. Subjects who continue to experience 
DLTs must come off study. If a CMP-001 injection is delayed due to toxicity, including a DLT, 
it should be given as soon as possible once the toxicity has resolved. 
 
The Investigator may escalate the subject back to the original dose level if: 1) the lower dose 
level was tolerated without any DLTs; 2) Sponsor approval is given.  
 
 
 
 

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2.2 
Trial Diagram 
 
 
 

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3.0 OBJECTIVE(S) & HYPOTHESIS(ES) 
3.1 
Primary Objective 
The primary objective of the study is: 
• 
To find the dose of CMP-001 that when given in combination with pembrolizumab in 
subjects with selected lymphoma results in optimal clinical efficacy and acceptable toxicity  
3.2 
Secondary Objective 
The secondary objectives of the study are:  
• To assess and describe the safety profile of CMP-001 when given in conjunction with 
pembrolizumab.  
• To assess and describe the pharmacodynamic effects of the addition of CMP-001 to 
pembrolizumab on immunologic function.  
• To estimate objective response rate  
3.3 
Exploratory Objective 
Exploratory study objectives include: 
• 
To assess changes in T cell function in response to treatment with CMP-001; 
• 
To assess multiple parameters of immune status in the tumor microenvironment (ie, in 
tumor tissue) prior to starting treatment with CMP-001 and correlating these with anti-lymphoma 
activity observed while on study to screen for potential predictive markers; and 
• 
To assess multiple parameters of immune status in the tumor microenvironment comparing 
pre- vs. post-CMP-001 samples as potential indicators of biological effect of CMP-001 on the 
tumor and the tumor microenvironment. 
 
 

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4.0 BACKGROUND & RATIONALE 
4.1 
Background 
This phase I/II study of CMP-001 plus pembrolizumab will be conducted in subjects with 
lymphomas who have had stable or progressive disease following previous treatment.  Although 
pembrolizumab has led to responses in a minority of patients with B cell lymphoma, most subjects 
do not achieve partial or complete responses and many of these patients ultimately experience 
disease progression. Additionally, there are patients with Hodgkin lymphoma that fail 
pembrolizumab. The purpose of this combination is to augment the immune response and improve 
efficacy.  
CMP-001 is composed of (i) a virus-like particle comprised of capsid proteins derived from 
bacteriophage Qbeta, which encapsulate (ii) a cytosine linked to a guanine by a phosphate bond 
(CpG) oligodeoxynucleotide (ODN) known as G10, which is a Toll-like receptor 9 (TLR9) agonist 
designed to induce high levels of type I interferon production and an anti-tumor CD8+ T cell 
response through activation of TLR9 in plasmacytoid dendritic cells (pDC). The therapeutic agent 
is a virus like particle referred to as QbG10. 
QbG10 has been previously studied in clinical trials under the name CYT003. In this protocol, the 
name CYT003 will refer to historical data using the product in non-oncology settings. The name 
CMP-001 will refer to Regeneron Pharmaceuticals’ plans for the agent. 
 Preclinical and Clinical Trial Data on CMP-001 
 Advanced Melanoma study (NCT02680184) 
Intratumoral administration of CMP-001 is currently being evaluated in combination with 
pembrolizumab in subjects with advanced melanoma resistant to checkpoint inhibitors.  
In study CMP-001-001, A Multicenter, Open-label Phase 1b clinical Study of CMP-001 in 
Combination with Pembrolizumab in Subjects with Advanced Melanoma, CMP-001 is being 
administered IT on a weekly (Schedule A) and every 3 weeks (Q3W) (Schedule B) schedule across 
a dose range of 1-10 mg. To date, approximately 45 subjects have been treated in the CMP-001-
001 study.  Preliminary analysis of safety demonstrates an acute toxicity profile that predominantly 
consists of Grade 1-2 AEs associated with cytokine release including mild fever, chills, rigors, 
nausea, vomiting and occasional hypotension   In some subjects, the severity of this AE profile is 
increased. These AEs typically present after the third CMP-001 dose and generally resolve within 
a few hours with standard supportive care. A treatment algorithm has been developed for the 
management of these reactions and can be found in Section 6.2.1.  CMP-001-001 AE summary of 
the Dose Escalation Phase are presented in Table 2.  
 
 
 

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Table 2: Related AEs Reported in More than One Subject in CMP-001-001 Study 
CMP001-001 Protocol 
Related AEs Reported in More than One Subject* 
 
N (%) of Subjects 
Schedule A^ 
(N=28) 
Schedule B^^ 
(n=11) 
Anemia 
4 (14.3%) 
- 
Chills 
15 (53.6%) 
- 
Constipation 
2 (7.1%) 
- 
Cough 
2 (7.1%) 
- 
Diarrhea 
3 (10.7%) 
- 
Fatigue 
7 (25.0%) 
2 (18.2%) 
Fever 
16 (57.1%) 
- 
Flushing 
2 (7.1%) 
- 
Headache 
6 (21.4%) 
2 (18.2%) 
Hypertension 
2 (7.1%) 
- 
Hypotension 
8 (28.6%) 
- 
Injection Site Pain 
2 (7.1%) 
3 (27.3%) 
Nausea 
8 (28.6%) 
- 
Pruritus 
3 (10.7%) 
- 
Rigors 
6 (21.4%) 
- 
Tachycardia 
2 (7.1%) 
- 
Vomiting 
8 (28.6%) 
2 (18.2%) 
*Based on EDC data as of 30 May 2017 
^ Schedule A includes Cohort 1 (1 mg, n=3); Cohort 2 (3 mg, n=12); Cohort 4 (5 mg, n=6); 
Cohort 6 (10 mg, n=3); Cohort 8 (10 mg, n=4) 
^^ Schedule B includes Cohort 3 (3 mg, n=4); Cohort 5 (5 mg, n=3); Cohort 7 (10 mg, n=3), 
Cohort 9 (10 mg, n=1) 
 
4.2 
Rationale 
It is hypothesized that through its TLR9-mediated immunostimulatory effects, CMP-001 will 
enhance the antitumor activity of anti-PD-1 antibodies. 
 Rationale for immune checkpoint blockade in lymphoma:  
Therapeutics based on checkpoint blockade, including those that interrupt the PD1 axis, have 
created huge excitement in the field of cancer immunotherapy.  There is strong biologic rationale 
to assess this approach in NHL.  In NHL, the lymphoma cells often express PD-L1 (B. J. Chen et 
al., 2013; Myklebust et al., 2013) as do circulating lymphoma cells (Rossille et al., 2014).  PD1 is 
detected on benign T cells within the NHL tumor microenvironment (Muenst, Hoeller, Willi, 
Dirnhofera, & Tzankov, 2010; Xerri et al., 2008).  Thus, lymphoma cells expressing PD-LI provide 
a negative signal to PD1-expressing T cells, thereby blunting the anti-lymphoma T cell response.  
Preliminary results of early phase clinical trials demonstrate anti-PD1 antibodies including 
pembrolizumab (Merck) and nivolumab (Bristol Meyers Squibb) have activity in NHL although 
only a subset of NHL subjects respond.  For example, phase II study of pembrolizumab as single 
agent in patients with CLL and B-cell NHL (MC1485, NCT02332980). Preliminary results in the 
eight evaluable indolent NHL patients showed 25% ORR (2PR) and 1 CR and 2 PR among 

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DLBCL (Ding et al.  ASH 2015). UI/MC Lymphoma SPORE investigators participated in studies 
demonstrating nivolumab also has single agent activity in relapsed/refractory NHL with 15-40% 
of subjects responding depending on histology (Lesokhin et al., 2016). In relapsed DLBCL, PD1 
blockade after autologous stem cell transplant resulted in ~50% overall response rate in subjects 
who had residual disease after transplant (Armand et al., 2013). In relapsed FL, 66% ORR and 50% 
CR were observed with the combination therapy of rituximab and anti-PD1 (Westin et al., 2014).  
Thus, PD1 blockade has clear efficacy in NHL, but there is considerable room for improvement.  
One potential explanation for the limited response rate of single agent anti-PD1 is the lack of 
lymphoma-specific T cells in some patients.  
 Rationale for Combining a TLR-9 Agonist with an Anti-PD-1 Antibody:  
A variety of observations support the potential for CpG ODNs to enhance the antitumor effects 
of checkpoint inhibitors in general, and anti-PD-1 specifically. Despite the strong induction of 
cytolytic T lymphocyte (CTL) responses seen in previous human clinical trials of TLR9 agonists 
in oncology, very few objective responses have been seen, and the T cell responses often are not 
sustained, especially within tumors (Appay et al., 2006). A possible explanation for this lack of 
clinical efficacy is provided by the recent finding that the T cells induced following TLR9 
agonist therapy in humans show very high levels of PD-1 expression (Fourcade et al., 2014). PD-
1 is a “checkpoint” molecule that negatively regulates T cell function when it interacts with its 
ligand PD-L1, commonly expressed on tumors (D. S. Chen & Mellman, 2013). Thus, although 
TLR9 agonists are capable of inducing large numbers of tumor-specific CD8+ T cells in cancer 
patients, the expression of PD-1 on these T cells blocks their function. The addition of an anti-
PD-1 antibody to CD8+ T cells from melanoma patients who had been treated with a TLR9 
agonist significantly increased the T cell function for cytokine secretion (Fourcade et al., 2014), 
providing a strong rationale for the use of the combination of TLR9 agonists and anti-PD-1 
antibodies in cancer therapy. 
In a separate study, a CpG ODN (not CMP-001) in combination with anti-CTLA-4 or anti-PD-1 
increased the survival of mice with MB49 bladder cancer, with anti-PD-1 plus CpG being 
superior to either agent alone. CpG plus anti-CTLA-4 or anti-PD-1 increased the numbers of 
circulating tumor-specific CD107a expressing CD8+ T cells as well as activated (CD25FoxP3-) 
CD4 splenocytes. Further, decreased levels of regulatory T cells (Tregs) were detected in the 
tumor area of treated animals after aCTLA-4 or aPD-1 plus CpG therapy (Mangsbo et al., 2010).  
In an ovarian cancer model, mice treated with a surrogate TLR9 agonist (not CMP-001) in 
combination with anti-PD-1 or anti-PD-L1 antibodies also showed improved survival 
(Duraiswamy, Freeman, & Coukos, 2013). Yet another study was conducted in primary 
melanomas in Hgf-Cdk4 R24C mice, which imitate human immune cell–poor melanomas with a 
poor outcome (Bald et al., 2014). This study demonstrated that treatment with 
immunostimulatory RNA, a TLR7 agonist with immune effects similar to the TLR9 agonist 
CMP-001, was associated with cytotoxic immune cell recruitment, subsequent upregulation of 
PD-L1 expression in tumor tissue, and an increased expression of PD-1 on peripheral blood CD8 
+ T cells. In this model, mice treated with the combination of TLR7 agonist RNA and anti-PD-1 
antibody had significantly prolonged survival compared to control animals. 

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 Rationale for Intratumoral Administration of TLR9 Agonist:  
The intended mechanism of action of CMP-001 in oncology is the activation of TLR-9 in 
plasmacytoid dendritic ecells (pDC) within the tumor or the tumor-draining lymph nodes (tumor-
associated pDC). Tumor-associated pDC activated by CMP-001 are expected to release large 
amounts of type I interferons (IFN), and increase their expression of costimulatory molecules and 
tumor antigen presentation to T-cells, culminating in the generation of a clinically effective anti-
tumor T-cell response.  In order for this response to be specific for the tumor, the pDC should have 
taken up the tumor antigens already, which requires them to be activated either within the tumor, 
or the draining lymph nodes, which in turn requires the intratumoral route of administration to 
reach a locally effective concentration of CMP-001: systemic administration of TLR-9 agonists 
results primarily in liver, spleen, and RES (reticuloendothelial system) uptake with little specific 
activation of pDC in peripheral lymph nodes. Immature tumor-associated pDC contribute to tumor 
growth and an adverse prognosis in cancer patients (Demoulin, Herfs, Delvenne, & Hubert, 2013; 
Lombardi, Khaiboullina, & Rizvanov, 2015). Activating and maturing these pDC through 
intratumoral administration of CMP-001 is expected to reverse the pDC functional effects from 
promoting to antagonizing tumor growth, and from supporting immune tolerance to inducing an 
anti-tumor CD8+ T cell response.  Peritumoral administration is an acceptable alternate if it is 
impossible to perform intratumoral administration in an individual patient because peritumoral 
injection will still activate tumor antigen-bearing pDC in the tumor-draining lymph nodes (though 
not in the tumor itself which is why intratumoral administration is preferred).  However, 
administration of CMP-001 subcutaneously in areas distant to a tumor is not expected to provide 
any positive signals to the tumor antigen-bearing pDC in the tumor or draining lymph nodes.  In 
non-clinical models, intratumoral dosing is far more effective than distant subcutaneous dosing 
and is able to induce regression not only of the directly injected tumor lesion but also of distant 
metastases (Heckelsmiller et al., 2002; Shirota, Shirota, & Klinman, 2012) supporting the intended 
intratumoral clinical route of administration.  
 Rationale for combining anti-PD1 and CMP-001 in lymphoma:  
We first evaluated the anti-tumor effects of CMP-001 injected intratumorally in combination with 
anti-PD1 in syngeneic, immunocompetent murine lymphoma models.  In these studies, mice were 
inoculated bilaterally with lymphoma.  Once tumor was palpable on both flanks, mice were treated 
with systemic anti-PD1, intratumoral CMP-001 (into the tumor on one flank only) or a 
combination of systemic anti-PD1 and unilateral intratumoral CMP-001.  Survival and tumor 
growth, including growth of the tumor injected with CMP-001, and the tumor on the contralateral 
flank that was not injected with CMP-001, were followed.  These studies demonstrated that the 
combination of systemic anti-PD1 and intratumoral CMP-001 induces regression of both the 
treated tumor and the contralateral tumor that was not treated with CMP-001. Survival of mice 
treated with both agents was superior to that of mice treat with either agent alone.  Depletion of T 
cells abrogated the antitumor therapeutic effect in the injected tumor as well as the contralateral 
tumor (data not shown) confirming the anti-tumor effect is T cell mediated. 

