An Open-label Phase 1b/2a Study of NT-I7 (Efineptakin Alfa) in Combination With Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors
Phase: PHASE1
Conditions: Any Advanced Solid Tumors, Triple Negative Breast Cancer, Non Small Cell Lung Cancer, Small Cell Lung Cancer, Microsatellite Stable Colorectal Cancer, Pancreatic Cancer, Ovarian Cancer
Sponsor: NeoImmuneTech

Protocol Number: NIT-110 
Official Title: An Open-label Phase 1b/2a Study of NT-I7 (Efineptakin Alfa) in Combination With 
Pembrolizumab in Subjects With Relapsed/Refractory Advanced Solid Tumors 
NCT Number: NCT04332653 
 
Document Date: 26 October 2023 

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
1 
 
 
 
 
An Open-label Phase 1b/2a Study of NT-I7 (efineptakin alfa) in Combination with 
Pembrolizumab in Subjects with Relapsed/Refractory Advanced Solid Tumors 
 
 
Protocol Number:  
NIT-110 (KEYNOTE A60) 
Version:  
v7.0 (incorporating Amendment 6) 
Products:  
NT-I7 (also known as efineptakin alfa, rhIL-7-hyFc)  
Pembrolizumab   
 
Abbreviated Title:  
NT-I7 (efineptakin alfa) in Combination with 
Pembrolizumab in Advanced Solid Tumors 
 
Study Phase:  
Phase 1b/2a 
IND Number: 
 
 
      146869 
IND Sponsor:  
NeoImmuneTech, Inc.  
 
2400 Research Blvd, Suite 250 
 
Rockville, MD 20850 
 
NIT110@neoimmunetech.com 
www.neoimmunetech.com 
Date of Protocol:                                     26 Oct 2023 
 
 
 
 

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
2 
 
Sponsor Signatory 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
 
 
Sponsor (print name) 
 
 
 
 
 
 
Title 
 
 
 
 
 
Date (dd-mmm-yyyy) 
 
26 Oct 2023

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
3 
 
Signature of Investigator 
  
 
 
Protocol Title:  
An Open-label Phase 1b/2a Study of NT-I7 (efineptakin alfa) in 
Combination with Pembrolizumab in Subjects with Relapsed/Refractory 
Advanced Solid Tumors 
Protocol Number:       NIT-110 (KEYNOTE A60) 
Version:  
                v7.0, dated 26 October 2023 
 
This protocol is a confidential communication of NeoImmuneTech, Inc. I confirm that I have 
read this protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practice and the applicable laws and regulations. 
Acceptance of this document constitutes my agreement that no unpublished information 
contained herein will be published or disclosed without prior written approval from the 
Sponsor. 
 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy by e-mail to 
NIT110@neoimmunetech.com 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator: 
 
 
Date: 
 
 
 
 
 
Printed Name:  
 
 
 
 
 
 
 
Investigator Title:  
 
 
 
 
Name/Address of Center:  
 
 
 
 
 
 
 

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
4 
 
 
Protocol Revisions 
 
Version 
Date 
Revisions 
1.0 
03 Dec 2019 
-- 
2.0 
04 Feb 2020 
Amendment#1 (Summary of Changes) 
 
• 
Added a third dose level (1200 µg/kg IM Q6W) if safety will permit, 
per recommendation from FDA. 
• 
With the additional dose level, number of subjects in the Phase 1b 
has been increased from up to 12 to up to 18. Total number of 
subjects in the study increased from up to 162 to up to 168. 
• 
Study design and treatment schema have been changed to introduce 
new dose level and more subjects. 
• 
Provided examples of dose levels for dose de-escalation if needed. 
• 
Rationale for dose selection has been updated to provide justification 
for the higher dose. 
• 
Provided more clarity on endpoint correlation for the primary 
objectives. 
• 
Objective and endpoints now have the descriptive methodology and 
statistical analysis details. 
• 
NT-I7 pharmaceutical information and name of active ingredient 
have been updated for consistency with vial label. 
• 
Storage and handling instructions of NT-I7 have been updated. 
• 
Updated DLT criteria per FDA recommendations. 
• 
PK will be collected from all subjects in Phase 1b and Phase 2a, per 
FDA recommendation. Earlier PK was planned only for subjects in 
Phase 1b. Hence, Table 5 has been modified accordingly. 
• 
Immunogenicity sample collection: Additional collection of pre-dose 
C2D1 has been newly added. Frequency of collection after cycle 5 
have changed to every 4 cycles. Sample collection will be done in all 
Phase 1b, and in up to 10 subjects per arm in Phase 2a. Section 7.4 
Schedule of Assessments have been modified accordingly. 
• 
Additional blood sample collection for TCR seq analysis have been 
added to go with corresponding biopsy-mandated subjects. 
• 
PK assessment in the Schedule of Assessments mentions to refer to 
Table 5. 
• 
Section 9 under concomitant therapy has been divided into two 
sections 9.1 – Prohibited Medications/Treatment and 9.2 – 
Medications Used with Caution.  
• 
Information on QT/QTc drugs have been clarified and moved under 
Section 9.2. 

CONFIDENTIAL 
 
 
 
 
 
 
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• 
Second biopsy have been clarified to indicate on-treatment biopsy in 
Section 12.1. Additional mention on the CD4+ and TCR repertoire 
analysis has been added.  
• 
Sample size and power calculation updated to reflect increased 
number of subjects. 
• 
DSMC meeting frequency, and updated information has been 
provided in Section 15.4. 
Statistical analysis plan summary has been updated. Secondary end 
point details have been updated. 
 
Administrative Changes 
 
• 
Protocol Number changed from NIT-110/PNA60 to NIT-110 
(PNA60). 
• 
Changed version number and date. 
• 
Added IND number. 
• 
Added study specific email ID. 
• 
Mention of MK-3475 IB has been changed to Pembrolizumab IB.  
• 
Expedited AE reporting (Section 11.3) email and phone number 
have been updated. 
• 
Data management and reporting in Section 14, has been updated 
providing the term Site Operations Manual, instead of Study 
Procedures Manual. Study Oversight information has been clarified. 
Subject enrollment and EDC information updated to refer to the 
EDC Completion Guidelines.  
 
 
 
3.0 
01 Jun 2021 
• 
Removed the alternate name for NT-I7, Hyleukin-7. 
• 
Included the International Nonproprietary Name for NT-I7, 
efineptakin alfa. 
• 
Provided clarification on the Exclusion criterion # 2 for prior 
treatment washout. 
• 
Updated section 2.4.1.2.3 to include recent studies under the NT-I7 
clinical development program. 
• 
Included additional pharmacokinetic assessment timepoints. 
• 
Provided additional clarification on dose modifications to manage 
AEs. 
• 
Provided clarification on medications that should be used with 
caution while on treatment. 
• 
Updated reporting criteria for AESI reporting to Sponsor and safety 
designee. 
• 
Provided clarification on MRI brain imaging conduct. 
• 
Updated dose modification and toxicity management of immune-
related AEs associated with NT-I7 and pembrolizumab. 

CONFIDENTIAL 
 
 
 
 
 
 
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• 
Provided clarification on dose interruption for pembrolizumab and 
removed inconsistencies in duration of treatment interruptions due to 
nontreatment-related events or unforeseen circumstances.   
• 
Incorporated dose modification guidance to address recent 
pembrolizumab safety communications. 
• 
Included clarification on clear communication of timing of reporting 
of ECI from site to Sponsor. 
• 
Included Biomarker Cohort to study design in subjects with CPI 
naïve R/R ovarian cancer. 
• 
Updated reporting criteria for SAE for clarity. 
• 
Updated Appendix A  
• 
Clarification on enrolment during interim analysis at the end of 
Stage I.   
• 
Removed reference to a Table 8 
 
 
4.0 
26 Jul 2021  
Amendment #3 (Summary of Changes) 
• 
Primary endpoint updated to iRECIST. 
• 
Applicable updates to iRECIST and RECIST throughout the 
document.  
• 
Rationale of amending iRECIST added in the statistical section. 
• 
iRECIST updated in the Appendix. 
• 
References updated as applicable. 
5.0 
17 Mar 2022 
• 
Updated header from “KEYNOTE A60” to “KEYNOTE PNA60” 
• 
Updated 178 subjects to 238 subjects 
• 
Clarified that Arms I, II, III, IV, and V will follow the Simon’s 2-
stage minimax design 
• 
Added that Arms IVa and Va will not follow the Simon’s two-stage 
minimax design 
• 
Clarified that the Biomarker Cohort (Ovarian Cancer) will not 
follow the Simon’s two-stage minimax design 
• 
Removed “5 arms” 
• 
Added “indications include” 
• 
Added Arms IVa and Va will enroll up to 25 evaluable subjects each 
with dose administration 
• 
Added Arms IVa, MSS-CRC, and Va, PaC, to Dose Expansion 
Phase 2a 
• 
Added Arms IVa and Va to Inclusion Criteria #5 
• 
Add/Clarified OC to Inclusion Criteria #5 
• 
Added patient specific criteria for Arms IVa and Va to Dose 
Expansion Phase 
• 
Added to Exclusion #2 that subjects with endocrine related AEs <2 
that require treatment may be eligible 
• 
Updated Study Rationale to justify the basis for adding arms IVa and 
Va 
• 
Added Background 
• 
Replaced “Pembrolizumab IB” with “Investigator’s Brochure” 