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4.3 
Justification for Dose  
 Justification for CMP-001 dosing:  
The first CMP-001 injection stimulates antibody formation to the VLP of CMP-001 and will be 
given subcutaneously.  Subsequently, CMP-001 will be administered by intratumoral injection 
every week for seven doses. The seventh dose (C7D1) is to be followed by booster doses given 
every 3 weeks. 
The starting dose for CMP-001, 5 mg, was selected based upon the combination with identical 
pembrolizumab dosing in a Phase I/II trial of the two agents in metastatic melanoma led at the 
University of Iowa (NCT02680184).  In the first 2 cohorts in melanoma, no DLT was seen at the 
5mg dose, while biologic activity and some toxicity was seen at the 7.5 mg dose.  
The highest dose considered in that study, 20 mg, is the maximum planned for consideration in 
CMP-001 given the current formulation.  
Rationale for weekly dosing of CMP-001 for the first seven doses is supported by the following 
points: 
• The safety of weekly dosing of up to 5 mg is well-supported by previous clinical trials of 
CYT003-QbG10 in non-oncology indications.  
• The efficacy of weekly dosing is supported by the observation that weekly vaccination of 
melanoma patients with the closely related compound CYT004 (essentially CYT003-
QbG10 conjugated to a tumor antigen) rapidly induced anti-tumor CD4+ and CD8+ T cell 
responses in the majority of subjects (Braun et al., 2012; Goldinger et al., 2012; Speiser et 
al., 2010). Thus, considering intratumoral administration of CMP001 as a kind of in situ 
vaccination, weekly dosing is also expected to induce anti-tumor immunity. 
• Within a week of the initial dose, humans produce an anti-Qb antibody response adequate 
to provide uptake of the second dose into the target TLR-9-responsive immune cells.  
• The desired Th1-like pharmacodynamic effects of CpG ODN injection persist in the 
draining lymph nodes of mice for more than one week (Lipford, Sparwasser, Zimmermann, 
Heeg, & Wagner, 2000) after a single injection; less frequent dosing may fail to sustain the 
desired IFN induction in the tumor microenvironment and draining lymph nodes, allowing 
the immune suppressive effects of the tumor to dominate. 
• More frequent than weekly dosing is not expected to provide any increased efficacy, and 
in the study of a different TLR-9 agonist in the treatment of hepatitis C virus infection, 
twice weekly subcutaneous injection of CPG-ODN even appeared to induce a slightly 
weaker immune response in the dose given three days after previous injection compared to 
the dose given 4 days after previous injection (McHutchison et al., 2007). 
In previous clinical trials of CYT004 and other TLR9 agonists as cancer vaccines, the anti-tumor 
T cell responses were detectable within 8 weeks (Braun et al., 2012; Fourcade et al., 2014), 
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T cell response.  Following this induction phase of therapy, the rationale for every 3-week 
intratumoral injections is to maintain and boost the anti-tumor response with the goal of achieving 
systemic control and eradication not only of the injected lesion but also distant disease.  
 Justification for Pembrolizumab dose:  
The planned dose of pembrolizumab for this study is 200 mg every 3 weeks (Q3W).  Based on the 
totality of data generated in the Keytruda development program, 200 mg Q3W is the appropriate 
dose of pembrolizumab for adults across all indications and regardless of tumor type.  As outlined 
below, this dose is justified by: 
• Clinical data from 8 randomized studies demonstrating flat dose- and exposure-efficacy 
relationships from 2 mg/kg Q3W to 10 mg/kg every 2 weeks (Q2W),  
• Clinical data showing meaningful improvement in benefit-risk including overall survival 
at 200 mg Q3W across multiple indications, and 
• Pharmacology data showing full target saturation in both systemic circulation (inferred 
from pharmacokinetic [PK] data) and tumor (inferred from physiologically-based PK 
[PBPK] analysis) at 200 mg Q3W 
Among the 8 randomized dose-comparison studies, a total of 2262 participants were enrolled with 
melanoma and non-small cell lung cancer (NSCLC), covering different disease settings (treatment 
naïve, previously treated, PD-L1 enriched, and all-comers) and different treatment settings 
(monotherapy and in combination with chemotherapy).  Five studies compared 2 mg/kg Q3W 
versus 10 mg/kg Q2W (KN001 Cohort B2, KN001 Cohort D, KN002, KN010, and KN021), and 
3 studies compared 10 mg/kg Q3W versus 10 mg/kg Q2W (KN001 Cohort B3, KN001 Cohort F2 
and KN006).  All of these studies demonstrated flat dose- and exposure-response relationships 
across the doses studied representing an approximate 5- to 7.5 fold difference in exposure.  The 2 
mg/kg (or 200 mg fixed-dose) Q3W provided similar responses to the highest doses studied.  
Subsequently, flat dose-exposure-response relationships were also observed in other tumor types 
including head and neck cancer, bladder cancer, gastric cancer and classical Hodgkin Lymphoma, 
confirming 200 mg Q3W as the appropriate dose independent of the tumor type.  These findings 
are consistent with the mechanism of action of pembrolizumab, which acts by interaction with 
immune cells, and not via direct binding to cancer cells. 
Additionally, pharmacology data clearly show target saturation at 200 mg Q3W.  First, PK data in 
KN001 evaluating target-mediated drug disposition (TMDD) conclusively demonstrated 
saturation of PD-1 in systemic circulation at doses much lower than 200 mg Q3W.  Second, a 
PBPK analysis was conducted to predict tumor PD-1 saturation over a wide range of tumor 
penetration and PD-1 expression.  This evaluation concluded that pembrolizumab at 200 mg Q3W 
achieves full PD-1 saturation in both blood and tumor. 
Finally, population PK analysis of pembrolizumab, which characterized the influence of body 
weight and other participant covariates on exposure, has shown that the fixed-dosing provides 
similar control of PK variability as weight based dosing, with considerable overlap in the 
distribution of exposures from the 200 mg Q3W fixed dose and 2 mg/kg Q3W dose.  Supported 

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by these PK characteristics and given that fixed-dose has advantages of reduced dosing complexity 
and reduced potential of dosing errors, the 200 mg Q3W fixed-dose was selected for evaluation 
across all pembrolizumab protocols. 
4.4 
Safety Endpoints 
The primary safety endpoint of this study is safety and tolerability of CMP-001 when given in 
conjunction with pembrolizumab.  
4.5 
Efficacy Endpoints 
The primary efficacy endpoint of this study is objective response rate of CMP-001 when combined 
with pembrolizumab.  
4.6 
Biomarker Research 
Biomarker research will assess changes in T cell function in response to treatment with CMP-001. 
Additionally, it will assess multiple parameters of immune status in the tumor microenvironment 
(ie, in tumor tissue) prior to starting treatment with CMP-001 and correlating these with anti-
lymphoma activity observed while on study to screen for potential predictive markers. We also 
plan to compare multiple parameters of immune status in the tumor microenvironment in pre- vs. 
post-CMP-001 samples as potential indicators of biological effect of CMP-001 on the tumor and 
the tumor microenvironment. 
5.0 STUDY POPULATION  
5.1 
Participant Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Male/female participants who are at least 18 years of age on the day of signing informed 
consent with histologically or cytologically confirmed diagnosis of relapsed or refractory 
Hodgkin Lymphoma or Non-Hodgkin Lymphoma (B and T cells). 
2. Male participants: A male participant must agree to use a contraception as detailed in 
Appendix C of this protocol during the treatment period and for at least five months after 
the final CMP-001 and pembrolizumab dose and refrain from donating sperm during this 
period. 
3. Female participants: A female participant is eligible to participate if she is not pregnant 
(see Appendix C), not breastfeeding, and at least one of the following conditions applies:  
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix C  
OR  
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix C during the 
treatment period and for at least 5 months after the last dose of study treatment. 

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4. The participant (or legally acceptable representative if applicable) provides written 
informed consent for the trial prior to the initiation of any study procedures.  The participant 
must be capable of understanding and complying with protocol requirements.   
5. Have measurable disease based on Cheson 2007 (Cheson et al., 2007).  Lesions situated in 
a previously irradiated area are considered measurable if progression has been 
demonstrated in such lesions. 
6. Subjects must have at least one tumor lesion with a longest diameter of ≥ 1 cm that can be 
easily palpated or detected by ultrasound to facilitate intratumoral injection of CMP-001 
(eg, tumor in skin, muscle, subcutaneous tissue or accessible lymph node). 
7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 
Evaluation of ECOG is to be performed within 7 days prior to the date of 
allocation/randomization.  
8. Patients previously treated with anti B cell directed therapy, such as anti-B cell antibody 
therapy within the past year or a history of CAR T therapy at any time, will be evaluated 
for the presence of B cells by flow cytometry on peripheral blood. Patients with > 100 
benign B cells will be considered eligible.  Those with < 100 benign B cells may still be 
enrolled at the investigator’s discretion but will only proceed to the therapeutic phase of 
the study if they have been shown to generate an anti-Qbeta antibody response, as 
demonstrated by ELISA assay, in response to the priming dose of vidutolimod. (Trial 
Schema, section 2.2) 
 
5.2 
Participant Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to first dose of 
study drug. (see Appendix C).  If the urine test is positive or cannot be confirmed as 
negative, a serum pregnancy test will be required. 
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an 
agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, 
OX-40, CD137) within 4 weeks of enrollment into this trial.  
 
3. Has received prior systemic anti-cancer therapy including investigational agents within 
4 weeks or within 5 half-lives, whichever is shorter, prior to first dose of study drug. 
Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 
or baseline. Participants with ≤Grade 2 neuropathy may be eligible. 
Note: If participant received major surgery, they must have recovered adequately from the 
toxicity and/or complications from the intervention prior to starting study treatment. 

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4. Has received prior radiotherapy within 2 weeks of start of study treatment.  Participants 
must have recovered from all radiation-related toxicities, not require corticosteroids, and 
not have had radiation pneumonitis.  A 1-week washout is permitted for palliative 
radiation (≤2 weeks of radiotherapy) to non-CNS disease. 
 
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose 
of study drug.  Administration of killed vaccines is allowed. 
 
6. Is currently participating in or has participated in a study of an investigational agent or 
has used an investigational device within 4 weeks, or within 5 half-lives, whichever is 
shorter, prior to the first dose of study treatment. 
Note:  Participants who have entered the follow-up phase of an investigational study may 
participate as long as it has been 4 weeks, or 5 half-lives, whichever is shorter, after the 
last dose of the previous investigational agent. 
 
7. Has a diagnosis of primary immunodeficiency disorder or is receiving chronic systemic 
steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other 
form of immunosuppressive therapy within 7 days prior to the first dose of study drug.  
 
8. Has a known additional malignancy that is progressing or has required active treatment 
within the past 3 years.  Note:  Participants with basal cell carcinoma of the skin, squamous 
cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in 
situ) that have undergone potentially curative therapy are not excluded. 
9. Has known active CNS metastases and/or carcinomatous meningitis.  Participants with 
previously treated brain metastases may participate provided they are radiologically stable, 
i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the 
repeat imaging should be performed during study screening), clinically stable and without 
requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients. 
 
11. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. 
with use of disease modifying agents, corticosteroids or immunosuppressive drugs). 
Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic 
treatment.  
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids 
or has current pneumonitis/interstitial lung disease. 
13. Has an active infection requiring systemic therapy. 
14. Has a known history of Human Immunodeficiency Virus (HIV).  Note: No HIV testing is 
required unless mandated by local health authority. 

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15. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] 
reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection. 
Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local 
health authority.  
 
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that 
might confound the results of the study, interfere with the subject’s participation for the 
full duration of the study, or is not in the best interest of the subject to participate, in the 
opinion of the treating investigator.   
17. Has known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the trial. 
18. Patients with allotransplant in past 5 years or those with evidence of graft vs. host disease 
(GVHD) will be excluded. 
19. Have inadequate organ function as defined in the following table (Table 3).  Specimens 
must be collected within 10 days prior to the start of study treatment. 
Table 3   Adequate Organ Function Laboratory Values 
System 
Laboratory Value 
Hematological 
 
Absolute neutrophil count 
(ANC) 
≥500/µL a, b 
Platelets 
≥50,000/µL a, b 
Hemoglobin 
≥8 g/dL a, b 
Renal 
 
Creatinine OR 
Measured or calculated c 
creatinine clearance 
(GFR can also be used in place 
of creatinine or CrCl) 
≤1.5 × ULN OR 
≥30 mL/min for participant with creatinine 
levels >1.5 × institutional ULN  
Hepatic 
 
Total bilirubin 
≤1.5 ×ULN OR direct bilirubin ≤ULN for 
participants with total bilirubin levels 
>1.5 × ULN 

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AST (SGOT) and ALT (SGPT) 
≤2.5 × ULN (≤5 × ULN for participants with 
liver metastases) 
Coagulation 
 
International normalized ratio 
(INR) OR prothrombin time (PT) 
Activated partial thromboplastin 
time (aPTT) 
≤1.5 × ULN unless participant is receiving 
anticoagulant therapy as long as PT or PTT 
is within therapeutic range of intended use of 
anticoagulants 
ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); 
AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); 
GFR=glomerular filtration rate; ULN=upper limit of normal. 
aGrowth factor and/or transfusion support is permissible to stabilize participant prior to 
study treatment if needed. 
bNo lower limit if cytopenia is related to bone marrow involvement. 
cCreatinine clearance (CrCl) should be calculated per institutional standard. 
Note: This table includes eligibility-defining laboratory value requirements for 
treatment; laboratory value requirements should be adapted according to local 
regulations and guidelines for the administration of specific chemotherapies. 
 
5.3 
Lifestyle Restrictions 
 Meals and Dietary Restrictions 
Participants should maintain a normal diet unless modifications are required to manage an AE such 
as diarrhea, nausea or vomiting. 
 Contraception 
Pembrolizumab or CMP-001 may have adverse effects on a fetus in utero.  Refer to Appendix C 
for approved methods of contraception. 
For this study, male participants will be considered to be of non-reproductive potential if they 
have azoospermia (whether due to having had a vasectomy or due to an underlying medical 
condition).   
 Pregnancy 
If a participant inadvertently becomes pregnant while on treatment with pembrolizumab, the 
participant will be immediately discontinued from study treatment.  The site will contact the 

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participant at least monthly and document the participant’s status until the pregnancy has been 
completed or terminated.  The outcome of the pregnancy will be reported to Merck within 2 
working days if the outcome is a serious adverse experience (eg, death, abortion, congenital 
anomaly, or other disabling or life-threatening complication to the mother or newborn).  The 
study Investigator will make every effort to obtain permission to follow the outcome of the 
pregnancy and report the condition of the fetus or newborn to Merck.  If a male participant 
impregnates his female partner, the study personnel at the site must be informed immediately and 
the pregnancy must be reported to Merck and followed as described in Section 8.2.2. 
 Use in Nursing Women 
It is unknown whether pembrolizumab or CMP-001 is excreted in human milk.  Since many drugs 
are excreted in human milk, and because of the potential for serious adverse reactions in the 
nursing infant, participants who are breast-feeding are not eligible for enrollment. 
5.4 
Concomitant Medications/Vaccinations (allowed & prohibited) 
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed during 
the ongoing trial.  If there is a clinical indication for one of these or other medications or 
vaccinations specifically prohibited during the trial, discontinuation from trial therapy or 
vaccination may be required.  The final decision on any supportive therapy or vaccination rests 
with the investigator and/or the participant's primary physician.  
 Acceptable Concomitant Medications 
All treatments that the investigator considers necessary for a participant’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care.  All concomitant medication will be recorded on the case report form (CRF) 
including all prescription, over-the-counter (OTC), herbal supplements, and IV medications and 
fluids.  If changes occur during the trial period, documentation of drug dosage, frequency, route, 
and date may also be included on the CRF. 
All concomitant medications received within 28 days before the first dose of trial treatment and 
30 days after the last dose of trial treatment should be recorded.  Concomitant medications 
administered after 30 days after the last dose of trial treatment should be recorded for SAEs and 
ECIs as defined in Section 8.2. 
 Prohibited Concomitant Medications 
Participants are prohibited from receiving the following therapies during the Screening and 
Treatment Phase (including retreatment for post-complete response relapse) of this trial: 
• Antineoplastic systemic chemotherapy or biological therapy  
• Immunotherapy not specified in this protocol 
• Chemotherapy not specified in this protocol 
• Investigational agents other than pembrolizumab and CMP-001 

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• Radiation therapy  
o Note:  Radiation therapy to a symptomatic solitary lesion or to the brain may be allowed 
at the investigator’s discretion. CMP-001 in this case must be suspended until radiation 
treatment is completed.  
• Live vaccines within 30 days prior to the first dose of study treatment and while 
participating in the study.  Examples of live vaccines include, but are not limited to, the 
following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and 
typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus 
vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live 
attenuated vaccines and are not allowed.  
• Systemic glucocorticoids for any purpose other than to modulate symptoms from an event 
of clinical interest of suspected immunologic etiology.  The use of physiologic doses of 
corticosteroids may be approved after consultation with the Sponsor. 
Participants who, in the assessment by the investigator, require the use of any of the 
aforementioned treatments for clinical management should be removed from the study.  All 
treatments that the Investigator considers necessary for a participant’s welfare may be 
administered at the discretion of the Investigator in keeping with the community standards of 
medical care.   
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing study.  If there is a clinical indication for any medication or vaccination 
specifically prohibited during the study, discontinuation from study therapy or vaccination may 
be required.  The final decision on any supportive therapy or vaccination rests with the 
investigator and/or the participant's primary physician.  However, the decision to continue the 
participant on study treatment requires the mutual agreement of the investigator, the Sponsor and 
the participant. 
There are no prohibited therapies during the Post-Treatment Follow-up Phase. 
 Rescue Medications & Supportive Care 
Participants should receive appropriate supportive care measures as deemed necessary by the 
treating investigator.  Suggested supportive care measures for the management of AEs with 
potential immunologic etiology are outlined along with the dose modification guidelines in 
Section 6.2.2, [Table 7].  Where appropriate, these guidelines include the use of oral or IV 
treatment with corticosteroids, as well as additional anti-inflammatory agents if symptoms do not 
improve with administration of corticosteroids.  Note that several courses of steroid tapering may 
be necessary as symptoms may worsen when the steroid dose is decreased.  For each disorder, 
attempts should be made to rule out other causes such as metastatic disease or bacterial or viral 
infection, which might require additional supportive care.  The treatment guidelines are intended 
to be applied when the Investigator determines the events to be related to pembrolizumab or 
CMP-001.  

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Note: If after the evaluation of the event, it is determined not to be related to pembrolizumab or 
CMP-001, the Investigator does not need to follow the treatment guidance.  Refer to [Table 7] in 
Section 6.2.2 for guidelines regarding dose modification and supportive care.  
It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, or skin 
photography as part of evaluation of the event.  
5.5 
Participant Withdrawal/Discontinuation Criteria 
Participants may discontinue study treatment at any time for any reason or be dropped from the 
study treatment at the discretion of the investigator should any untoward effect occur.  In addition, 
a participant may be discontinued from study treatment by the investigator or the Sponsor if study 
treatment is inappropriate, the trial plan is violated, or for administrative and/or other safety 
reasons.  Specific details regarding procedures to be performed at study treatment discontinuation 
are provided in Section 8.1.6 – Other Procedures. 
A participant must be discontinued from study treatment but continue to be monitored in the 
study for any of the following reasons: 
• The participant or participant’s legally acceptable representative requests to discontinue 
study treatment 
• Confirmed radiographic disease progression as per Cheson 2007 criteria if accompanied 
by medically significant clinical deterioration, in the judgment of investigator. 
(Continuation of treatment through suspected pseudo-progression is permitted).  
• Any progression or recurrence of any malignancy, or any occurrence of another 
malignancy that requires active treatment 
• Unacceptable adverse experiences as described in Section 6.2.2. 
• The participant has a medical condition or personal circumstance which, in the opinion of 
the investigator and/or sponsor, placed the participant at unnecessary risk from continued 
administration of study treatment. 
• The participant has a confirmed positive serum pregnancy test 
• Noncompliance with study treatment or procedure requirements 
• Discontinuation of treatment may be considered for participants who have attained a 
confirmed complete response (CR) and have been treated for at least 8 every 3 week 
doses of Pembrolizumab beyond the date when the initial CR was declared.   
• The participant is lost to follow-up 
• Completion of 35 treatments (approximately 2 years) with pembrolizumab 
Note: The number of treatments is calculated starting with the first dose. 
• Administrative reasons 

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Subjects discontinuing study treatment earlier than planned or withdrawing from the study should 
undergo the End of Treatment (EOT) clinical and laboratory assessments (see Section 7.0 TRIAL 
FLOW CHART) as soon as possible after study treatment is stopped.  The required 30 day follow-
up phone call should also be completed.  The reason for withdrawal will be recorded in the 
electronic case report form (eCRF) and the subject’s source medical record.  
If a subject withdraws from the study prior to completion of the 21 day assessment period for a 
reason other than a DLT, then a replacement subject will be enrolled at that dose level. 
5.6 
Clinical Criteria for Early Trial Termination 
Early trial termination will be the result of the criteria specified below: 
1. Quality or quantity of data recording is inaccurate or incomplete 
2. Poor adherence to protocol and regulatory requirements 
3. Incidence or severity of adverse drug reaction in this or other studies indicates a potential health 
hazard to participants as detailed in section 6.2 
4. Plans to modify or discontinue the development of the study drug 
In the event of Merck decision to no longer supply study drug, ample notification will be provided 
so that appropriate adjustments to participant treatment can be made. 
6.0 TREATMENT OF SUBJECTS 
6.1 
Study Drug Administration 
 Recommended Prophylaxis Before and After CMP001 Dosing 
To reduce the incidence and severity of symptoms associated with CMP-001 administration, 
prophylaxis is required. All recommended prophylaxis should be administered before 
initiation of the CMP-001 injection. The medications are recommended for oral administration, 
but IV is acceptable at the discretion of the Investigator. There is no waiting period between the 
end of prophylaxis and the start of the CMP-001 injection. The optimal recommended regimen 
that has been effective for the treatment of CMP-001 associated AEs, should include all the 
following components: 
• Intravenous fluids (eg, approximately 1000 cc IV normal saline) 
• Antipyretics (eg, acetaminophen 1000 mg and a non-steroidal anti-inflammatory agent 
such as indomethacin 50 mg or ibuprofen 600 to 800 mg) 
• Anti-emetics (eg, ondansetron 8 mg)  
• Antihistamine: (diphenhydramine 50 mg, with or without an H2-antagonist) 
• Recommended: hydrocortisone 25 mg at the investigator’s discretion. 
 
Subjects with a history of adrenal insufficiency are at increased risk for moderate to severe AEs 
such as hypotension. It is strongly recommended that these subjects receive stress dose steroids 

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(eg, 50 to 100 mg hydrocortisone orally every 8 hours) before and for 24 to 48 hours after each 
CMP-001 injection.  
 
It is also highly recommended to continue to administer IV fluids during the observation period 
immediately following the CMP-001 injection, rather than waiting to initiate fluids if 
hypotension is detected. Antipyretics, antiemetics, and antihistamines may be repeated 
at the Investigator’s discretion. 
 
The algorithm (Figure 2)  is provided as guidance for the treatment of AEs associated with 
CMP-001. 
 
 Administration of CMP-001 
If possible, the full volume should be injected into a single progressing lesion and as 
appropriate for the subject’s dose cohort. If the full volume cannot be injected within the 
tumor, then the remaining drug volume should be injected into a second accessible tumor, if 
present. If the full volume still cannot be administered into the tumor then peritumoral 
injection of any remaining volume is acceptable. 
If over time an injected tumor is clearly responding to therapy (eg, regresses below the 
minimum size that can readily be injected with the required volume), or if in the judgment of 
the Investigator, the subject cannot tolerate continued injections in that lesion because of local 
injection site reaction or other issues, then the injection may instead be administered 
intratumorally into a different progressing tumor lesion, or peritumorally at the original site or 
at a new tumor lesion. 
If a single lesion is the only injectable lesion and decreases or disappears over time, we plan to 
continue injecting into the tumor bed for the entire 7 weeks (+) course of treatment and until 
first radiological assessment. If after the first radiological assessment at week 7, there is no 
tumor site available for injection, we plan to continue with Pembrolizumab +/- injection to 
tumor bed until progression, toxicity or if in the investigator’s opinion continued treatment is 
in subject’s best interest. 
CMP-001 should be injected using aseptic technique. Use of topical and/or local anesthetic is 
permitted. For administration of CMP-001 a single cutaneous insertion point should be used 
and multiple needle tracks within the tumor should be injected until the full volume has been 
instilled. 
The information on dose, volumes, and numbers of sites injected will be recorded for analysis.   
 
 Goals for Injection 
The clinical goal of intratumoral therapy with CMP-001 is to induce a systemic CTL response 
that eradicates the injected tumor and distant metastases. The direct immunologic goals of 
intratumoral therapy are: i) to alter the tumor microenvironment in a Th1 manner by inducing 
the production of type I IFN by tumor infiltrating pDC (AKA IFN-producing cells) through 
TLR9; ii) to trigger the maturation of tumor-infiltrating pDC from an immature tumor-
protective phenotype to a mature, anti-tumor CTL inducer; and iii) to alter the tumor draining 

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lymph node microenvironment in a Th1 manner. 
Intratumoral injection is required to achieve the first goal, but either intratumoral or peritumoral 
injection can achieve the second goal: in both cases the injected CMP-001 traffics via 
lymphatics to draining lymph nodes (DLNs) where it activates resident pDC inducing a Th1-
like cytokine/chemokine milieu within the tumor-draining lymph nodes. In addition, some 
tumor- infiltrating pDC also may mature and migrate from the tumor into the DLN following 
TLR9 activation from intratumoral CMP-001 injection. For these reasons, peritumoral injection 
is permitted whenever the entire dose cannot be injected into the selected tumor(s). 
 
 Tumor Selection 
Tumors selected for CMP-001 intratumoral injection should be at least 0.5 cm in diameter and 
may be cutaneous, subcutaneous, and/or nodal tumors that are visible, palpable, or detectable 
by ultrasound guidance; visceral tumors are not injected. Patient candidates for CMP-001 
injection may have more than one accessible tumor as a candidate for intratumoral injection. 
The most preferred of these to be selected for injection is the most aggressively progressing 
tumor in the judgment of the Investigator. Such tumors may have additional mutations 
compared to non- progressing tumors, and perhaps express neoantigens that may be 
particularly good targets for the induction of a therapeutic immune response. Tumors that are 
already regressing are not preferred for injection because they are believed to already have a 
tumor microenvironment supporting immune rejection, and there may be less additional 
benefit to CMP-001 injection compared to selecting progressing or stable tumors. When 
several progressing tumors are available for injection, the Investigator should select the one 
that is most amenable to injection (eg, the most superficial) and/or the tumor that is the 
smallest capable of receiving the entire volume of CMP-001 to be delivered (see Table 4). The 
rationale for selecting the smallest appropriate tumor is to have the highest possible 
intratumoral concentration of CMP-001, which is expected to maximize the induction of a 
Th1-like tumor microenvironment.  
 
 Dosage and Regimen 
All subjects to be treated with CMP-001 must have at least one such appropriate tumor 
for CMP-001 injection (eg, tumor in skin, subcutaneous tissue or accessible lymph 
node). 
At Screening, the selected tumor(s) must be large enough to allow intratumoral injection of the 
intended volume of CMP-001 (Table 4; Table 5). If possible, the entire dose volume should be 
injected into a single tumor. The tumor selected for injection need not be the largest lesion. If 
the subject has no single tumor large enough to allow injection of the entire volume of CMP-
001, then the volume may be split among 2 or more smaller lesions. However, the minimal 
number of lesions should be chosen to allow injection of the entire volume, instead of splitting 
the dose among a larger number of smaller lesions. The same tumor(s) should be injected each 
week during therapy, if possible, except as outlined below to involuting tumors. 
Dosing of CMP-001 is intended to be given weekly for seven weeks (and then at 3-week 
intervals for the duration of treatment). To assure maximum effectiveness, consecutive doses 

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of CMP-001 should always be administered at least 96 hours apart. 
 
 Dividing the CMP-001 Dose between Two or More Tumors 
It is preferred to inject the entire CMP-001 dose into a single progressing tumor that is 
amenable to injection if one of the appropriate size for the entire volume is available (Table 4). 
If no single progressing tumor is large enough, then the dose should be split between one or 
more smaller progressing tumors, or a smaller progressing tumor and one or more non-
progressing tumors.  
 
 Changing the Selected Tumor 
Therapy of a selected lesion generally should continue per protocol unless the tumor is 
dramatically responding clinically through involution. Inflammation of the injected tumor is 
expected following the 2nd and subsequent injections but should not be mistaken for a clinically 
effective anti-tumor response. It is expected that injection of the selected lesion may need to be 
continued for the full 7 weekly doses to maintain the Th1-like cytokine/chemokine milieu for 
long enough to drive an effective CTL response before a clinical response may be apparent, and 
that continued injections every 3 weeks may be required to maintain the Th1 effects for maximal 
achievable clinical response. If during therapy the injected tumor is clearly involuting and 
shrinking, and if a different eligible accessible tumor is progressing, then the Investigator should 
change the selection to the progressing tumor, injecting the full or maximal feasible dose (as 
outlined in Table 4) of CMP-001 into that tumor(s), and continuing to inject the new tumor(s) 
until the end of the study (or that tumor shows involution, in which case a third progressing tumor 
may be selected). 
Table 4:  Selection of CMP-001 Injection Volume Based on Lesion Size 
Lesion Size (Longest Dimension) 
CMP-001 Injection Volume1 
>0.5 to 1.5 cm 
Up to 0.5 mL 
>1.5 to 2.5 cm 
Up to 1 mL 
>2.5 to 3.5 cm 
Up to 2 mL 
>3.5 to 5 cm 
Up to 3 mL 
> 5 cm 
Up to 4 mL 
1: 
These volumes are intended only as a guideline to the Investigator of what may be injected for tumors in a 
particular size range. If the Investigator has selected a tumor for injection and is unable to deliver the 
intended intratumoral volume because of patient pain or other factors, then the remainder of the dose 
may instead be injected peritumorally. 
 
Table 5: CMP-001 Injection Volumes 
Dose 
Cohort 
Volume to be injected for 1mg/mL 
Concentration 
Volume to be Injected for 5 
mg/mL concentration 
7.5 mg 
7.5 mL 
1.5 mL 
10 mg 
10.0 mL 
2 mL 
 

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 Procedure of CMP-001 Administration  
Topical or local anesthesia may be performed as appropriate in the Investigators’ judgment. 
Using standard aseptic technique, the needle is inserted near the tumor periphery (Figure 1, left 
panel) and is advanced into the tumor to the desired depth (usually to the needle hub, if the 
tumor size permits) while maintaining gentle backward pressure on the syringe plunger to 
confirm extravascular location of the needle tip. The syringe and needle are then slowly 
withdrawn to within a few mm of the skin or tumor surface while maintaining gentle downward 
pressure on the plunger to inject the desired volume of CMP-001 along the needle track (Figure 
1, middle panel). With the tip of the needle still within the skin, the syringe is then rotated by 
~20-40o and the process of insertion and injection during needle withdrawal is repeated (Figure 
1, right panel). Using this process, CMP-001 is injected along multiple tracks through a single 
insertion point as far as the radial reach of the needle allows within the tumor; two insertion 
points can be used if the tumor is larger than the radial reach of the needle and the intended 
CMP-001 volume cannot be delivered from a single insertion point. If gentle injection pressure 
along 5 needle tracks within the tumor has not succeeded in delivering the desired volume, then 
the remainder of the CMP-001 may be injected peritumorally, around the same lesion.  
 