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
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• 
Replaced “pembrolizumab” with “MK-3475” 
• 
Deleted “and regardless or tumor type” 
• 
Added Arms IVa and Va throughout the protocol where applicable 
• 
Clarified text regarding the life of administration to “completion of 
35 cycles of administration (approximately 2 years)” with NT-I7 and 
pembrolizumab 
• 
Updated “5.5 Biomarker Cohort” to “5.5 Subject Expansion” 
• 
Updated “5.5 Biomarker Cohort” to “5.6” 
• 
Updated the Study Schema 
• 
Added Arms IVa and Va to footnote 21 
• 
Clarified in footnote 24 that Biomarker Cohort applies to NT-I7 
increase to 1200 ug/kg on C5D1 
• 
Added in footnote 24 that Arms IVa and Va apply to NT-I7 increase 
to 1200 ug/kg on C5D1 
• 
Added to footnote 25 Arms IVa and Va 
• 
Added footnote 26 as option applicable to Arms IVa and Va 
• 
Moved “Dose re-escalation” to another section 
• 
Replaced PRA Health Sciences with ICON 
• 
Clarified ICON contact numbers 
• 
Deleted the requirement for a MRI brain scan with Arms I, II, and III 
at initial tumor imaging 
• 
Added that a MRI brain scan is preferred with Arms I, II, and III at 
initial tumor imaging 
• 
Clarified which arms will and will not have an interim analysis 
• 
Clarified which arms the DMC will conduct an interim analysis 
• 
Updated “1st tumor assessment” to “2nd tumor assessment” 
• 
Updated 150 subject to 210 subjects for phase 2a efficacy 
• 
Deleted “in each Phase 2a arm” 
• 
Added “Description analysis will be performed for Arms IVa and Va 
at the end of the enrollment” 
• 
Add “evaluable” 8 and 17 subjects when applicable 
• 
Added the missing word “protocol” to section 11 
• 
Updated references 
 
Administrative Changes 
• 
Updated version number and date 
• 
Updated Table of Contents 
• 
Corrected typos, spelling and grammatical errors throughout 
• 
Administrative changes to dates, version numbers, and colors 
• 
Updated the title of sponsor signatory 
 
6.0 
17 Nov 2022 
Amendment #5 (Summary of Changes) 
• 
Throughout: Minor grammatical corrections 
• 
Administrative: Updated date, version, and NIT signatory 
• 
Section 1.1 Synopsis and Section 4.1 Inclusion Criteria: Added 
language indicating that MMR-deficient subjects in Arms IV 

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and IVa (CPI-naïve R/R MSS-CRC) specifically are not eligible 
for the study. 
• 
Section 1.1: Corrected numbering of Arms in Phase I (I, II, III, 
IV and V rather than I, II, III, V and V).  
• 
Sections 1.1, 2.3, 3, 4.1, 6.4, 13.1, 15.5: Removed “v.” from 
RECIST v1.1, to align with how RECIST 1.1 is written in the 
appendix. 
• 
Sections 1.1 and 5.7: Updated Study Schema to clarify the 
dosing for Biomarker Cohort. 
• 
Sections 1.1 and 5.8: Updated Study Treatment figure to include 
C6D15 optional biopsy, pembrolizumab only arrows, and 
iRECIST language. 
• 
Section 2.4.1.2: Updated language to indicate that GX-I7-CA-
003 study is complete. 
• 
Section 2.4.1.2.3: Added statement that NIT-104 has closed to 
further enrollment and updated the title, location, and study 
design of NIT-109. 
• 
Section 3: Added Biomarker Cohort to opening paragraph about 
study objectives. 
• 
Section 4, Subject Selection: Revised language to remove 
possibility of Sponsor approval of protocol waivers or 
exemptions for recruitment/enrollment criteria. 
• 
Section 4.5: Revised language to indicate that subject must 
adhere to contraception requirement from time of consent rather 
than the day of study medication. 
• 
Section 5.2: Updated to indicate that GX-I7-CA-003 study is 
complete. 
• 
Section 5.4: Defined the RP2D for dose expansion. 
• 
Section 6.1, Table 3: Added sections 5.4 and 5.6 to footnote for 
referencing dose levels. 
• 
Section 6.1.1: Corrected NT-I7 chemical formula. 
• 
Section 6.4: Divided and rearranged section into three 
subsections for clarity and readability.  
• 
Section 6.5 Study Treatment Beyond Progression: Revised 
iRECIST language for clarity. 
• 
Section 6.6 Duration of Follow-Up and End of Study: Added 
language including subjects who have completed all 35 cycles 
of treatment, included iRECIST, and revised 6 weeks to 9 
weeks. 
• 
Section 7.1: Clarified language around confirmed PD and ICF. 
• 
Section 7.4 Schedule of Assessments:  
o 
Revised language for CT/MRI Tumor Evaluation by 
RECIST 1.1 and iRECIST 
o 
Moved merged cells for general imaging information 
to start at Cycle 4, including a mark for imaging at 
Cycle 2 Day 1 
o 
In Footnote 16, added language indicating that patients 
do not need to undergo additional imaging if it is less 
than 4 weeks after the previous scan. 

CONFIDENTIAL 
 
 
 
 
 
 
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(KEYNOTE PNA60) 
          
 
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o 
Clarified language, including removing language about 
optional C6D15 biopsy from footnote 21, as it is also 
in footnote 24.  Also, moved footnote 21 from general 
TCR-seq Analysis heading to C1D1. 
o 
In Footnote 26, changed V to Va 
o 
Added AE review at screening and revised footnote 9, 
linking section 11 
o 
Added Footnote 27 to the C1D2 Adverse Events 
Review to clarify that this visit can be performed by 
telephone. 
o 
Separated Footnote 23 into two footnotes (23 for 
Safety Followup and newly created 28 for Survival 
Followup) to clarify that Survival Followup is by 
telephone only and performed every 90 days starting 
90 days after Safety Followup Day 90, and added 
“outcome of any ongoing adverse events” to the 
rationale for the followup. Clarified that Safety 
Followup visits will be performed in the clinic only. 
o 
Separated Footnote 17 into two footnotes; 17 retained 
screening biopsy language and was moved from the 
Tumor Biopsy heading to the screening timepoint in 
the table. The remainder of the footnote became new 
footnote 29, which is attached to the Tumor Biopsy 
C2D8 timepoint in the table. Deleted the language 
about pre-treatment biopsies needing to be taken within 
28 days of dosing.  
o 
Added C2D15±7days timepoint to align with language 
in footnotes 21 and 29 and clarified language in 
footnote 29 to change C2D22 to C3D1.  
• 
Section 9.1 Prohibited Medications/Treatment: Revised 
language to include attenuated vaccines and to add restriction 
out to 90 days following the last dose of study drug.  
• 
Section 11.4 Adverse Events of Special Interest in NT-I7: 
Revised language for clarity, to match language used in other 
NT-I7 protocols, removing reference to Hy's law for drug-
induced liver injury. 
• 
Section 13.3 End of Treatment and Follow-Up Tumor Imaging: 
iRECIST is not optional in this study; removed language 
suggesting that it was dependent on investigator choice. Revised 
imaging schedule from every 12 weeks to 90 days (+/- 7 days). 
• 
Section 15.4 Data Monitoring Committee (DMC): Changed 
name from Data and Safety Monitoring Committee to Data 
Monitoring Committee and revised descriptive language about 
the committee purpose and procedures. 
• 
Appendix A: Deleted bullets about central imaging vendor, 
because this study does not use one. 
7.0 
26 Oct 2023 
Amendment #6 (Summary of Changes) 
 
• 
Throughout: Minor corrections to grammar and formatting. 