 
 
 
Figure 1: Method for CMP-001 Intratumoral Injection 
 
 
Essentially the same process is performed for cutaneous, subcutaneous, and nodal injections, but 
for deeper injections, the tip of the needle may be kept within the tumor and a longer needle may 
be used. 
Injections will be performed by Oncologist if easily accessible lesions or by interventional 
radiologist for lesions that need image guidance for injections. Interventional radiologist will be 
sub-investigators on this study. This is based on our experience on other trials that required 
injection of drug directly into tumors. 
 

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 Observation Period Following CMP-001 Dosing 
Following the first 5 doses of CMP-001 (W1D1, W2D1, W3D1, W4D1, W5D1), subjects must be 
observed for a period of at least four hours for signs and symptoms of reactions to the CMP-001 
injection and other AEs.  
Based upon the discretion of the Investigator, observation periods can be reduced to one hour for 
individual subjects who demonstrate mild to no AEs post CMP-001 injection for the first 5 
doses. Reduced observation periods can be implemented starting with the 6th dose of CMP-001 
(W6D1).  
 
 Administration of Pembrolizumab 
Pembrolizumab (KEYTRUDA) is to be administered at a dose of 200 mg fixed dose 
administered as an IV infusion over 30 minutes every 3 weeks as per label instruction.  
Table 6  Pembrolizumab Trial Treatment 
Drug 
Dose/Potency 
Dose 
Frequency 
Route of 
Administration 
Regimen/Treatment 
Period 
Use 
Pembrolizumab 200 mg 
Q3W 
IV infusion 
Day 1 of each 3 
week cycle 
Experimental 
 
6.2 
Dose Modifications and Management of Study-Drug Associated Adverse Events 
The following sections provide guidance on the management of toxicities that may be associated 
with CMP-001 and pembrolizumab. In most cases management of toxicity may require either a 
temporary or permanent discontinuation of both CMP-001 and pembrolizumab. However, if in the 
opinion of the investigator, a toxicity is more clearly related to one drug, the administration of that 
drug may be modified with PI consultation and approval.  If a subject develops moderate to severe 
toxicity with CMP-001, we will consider stress dose steroids prior to subsequent CMP-001 doses. 
 CMP-001 Associated Adverse Events (see Table 2) 
The safety profile for intratumoral CMP-001 in combination with Pembrolizumab has been 
reported in melanoma clinical trial (N=159) and treatment related adverse events described in 
detail in Invetigator Brochure version 07 (26July2021). Allergic reactions of an immediate type, 
including anaphylaxis, have been observed after CMP-001 administration. Investigators must be 
vigilant in identifying and managing these disorders according to institutional guidelines. 
 
 Injection Site Reactions 
If subjects develop inflammation at the injection site this may be managed using cold compresses 
and/or acetaminophen or non-steroidal anti-inflammatory agents. If flu-like symptoms  
(i.e., fever, myalgia, and headache) arise, these may be managed using acetaminophen or  
non-steroidal anti-inflammatory agents.  

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 Prophylaxis and Treatment of Adverse Events Associated with CMP-001 
CMP-001 is designed to specifically activate TLR9, which is expressed in the endosomes of 
pDCs. Upon activation through TLR9, pDCs secrete cytokines, including type I IFNs and 
associated Th1-promoting cytokines. Given this mechanism of action, it is expected that the AE 
profile associated with CMP-001 administration may be similar to that seen after administration 
of IFNs (eg, flu-like symptoms such as fever and headaches). The recommended algorithm for 
the treatment of AEs associated with CMP-001 (Figure 2) is currently being studied in 
Regeneron-sponsored studies. The first line of treatment for hypotension unresponsive to 
supportive care such as fluids, is stress dose steroids. Additional treatment measures may include 
the use of drugs targeting specific cytokines believed to be involved in the development of 
cytokine release syndrome associated hypotension.  
 
 
 
 

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Figure 2: Recommended Treatment Algorithm for Cytokine Release Symptoms 
 
 
 

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 Pembrolizumab-Associated Adverse Events 
AEs associated with pembrolizumab exposure may represent an immunologic etiology. These 
immune-related AEs (irAEs) may occur shortly after the first dose or several months after the last 
dose of pembrolizumab treatment and may affect more than on body system simultaneously. 
Therefore, early recognition and initiation of treatment is critical to reduce complications.  Based 
on existing clinical study data, most irAEs were reversible and could be managed with 
interruptions of pembrolizumab, administration of corticosteroids and/or other supportive care. 
For suspected irAEs, ensure adequate evaluation to confirm etiology or exclude other causes. 
Additional procedures or tests such as bronchoscopy, endoscopy, skin biopsy may be included as 
part of the evaluation. Based on the severity of irAEs, withhold or permanently discontinue 
pembrolizumab and administer corticosteroids. Dose modification and toxicity management 
guidelines for irAEs associated with pembrolizumab are provided in Table 7.  
 

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Table 7 Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab 
monotherapy and IO Combinations  
General instructions: 
1. Severe and life-threatening irAEs should be treated with IV corticosteroids followed by oral steroids. Other immunosuppressive treatment should 
begin if the irAEs are not controlled by corticosteroids. 
2. Study intervention must be permanently discontinued if the irAE does not resolve or the corticosteroid dose is not ≤10 mg/day within 12 weeks of 
the last study intervention treatment.  
3. The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue at least 4 weeks. 
4. If study intervention has been withheld, study intervention may resume after the irAE decreased to ≤ Grade 1 after corticosteroid taper. 
 
irAEs 
Toxicity 
Grade 
(CTCAE v5.0) 
Action With 
Pembrolizumab 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Pneumonitis  
Grade 2 
Withhold  
•  Administer corticosteroids (initial dose of 
1 to 2 mg/kg prednisone or equivalent) 
followed by taper 
•  Add prophylactic antibiotics for 
opportunistic infections 
•  Monitor participants for signs and symptoms of 
pneumonitis 
•  Evaluate participants with suspected 
pneumonitis with radiographic imaging and 
initiate corticosteroid treatment 
Recurrent 
Grade 2,  
Grade 3 or 4  
Permanently 
discontinue 
Diarrhea/Colitis  
Grade 2 or 3 
Withhold 
•  Administer corticosteroids (initial dose of 
1 to 2 mg/kg prednisone or equivalent) 
followed by taper 
 
•  Monitor participants for signs and symptoms of 
enterocolitis (ie, diarrhea, abdominal pain, 
blood or mucus in stool with or without fever) 
and of bowel perforation (ie, peritoneal signs 
and ileus) 
•  Participants with ≥Grade 2 diarrhea suspecting 
colitis should consider GI consultation and 
performing endoscopy to rule out colitis 
•  Participants with diarrhea/colitis should be 
advised to drink liberal quantities of clear 
fluids. If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be 
substituted via IV infusion 
Recurrent 
Grade 3 or 
Grade 4 
Permanently 
discontinue 

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irAEs 
Toxicity 
Grade 
(CTCAE v5.0) 
Action With 
Pembrolizumab 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
AST or ALT 
Elevation or 
Increased 
Bilirubin 
Grade 2 a 
Withhold 
•  Administer corticosteroids (initial dose of 
0.5 to 1 mg/kg prednisone or equivalent) 
followed by taper 
•  Monitor with liver function tests (consider 
weekly or more frequently until liver enzyme 
value returned to baseline or is stable) 
Grade 3 b or 4 c 
Permanently 
discontinue 
•  Administer corticosteroids (initial dose of 
1 to 2 mg/kg prednisone or equivalent) 
followed by taper 
T1DM or 
Hyperglycemia 
New onset 
T1DM or  
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of 
β-cell failure 
Withhold d 
•  Initiate insulin replacement therapy for 
participants with T1DM 
•  Administer antihyperglycemic in 
participants with hyperglycemia 
•  Monitor participants for hyperglycemia or other 
signs and symptoms of diabetes 
Hypophysitis 
Grade 2 
Withhold 
•  Administer corticosteroids and initiate 
hormonal replacements as clinically 
indicated 
•  Monitor for signs and symptoms of hypophysitis 
(including hypopituitarism and adrenal 
insufficiency) 
Grade 3 or 4 
Withhold or 
permanently 
discontinue d 
Hyperthyroidism 
Grade 2 
Continue 
•  Treat with nonselective beta-blockers 
(eg, propranolol) or thionamides as 
appropriate 
•  Monitor for signs and symptoms of thyroid 
disorders 
Grade 3 or 4 
Withhold or 
permanently 
discontinue d 
Hypothyroidism 
Grade 2, 3 or 4 
Continue 
•  Initiate thyroid replacement hormones 
(eg, levothyroxine or liothyronine) per 
standard of care 
•  Monitor for signs and symptoms of thyroid 
disorders 
Grade 2 
Withhold 
•  Monitor changes of renal function 

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irAEs 
Toxicity 
Grade 
(CTCAE v5.0) 
Action With 
Pembrolizumab 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
Nephritis: 
grading 
according to 
increased 
creatinine or 
acute kidney 
injury 
Grade 3 or 4 
Permanently 
discontinue 
•  Administer corticosteroids (prednisone 1 
to 2 mg/kg or equivalent) followed by 
taper 
Neurological 
Toxicities 
Grade 2 
Withhold 
•  Based on severity of AE administer 
corticosteroids 
•  Ensure adequate evaluation to confirm etiology 
and/or exclude other causes 
Grade 3 or 4 
Permanently 
discontinue 
Myocarditis 
Grade 1 
Withhold 
•  Based on severity of AE administer 
corticosteroids 
•  Ensure adequate evaluation to confirm etiology 
and/or exclude other causes 
Grade 2, 3 or 4 
Permanently 
discontinue 
Exfoliative 
Dermatologic 
Conditions 
Suspected SJS, 
TEN, or 
DRESS 
Withhold 
•  Based on severity of AE administer 
corticosteroids 
•  Ensure adequate evaluation to confirm etiology 
or exclude other causes 
Confirmed SJS, 
TEN, or 
DRESS 
Permanently 
discontinue 
All Other irAEs 
Persistent Grade 2 Withhold 
•  Based on severity of AE administer 
corticosteroids 
•  Ensure adequate evaluation to confirm etiology 
or exclude other causes 
Grade 3 
Withhold or 
discontinue based 
on the event e  
Recurrent 
Grade 3 or 
Grade 4  
Permanently 
discontinue 

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irAEs 
Toxicity 
Grade 
(CTCAE v5.0) 
Action With 
Pembrolizumab 
Corticosteroid and/or Other 
Therapies 
Monitoring and Follow-up 
AE(s)=adverse event(s); ALT= alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common Terminology Criteria for Adverse Events; DRESS=Drug 
Rash with Eosinophilia and Systemic Symptom; GI=gastrointestinal; IO=immuno-oncology; ir=immune related; IV=intravenous; SJS=Stevens-Johnson Syndrome; 
T1DM=type 1 diabetes mellitus; TEN=Toxic Epidermal Necrolysis; ULN=upper limit of normal. 
Note: Non-irAE will be managed as appropriate, following clinical practice recommendations. 
a AST/ALT: >3.0 to5.0 x ULN if baseline normal; >3.0 to 5.0 x baseline, if baseline abnormal;  
bilirubin:>1.5 to 3.0 x ULN if baseline normal; >1.5 to 3.0 x baseline if baseline abnormal 
b AST/ALT: >5.0 to 20.0 x ULN, if baseline normal; >5.0 to 20.0 x baseline, if baseline abnormal; bilirubin:>3.0 to 10.0 x ULN if baseline normal; >3.0 to 10.0 x baseline 
if baseline abnormal 
c AST/ALT: >20.0 x ULN, if baseline normal; >20.0 x baseline, if baseline abnormal;  
bilirubin: >10.0 x ULN if baseline normal; >10.0 x baseline if baseline abnormal 
d The decision to withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician. If control achieved or ≤ Grade 2, 
pembrolizumab may be resumed. 
e Events that require discontinuation include, but are not limited to: encephalitis and other clinically important irAEs (eg, vasculitis and sclerosing cholangitis). 
 
 
 Dose modification and toxicity management of infusion-reactions related to pembrolizumab 
Pembrolizumab may cause severe or life-threatening infusion-reactions including severe hypersensitivity or anaphylaxis. Signs and 
symptoms usually develop during or shortly after drug infusion and generally resolve completely within 24 hours of completion of 
infusion. Dose modification and toxicity management guidelines on pembrolizumab associated infusion reaction are provided in Table 
8. 

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Table 8 Pembrolizumab Infusion Reaction Dose modification and Treatment Guidelines 
NCI CTCAE Grade 
Treatment 
Premedication at Subsequent 
Dosing 
Grade 1 
Mild reaction; infusion 
interruption not 
indicated; intervention 
not indicated 
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator. 
None 
Grade 2 
Requires therapy or 
infusion interruption but 
responds promptly to 
symptomatic treatment 
(e.g., antihistamines, 
NSAIDs, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤24 hrs 
Stop Infusion. 
Additional appropriate medical therapy may 
include but is not limited to: 
IV fluids 
Antihistamines 
NSAIDs 
Acetaminophen 
Narcotics 
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator. 
If symptoms resolve within 1 hour of stopping drug 
infusion, the infusion may be restarted at 50% of 
the original infusion rate (e.g. from 100 mL/hr to 50 
mL/hr).  Otherwise dosing will be held until 
symptoms resolve and the participant should be 
premedicated for the next scheduled dose. 
Participants who develop Grade 2 toxicity 
despite adequate premedication should be 
permanently discontinued from further study 
drug treatment 
Participant may be 
premedicated 1.5h (± 30 
minutes) prior to infusion of 
Pembrolizumab with: 
Diphenhydramine 50 mg po 
(or equivalent dose of 
antihistamine). 
Acetaminophen 500-1000 mg 
po (or equivalent dose of 
analgesic). 
Grades 3 or 4 
Grade 3: 
Prolonged (i.e., not 
rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following 
initial improvement; 
hospitalization indicated 
for other clinical 
sequelae (e.g., renal 
impairment, pulmonary 
infiltrates) 
Grade 4: 
Life-threatening; pressor 
or ventilatory support 
indicated 
Stop Infusion. 
Additional appropriate medical therapy may 
include but is not limited to: 
Epinephrine** 
IV fluids 
Antihistamines 
NSAIDs 
Acetaminophen 
Narcotics 
Oxygen 
Pressors 
Corticosteroids 
Increase monitoring of vital signs as medically 
indicated until the participant is deemed medically 
stable in the opinion of the investigator. 
Hospitalization may be indicated. 
**In cases of anaphylaxis, epinephrine should be 
used immediately. 
Participant is permanently discontinued from 
further study drug treatment. 
No subsequent dosing 
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of 
drug administration. 
For further information, please refer to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE) at 
http://ctep.cancer.gov 
 

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Other allowed dose interruption for pembrolizumab  
Pembrolizumab may be interrupted for situations other than treatment-related AEs such as 
medical / surgical events or logistical reasons not related to study therapy. Participants should be 
placed back on study therapy within 3 weeks of the scheduled interruption, unless otherwise 
discussed with the Sponsor. The reason for interruption should be documented in the patient's 
study record.

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7.0 TRIAL FLOW CHART 
 
Procedure or 
Assessment 
Screening 
(Day -21 
to -1) a 
W1 
D1 
 
W2 
D1 
 
W3 
D1 
 
W4 
D1 
 
W5 
D1 
 
W6 
D1 
 
W7 
D1 
 
W10 
D1 
Every 3 Weeks 
Post W10 (W13, 
W16 etc.) 
End of 
Treatment 
b 
30 Day 
Follow up 
visit n 
Long Term 
Survival 
Follow-upO 
CMP-001 Dose Number 
n/a 
1 
2 
3 
4 
5 
6 
7 
8 
9+ 
n/a 
n/a 
n/a 
Visit Windows 
n/a 
n/a 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
+2 
days 
+7 
days 
±7 days 
±7 days 
+7 days 
+ 1 month 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Criteria Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History, Demographics, 
Cancer History including Prior 
Cancer Medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam c 
X 
X 
 
X 
X 
 
 
X 
X 
X 
X 
 
 
Vital Signs d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
ECOG Performance Status 
X 
X 
 
X 
X 
 
 
X 
X 
X 
X 
 
 
Body Weight 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Electrocardiogram (ECG) e 
X 
X 
 
X 
 
 
 
X 
 
 
X 
 
 
Autoimmune lab panel f 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Clinical Laboratory Tests  
(hematology, serum chemistry, 
urinalysis) g 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Coagulation Tests 
(PTT & INR) h 
 
X 
 
 
 
 
 
X 
X 
X 
 
 
 
Thyroid Function Tests 
X 
 
 
X 
 
 
 
X 
 
 
X 
 
 
Research blood Samples I  
X 
X 
 
X 
 
 
X 
 
X 
- 
 
 
 
Tumor Biopsy j 
X 
 
 
X 
 
 
X 
 
X 
- 
 
 
 
Urine Pregnancy Test k 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
Disease Assessment (PET-
CT/CT)a, l 
X 
At W7D1 (or two cycles)  and then as clinically indicated 
 
Adverse Event Monitoringn 
 
Assessed continually from W1D1 through EOT +30 days 
 
Concomitant Medications 
 
Assessed continually from 28 days prior to first CMP-001 dose through EOT +30 days 
 
CMP-001 dosing m 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Pembrolizumab Dosing  
 
 
Pembrolizumab will be given according to pembrolizumab label (every 3 week) 
 
 
 

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Footnotes for Trial Flow Sheet: 
a. 
Computed tomography (CT neck/chest/abdomen/pelvis with contrast) or PET-CT scans may be performed ≤3 weeks prior to first CMP-001 dose but up to 4 weeks will be acceptable. MRI 
will only be considered in specific situation if needed.  
b. 
End-of-treatment (EOT) assessments to be performed within 7 days following removal of subject from CMP-001 treatment. Removal of a subject from CMP-001 treatment is defined as the 
time in which the Investigator decides to discontinue CMP-001 treatment for a subject. 
c. 
A full physical exam will be conducted at Screening and EOT.  The Screening physical exam may be performed up to 72 hours prior to the Week 1 Day 1 (W1D1) visit. If the full physical 
exam is performed >72 hours prior to the W1D1 visit, then a brief (symptom directed) physical exam must be performed within 72 hours prior to initiation of CMP-001.  
d. 
For the first five CMP-001 dosing visits, vital signs are to be collected prior to CMP-001 dosing, and at 30 (±15) minute intervals for 4 hours post end of CMP-001 dosing.  Based upon the 
discretion of the Investigator, observation periods can be reduced to 1 hour for individual subjects who demonstrate mild to no adverse events.  Reduced observation periods can be 
implemented only after the 6th dose of CMP-001. Vital signs should be performed prior to collection of clinical laboratory tests when they are performed at the same visit. On days that 
CMP-001 and Pembrolizumab are both given, vital signs should be collected following the administration of CMP-001. When CMP-001 intratumoral injection and pembrolizumab dosing 
fall on the same day, it is recommended that CMP-001 intratumoral injection precede pembrolizumab dosing.  
e. 
Electrocardiograms (ECGs) should be obtained at Screening and prior to CMP-001 intratumoral injection at the 1st, 3rd, and 7th CMP-001 injection (on W1D1, W3D1, W7D1), and EOT 
visit.   
f. 
Autoimmune lab panel to be collected at Screening and EOT. Table 9 
g. 
Clinical laboratory tests may be performed up to 72 hours prior to administration of CMP-001.  
h. 
Partial thromboplastin time (PTT) and international normalized ratio (INR) tests should be obtained, and results reviewed as per schedule above. These may be obtained up to 72 hours prior 
to administration of CMP-001. 
i. 
Blood samples (20 ml) for research including exploratory biomarker, immunogenicity studies, and assessment of pharmacodynamics are to be collected at screening and then on following 
days and times: 
Blood draw pre-treatment W1D1 or before, W3D1, W6D1, W10D1 prior to dosing with CMP-001 – Additional blood draw with subsequent cycles may be requested. 
j. 
Archival tumor samples should be identified at Screening, if available for potential access later. Additional tumor biopsies are optional and may be collected at other times then specified 
below at the discretion of the Investigator. Optional tumor biopsies (fresh frozen when feasible and typically FNA), will be collected prior to starting treatment on W1D1, W3D1, W6D1, 
W10D1. If pre-treatment biopsy prior to W1D1 treatment not done, it can be scheduled with W2D1 intra-tumor injection. 
k. 
In women of childbearing age, Urine pregnancy testing should be performed at Screening and prior to 1st CMP-001 injection (W1D1), prior to 4th CMP-001 injection (W4D1), prior to 7th 
CMP-001 injection (W7D1), followed by every 3 weeks prior to treatment and EOT. A negative test within 72 hours of treatment is acceptable.  
l. 
CT neck/chest/abdomen/pelvis with contrast or PET-CT scans to assess response will be at W7D1 (or after two cycles) and then as clinically indicated.  Subjects may be asked to provide 
historical scans (scans performed prior to Screening) for informational purposes prior to starting CMP-001 therapy, if available.  
m. 
The first CMP-001 injection stimulates antibody formation to the VLP of CMP-001 and will be given subcutaneously.  Subsequently, CMP-001 should be administered as close to the tumor 
as possible if intratumoral injection not possible. A window of ± 2 day is permitted for the CMP-001 dose schedule for the first weekly CMP-001 injections and a window of ±7 days is 
permitted for every 3 week CMP-001 injections.  To assure maximum effectiveness, consecutive IT injections of CMP-001 should always be administered at least 96 hours apart.  No CMP-
001 dose should be skipped.  If a CMP-001 dose needs to be delayed due to toxicity the dose should be completed as soon as the toxicity has resolved.   
n. 
The 30-Day Follow-up (+7 Days) or before new treatment is started is a safety follow up visit that may be conducted in the study clinic OR via phone.  The subject should be questioned for 
any new AEs or ConMeds, no other safety assessments are required unless the Investigator identifies a new safety concern that requires further follow-up.  This visit should occur 30 days 
(+7) after the EOT visit. SAEs that occur within 90 days of the end of treatment or before initiation of a new anti-cancer treatment, whichever comes first should also be followed and 
recorded. 
o. 
All subjects will be followed for survival for 2 years (3 + 1 month). Survival follow up may be accomplished by visit or phone contact for two years or until subject death, subject consent is 
withdrawn, subject is lost to follow up or the study is completed. 

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8.0 TRIAL PROCEDURES 
8.1 
Trial Procedures 
The Trial Flow Chart - Section 7.0 summarizes the trial procedures to be performed at each visit.  
Individual trial procedures are described in detail below.  It may be necessary to perform these 
procedures at unscheduled time points if deemed clinically necessary by the investigator. 
Furthermore, additional evaluations/testing may be deemed necessary by the Sponsor and/or 
Merck for reasons related to participant safety. In some cases, such evaluation/testing may be 
potentially sensitive in nature (e.g., HIV, Hepatitis C, etc.), and thus local regulations may require 
that additional informed consent be obtained from the participant.  In these cases, such 
evaluations/testing will be performed in accordance with those regulations. 
 Administrative Procedures 
 Informed Consent 
Consent must be documented by the participant’s dated signature or by the participant’s legally 
acceptable representative’s dated signature on a consent form along with the dated signature of the 
person conducting the consent discussion.  
A copy of the signed and dated consent form should be given to the participant before participation 
in the trial. 
The initial informed consent form, any subsequent revised written informed consent form and any 
written information provided to the participant must receive the IRB/ERC’s approval/favorable 
opinion in advance of use.  The participant or his/her legally acceptable representative should be 
informed in a timely manner if new information becomes available that may be relevant to the 
participant’s willingness to continue participation in the trial.  The communication of this 
information will be provided and documented via a revised consent form or addendum to the 
original consent form that captures the participant’s dated signature or by the participant’s legally 
acceptable representative’s dated signature. 
Specifics about a trial and the trial population will be added to the consent form template at the 
protocol level.   
The informed consent will adhere to IRB/ERC requirements, applicable laws and regulations and 
Sponsor requirements. 
 Inclusion/Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed by the investigator or qualified designee to 
ensure that the participant qualifies for the trial.  

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 Medical History 
A medical history will be obtained by the investigator or qualified designee.  Medical history will 
include all active conditions, and any condition diagnosed within the prior 10 years that are 
considered to be clinically significant by the Investigator.  Details regarding the disease for which 
the participant has enrolled in this study will be recorded separately and not listed as medical 
history.   
 Prior Medications 
The investigator or qualified designee will review prior medication use, including any protocol-
specified washout requirement, and record prior medication taken by the participant within 28 days 
before starting the trial.  Treatment for the disease for which the participant has enrolled in this 
study will be recorded separately and not listed as a prior medication.  
 Concomitant Medications 
The investigator or qualified designee will record medication, if any, taken by the participant 
during the trial.  All medications related to reportable SAEs and ECIs should be recorded as 
defined in Section 8.2. 
 Disease Details 
The investigator or qualified designee will obtain prior and current details regarding disease status.  
 Prior Treatment Details 
The investigator or qualified designee will review all prior cancer treatments including systemic 
treatments, radiation and surgeries. 
 Subsequent Anti-Cancer Therapy Status 
The investigator or qualified designee will review all new anti-neoplastic therapy initiated after 
the last dose of trial treatment.  If a participant initiates a new anti-cancer therapy within 30 days 
after the last dose of trial treatment, the 30 days Safety Follow-up visit must occur before the first 
dose of the new therapy.  Once new anti-cancer therapy has been initiated the participant will move 
into survival follow-up.  
 Assignment of Screening Number 
During the Screening process, each potential subject will be assigned a Screening Identification 
(ID) and once enrolled each subject will be assigned a unique Subject ID number. This number 
will be recorded on the subject’s eCRF pages and used to identify the subject throughout the study. 
Once any subject number is assigned, it cannot be reassigned to any other subject. Screening ID 
will be assigned sequentially and PI will assign the subject ID once patient is enrolled on the study.  
Subjects will be assigned to a dose level based on the sequence in which they are screened and 
meet eligibility criteria relative to the availability of enrollment needs.  

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 Assignment of Randomization Number 
This is an open-label study. 
 Trial Compliance (Medication/Diet/Activity/Other) 
Dosing of CMP-001 is by intratumoral injections, and is done at the study site, by qualified site 
personnel. Any deviations in planned dosing will be documented in the source documents and 
eCRF. 
 Clinical Procedures/Assessments 
 Adverse Event (AE) Monitoring 
The investigator or qualified designee will assess each participant to evaluate for potential new or 
worsening AEs as specified in the Trial Flow Chart 7.0 and more frequently if clinically indicated.  
Adverse experiences will be graded and recorded according to NCI CTCAE Version 4.0 (see 
Appendix B). Toxicities will be characterized in terms regarding seriousness, causality, toxicity 
grading, and action taken with regard to trial treatment.  
Please refer to section 8.2 for detailed information regarding the assessment and recording of AEs.   
 Full Physical Exam 
The investigator or qualified designee will perform a complete physical exam during the screening 
period.  Clinically significant abnormal findings should be recorded as medical history.  A full 
physical exam should be performed during screening,  
 Directed Physical Exam 
For cycles that do not require a full physical exam per the Trial Flow Chart, the investigator or 
qualified designee will perform a directed physical exam as clinically indicated prior to trial 
treatment administration.   
 Vital Signs 
The investigator or qualified designee will take vital signs at screening, prior to the administration 
of each dose of trial treatment and at treatment discontinuation as specified in the Trial Flow Chart 
(Section 7.0).  Vital signs should include temperature, pulse, respiratory rate, weight and blood 
pressure.  Height will be measured at screening only. 
 Electrocardiogram 
A single standard, 12-lead ECG will be obtained as per schedule in Trial Flow Chart 7.0. Assessed 
ECG parameters will include heart rate and PR, QRS, QT, and QT corrected for heart rate (QTc) 
intervals. QT will be corrected using Bazett’s (QTcB) or Fridericia’s (QTcF) formula. 

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The ECG results will be interpreted locally at the site by a delegated medically qualified person. 
If indicated, ECG findings may be confirmed by a cardiologist or internist. 
 Eastern Cooperative Oncology Group (ECOG) Performance Scale 
The investigator or qualified designee will assess ECOG status (see Appendix A) at screening, 
prior to the administration of each dose of trial treatment and discontinuation of trial treatment as 
specified in the Trial Flow Chart, Section 7.   
 
 Response/Efficacy Assessments 
Disease status will be assessed by CT or PET-CT scans. Calipers may be used to measure 
superficial cutaneous tumors. Scans will be obtained at Screening and on follow up as per Trial 
Flow Chart, Section 7. These can be performed up to five days prior to starting the next cycle of 
therapy. The assessment method used at Screening (baseline value) to determine disease 
status/progression (CT vs. PET-CT) should be used throughout the course of the study if possible.  
Antitumor activity will be described as ORR using Cheson 2007.(Cheson et al., 2007) For detail 
refer to Appendix D. Other secondary endpoints that will be assessed include complete response 
(CR), progression-free survival (PFS), best overall response (BOR), time to response (TTR), stable 
disease (SD) and duration of response (DOR).  
 
 Laboratory Procedures/Assessments 
Details regarding specific laboratory procedures/assessments to be performed in this trial are 
provided below.  
Laboratory tests for hematology, chemistry, urinalysis, and others are specified in Table 9.   

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Table 9 Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Other 
Hematocrit 
Albumin 
Blood 
Serum β-human chorionic gonadotropin† 
Hemoglobin 
Alkaline phosphatase 
Glucose 
  (β-hCG)† 
Platelet count 
Alanine aminotransferase (ALT) 
Protein 
PT (INR) 
WBC (total and differential) 
Aspartate aminotransferase (AST) 
Specific gravity  
aPTT 
Red Blood Cell Count 
Lactate dehydrogenase (LDH) 
Microscopic exam (If abnormal)  
Total thriiodothyronine (T3) 
Absolute Neutrophil Count 
Carbon Dioxide ‡ 
results are noted 
Free tyroxine (T4) 
Absolute Lymphocyte Count 
  (CO2 or biocarbonate) 
Urine pregnancy test † 
Thyroid stimulating hormone (TSH) 
 
Uric Acid 
 
Autoimmune lab panel (anti-dsDNA, ANA, 
ANCA, RF, and anti- RNP) 
 
Calcium 
 
 
 
Chloride 
 
 
 
Glucose 
 
  
 
Phosphorus 
 
  
 
Potassium   
 
  
 
Sodium 
 
  
 
Magnesium 
 
  
 
Total Bilirubin 
 
  
 
Direct Bilirubin (If total bilirubin is 
elevated above the upper limit of 
normal) 
 
 
 
Total protein 
 
 
 
Blood Urea Nitrogen 
 
 
† Perform on women of childbearing potential only. If urine pregnancy results cannot be confirmed as negative, a serum pregnancy test will be required.   
‡ If considered standard of care in your region. 
 