CONFIDENTIAL 
 
 
 
 
 
 
      NIT-110 
(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
10 
• 
Administrative: Updated version and date 
• 
Section 1.1 Synopsis: Added inclusion criterion #9 indicating 
that an ECG with QTcF <470 ms is required and that pts with 
QTcF equal to or greater than 470 ms will require clearance by a 
local cardiologist. Additional precautions for myocarditis are 
included due to two fatal events in NIT-sponsored studies with 
NT-I7 in combination with checkpoint inhibitors. 
• 
Section 2.3 Study Rationale: Efficacy data for Arms IV and V 
was updated with data from the completed cohorts and 
references have been added.  
• 
Section 2.4.1.2.2 Completed Study GX-I7-CA-003: Table 1 has 
been deleted, as this information is available in the NT-I7 
Investigator’s Brochure. 
• 
Section 2.4.1.3 Benefit-Risk Conclusions: Have updated in 
accordance with NT-I7 IB v10. 
• 
Section 3, Objectives and Endpoints: Revised the method that 
will be used to identify tumor-infiltrating lymphocytes for 
compliance with Good Clinical Laboratory Practice (GCLP).  
• 
Section 4 Subject Selection: Added language stating that 
informed consent is considered to be withdrawn for patients 
who do not meet eligibility criteria after screening is completed 
("screen failure"). 
• 
Section 4.1 Inclusion Criteria: Added inclusion criterion #9 
indicating that an ECG with QTcF <470 ms is required and that 
pts with QTcF equal to or greater than 470 ms will require 
clearance by a local cardiologist. Additional precautions for 
myocarditis are included due to two fatal events in NIT-
sponsored studies with NT-I7 in combination with checkpoint 
inhibitors. 
• 
Section 6.4.2 Subject Discontinuation/Withdrawal from Study: 
Added language indicating that a subject may be withdrawn 
from the study if they do not meet eligibility criteria ("screen 
failure"). 
• 
Section 6.4.2 Subject Discontinuation/Withdrawal from Study. 
Added an option for subjects to partially withdraw from active 
participation in the study and scheduled visits, but allow status 
followup via telephone or medical record review. 
• 
Section 7.1 Informed Consent: Added language to clarify that 
informed consent must be obtained prior to performing any 
study-specific procedures. 
• 
Section 7.4, Schedule of Assessments:  
o 
Removed prior and concomitant medications from 
Survival Follow-up to align with Footnote 4. 
o 
Added adverse events review to 90-day Safety Follow-
up visit and revised Footnote 9 to indicate review of 
AEs and SAEs through 30-day safety follow-up and 
SAEs only from 30-days to 90-day safety follow-up 
visit. 

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(KEYNOTE PNA60) 
          
 
V7.0 incorporating Amendment 6, 26Oct2023 
11 
o 
Revised 12-lead EKG row to add testing at C5D1 and 
Subsequent Cycles. Additional precautions for 
myocarditis are included due to two fatal events in 
NIT-sponsored studies with NT-I7 in combination with 
checkpoint inhibitors. 
o 
Added row for Cardiac Enzymes with testing at 
Screening, C1D1, C5D1, Subsequent Cycles, and End 
of Treatment. Additional precautions for myocarditis 
are included due to two fatal events in NIT-sponsored 
studies with NT-I7 in combination with checkpoint 
inhibitors. 
o 
Added rows for Echocardiogram and Cardiologist visit 
at Screening, C1D1, C5D1, Subsequent Cycles, and 
End of Treatment. Additional precautions for 
myocarditis are included due to two fatal events in 
NIT-sponsored studies with NT-I7 in combination with 
checkpoint inhibitors. 
o 
Revised Footnote 10 to incorporate guidance for serum 
cardiac enzyme testing and increase frequency of 
duplicate EKG to every 4 weeks. Additional 
precautions for myocarditis are included due to two 
fatal events in NIT-sponsored studies with NT-I7 in 
combination with checkpoint inhibitors. 
o 
Added Footnote 30 to include procedures for 
echocardiogram and cardiologist visit if ECG or serum 
cardiac enzyme levels are clinically significant. This 
change is in response to two fatal events in NIT-
sponsored studies with NT-I7 in combination with 
checkpoint inhibitors. 
• 
Section 8.1 Dose Modification of NT-I7: Revised the guidance 
for myocarditis; rather than withholding until resolved at Grade 
1, any grade of myocarditis will result in NT-I7 discontinuation. 
Additional precautions for myocarditis are included due to two 
fatal events in NIT-sponsored studies with NT-I7 in 
combination with checkpoint inhibitors.   
• 
Section 8.2 Dose Modification of Pembrolizumab: Updated 
information, including Tables 4 and 5, to match the guidance in 
the pembrolizumab IB v23. 
• 
Section 11.1 Adverse Events and Potential Risks List: Deleted 
section 11.1.1 and the associated table, and revised language to 
refer to the latest version of the NT-I7 IB for adverse events and 
potential risks. 
• 
Section 11.3.1 Time Period and Frequency for Collecting AE, 
SAE and Other Reportable Safety Event Information: Deleted 
mention of Events of Clinical Interest from the guidance about 
all AEs, as these are considered SAEs. 
• 
Section 11.3.2 Expedited Reporting Guidelines: Revised 
window of time for reporting a death via both expedited and 
routine reporting from 30 to 90 days after last administration of 
study agent. Revised classification of death due to PD to be 

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“Grade 5 “Malignant neoplasm progression” under the system 
organ class (SOC) ‘Neoplasms benign, malignant and 
unspecified (incl cysts and polyps)’”. 
• 
Section 11.6 Events of Clinical Interest (ECI) in 
Pembrolizumab: Removed “non-serious and serious” language, 
to clarify that ECIs must be reported as serious.  
• 
Section 11.8 Pregnancy: Revised reporting window for 
pregnancy from 120 days to 90 days after the last dose of study 
treatment, for consistency with section 11.3.1.  
• 
Section 14.1 Responsibility for Data Submission: Added 
language clarifying expectations surrounding data submission.  
• 
Section 14.3 Study Oversight: Added language clarifying 
expectations about conduct and cooperation with study 
oversight and access to study-related records, including a 
statement that protocol waivers will be prohibited. 
• 
Signature of Investigator page: Moved before Protocol 
Revisions to align with NIT protocol formatting.  
 
 
 
 
 

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Contents 
Signature of Investigator ...............................................................................................................3 
1. 
Protocol Summary ........................................................................................................17 
1.1. 
Synopsis ..........................................................................................................................17 
2. 
Introduction ...................................................................................................................30 
2.1. 
PD-1 Blockade and Solid Tumors ..................................................................................30 
2.1.1. 
Triple Negative Breast Cancer ........................................................................................30 
2.1.2. 
Non-small Cell Lung Cancer ..........................................................................................31 
2.1.3. 
Small Cell Lung Cancer ..................................................................................................32 
2.1.4. 
Colorectal Cancer............................................................................................................33 
2.1.5. 
Pancreatic Cancer............................................................................................................33 
2.1.6. 
Ovarian Cancer ...............................................................................................................33 
2.2. 
Background .....................................................................................................................34 
2.3. 
Study Rationale ...............................................................................................................36 
2.4. 
Agents .............................................................................................................................37 
2.4.1. 
NT-I7 (aka efineptakin alfa, rhIL-7-hyFc) ......................................................................37 
2.4.2. 
Pembrolizumab Background ...........................................................................................43 
2.4.2.1. Pharmaceutical and Therapeutic Background ................................................................43 
3. 
Objectives and Endpoints ............................................................................................46 
4. 
Subject Selection ...........................................................................................................52 
4.1. 
Inclusion Criteria ............................................................................................................52 
4.2. 
Exclusion Criteria ...........................................................................................................54 
4.3. 
Inclusion of Women and Minorities ...............................................................................56 
4.4. 
Meals and Dietary Restrictions .......................................................................................56 
4.5. 
Contraception ..................................................................................................................56 
5. 
Study Design ..................................................................................................................58 
5.1. 
Overall Design ................................................................................................................58 
5.2. 
Rationale for Dose Selection ..........................................................................................59 
5.3. 
Dose Escalation (Phase 1b).............................................................................................59 
5.4. 
Dose Expansion (Phase 2a).............................................................................................60 
5.5. 
Subject Expansion (Arm IVa and Va) ............................................................................61 
5.6. 
Biomarker Cohort ...........................................................................................................61 
5.7. 
Study Schema .................................................................................................................62 
5.8. 
Treatment Schema ..........................................................................................................63 
6. 
Study Treatment ...........................................................................................................64 
6.1. 
Study Treatment Administration ....................................................................................64 
6.1.1. 
NT-I7...............................................................................................................................64 
6.1.2. 
Pembrolizumab ...............................................................................................................65 
6.2. 
Dose-Limiting Toxicity ..................................................................................................66 
6.2.1. 
DLT criteria ....................................................................................................................66 
6.3. 
Subject Replacement.......................................................................................................67 