 
 

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 Pregnancy Testing 
At Screening, a pregnancy test will be performed on females of childbearing potential, using a 
dipstick urine test by site personnel. If positive, the test will be confirmed with a serum sample 
(the same sample submitted for chemistry panel). If a serum pregnancy test is required, pregnancy 
test results must be confirmed to be negative in order for the subject to be considered eligible for 
inclusion in the study. 
Urine pregnancy tests will also be performed for females of childbearing potential as described in 
Trial Flow Chart (Section 7.0).   
 Immunogenicity 
Plasma will be assayed for the presence of anti-pembrolizumab and anti-Qbeta capsid protein 
antibodies as per Trial Flow Chart, 7.0. 
 
 Exploratory Biomarker Sampling 
 Blood Biomarkers 
Blood samples will be assayed for immunologic studies as per Trial Flow Chart, 7.0. Sample will 
be assayed for 25 cytokines and chemokines. Blood samples will be collected and processed in Dr. 
Weiner’s lab. 
 
 Biomarkers in Tumor Tissue 
At Screening, tissue samples (archival tissue or biopsies) will be assayed for Immunoscore 
(including PD-L1 status) or another multiparameter assessment. Archival tissue should be obtained 
for Immunoscore (including PD-L1 status) assessment if available. If tumor PD-L1 status has been 
obtained prior to study entry then this value should be recorded in the eCRF. 
Tumor biopsies are not mandatory and require additional informed consent for the procedure(s). 
Intra-subject changes in immune status from pre- to post-treatment may be evaluated using 
optional tumor biopsies (fresh frozen or single cell suspension), collected prior to starting 
treatment and at >4 weeks after initiation of weekly CMP-001 treatment, and evaluated using 
Analysis of Immunoscore or other multi-parameter assessment of the tumor microenvironment. 
Descriptive exploratory statistical analyses will be conducted to assess two possible relationships: 
1) Baseline measures of tumor biomarkers relative to clinical outcomes for antitumor activity and 
2) Change in tumor biomarkers from baseline (pre-treatment with CMP-001) to on-treatment or 
post-treatment with CMP-001 as an indication of pharmacodynamic effects. 
 Assessment of  Pharmacodynamics 
Elevation of IP-10 is a biomarker of the activity of type I and II interferons, which are expected 
to be induced by treatment with CMP-001. 

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Blood samples will be obtained for assessment of concentrations of the chemokine IP-10 as per 
Trial Flow Chart, 7.0. 
 
 Other Procedures 
 Withdrawal/Discontinuation 
When a participant discontinues/withdraws prior to trial completion, all applicable activities 
scheduled for the final trial visit should be performed at the time of discontinuation.  Any adverse 
events which are present at the time of discontinuation/withdrawal should be followed in 
accordance with the safety requirements outlined in Section 8.2 - Assessing and Recording 
Adverse Events.  Participants who a) attain a CR or b) complete 24 months of treatment with 
pembrolizumab may discontinue treatment.  After discontinuing treatment following assessment 
of CR, these participants should return to the site for a Safety Follow-up Visit (described in Section 
8.1.7.4) and then proceed to the Follow-Up Period of the study (described in Section 8.1.7.5). 
 Blinding/Unblinding 
Open labeled study  
 Visit Requirements 
Visit requirements are outlined in Section 7.0 - Trial Flow Chart. Specific procedure-related details 
are provided above in Section 8.0 - Trial Procedures. 
 Screening 
As described in Trial Flow Chart, Section 7.0 
8.1.7.1.1 Screening Period 
As described in Trial Flow Chart, Section 7.0 
 Treatment Period 
As described in Trial Flow Chart, Section 7.   
 Post-Treatment Visits 
As described in Trial Flow Chart, Section 7.   
 Safety Follow-Up Visit 
The mandatory Safety Follow-Up Visit should be conducted approximately 30 days after the last 
dose of study treatment or before the initiation of a new anti-cancer treatment, whichever comes 
first.  All AEs that occur prior to the Safety Follow-Up Visit should be recorded.  Participants with 
an AE of Grade > 1 will be followed until the resolution of the AE to Grade 0-1 or until the 
beginning of a new anti-cancer therapy, whichever occurs first.  SAEs that occur within 90 days 

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of the end of treatment or before initiation of a new anti-cancer treatment, whichever comes first 
should also be followed and recorded.  
8.2 
Assessing and Recording Adverse Events 
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation participant administered a pharmaceutical product and which does not necessarily 
have to have a causal relationship with this treatment. An adverse event can therefore be any 
unfavorable and unintended sign (including an abnormal laboratory finding, for example), 
symptom, or disease temporally associated with the use of a medicinal product or protocol-
specified procedure, whether or not considered related to the medicinal product or protocol-
specified procedure.  Any worsening (i.e., any clinically significant adverse change in frequency 
and/or intensity) of a preexisting condition that is temporally associated with the use of the Merck’s 
product, is also an adverse event. 
Changes resulting from normal growth and development that do not vary significantly in frequency 
or severity from expected levels are not to be considered adverse events.  Examples of this may 
include, but are not limited to, teething, typical crying in infants and children and onset of menses 
or menopause occurring at a physiologically appropriate time. 
Merck product includes any pharmaceutical product, biological product, device, diagnostic agent 
or protocol-specified procedure, whether investigational (including placebo or active comparator 
medication) or marketed, manufactured by, licensed by, provided by or distributed by Merck for 
human use. 
Adverse events may occur during the course of the use of Merck product in clinical trials, or as 
prescribed in clinical practice, from overdose (whether accidental or intentional), from abuse and 
from withdrawal. 
● All AEs from Week 1 Day 1 (treatment initiation) through 30 days following cessation of 
study treatment must be reported by the investigator.  
● All AEs meeting serious criteria, from the time of treatment allocation/randomization through 
90 days following cessation of study treatment, or 30 days following cessation of study treatment 
if the participant initiates new anticancer therapy, whichever is earlier must be reported by the 
investigator.  
● All pregnancies and exposure during breastfeeding, from the time of treatment 
allocation/randomization through 120 days following cessation of study treatment, or 30 days 
following cessation of study treatment if the participant initiates new anticancer therapy must be 
reported by the investigator.  
● Additionally, any SAE brought to the attention of an investigator at any time outside of the 
time period specified above must be reported immediately by the investigator if the event is 
considered to be drug-related. 
Investigators are not obligated to actively seek AE or SAE or other reportable safety events in 
former study participants. However, if the investigator learns of any SAE, including a death, at 

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any time after a participant has been discharged from the study, and he/she considers the event to 
be reasonably related to the study treatment or study participation, the investigator must 
promptly notify Merck. 
 Definition of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor and to Merck 
For purposes of this study, an overdose of pembrolizumab will be defined as any dose of 1,000 mg 
or greater (≥5 times the indicated dose).  No specific information is available on the treatment of 
overdose of pembrolizumab. In the event of overdose, the participant should be observed closely 
for signs of toxicity.  Appropriate supportive treatment should be provided if clinically indicated. 
If an adverse event(s) is associated with (“results from”) the overdose of a Merck product, the 
adverse event(s) is reported as a serious adverse event, even if no other seriousness criteria are 
met. 
If a dose of Merck’s product meeting the protocol definition of overdose is taken without any 
associated clinical symptoms or abnormal laboratory results, the overdose is reported as a non-
serious Event of Clinical Interest (ECI), using the terminology “accidental or intentional overdose 
without adverse effect.” 
All reports of overdose with and without an adverse event must be reported within 24 hours to the 
Sponsor and within 2 working days hours to Merck Global Safety. (Attn: Worldwide Product 
Safety; FAX 215-661-6229) 
 Reporting of Pregnancy and Lactation to the Sponsor and to Merck 
Although pregnancy and infant exposure during breast feeding are not considered adverse events, 
it is the responsibility of investigators or their designees to report any pregnancy or lactation in a 
participant (spontaneously reported to them) that occurs during the study. 
Pregnancies and infant exposures during breastfeeding that occur after the consent form is signed 
but before treatment allocation/randomization must be reported by the investigator if they cause 
the participant to be excluded from the trial, or are the result of a protocol-specified intervention, 
including but not limited to washout or discontinuation of usual therapy, diet, placebo treatment 
or a procedure.   
Pregnancies and infant exposures during breastfeeding that occur from the time of treatment 
allocation/randomization through 120 days following cessation of Sponsor’s product, or 30 days 
following cessation of treatment if the participant initiates new anticancer therapy, whichever is 
earlier, must be reported by the investigator.  All reported pregnancies must be followed to the 
completion/termination of the pregnancy. Pregnancy outcomes of spontaneous abortion, missed 
abortion, benign hydatidiform mole, blighted ovum, fetal death, intrauterine death, miscarriage 
and stillbirth must be reported as serious events (Important Medical Events). If the pregnancy 
continues to term, the outcome (health of infant) must also be reported. 
Such events must be reported within 24 hours to the Sponsor and within 2 working days to Merck 
Global Safety. (Attn: Worldwide Product Safety; FAX 215-661-6229) 

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 Immediate Reporting of Adverse Events to the Sponsor and to Merck 
 Serious Adverse Events 
A serious adverse event is any adverse event occurring at any dose or during any use of Merck’s 
product that: 
• Results in death; 
• Is life threatening; 
• Results in persistent or significant disability/incapacity; 
• Results in or prolongs an existing inpatient hospitalization; 
• Is a congenital anomaly/birth defect; 
• Is another important medical event?  
• Note: In addition to the above criteria, adverse events meeting either of the below criteria, 
although not serious per ICH definition, are reportable to the Merck in the same timeframe 
as SAEs to meet certain local requirements. Therefore, these events are considered serious 
by Merck for collection purposes. 
• Is a new cancer (that is not a condition of the study); 
• Is associated with an overdose. 
 
Refer to Table 10 for additional details regarding each of the above criteria. 
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious adverse event, 
including death due to any cause that occurs to any participant must be reported within 24 hours 
to the Sponsor and within 2 working days to Merck Global Safety if it causes the participant to be 
excluded from the trial, or is the result of a protocol-specified intervention, including but not 
limited to washout or discontinuation of usual therapy, diet, placebo treatment or a procedure. 
For the time period beginning at treatment allocation/randomization through 90 days following 
cessation of treatment, or 30 days following cessation of treatment if the participant initiates new 
anticancer therapy, whichever is earlier, any serious adverse event, or follow up to a serious 
adverse event, including death due to any cause whether or not related to the Merck product, must 
be reported within 24 hours to the Sponsor and within 2 working days to Merck Global Safety. 
Additionally, any serious adverse event, considered by an investigator who is a qualified physician 
to be related to Merck product that is brought to the attention of the investigator at any time 
following consent through the end of the specified safety follow-up period specified in the 
paragraph above, or at any time outside of the time period specified in the previous paragraph also 
must be reported immediately to Merck Global Safety. 
All participants with serious adverse events must be followed up for outcome. 
SAE reports and any other relevant safety information are to be forwarded to the Merck Global 
Safety facsimile number:  +1-215-661-6229 

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A copy of all 15 Day Reports and Annual Progress Reports is submitted as required by FDA, 
European Union (EU), Pharmaceutical and Medical Devices agency (PMDA) or other local 
regulators. Investigators will cross reference this submission according to local regulations to the 
Merck Investigational Compound Number (IND, CSA, etc.) at the time of submission.  
Additionally investigators will submit a copy of these reports to Merck & Co., Inc. (Attn: 
Worldwide Product Safety; FAX 215-661-6229) at the time of submission to FDA. 
 Events of Clinical Interest 
Selected non-serious and serious adverse events are also known as Events of Clinical Interest (ECI) 
and must be reported within 2 working days to Merck Global Safety. (Attn: Worldwide Product 
Safety; FAX 215-661-6229). 
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any participant must be 
reported within 2 working days to Merck Global Safety if it causes the participant to be excluded 
from the trial, or is the result of a protocol-specified intervention, including but not limited to 
washout or discontinuation of usual therapy, diet, placebo treatment or a procedure. 
For the time period beginning at treatment allocation/randomization through 90 days following 
cessation of treatment, or 30 days following cessation of treatment if the participant initiates new 
anticancer therapy, whichever is earlier, any ECI, or follow up to an ECI, whether or not related 
to Merck product, must be reported within 2 working days to Merck Global Safety. 
Events of clinical interest for this trial include: 
1.  an overdose of Merck product, as defined in Section 8.2.1 - Definition of an Overdose for This 
Protocol and Reporting of Overdose to the Sponsor, that is not associated with clinical symptoms 
or abnormal laboratory results.  
2.  an elevated AST or ALT lab value that is greater than or equal to 3X the upper limit of normal 
and an elevated total bilirubin lab value that is greater than or equal to 2X the upper limit of normal 
and, at the same time, an alkaline phosphatase lab value that is less than 2X the upper limit of 
normal, as determined by way of protocol-specified laboratory testing or unscheduled laboratory 
testing.* 
*Note:  These criteria are based upon available regulatory guidance documents. The purpose 
of the criteria is to specify a threshold of abnormal hepatic tests that may require an additional 
evaluation for an underlying etiology.  
 
 Evaluating Adverse Events 
An investigator who is a qualified physician will evaluate all adverse events according to the NCI 
Common Terminology for Adverse Events (CTCAE), version 4.0. Any adverse event which 
changes CTCAE grade over the course of a given episode will have each change of grade recorded 
on the adverse event case report forms/worksheets. 
All adverse events regardless of CTCAE grade must also be evaluated for seriousness. 

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Table 10 Evaluating Adverse Events 
An investigator who is a qualified physician, will evaluate all adverse events as to: 
V4.0 CTCAE 
Grading 
Grade 1 
Mild; asymptomatic or mid symptoms; clinical or diagnostic observations only; intervention not indicated. 
Grade 2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. 
 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation or hospitalization indicated; disabling; 
limiting self-care ADL. 
 
Grade 4 
Life threatening consequences; urgent intervention indicated. 
 
Grade 5 
Death related to AE 
Seriousness 
A serious adverse event is any adverse event occurring at any dose or during any use of Merck product that: 
 
†Results in death; or 
 
†Is life threatening; or places the participant, in the view of the investigator, at immediate risk of death from the event as it occurred (Note: This does not include an 
adverse event that, had it occurred in a more severe form, might have caused death.); or 
 
†Results in a persistent or significant disability/incapacity (substantial disruption of one’s ability to conduct normal life functions); or 
 
†Results in or prolongs an existing inpatient hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay, even if the 
hospitalization is a precautionary measure for continued observation. (Note: Hospitalization for an elective procedure to treat a pre-existing condition that has not 
worsened is not a serious adverse event.  A pre-existing condition is a clinical condition that is diagnosed prior to the use of a Merck product and is documented in the 
patient’s medical history.); or 
 
†Is a congenital anomaly/birth defect (in offspring of participant taking the product regardless of time to diagnosis);or 
 
Is a new cancer (that is not a condition of the study) (although not serious per ICH definition, is reportable to the Sponsor within 24 hours and to Merck within 2 
working days to meet certain local requirements); or 
 
Is an overdose (whether accidental or intentional).  Any adverse event associated with an overdose is considered a serious adverse event for collection purposes. An 
overdose that is not associated with an adverse event is considered a non-serious event of clinical interest and must be reported within 24 hours to the Sponsor and to 
Merck within 2 working days.. 

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Other important medical events that may not result in death, not be life threatening, or not require hospitalization may be considered a serious adverse event when, 
based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes 
listed previously (designated above by a †). 
Duration 
Record the start and stop dates of the adverse event. If less than 1 day, indicate the appropriate length of time and units 
Action taken  
Did the adverse event cause Merck product to be discontinued? 
Relationship to 
Merck Product  
Did Merck product cause the adverse event? The determination of the likelihood that Merck  product caused the adverse event will be provided by an investigator who 
is a qualified physician. The investigator’s signed/dated initials on the source document or worksheet that supports the causality noted on the AE form, ensures that a 
medically qualified assessment of causality was done. This initialed document must be retained for the required regulatory time frame. The criteria below are intended 
as reference guidelines to assist the investigator in assessing the likelihood of a relationship between the test drug and the adverse event based upon the available 
information. 
The following components are to be used to assess the relationship between Merck product and the AE; the greater the correlation with the components and their 
respective elements (in number and/or intensity), the more likely Merck product caused the adverse event (AE): 
 
Exposure 
Is there evidence that the participant was actually exposed to Merck product such as: reliable history, acceptable compliance assessment (pill count, 
diary, etc.), expected pharmacologic effect, or measurement of drug/metabolite in bodily specimen? 
 
Time Course 
Did the AE follow in a reasonable temporal sequence from administration of Merck product?  
Is the time of onset of the AE compatible with a drug-induced effect (applies to trials with investigational medicinal product)? 
 
Likely Cause 
Is the AE not reasonably explained by another etiology such as underlying disease, other drug(s)/vaccine(s), or other host or environmental factors 
 

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Relationship 
The following components are to be used to assess the relationship between the test drug and the AE: (continued) 
to Merck 
Product 
(continued)  
Dechallenge 
Was Merck product discontinued or dose/exposure/frequency reduced? 
If yes, did the AE resolve or improve? 
If yes, this is a positive dechallenge. If no, this is a negative dechallenge. 
(Note: This criterion is not applicable if: (1) the AE resulted in death or permanent disability; (2) the AE resolved/improved despite continuation of 
the Sponsor’s product; or (3) the trial is a single-dose drug trial); or (4) Sponsor’s product(s) is/are only used one time.) 
 
Rechallenge 
Was the participant re-exposed to Merck product in this study? 
If yes, did the AE recur or worsen? 
If yes, this is a positive rechallenge. If no, this is a negative rechallenge. 
(Note: This criterion is not applicable if: (1) the initial AE resulted in death or permanent disability, or (2) the trial is a single-dose drug trial); or (3) 
Sponsor’s product(s) is/are used only one time). 
NOTE: IF A RECHALLENGE IS PLANNED FOR AN ADVERSE EVENT WHICH WAS SERIOUS AND WHICH MAY HAVE BEEN 
CAUSED BY MERCK PRODUCT, OR IF REEXPOSURE TO MERCK PRODUCT POSES ADDITIONAL POTENTIAL SIGNIFICANT RISK 
TO THE PARTICIPANT, THEN THE RECHALLENGE MUST BE APPROVED IN ADVANCE BY THE SPONSOR AS PER DOSE 
MODIFICATION GUIDELINES IN THE PROTOCOL. 
 
Consistency 
with Trial 
Treatment 
Profile 
Is the clinical/pathological presentation of the AE consistent with previous knowledge regarding Merck product or drug class pharmacology or 
toxicology? 
The assessment of relationship will be reported on the case report forms /worksheets by an investigator who is a qualified physician according to his/her best clinical judgment, including 
consideration of the above elements. 
Record one of the following 
Use the following scale of criteria as guidance (not all criteria must be present to be indicative of Merck product relationship). 
Yes, there is a reasonable 
possibility of Merck product 
relationship. 
There is evidence of exposure to Merck product.  The temporal sequence of the AE onset relative to the administration of Merck product is reasonable.  
The AE is more likely explained by Merck product than by another cause. 
No, there is not a reasonable 
possibility of Merck product 
relationship 
Participant did not receive the Merck  product OR temporal sequence of the AE onset relative to administration of Merck product is not reasonable 
OR the AE is more likely explained by another cause than the Merck product.  (Also entered for a participant with overdose without an associated 
AE.) 

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 Sponsor Responsibility for Reporting Adverse Events 
All Adverse Events will be reported to regulatory authorities, IRB/IECs and investigators in 
accordance with all applicable global laws and regulations.  
 
9.0 STATISTICAL ANALYSIS PLAN 
9.1 
Statistical Analysis Plan Summary 
Data analyses will be primarily descriptive in nature. Descriptive statistics will be presented for 
safety, pharmacodynamic, and exploratory endpoints. For categorical variables, summary 
tabulations of the number and percentage within each category (with a category for missing data, 
if applicable) of the parameter will be presented. For continuous variables, data will be presented 
as number (n), mean, median, standard deviation, and range (minimum and maximum). Discrete 
variables will be presented as frequencies or proportions. No formal statistical comparisons 
between dose groups will be performed. Data from all investigational sites will be pooled in the 
summary tables and analyses. Data collected on patients who are screen failures will not be 
included in any summary tables, listings, or analyses. 
A detailed statistical analysis plan (SAP) will be finalized before database lock and will 
document the analysis methods, data handling procedures, and other statistical analysis issues.  
 
9.2 
Efficacy and Toxicity Analysis 
The primary statistical analysis is based on the Bayesian optimal interval design (BOIN12) of Lin 
et al. (Lin et al., 2020).  An adaptive escalation schema (see Section 2.1.2) is used to find a dose 
with optimal clinical efficacy and acceptable toxicity.  The design has a minimum sample size of 
3 patients and a maximum of 21.  The operating characteristics of the design were estimated from 
10,000 
trials 
simulated 
with 
the 
BOIN12 
shiny 
app 
(V1.5.2.0) 
available 
at 
http://www.trialdesign.org.  True efficacy rate of 0.50 and toxicity rates 0.30 or lower are deemed 
to be clinically desirable.  Efficacy of 0.10 or less is uninteresting clinically.  The trial design has 
36% and 49% probabilities (85% total power, 15.6 expected number of patients treated) of 
selecting dose 7.5 mg or 10 mg if their efficacy rates are 0.40 and 0.50, respectively, and their 
toxicity rates are both 0.20.  The selection probabilities decrease to 70%, 47%, and 24% at higher 
toxicity rates of 0.30, 0.40, and 0.50.  Conversely, the design has a total selection probability of 
3% (type I error, 7.9 expected number of treated patients) at efficacy rates of 0.10 and toxicity 
rates of 0.20.  Selection probabilities and expected numbers of treated patients for these and other 
true efficacy and toxicity rate scenarios are summarized in Table B of APPENDIX F.  
9.3 
Analysis Populations 
Study populations will be defined as follows: 
• Safety and Efficacy Population: all subjects who receive at least 1 dose of CMP-001 and at 
least 1 recorded post-baseline assessment of objective response, assessed according to 
Cheson 2007 criteria. 

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• Pharmacodynamic Population: All subjects receiving any amount of study 
medication (placebo or active) and having any measurable IP-10 data. 
 
9.4 
Disposition 
The number and percentage of subjects who enroll into the study (sign informed consent), who are 
dosed with CMP-001, and who discontinue, and the primary reason for discontinuation will be 
summarized by dose group. 
Study completion information, including the reason for study withdrawal, if applicable, will be 
presented in a by-subject data listing. 
 
9.5 
Demographics and Other Baseline Characteristics 
Demographics and other baseline characteristics (age, sex, race, body weight, height, and BMI) 
will be summarized for each dose group using descriptive statistics (number of subjects, mean, 
standard deviation, median, minimum, and maximum for continuous variables, and the number and 
percentage of subjects for categorical variables) for the Safety Population. 
Cancer History: At Screening, lymphoma and any other cancer type history will be obtained, and 
will include date of diagnosis, and prior and concomitant therapies. Lymphoma history (age at 
diagnosis, duration of disease, prior treatments, and location of tumors) will be summarized by 
dose group using descriptive statistics for the Safety Population, and listed by subject. 
Medical and Surgical History: Medical and surgical history (excluding lymphoma history) will be 
listed by subject. Medical history will be coded using the most recent version of the MedDRA 
available at the time of study start. 
 
9.6 
Protocol Deviations 
Protocol deviations (including but not limited to failure to meet study eligibility criteria, use of 
disallowed concomitant medications, and study drug overdoses) will be presented by subject in a 
by-subject data listing. Prior to database lock all deviations will be reviewed and classified as 
major or minor. 
 
10.0 LABELING, PACKAGING, STORAGE AND RETURN OF CLINICAL SUPPLIES 
10.1 Investigational Product  
The investigator shall take responsibility for and shall take all steps to maintain appropriate records 
and ensure appropriate supply, storage, handling, distribution, and usage of investigational product 
in accordance with the protocol and any applicable laws and regulations. 
CMP-001 drug product is supplied as a 5 mg/ml concentration. CMP-001 is a colorless to pale 
yellow/brown opalescent liquid.  

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NOTE: CMP-001 may require a dilution at the investigational site to a 1.0 mg/mL using normal 
saline (refer to Pharmacy Manual for diluting instructions). Table 5 
Pembrolizumab will be provided by Merck as summarized in Table 11. 
Table 11  Product Descriptions 
Product Name & Potency 
Dosage Form 
Pembrolizumab 100 mg/ 4mL 
Solution for Injection 
 
10.2 Packaging and Labeling Information 
Supplies will be labeled in accordance with regulatory requirements. 
10.3 Clinical Supplies Disclosure 
This trial is open-label; therefore, the participant, the trial site personnel, the Sponsor and/or 
designee are not blinded to treatment. Drug identity (name, strength) is included in the label text; 
random code/disclosure envelopes or lists are not provided. 
10.4 Storage and Handling Requirements 
Clinical supplies must be stored in a secure, limited-access location under the storage conditions 
specified on the label.   
Receipt and dispensing of trial medication must be recorded by an authorized person at the trial 
site. 
Clinical supplies may not be used for any purpose other than that stated in the protocol. 
10.5 Returns and Reconciliation 
The investigator is responsible for keeping accurate records of the clinical supplies received from 
Merck or designee, the amount dispensed to and returned by the participants and the amount 
remaining at the conclusion of the trial.  
Upon completion or termination of the study, all unused and/or partially used investigational 
product will be destroyed at the site per institutional policy. It is the Investigator’s responsibility 
to arrange for disposal of all empty containers, provided that procedures for proper disposal 
have been established according to applicable federal, state, local and institutional guidelines and 
procedures, and provided that appropriate records of disposal are kept. 
 

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ECOG PERFORMANCE STATUS 
 
Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease 
performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous 
activity, but ambulatory and able to carry out work of a light or 
sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time. Ambulatory and capable of all self-care, but 
unable to carry out any work activities. Up and about more than 50% 
of waking hours. 
3 
In bed >50% of the time. Capable of only limited self-care, confined 
to bed or chair more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. 
Totally confined to bed or chair. 
5 
Dead. 
* As published in Am. J. Clin. Oncol.:  Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., 
McFadden, E.T., Carbone, P.P.: Toxicity And Response Criteria Of The Eastern Cooperative Oncology 
Group. Am J Clin Oncol 5:649-655, 1982. The Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
 
 
 
 
 
 
 
 
 
 

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COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS V4.0 (CTCAE) AND LEE 2014 CRS CRITERIA 
The descriptions and grading scales found in the revised NCI Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.0 will be utilized for adverse event reporting. 
(http://ctep.cancer.gov/reporting/ctc.html) 
 
Lee 2014 CRS grading criteria: (https://www.ncbi.nlm.nih.gov/pubmed/24876563) 
 
 
 
 
 
 
 

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CONTRACEPTIVE GUIDANCE AND PREGNANCY TESTING 
 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below)  
Women in the following categories are not considered WOCBP: 
● 
Premenarchal 
● 
Premenopausal female with 1 of the following: 
○ Documented hysterectomy 
○ Documented bilateral salpingectomy 
○ Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
● 
Postmenopausal female 
○ A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause.  
▪ 
A high follicle stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception 
or hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, confirmation with two FSH measurements in the postmenopausal range 
is required.  
○ Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-hormonal highly effective contraception methods if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
Contraception Requirements 
Male Participants: 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to one of the following during the protocol defined time frame in section 5.1:  
● Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long term and persistent basis) and agree to remain abstinent 
● Use a male condom plus partner use of a contraceptive method with a failure rate of <1% per 
year as described in Table 12 when having penile-vaginal intercourse with a woman of 
childbearing potential who is not currently pregnant. 
○ Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile 
penetration. 
 

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Female Participants: 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in Table 12 
during the protocol-defined time frame in Section 5.1.  
Table 12  
Highly Effective Contraception Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of <1% per year when used consistently and correctly. 
● Combined (estrogen- and progestogen- containing ) hormonal contraception b, c 
○ Oral  
○ Intravaginal  
○ Transdermal  
○ Injectable 
● Progestogen-only hormonal contraception b, c 
○ Oral  
○ Injectable  
Highly Effective Methods That Have Low User Dependency  
Failure rate of <1% per year when used consistently and correctly. 
● Progestogen- only contraceptive implant b, c  
● Intrauterine hormone-releasing system (IUS) b  
● Intrauterine device (IUD) 
● Bilateral tubal occlusion 
● Vasectomized partner  
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used.  
● Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant.)  
Notes:  
Use should be consistent with local regulations regarding the use of contraceptive methods for 
participants of clinical studies.  
 
a) Typical use failure rates are lower than perfect-use failure rates (i.e. when used consistently and 
correctly).  
b) If hormonal contraception efficacy is potentially decreased due to interaction with study treatment, 
condoms must be used in addition to the hormonal contraception during the treatment period and for at 
least 5 months after the last dose of study treatment. 
c) If locally required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, 
acceptable hormonal contraceptives are limited to those which inhibit ovulation.  
 

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Pregnancy Testing 
WOCBP should only be included after a negative highly sensitive urine or serum pregnancy test 
and in accordance with local requirements. Schedule as per Flow Chart 7.0 

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DESCRIPTION OF THE CHESON 2007 CRITERIA FOR 
ASSESSMENT OF DISEASE RESPONSE 
Response criteria were adapted from Cheson 2007 and Lugano 2014.  
 
CHESON 2007 
Refer to Cheson 2007 publication for complete guide on the response criteria. (Cheson et al., 
2007). Lugano classification may be consulted for any clarification especially for PET based 
response assessment. 
 
 
 

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DATA AND SAFETY MONITORING PLAN  
 
Type of Clinical Trial: 
        Investigator-initiated (UI/HCCC) 
 Investigator-initiated, participating site 
 Pilot study 
       Phase I 
  Phase I/II 
 Phase II 
 Phase III 
 Compassionate-use/Expanded Access  
       Interventional Treatment 
 Interventional Non-Treatment 
 Non-Interventional 
 
 
Study risk-level:  
 
  Level 1—low risk of morbidity or death, * <1% of death or any adverse event 
  Level 2—risk of death* <1% or any adverse event 1% – 5% 
  Level 3—risk of death* 1% – 5% or grade 4 – 5 SAE 1% – 5% 
  Level 4—risk of death* >5% or grade 4 – 5 SAE >5% 
  Drugs being used on a “compassionate” basis 
 
* Risk of death” refers specifically to 100-day treatment-related mortality 
___________________________ 
 
Reporting and Monitoring Requirements:  
All institutional investigator initiated trials (IITs), regardless of assigned risk level are subject to 
routine DSMC monitoring activities which may include but are not limited to review of signed 
consent documents, eligibility and adverse event reporting.  
 