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6.4. 
Discontinuation of Study Intervention, Subject 
Discontinuation/Withdrawal, and Study Termination ....................................................67 
6.4.1. 
Discontinuation of Study Intervention ............................................................................67 
6.4.2.  Subject Discontinuation/Withdrawal from Study .........................................................69 
6.4.3.  Study Termination ............................................................................................................70 
6.5. 
Study Treatment Beyond Progression ............................................................................70 
6.6. 
Duration of Follow-Up and End of Study ......................................................................71 
7. 
Study Procedures and Assessments ............................................................................72 
7.1. 
Informed Consent ...........................................................................................................72 
7.2. 
Study Procedures ............................................................................................................72 
7.3. 
NT-I7 Pharmacokinetics .................................................................................................72 
7.4. 
Schedule of Assessments ................................................................................................74 
8. 
Dosing Delays/ Dose Modifications .............................................................................79 
8.1. 
Dose Modification of NT-I7 ...........................................................................................79 
8.1.1. 
Criteria to Resume for Dosing ........................................................................................80 
8.2. 
Dose Modification of Pembrolizumab ............................................................................81 
8.2.1. 
Dose Modification and Toxicity Management of Infusion-
reactions Related to Pembrolizumab ..............................................................................87 
8.2.2. 
Other Allowed Dose Interruptions for Pembrolizumab ..................................................88 
9. 
Concomitant Therapy...................................................................................................89 
9.1. 
Prohibited Medications/Treatment .................................................................................89 
9.2. 
Medications Used with Caution ......................................................................................90 
10. 
Rescue Medications and Supportive Care ..................................................................90 
11. 
Adverse Events: Assessing and Reporting Requirements.........................................91 
11.1. 
Adverse Events and Potential Risks List ........................................................................91 
11.2. 
Adverse Event Characteristics ........................................................................................91 
11.3. 
Expedited Adverse Event Reporting...............................................................................92 
11.3.1. Time Period and Frequency for Collecting AE, SAE and Other 
Reportable Safety Event Information .............................................................................92 
11.3.2. Expedited Reporting Guidelines .....................................................................................93 
11.3.3. Routine Adverse Event Reporting ..................................................................................93 
11.4. 
Adverse Events of Special Interest in NT-I7 ..................................................................93 
11.5. 
Treatment of Overdose for NT-I7 ...................................................................................94 
11.6. 
Events of Clinical Interest (ECI) in Pembrolizumab ......................................................94 
11.7. 
Treatment of Overdose for Pembrolizumab ...................................................................95 
11.8. 
Pregnancy........................................................................................................................95 
11.9. 
Use in Nursing Women...................................................................................................96 
11.10. 
Secondary Malignancy ...................................................................................................96 
11.11. 
Second Malignancy.........................................................................................................96 
12. 
Correlative Studies and Biomarker Evaluations .......................................................97 
12.1. 
Tumor Tissue for Biomarker Analyses ...........................................................................97 
12.2. 
Planned Peripheral Blood Biomarker Analyses..............................................................97 

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12.3. 
Other Procedures: Biopsy (core needle, punch, or surgical 
excision) ..........................................................................................................................98 
13. 
Tumor Imaging and Assessment of Disease ...............................................................99 
13.1. 
Initial Tumor Imaging .....................................................................................................99 
13.2. 
Tumor Imaging During the Study .................................................................................100 
13.3. 
End of Treatment and Follow-up Tumor Imaging........................................................100 
13.4. 
Response Criteria ..........................................................................................................101 
13.4.1. Evaluation of Target Lesions ........................................................................................101 
13.4.2. Evaluation of Non-Target Lesions ................................................................................101 
13.4.3. Evaluation of Best Overall Response ...........................................................................101 
13.4.4. Duration of Response ....................................................................................................103 
13.4.5. Progression-Free Survival (PFS) ..................................................................................103 
13.4.6. Response Review ..........................................................................................................103 
14. 
Data Management and Reporting .............................................................................104 
14.1. 
Responsibility for Data Submission .............................................................................104 
14.2. 
Compliance with Study Registration and Results Posting 
Requirements ................................................................................................................104 
14.3. 
Study Oversight ............................................................................................................105 
14.4. 
Subject Enrollment and EDC ........................................................................................105 
15. 
Statistical Considerations ...........................................................................................107 
15.1. 
Sample Size and Power Calculation .............................................................................107 
15.2. 
Stratification Factors .....................................................................................................107 
15.3. 
Interim Analyses ...........................................................................................................107 
15.4. 
Data Monitoring Committee (DMC) ............................................................................108 
15.5. 
Statistical Analysis Plan Summary ...............................................................................108 
16. 
References ....................................................................................................................112 
17. 
Abbreviations ..............................................................................................................119 
Appendix A – Assessment of Disease .......................................................................................123 
 
List of Figures 
Figure 1: Synergistic anti-tumor efficacy of NT-I7 with anti-PD-1 on MC38 tumor model in 
sham and TILP hosts. .................................................................................................................... 37 
Figure 2: Synergistic anti-tumor efficacy of NT-I7 and anti-PD-1 combination therapy is 
associated with a greater increase in CD4+ and CD8+ T cell infiltration than in monotherapy. . 38 
Figure 3: Down-regulation of PD-1 and TIM-3 immune checkpoint expression on CD8+ TILs is 
correlated with enhanced anti-tumor activity of NT-I7 and anti-PD-1 combination therapy....... 38 
Figure 4: NT-I7 monotherapy promotes an immune-favorable tumor microenvironment (TME)
....................................................................................................................................................... 39 

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Figure 5: Imaging and treatment for clinically stable subjects treated with NT-I7+pembrolizumab 
after first radiologic evidence of PD assessed by the investigator.............................................. 124 
 
List of Tables 
Table 1: Objectives and endpoints ................................................................................................ 46 
Table 2: Study treatment details ................................................................................................... 64 
Table 3: Pharmacokinetic Timepoints (All Subjects in Phase 1b and Phase 2a, and Biomarker 
Cohort) .......................................................................................................................................... 73 
Table 4:  Dose Modification and Toxicity Management Guidelines for Immune-related AEs 
Associated with Pembrolizumab ................................................................................................... 82 
Table 5: Pembrolizumab infusion reaction dose modification and treatment guidelines ............. 87 
Table 6: Imaging and treatment after first radiologic evidence of progressive disease .............. 125 
 
 
 

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1. 
Protocol Summary 
1.1. 
Synopsis 
 
Title 
An Open-label Phase 1b/2a Study of NT-I7 (efineptakin alfa) in Combination 
with Pembrolizumab in Subjects with Relapsed/Refractory Advanced Solid 
Tumors 
 
Study Phase 
Phase 1b/2a 
 
Clinical 
Indications 
o CPI treated R/R triple negative breast cancer (TNBC) 
o CPI treated R/R non-small cell lung cancer (NSCLC) 
o CPI treated R/R small cell lung cancer (SCLC) 
o CPI naïve R/R microsatellite stable colorectal cancer (MSS-CRC)  
o CPI naïve R/R pancreatic cancer (PC) 
o CPI naïve R/R ovarian cancer (OC) 
CPI: Checkpoint inhibitors = anti-PD-1/anti-PD-L1 
R/R: Relapsed/Refractory 
 
Study Type 
Phase 1b/2a, non-randomized, open-label study of NT-I7 in combination with 
pembrolizumab 
 
Primary 
Objectives 
Phase 1b: 
• To determine the safety and tolerability, including determination of the 
Maximum Tolerated Dose (MTD) and/or the Recommended Phase 2 Dose 
(RP2D) of NT-I7 in combination with pembrolizumab in subjects with 
advanced solid tumors. 
Phase 2a:  
• To assess the preliminary anti-tumor activity of NT-I7 in combination with 
pembrolizumab in subjects with CPI-treated R/R tumors (TNBC, NSCLC, 
SCLC), and CPI-naïve R/R tumors (MSS-CRC and PC) based on Objective 
Response Rate (ORR) as assessed by Response Evaluation Criteria in Solid 
Tumors 1.1 (RECIST 1.1) and immune Response Evaluation Criteria in 
Solid Tumors (iRECIST). 
 
Biomarker Cohort: 
• To assess a potential correlation between tumor infiltrating lymphocytes 
(TILs) and clinical benefits in subjects with CPI-naïve R/R OC. 

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Secondary 
Objectives 
Phase 1b/2a: 
• To further assess the anti-tumor activity of NT-I7 in combination with 
pembrolizumab in these patient populations based on Duration of Response 
(DoR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and 
Overall Survival (OS) by RECIST 1.1. and iRECIST. 
• To evaluate immunogenicity of NT-I7 administered in combination with 
pembrolizumab in these patient populations. 
 
Biomarker Cohort: 
• To assess the safety and tolerability of NT-I7 in combination with 
pembrolizumab in subjects with CPI-naïve R/R OC 
• To assess the anti-tumor activity of NT-I7 in combination with 
pembrolizumab in subjects with CPI-naïve R/R OC based on ORR, DoR, 
DCR, PFS, and OS by RECIST 1.1 and iRECIST. 
• To evaluate immunogenicity of NT-I7 administered in combination with 
pembrolizumab in these patient populations. 
 
Exploratory 
Objectives 
Phase 1b/2a/Biomarker Cohort: 
• To make a preliminary assessment of PK parameters in subjects enrolled in 
Phase 1b, Phase 2a and Biomarker Cohort.  
• To make a preliminary assessment of biomarkers that might act as 
pharmacodynamic indicators of NT-I7 activity in combination with 
pembrolizumab in subjects with CPI-treated R/R tumors (TNBC, NSCLC, 
SCLC), and CPI-naïve R/R tumors (MSS-CRC, PC, and OC). 
• To make a preliminary assessment of biomarkers that might act as 
predictors of anti-tumor activity of NT-I7 in combination with 
pembrolizumab in subjects with CPI-treated R/R tumors (TNBC, NSCLC, 
SCLC), and CPI-naïve R/R tumors (MSS-CRC, PC, and OC). 
 
Study Design 
This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination 
with pembrolizumab. The study consists of a dose escalation phase (Phase 
1b) followed by a dose expansion phase (Phase 2a) and a Biomarker cohort. 
 
The Phase 1b is designed to assess the safety and tolerability, including 
determination of the MTD and/or the RP2D, of NT-I7 in combination with 
pembrolizumab in subjects with advanced solid tumors. The Phase 1b will 
follow the standard 3+3 study design. Three dose levels of NT-I7 are planned 
[DL 1 (480 µg/kg IM Q6W), DL 2 (960 µg/kg IM Q6W), and DL 3 (1200 
µg/kg IM Q6W)], and up to 18 subjects will be enrolled (up to 6 subjects per 
dose level). Doses may be de-escalated to one or two levels (e.g., 360 µg/kg 

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or 240 µg/kg IM Q6W) depending on the pre-defined Dose-Limiting 
Toxicity (DLT) criteria. Pembrolizumab dose is fixed at 200 mg IV Q3W for 
all dose levels. Upon completion of Phase 1b, the MTD was not reached. 
There was 1 DLT (Grade 3 ALT increased) observed at the highest dose 
level tested (1,200 µg/kg; n=6 patients). The RP2D was determined to be 
NT-I7 1,200 µg/kg (IM Q6W) and pembrolizumab 200 mg (IV Q3W). 
 
For Phase 2a, Arms I, II, III, IV, and V will follow the Simon’s minimax 
two-stage design. Indications include CPI-treated R/R tumors (TNBC, 
NSCLC, SCLC), and CPI-naïve R/R tumors (MSS-CRC and PC). Each arm 
will enroll up to 17 evaluable subjects in Stage 1 and, if the Go/No Go 
criterion is met, an additional 8 evaluable subjects in Stage 2 for a total of 25 
evaluable subjects per arm. Exact 95% binomial Clopper-Pearson confidence 
interval estimates of ORR from each arm is planned to support the primary 
hypothesis tests. Enrollment of up to 30 subjects per arm is planned to 
account for non-evaluable subjects and dropouts. Approximately 210 
subjects are planned in total for the Phase 2a. Subjects in the Phase 2a will be 
treated at the RP2D for the combination as determined in the Phase 1b.  
 
Arms IVa (MSS-CRC) and Va (PC) will enroll up to 25 evaluable subjects 
respectively. NT-I7 will be administered at 1200 µg/kg IM Q6W. 
Pembrolizumab dose is fixed at 200 mg IV Q3W. 
 
The Biomarker Cohort will enroll up to 10 evaluable subjects with CPI-naïve 
R/R Ovarian Cancer (OC). The starting dose level of NT-I7 is planned at 960 
µg/kg IM Q6W to further evaluate the tolerability of the starting regimen. 
Pembrolizumab dose is fixed at 200 mg IV Q3W. Subjects who tolerate at 
least 4 cycles of treatment without Grade ≥ 3 AEs and all Grade 2 AEs have 
resolved to Grade ≤ 1, the dose may be escalated to NT-I7 1200 µg/kg IM 
Q6W at Cycle 5. This cohort will test intra-patient dose escalation and collect 
samples for biomarker analyses at 2 different dosages. 
One treatment cycle is defined as 21 days (3 weeks) with NT-I7 administered 
intramuscularly (IM) once every 6 weeks (Q6W), and pembrolizumab 
administered intravenously (IV) once every 3 weeks (Q3W). On days where 
both drugs are given, pembrolizumab will be given prior to NT-I7. The 
treatment will be continued up to a maximum of 2 years or up to 35 cycles 
only. 
  Dose Escalation Phase (Phase 1b) 
Phase 1b dose escalation for NT-I7 will follow the standard 3+3 design with 
three dose levels, and doses may be de-escalated to one or two levels (e.g., 
360 µg/kg or 240 µg/kg IM Q6W) depending on the pre-defined Dose-
Limiting Toxicity (DLT) criteria. Pembrolizumab dose is fixed at 200 mg IV 

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Q3W for this study.  
Subjects are required to complete Cycle 1 to be considered evaluable for MTD 
determination unless discontinuation occurred due to a DLT (i.e., in the dose-
determining set). 
Once the RP2D has been selected, the study will proceed to the Dose 
Expansion Phase (Phase 2a) to further evaluate RP2D in a larger number of 
subjects and selected tumor types as described. In the event of unacceptable 
toxicity in the expansion phase, a lower dose will be explored. 
  
  Dose Expansion Phase (Phase 2a): 
 The selected arms in Phase 2a, arms I, II, III, IV, and V will follow the 
Simon’s two-stage minimax design in each arm, and 5 arms are planned:  
o Arm I 
: CPI-treated R/R TNBC 
o Arm II : CPI-treated R/R NSCLC 
o Arm III : CPI-treated R/R SCLC 
o Arm IV : CPI-naïve R/R MSS-CRC 
o Arm V : CPI-naïve R/R PC 
 
In Stage 1 for arms I, II, III, IV, and V, up to 17 evaluable subjects will be 
enrolled and treated per arm. If at least one subject achieves objective 
response (complete response [CR] or partial response [PR]) in an arm, that 
arm may be expanded by enrolling up to 8 evaluable additional subjects in 
Stage 2. Study enrollment will continue while the first 17 possible evaluable 
subjects are undergoing evaluation to confirm response. If no objective 
response is observed in an arm during Stage 1, further enrollment will be 
stopped in that arm. 
 
Arms IVa (MSS-CRC), Va (PC), and the Biomarker Cohort will not follow 
the Simon’s two-state minimax design.  Arms IVa and Va will enroll up to 
25 evaluable subjects per arm.  NT-I7 will be administered at 1200 ug/kg IM 
Q6W, with Pembrolizumab fixed dose at 200 mg IV Q3W. 
 
o Arm IVa : CPI-naïve R/R MSS-CRC 
o Arm Va : CPI-naïve R/R PC 
 
Biomarker Cohort: 
The Biomarker Cohort is designed to assess the correlation between tumor 
infiltrating lymphocytes (TILs) and clinical benefits of NT-I7 in combination 
with pembrolizumab in subjects with CPI naïve R/R Ovarian Cancer (OC). Up 
to 10 evaluable subjects will be enrolled to obtain at least 4 pairs of evaluable 

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pre- and on-treatment tumor biopsies. The starting dose level of NT-I7 is 
planned at 960 µg/kg IM Q6W. Pembrolizumab dose is fixed at 200 mg IV 
Q3W for all dose levels. Subjects who tolerate at least 4 cycles of treatment 
without Grade ≥ 3 AEs and all Grade 2 AEs have resolved to Grade ≤ 1, the 
dose may be escalated to NT-I7 1200 µg/kg IM Q6W at Cycle 5. 
                    