All institutional IITs have the following reporting requirements as part of their DSMP: 
• 
Register all subjects in HCCC’s Clinical Trial Management System, OnCore 
• 
Document Adverse Events  
• 
Document protocol deviations  
• 
Provide an annual progress report to the DSMC via OnCore data export 
Selected monitoring strategy based on risk-level:  

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Risk Level 4 
Interventional treatment trials involving investigational agents or devices with a risk of death* 
(>5% or grade 4 – 5 SAE >5%), e.g. all investigator initiated INDs, most Phase I/II trials, gene 
therapy, gene manipulation or viral vector systems high-risk clinical procedures if performed 
solely for research purposes.  The use of a new chemical or drug for which there is limited or no 
available safety data in humans. 
 
Study Safety Review 
An independent study monitor and/or the DSMC Chair (or designee), will review study data 
(provided by the PI/available in OnCore) and communicate with the PI at least biannually.  A copy 
of this communication will be forwarded to the DSMC and PRMC Chairs.   
 
Additional Reporting Requirements:  
- A scanned copy of the completed eligibility checklist, with screening information and PI 
signature, will be attached in OnCore for ongoing review by DSMC staff.  
- Serious adverse events will be entered directly into an OnCore SAE report by the research 
team.  OnCore will send an automatic notification to the DSMC Chair/acting Chair and staff 
for review.  
- The DSMC utilizes a risk-based monitoring approach.  The trial's research records will be 
monitored at minimum twice per year.  Monitoring may be done more frequently depending 
on the protocol, risks to subjects, reported serious/adverse events, patient population and 
accrual rate.   Records for a minimum of 25% of subjects will be monitored for the entire 
study.    
Monitoring will involve the following: 
• review eligibility of patients accrued to the study, 
• check for the presence of a signed informed consent, 
• determine compliance with protocol’s study plan, 
• determine whether SAEs are being appropriately reported to internal and external 
regulatory agencies,  
• compare accuracy of data in the research record with the primary source documents, 
• review investigational drug processing and documentation, 
• assess cumulative AE/SAE reports for trends and compare to study stopping rules. 
 
Routine Adverse Event Reporting 
 
For non-serious Adverse Events, documentation must begin after the subject signs the Informed 
Consent Document until 30 days after the last dose of CMP-001.  Collected information should be 
recorded in the electronic/Case Report Forms (eCRF/CRF) for that subject. A description of the 
event, its severity or toxicity grade (according to NCI’s Common Toxicity Criteria (CTCAE)), 

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onset and resolved dates (if applicable), and the relationship to the study drug should be included. 
Documentation should occur in real time. The principal investigator has final responsibility for 
determining the attribution of the event as it is related to the study drug. 
 
Serious Adverse Event Reporting 
 
For any experience or condition that meets the definition of a serious adverse event (SAE), 
recording of the event must begin after signing of the informed consent and continue through the 
30 days after the last dose of CMP-001. 
Investigators must report to the DSMC any serious adverse events (SAE), whether or not they are 
considered related to the investigational agent(s)/intervention (21 CFR 312.64). SAEs must be 
reported via an OnCore SAE Report within 24 hours of learning of the event.  
 
An adverse event is considered serious if it results in ANY of the following outcomes:   
 
1. Death 
2. A life-threatening adverse event  
3. An adverse event that results in inpatient hospitalization OR prolongation of existing 
hospitalization for ≥ 24 hours  
4. A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions  
5. A congenital anomaly/birth defect.  
6. Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. (FDA, 21 CFR 
312.32; ICH E2A and ICH E6). 
 
FDA Reporting Requirements (for Sponsor-Investigators)  
It is the responsibility of the IND sponsor-investigator to comply with IND safety reporting as 
set forth in the Code of Federal Regulations, Section 312.32. This responsibility includes 
providing an annual IND report to the FDA.  
All IND safety reports must be submitted on Form 3500A  and be accompanied by Form 1571. 
The type of report (initial or follow-up) should be checked in the respective boxes on Forms 3500A 
and 1571. See Instructions for completing Form 3500A.  Please note all instance of UIHC, 
location, and faculty / staff should be redacted from supporting documentation and the 3500A. 
Instructions for completing Form 3500A.  Please note all instance of UIHC, location, and faculty 
/ staff should be redacted from supporting documentation and the 3500A. 
The submission must be identified as: 
• 
“IND safety report” for 15-day reports, or 

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• 
“7-day IND safety report” for unexpected fatal or life-threatening suspected adverse 
reaction reports, or 
• 
“Follow-up IND safety report” for follow-up information. 
For detailed explanation of the above definitions, requirements, and procedures related to IND 
application safety reports and the responsibilities of IND applications sponsors with regard to 
such reporting, refer to Guidance for Industry and Investigators: Safety Reporting Requirements 
for INDs and BA/BE Studies (PDF - 227KB) 
In addition to completing appropriate patient demographic and suspect medication information, 
the report should include the following information within the Event Description (section 5) of 
the MedWatch 3500A form: 
 
• Treatment regimen (dosing frequency, combination therapy) 
• Protocol description (and number, if assigned) 
• Description of event, severity, treatment, and outcome, if known (grading the event per 
CTCAE) 
• Supportive laboratory results and diagnostics 
• Sponsor-Investigator’s assessment of the relationship of the adverse event to each 
investigational product and suspect medication 
 
Data Monitoring and Management  
Subject Registration 
 
All studies that undergo PRMC review and/or utilize HCCC Clinical Research Services (CRS) 
resources are required to register subjects in OnCore. Each subject registration includes the 
following: 
• The subject’s IRB approved (version date) consent form and the date of their consent.  
• Date of eligibility and eligibility status (eligible, not eligible) 
• On study date and subject’s disease site (and histology if applicable) 
• On treatment date (if applicable)  
 
All subject registration information is expected to be entered into OnCore within 2 (two) business 
days after the subject’s study visit.  
 
 
Subject Data 
 
For HCCC investigator initiated trials, research staff are responsible for entering subject study data 
(data collection) into OnCore electronic case report forms (eCRFs). These eCRFs must be 
approved by the PI and statistician prior to study activation to ensure sufficient and necessary data 
acquisition. All information entered into eCRFs will be traceable to the source documents which 
are generally maintained in the subject’s file.  

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eCRF data entry needs to be timely and should be entered into OnCore as soon as possible but no 
later than 14 (fourteen) business days after the subject’s visit, including adverse events, tumor 
measurements, administration of study medication, concomitant medications, labs, and vitals. 
Physical exam assessments must be entered no later than 14 (fourteen) business days following 
completion of the physician’s clinic note in the medical record.  
Timely data entry facilitates remote monitoring of data, allows the data to progress appropriately 
through the data cleaning process, and helps prevent a backlog of data queries. 
 
Forms Monitoring 
 
OnCore eCRF data are monitored on a routine basis (dependent on accrual) to ensure all data are 
entered completely, accurately, and within time requirements outlined above. The assigned DSMC 
monitor will coordinate and complete the data monitoring review. When the time comes to monitor 
a study (based on patient accrual and assigned risk level of trial) the monitor arranges for a 
selection of cases to be reviewed from among the subjects registered in OnCore.  As part of the 
forms monitoring process, the assigned monitor will issue queries via OnCore (linked to the eCRF) 
to resolve missing, incomplete, and/or incorrect information. A member of the research team is 
expected to respond to these monitoring queries within 14 (fourteen) business days.  
 
The monitoring process can often identify misunderstandings or deficiencies in the written, 
research protocol requirements earlier in the study process and thereby improve data quality and 
reduce rework.  
 
Final Reports 
 
A summary of each subject’s data record is continually available to the PI, research staff, and 
DSMC from OnCore’s Biostat Console. The availability of this information is a valuable tool for 
the preparation of final reports and manuscripts as well as ongoing deficiency reports. 
 
 
 
 
 
 

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BOIN12 TRIAL DESIGN CHARACTERISTICS 
 
Table A. Rank-based desirability score (RDS) table for the BOIN12 design, where “E” means 
elimination.  A larger value of RDS means higher desirability, and any value of RDS is deemed 
higher than “E”.  #Pts denotes the number of evaluable patients treated at current dose; #Tox 
denotes the number of evaluable patients who experience toxicity; #Eff denotes the number of 
evaluable patients who experience efficacy. 
#Pts 
#Tox 
#Eff 
RDS 
#Pts 
#Tox 
#Eff 
RDS 
#Pts 
#Tox 
#Eff 
RDS 
#Pts 
#Tox 
#Eff 
RDS 
0 
0 
0 
62 
6 
3 
5 
74 
9 
4 
3 
4 
12 
2 
11 
106 
3 
0 
<= 0 
E 
6 
3 
6 
93 
9 
4 
4 
15 
12 
2 
12 
116 
3 
0 
1 
42 
6 
>= 4 
Any 
E 
9 
4 
5 
33 
12 
3 
<= 
3 
E 
3 
0 
2 
69 
9 
0 
<= 2 
E 
9 
4 
6 
48 
12 
3 
4 
3 
3 
0 
3 
96 
9 
0 
3 
19 
9 
4 
7 
67 
12 
3 
5 
12 
3 
1 
<= 0 
E 
9 
0 
4 
36 
9 
4 
8 
84 
12 
3 
6 
26 
3 
1 
1 
34 
9 
0 
5 
54 
9 
4 
9 
102 
12 
3 
7 
41 
3 
1 
2 
60 
9 
0 
6 
72 
9 
>= 5 
Any 
E 
12 
3 
8 
57 
3 
1 
3 
88 
9 
0 
7 
89 
12 
0 
<= 3 
E 
12 
3 
9 
73 
3 
2 
<= 0 
E 
9 
0 
8 
104 
12 
0 
4 
11 
12 
3 
10 
87 
3 
2 
1 
27 
9 
0 
9 
117 
12 
0 
5 
24 
12 
3 
11 
103 
3 
2 
2 
53 
9 
1 
<= 2 
E 
12 
0 
6 
40 
12 
3 
12 
114 
3 
2 
3 
80 
9 
1 
3 
14 
12 
0 
7 
56 
12 
4 
<= 
3 
E 
3 
>= 3 
Any 
E 
9 
1 
4 
30 
12 
0 
8 
71 
12 
4 
4 
2 
6 
0 
<= 1 
E 
9 
1 
5 
47 
12 
0 
9 
86 
12 
4 
5 
9 
6 
0 
2 
28 
9 
1 
6 
65 
12 
0 
10 
101 
12 
4 
6 
22 
6 
0 
3 
49 
9 
1 
7 
82 
12 
0 
11 
113 
12 
4 
7 
37 
6 
0 
4 
70 
9 
1 
8 
100 
12 
0 
12 
119 
12 
4 
8 
52 
6 
0 
5 
91 
9 
1 
9 
115 
12 
1 
<= 3 
E 
12 
4 
9 
68 
6 
0 
6 
110 
9 
2 
<= 2 
E 
12 
1 
4 
8 
12 
4 
10 
83 
6 
1 
<= 1 
E 
9 
2 
3 
10 
12 
1 
5 
20 
12 
4 
11 
98 
6 
1 
2 
23 
9 
2 
4 
25 
12 
1 
6 
35 
12 
4 
12 
112 
6 
1 
3 
44 
9 
2 
5 
43 
12 
1 
7 
50 
12 
5 
<= 
3 
E 
6 
1 
4 
64 
9 
2 
6 
59 
12 
1 
8 
66 
12 
5 
4 
1 
6 
1 
5 
85 
9 
2 
7 
77 
12 
1 
9 
81 
12 
5 
5 
6 
6 
1 
6 
105 
9 
2 
8 
95 
12 
1 
10 
97 
12 
5 
6 
17 
6 
2 
<= 1 
E 
9 
2 
9 
111 
12 
1 
11 
109 
12 
5 
7 
32 
6 
2 
2 
18 
9 
3 
<= 2 
E 
12 
1 
12 
118 
12 
5 
8 
46 
6 
2 
3 
39 
9 
3 
3 
7 
12 
2 
<= 3 
E 
12 
5 
9 
63 
6 
2 
4 
58 
9 
3 
4 
21 
12 
2 
4 
5 
12 
5 
10 
78 
6 
2 
5 
79 
9 
3 
5 
38 
12 
2 
5 
16 
12 
5 
11 
94 
6 
2 
6 
99 
9 
3 
6 
55 
12 
2 
6 
29 
12 
5 
12 
108 
6 
3 
<= 1 
E 
9 
3 
7 
75 
12 
2 
7 
45 
12 
>= 6 
Any 
E 
6 
3 
2 
13 
9 
3 
8 
90 
12 
2 
8 
61 
 
 
 
 
6 
3 
3 
31 
9 
3 
9 
107 
12 
2 
9 
76 
 
 
 
 
6 
3 
4 
51 
9 
4 
<= 2 
E 
12 
2 
10 
92 
 
 
 
 
 

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Table B.  Operating characteristics of the BOIN12 design. 
 
CMP-001 Dose Level 
Stop % 
7.5 mg 
10 mg 
Scenario 1  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.1  
0.1  
 
No. Pts treated  
4.2  
3.7  
 
Select %  
1.9  
1.2  
96.9  
Scenario 2  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.1  
0.2  
 
No. Pts treated  
4.2  
5.2  
 
Select %  
2.3  
10.7  
87  
Scenario 3  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.2  
0.3  
 
No. Pts treated  
5.7  
6.5  
 
Select %  
12.4  
26.1  
61.5  
Scenario 4  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.3  
0.4  
 
No. Pts treated  
6.8  
7.5  
 
Select %  
26.3  
40.3  
33.4  
Scenario 5  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.4  
0.5  
 
No. Pts treated  
7.6  
8  
 
Select %  
35.8  
48.8  
15.4  
Scenario 6  
 
 
 
DLT rate  
0.2  
0.2  
 
Efficacy rate  
0.5  
0.5  
 
No. Pts treated  
8.7  
7.2  
 
Select %  
52.3  
38.2  
9.5  
Scenario 7  
 
 
 
DLT rate  
0.3  
0.3  
 
Efficacy rate  
0.4  
0.5  
 
No. Pts treated  
7.8  
6.4  
 
Select %  
40.3  
29.5  
30.1  
Scenario 8  
 
 
 
DLT rate  
0.3  
0.3  
 
Efficacy rate  
0.5  
0.5  
 
No. Pts treated  
8.9  
5.7  
 

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CMP-001 Dose Level 
Stop % 
7.5 mg 
10 mg 
Select %  
53.9  
22.9  
23.2  
Scenario 9  
 
 
 
DLT rate  
0.4  
0.4  
 
Efficacy rate  
0.4  
0.5  
 
No. Pts treated  
7.7  
4.4  
 
Select %  
35.3  
11.9  
52.7  
Scenario 10  
 
 
 
DLT rate  
0.4  
0.4  
 
Efficacy rate  
0.5  
0.5  
 
No. Pts treated  
8.6  
3.9  
 
Select %  
44.8  
9.1  
46.1  
Scenario 11  
 
 
 
DLT rate  
0.5  
0.5  
 
Efficacy rate  
0.4  
0.5  
 
No. Pts treated  
7.1  
2.7  
 
Select %  
21.3  
3  
75.6  
Scenario 12  
 
 
 
DLT rate  
0.5  
0.5  
 
Efficacy rate  
0.5  
0.5  
 
No. Pts treated  
7.8  
2.5  
 
Select %  
26.8  
2.5  
70.7  
 
 
 

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