 

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Treatment 
Schema 
 
  
Rationale for 
Dose Selection 
Ongoing clinical study of NT-I7 monotherapy in patients with advanced solid 
tumors (Study GX-I7-CA-003) demonstrated an increase of ALC and multiple 
T-cell subsets in the peripheral blood in a dose-dependent manner until 720 
µg/kg where the increases appeared to plateau. However, comparative tumor 
infiltrating lymphocytes (TIL) data in cancer patients is not yet available, 
although it is possible that higher TIL responses may be observed at doses 
higher than 720 µg/kg. Further, our preclinical data also suggested a dose-
dependent increase in the peripheral ALC which appeared to plateau out at 2.5 
mg/kg (i.e., no significant difference between 2.5 mg/kg and the higher dose of 
10 mg/kg), but there were significantly more TILs, especially CD8+ T cells, at 
the 10 mg/kg dose. This animal dose of 10 mg/kg roughly translates to 810 
µg/kg human dose. In addition, since 10 mg/kg was the highest dose tested in 

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the animal model, it is not known whether higher doses would result in more 
TILs. Thus, both 960 µg/kg and 1200 µg/kg dose levels are selected for testing. 
The 480 µg/kg dose is chosen as the starting dose for NT-I7 based on the 
following rationales: 1) the safety profile of the combination, pembrolizumab + 
NT-I7, is not known; 2) based on the data from Study GX-I7-CA-003, 480 
µg/kg dose did increase peripheral ALC and multiple subsets of T cells, thus 
can potentially provide benefit to the patients; 3) there are large differences 
between 480 µg/kg , 960 µg/kg and 1200 µg/kg doses that may allow detection 
of the differences in pharmacodynamic parameters (e.g. peripheral ALC and 
TILs) between the three dose levels. 
Hence, based on the preclinical and clinical data, 480, 960, and 1200 µg/kg are 
selected for testing in this study. 
Eligibility 
Criteria 
Inclusion Criteria:  
Subjects must meet all of the following criteria to be included in the study: 
1. Must be ≥18 years on the day of signing informed consent. 
2. Be willing and able to provide written informed consent/assent for the 
study.  
3. Subjects with histologically or cytologically confirmed advanced or 
metastatic solid tumors who have disease progression after treatment with 
all available therapies for metastatic disease that are known to confer 
clinical benefit, or are intolerant to treatment, or refuse standard treatment. 
4. Have measurable disease per RECIST 1.1 as assessed by the enrolling 
physician. Lesions situated in a previously irradiated area are considered 
measurable if progression has been demonstrated in such lesions.  
5. Subjects enrolling in the Phase 1b, Arms I, IV, IVa, V, and Va of the 
Phase 2a, and the Biomarker Cohort OC must have biopsiable disease 
(i.e., have at least 1 tumor lesion that is accessible and feasible for 
biopsy) as determined by the enrolling physician. Willing to provide 
archival tumor tissue sample or newly obtained core or excisional biopsy 
of a tumor lesion not previously irradiated. Formalin-fixed, paraffin 
embedded (FFPE) tissue block is preferred to slide. Newly obtained 
biopsy is preferred to archived tissue. 
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 
7. Subjects must have a life expectancy of greater than or equal to 12 
weeks per assessment from the enrolling physician. 
8. Subjects must have adequate organ function as defined below: 
a. Absolute neutrophil count ≥1,500/µL 
b. Platelets ≥100,000/µL 
c. Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without 
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d. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) OR 
direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5 × 
ULN 
e. AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (AST and/or ALT ≤5 × ULN 
for subjects with liver metastasis) 
f. Alkaline phosphatase ≤2.5 × ULN (≤5 x ULN for subjects with 
documented liver involvement or bone metastases) 
g. Creatinine ≤1.5 × ULN or Creatinine clearance (CrCl) ≥30 mL/min 
for subject with creatinine levels >1.5 x ULN. CrCl should be 
calculated per institutional standard  
h. INR and aPTT ≤1.5 × ULN unless the subject is receiving 
anticoagulant therapy as long as PT or aPTT is within therapeutic 
range of intended use of anticoagulants. 
9. ECG demonstrating Fridericia's corrected QT interval (QTcF) < 470 ms. 
Patients with QTcF ≥ 470 ms will require clearance by a local 
cardiologist. 
10. Female subjects who are either postmenopausal for at least 1 year, are 
surgically sterile for at least 6 weeks; female subjects of childbearing 
potential must agree to remain abstinent (refrain from heterosexual 
intercourse) or to use dual methods of contraception for the duration of 
study treatment and for 120 days after the last dose of study treatment 
(pembrolizumab and/or NT-I7). Female subjects of childbearing potential 
(including women who have had a tubal ligation) must have a negative 
serum or urine pregnancy test within 72 hours prior to Cycle 1, Day 1. If 
the urine test is positive, or cannot be confirmed as negative, a serum 
pregnancy test will be required. 
11. Non-sterile male subjects who are sexually active with female partners of 
childbearing potential must agree to remain abstinent (refrain from 
heterosexual intercourse) or to use highly effective method(s) of 
contraception for the duration of study treatment and for 120 days after 
the last dose of study treatment (pembrolizumab and/or NT-I7). 
12. And meet the requirements for the intended stages and arms (disease 
specific inclusion criteria), as following: 
Applicable to the Dose escalation phase (Phase 1b) only: 
a. Relapsed/refractory advanced solid tumors 
Note: Prior anti-PD-1/anti-PD-L1 requires a 4-week washout 
period. 
b. Willing to provide pre- and on-treatment biopsies 
Applicable to the Dose expansion phase (Phase 2a) only: 
Anti-PD-1/anti-PD-L1 refractory criteria for CPI-treated TNBC, 
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Subjects must have progressed on treatment with an anti-PD-1/anti-PD-L1 
monoclonal antibody (mAb) administered either as monotherapy, or in 
combination with other checkpoint inhibitors or other therapies. PD-1/PD-L1 
treatment progression is defined by meeting all of the following criteria: 
a. Has received at least 2 doses of an approved anti-PD-1/anti-PD-L1 mAb.  
Note: Prior anti-PD-1/anti-PD-L1 requires a 4-week washout period. 
b. Has demonstrated disease progression after anti-PD-1/anti-PD-L1 treatment 
as defined by RECIST 1.1. The initial evidence of disease progression (PD) 
is to be confirmed by a second assessment no less than four weeks from the 
date of the first documented PD, in the absence of rapid clinical progression. 
(1) Note: This determination is made by the investigator. Once PD is 
confirmed, the initial date of PD documentation will be considered the date 
of disease progression. 
c. Progressive disease has been documented within 12 weeks from the last 
dose of anti-PD-1/anti-PD-L1 mAb.  
Specific to Arm I: CPI-treated R/R TNBC  
a. Histopathologic or cytologic documented TNBC. Tumors must have been 
confirmed negative for ER and PR by IHC (<1% positive tumor nuclei, as 
per ASCO-CAP guideline recommendations) and negative for HER2 by 
IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH).  
b. Received one or more prior therapies for TNBC in the advanced or 
metastatic setting, and prior treatment (for advanced, metastatic or (neo) 
adjuvant) must have included a taxane and/or anthracycline-based therapy 
and anti-PD-1/anti-PD-L1.  
c. Willing to provide pre- and on-treatment biopsies. 
Specific to Arm II: CPI-treated R/R NSCLC  
a. Had prior treatment with CPI. Subjects with EGFR, BRAF, or ROS1 
mutations or ALK translocations are required to have received prior 
therapy with the appropriate TKI; prior platinum-based chemotherapy is 
not required for this specific patient population.   
 
Specific to Arm III: CPI-treated R/R SCLC 
 
a. Recurrent extensive-stage SCLC. 
b. Received prior CPI therapy.  
Specific to Arm IV and IVa: CPI-naïve R/R MSS-CRC 
a. MSS-CRC (categorized as MSS by immunohistochemistry (IHC) or 
polymerase chain reaction (PCR)-based local assay at any time prior to 

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screening or by the central laboratory). Note: Subjects that are MMR 
deficient, microsatellite instability-high (MSI-H) or microsatellite unstable 
CRC are not eligible. 
b. Previously treated with standard therapies, which must include 
fluoropyrimidine, oxaliplatin, and irinotecan; subjects treated with CPI are 
not eligible.  
c. Willing to provide pre- and on-treatment biopsies. 
Specific to Arm V and Va: CPI-naïve R/R Pancreatic Cancer  
a. Have documented radiographic progression to or documented intolerance 
of first line systemic chemotherapy which included either gemcitabine or 
Fluorouracil (5-FU)-based regimen (including capecitabine); subjects 
treated previously with CPI are not eligible. 
b. Willing to provide pre- and on-treatment biopsies. 
Specific to Biomarker Cohort: CPI-naïve R/R Ovarian Cancer  
a. Up to 5 prior lines of treatment, including platinum-based treatment(s); 
subjects treated previously with CPIs are not eligible. 
b. Willing to provide pre- and on-treatment tumor biopsies. 
 
Exclusion Criteria 
Subjects meeting any of the following criteria are not eligible for enrollment 
in the study: 
1. Pregnant, lactating or breastfeeding or expecting to conceive or father 
children within the study duration from screening through 120 days after 
the last dose of study treatment.  
2. Receiving chemotherapy or any anti-cancer therapy (approved or 
investigational) with half-life <1 week within 30 days or 5 half-lives, 
whichever is shorter, prior to first dose of study treatment. Receiving 
treatment with immune CPIs, immunomodulatory monoclonal antibodies 
(mAbs), and/or mAb-derived therapies within 4 weeks prior to first dose of 
study treatment. 
Note: All AEs related to previous therapies, except alopecia, must be 
resolved to ≤Grade 1 or baseline. Subjects with Grade <2 neuropathy may 
be eligible.  Subjects with endocrine-related AEs Grade <2 requiring 
treatment or hormone replacement may be eligible. 
 
3. Has received prior radiotherapy within 2 weeks of start of study treatment. 
Subjects must have recovered from all radiation-related toxicities, not 
require corticosteroids, and not have had radiation pneumonitis. A 1-week 

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washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to 
non-CNS disease. 
4. Has known active central nervous system (CNS) metastases and/or 
carcinomatous meningitis. Subjects with previously treated brain 
metastases may participate provided they are radiologically stable 
(without evidence of progression by repeat imaging (during screening) for 
at least 4 weeks prior to the first dose of study treatment and any 
neurologic symptoms have returned to baseline), have no evidence of new 
or enlarging brain metastases, and are not using systemic steroids for CNS 
symptom management for at least 14 days prior to first dose of study 
treatment.  
5. Subjects who have not recovered from AEs (other than alopecia, vitiligo, 
neuropathy or endocrinopathy managed with replacement therapy) due to 
prior agents administered (i.e., have residual toxicities >Grade 1).  
6. Concurrent or previous other malignancy within 3 years of study entry, 
except cured basal or squamous cell skin cancer, transitional cell 
carcinoma of urothelial cancer, carcinoma in-situ of the breast or cervix.  
7. History of severe hypersensitivity reactions to monoclonal antibodies 
(mAbs) or intravenous immunoglobulin preparations; any history of 
anaphylaxis; prior history of human anti-human antibody response; 
known allergy to any of the study medications, their analogues, or 
excipients in the various formulations of any agent. Note: Subjects with 
severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its 
excipients are also excluded. 
8. Subjects who have spinal cord compression, not definitively treated with 
surgery and/or radiation, or previously diagnosed and treated spinal cord 
compression without evidence that disease has been clinically stable for 
≥2 weeks prior to screening. 
9. Subjects who have autoimmune disease history within the past 2 years, 
including but not limited to systemic lupus erythematosus, rheumatoid 
arthritis, inflammatory bowel disease, vascular thrombosis associated with 
antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s 
syndrome, Bell’s palsy, Guillain-Barre syndrome, multiple sclerosis, 
vasculitis or glomerulonephritis.  
10. Have active and clinically relevant bacterial, fungal, viral, or TB 
infection, including known Hepatitis A, B, or C or HIV (testing not 
required).  
11. Clinically significant cardiac disease, including, but not limited to, any of 
the following: Congestive heart failure requiring treatment (New York 
Heart Association Grade ≥ 2); clinically significant and uncontrolled atrial 
fibrillation; history of acute coronary syndromes including myocardial 
infarction, unstable angina, coronary artery bypass grafting, coronary 
angioplasty, or stenting < 6 months prior to screening; symptomatic 
chronic heart failure, history or current evidence of clinically significant 
cardiac arrhythmia and/or conduction abnormality < 6 months prior to 

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screening except controlled atrial fibrillation and paroxysmal 
supraventricular tachycardia. 
12. Subjects who have received treatment with systemic immunosuppressive 
medications (including, but not limited to, systemic prednisone >10 
mg/day or its equivalent, cyclophosphamide, azathioprine, methotrexate, 
thalidomide and antitumor necrosis factor [anti-TNF] agents) within 7 
days prior to first dose of study treatment. Note: Replacement therapy 
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency) is not considered a form of 
systemic treatment and is allowed. 
13. History of allergy or intolerance (unacceptable AEs) to study drug 
components or polysorbate-80-containing infusions. (Note: Polysorbate 
80 is a buffer used to make NT-I7). 
14. Has a history of non-infectious pneumonitis that required steroids or 
current pneumonitis.  
15. 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 enrolling 
physician. 
16. Has a known psychiatric or substance abuse disorder that would interfere 
with the subject’s ability to cooperate with the requirements of the study. 
17. Has received a live vaccine within 30 days prior to the first dose of study 
drug. Examples of live vaccines include, but are not limited to, the 
following: measles, mumps, rubella, varicella/zoster (chicken pox), 
yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid 
vaccine. Seasonal influenza vaccines for injection are generally killed 
virus vaccines and are allowed; however, intranasal influenza vaccines 
(e.g., FluMist®) are live attenuated vaccines and are not allowed. 
18. Has had an allogenic tissue/solid organ transplant or bone marrow 
transplant.  
19. 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 (e.g., CTLA-4, OX-40, CD137) and was discontinued from that 
treatment due to a Grade 3 or higher irAE. 
 
Number of 
Subjects 
Up to 238 subjects are planned to be enrolled (up to 18 subjects in the Phase 1b, 
up to 210 subjects in the Phase 2a and up to 10 subjects in the Biomarker 
Cohort). 
Power 
Calculations 
This will provide an estimated 80% power per selected arms in the Phase 2a 
stage of the study for the primary hypothesis test using the Simon minimax 
design, for 4% vs 21% ORR, at 1-sided alpha = 0.025, as well as approximately 
25 evaluable subjects per arms for 95% exact binomial Clopper-Pearson 
confidence intervals for ORR from the design (per arm). The design has futility 
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maximum sample size of 25 evaluable subjects per arm. To account for non-
evaluable subjects, it is planned to enroll up to 30 subjects per arm in Phase 2a. 
Number of 
Clinical Sites 
Approximately 8 study sites are planned to participate in this study 
Duration of 
Participation 
Each subject will participate in the study from the time the Informed Consent 
Form (ICF) is signed through final protocol-specific follow-up. The active 
study will end when the last subject completes the 90-day safety follow up visit, 
approximately 24 months after enrollment.   
Estimated 
Duration of 
Study 
 Approximately 36 months after the last subject is enrolled.   
 

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2. 
Introduction 
2.1. 
PD-1 Blockade and Solid Tumors 
The immune system functions to protect the host immunity by a series of co-inhibitory and co-
stimulatory receptors and their ligands, known as immune checkpoints (2, 3). Several evidence 
suggest that tumors exploit these mechanisms to escape anti-tumor immune responses and 
ultimately progress, disseminate, and metastasize (2, 4). Among the significant pathways, 
programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a vital 
role in the physiological immune homeostasis and putatively serve as a means through which 
cancer cells evade the immune system (5).  
Conventional therapies usually target a particular molecule in the tumor cells, in which most 
tumor responses last until the cancer develops a way to bypass the blocked pathway, whereas 
PD-1/PD-L1 blockade releases negative regulators of immune checkpoints. In addition, 
numerous tumor types express high PD-L1 levels suggesting that PD-1/PD-L1 pathway 
activation is a common mechanism used by these tumors to avoid immune surveillance and to 
continue rapid growth. In many tumor types, high levels of PD-L1 expression correlate with 
better response to PD-1/PD-L1 inhibitors. Thus, development and application of immune CPIs 
that block PD-1/PD-L1 interaction result in very durable response and prolonged survival in 
patients. However, adverse events, low response rates and eventual progressions warrant for 
better understanding of PD-1/PD-L1 pathway to predict patient response and improve treatment 
efficacy and safety (6).  
With the approval of pembrolizumab for the treatment of advanced melanoma in September 
2014, to date, at least 500 clinical studies with PD-1 signal inhibitors have been conducted with 
nine types of antibodies from eight pharmaceutical companies on at least 20 types of solid and 
hematological malignant tumors 3 and the list is expanding. This basket study aims to study 
TNBC, NSCLC, SCLC, MSS-CRC, and PC where there are challenges, and room to improve 
current standards of immunotherapy. 
2.1.1. 
Triple Negative Breast Cancer 
Until October of 2018, phase 1 and 2 clinical studies evaluating PD-1 protein blockade as 
monotherapy in advanced TNBC showed disappointing response rates of 5 to 10% in unselected 
patient populations.  
The approval of atezolizumab, a PD-L1 inhibitor, in advanced TNBC based on the Impassion 
130 study has completely changed the field of immunotherapy in breast cancer (7). In this Phase 
3 registration study, the median progression-free survival (PFS) in the intent-to-treat (ITT) 
population was significantly improved following the addition of atezolizumab as compared to 
nab-paclitaxel alone (7.2 vs. 5.5 months); further, among the PD-L1+ population, the respective 
PFS benefit was more pronounced (7.5 vs. 5.0 months). However, the current FDA approval of 
atezolizumab in the treatment of TNBC applies only to patients whose breast cancers express 
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In other studies, such as the Phase 1b KEYNOTE-012, pembrolizumab achieved an ORR of 
18.5% in metastatic TNBC (8). It is worth noting that 15.6% patients were treatment-naïve at the 
time of metastatic disease in this study. In another Phase 2 KEYNOTE-086 study (cohort A), 
pembrolizumab led to an ORR and disease control rate of 5.3 and 7.6%, respectively, in 
pretreated TNBC patients (9). Preliminary data are available for the open-label Phase 1b/2 
KEYNOTE-150 study assessing the combination of eribulin and pembrolizumab (10). Among 
107 metastatic TNBC patients (106 evaluable for efficacy), 65 were CPI-naïve, while 41 had 
received one to two prior lines of therapy. Half of the patients in the study had PD-L1+ TNBC 
(45.8%). The ORR of the combination treatment in the overall population and that in the 
untreated and pretreated patients was 26.4, 29.2, and 22.0%, respectively.  
In a Phase 3 KEYNOTE-119 trial evaluating pembrolizumab monotherapy compared to single-
agent chemotherapy in previously treated metastatic TNBC, ORR were 9.5% vs 10.6% (ITT), 
12.3% vs 9.4% (CPS ≥ 1), 17.7% vs 9.2% (CPS ≥ 10), and 26.3% vs 11.5% (CPS ≥ 20) (11).  
Despite these practice-changing treatments in TNBC, there is significant room for improvement 
in the first-line treatment as well as treatment for patients who relapse after the initial response to 
CPIs. 
2.1.2. 
Non-small Cell Lung Cancer 
Pembrolizumab was approved in October 2015 for treatment of previously treated advanced or 
metastatic PD-L1-positive (at least 1%) NSCLC, based on the results of the randomized Phase 
1b study KEYNOTE-001 (12).   
Pembrolizumab was also approved for the first-line treatment of patients with metastatic NSCLC 
whose tumors have high PD-L1 expression (≥50%) with no EGFR or ALK genomic tumor 
aberrations based on the study of KEYNOTE-024 (13). The ORR was 44.8% in the 
pembrolizumab group and 27.8% in the chemotherapy group. In the Phase 3 KEYNOTE-042 
study, subjects with previously untreated locally advanced or metastatic NSCLC without a 
sensitizing EGFR or ALK genomic tumor aberrations were given either pembrolizumab or 
chemotherapy. The ORRs were reported based on the PD-L1 expression in pembrolizumab vs 
chemotherapy patients; 39.1% vs 32.0% (TPS ≥ 50%), 33.2% vs 28.9% (TPS ≥ 20%), and 27.2% 
vs 26.5% (TPS ≥ 1%) (14). 
In May 2017, pembrolizumab was approved in combination with pemetrexed and carboplatin for 
the first-line treatment of metastatic non-squamous NSCLC, irrespective of PD-L1 expression, 
based on the study of KEYNOTE-021 (15). In this Phase 2 open-label study, 55% patients in the 
pembrolizumab plus chemotherapy group achieved an objective response compared with 29% 
patients in the chemotherapy alone group.  
In August 2018, FDA has approved an expanded label for pembrolizumab in combination with 
pemetrexed and platinum chemotherapy for the first-line treatment of patients with metastatic 
non-squamous NSCLC, with no EGFR or ALK genomic tumor aberrations, based on results of 
the KEYNOTE-189 study (16). Median PFS was 8.8 months in the pembrolizumab-combination 
group and 4.9 months in the placebo-combination group. 

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Data from Phase 1 and Phase 3 studies of nivolumab and a Phase 2 study of atezolizumab—all in 
patients with previously treated NSCLC—provide further support for the durability of benefit 
with anti-PD-1 or anti-PD-L1 therapy in patients with NSCLC. Overall survival with nivolumab 
in the Phase 1 study was 18% after 3 years of follow-up and 16% after 5 years of follow-up. 
Similarly, in a pooled analysis after 3 years of follow-up in the Phase 3 CheckMate 017 and 
CheckMate 057 studies, an OS benefit was shown with nivolumab versus docetaxel. The 3-year 
survival for atezolizumab versus docetaxel in the Phase 2 POPLAR study was 18.7% versus 
10.0%.  
Although, immunotherapy is booming in the NSCLC space, tumor heterogeneity, mutational 
density, and the microenvironment play a vital role in the variability of responses and outcomes 
in immunotherapy-treated NSCLC patients regardless of the PD-L1 status (17). Further, there are 
challenges such as CPIs as monotherapy or in combination with chemotherapy only benefit a 
fraction of the patient population, primary resistance does exist and acquired resistance 
eventually develops. 
2.1.3. 
Small Cell Lung Cancer 
Small cell lung cancer (SCLC) accounts for ~15% of all lung cancer and is the leading cause of 
cancer death among men and the second leading cause of cancer death among women worldwide 
(18). The prognosis of patients with SCLC is dismal with a 5-year survival rate of less than 5% 
and an average overall survival period of only 2–4 months for patients not receiving any active 
treatment (19).  
Immunotherapy has been the most promising treatment with encouraging results. While 
nivolumab was the first FDA approved third-line drug for recurrent SCLC based on the 
Checkmate-032 study, atezolizumab + chemotherapy was the first Phase 3 (Impower 133) study 
that showed improved efficacy in the extensive stage SCLC in the first line setting (20).  
Very recently, FDA granted accelerated approval of pembrolizumab in SCLC with disease 
progression on or after platinum-based chemotherapy and at least one other prior line of therapy 
based on the KEYNOTE-158 study (21). Importantly, studies such as KEYNOTE-028 (Phase 
1b) and KEYNOTE-158 (Phase 2) have included patients with chemotherapy-refractory SCLC 
(≥3 lines of systemic therapy) treated with pembrolizumab. Of 83 evaluable patients obtained 
from the pooled data of KEYNOTE-028 (Phase 1b) and KEYNOTE-158 (Phase 2), ORR was 
19.3%; 14 of 16 responders were PD-L1–positive. 
In the ongoing Phase 1/2 CheckMate-032 study, patients received 3 mg/kg of nivolumab every 
2 weeks, yielding an ORR of 11.9% regardless of PD-L1 expression. Among the responders, the 
median duration of response (DoR) was 17.9 months. 
Checkmate 331 is a Phase 3 study of nivolumab or chemotherapy in relapsed SCLC after 
platinum-based first-line chemotherapy (22). At a follow-up of 15.8 months, no statistically 
significant improvement in OS was seen with nivolumab versus chemotherapy; median PFS was 
1.4 months with nivolumab (1.4–1.5) and 3.8 months (3.0–4.2) with chemotherapy. Also, no 
differences were observed in terms of response rate (14% and 16%, respectively). 

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Despite immunotherapy having become a primary component of SCLC treatment, there are still 
many challenges, such as efficacy being very modest and limited to a small subset of patients.  
2.1.4. 
Colorectal Cancer 
In the colorectal arena, the first FDA-approved CPIs were pembrolizumab and nivolumab for the 
treatment of refractory deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) 
metastatic CRC.  
The notable success of these inhibitors in dMMR/MSI-H CRC has been attributed to the 
favorable immunogenic features of these tumors that contrast starkly with the “immune-cold” 
features of proficient mismatch repair/microsatellite stable (pMMR/MSS) CRC. It is estimated 
that dMMR CRC can yield about 20-times higher tumor mutational burden than pMMR, which 
is accountable for the higher TIL response and improved CPI efficacy (23). 
It is perplexing that the objective response rate (ORR) was 0% (0 of 18) for patients with 
pMMR/MSS CRC as noted in the KEYNOTE-016 study (24). In this context, it is high time that 
combinatorial approaches are tested to sensitize the ‘immunologically cold’ MSS tumors. 
Specifically, strategies involving overcoming of the immunosuppressive tumor 
microenvironment, boosting effector T-cell function, increasing tumor antigenicity, and up-
regulating diverse molecular mediators to elicit a more pro-inflammatory tumor milieu are of 
considerable interest.  
2.1.5. 
Pancreatic Cancer 
Several clinical studies in PC have shown that high PD‐L1 expression relates to worse outcomes 
suggesting that blockade of PD‐1/PD‐L1 interaction may be effective in this tumor type (25-27) . 
However, data from 160 evaluable patients with advanced solid tumors in the Phase 1 anti-PD-
L1, BMS-936559 (MDX1105) study showed no clinical response in PC patients.  
In other two anti PD-1 studies, abominable results were achieved in PC cohorts. Specifically, in 
the KEYNOTE-001 study with pembrolizumab, out of the 30 patients, there was only one patient 
with pancreatic neuroendocrine tumor who achieved the best response as stable disease (SD) 
(28). Similarly, in a study of 7 patients with stage IV PC treated with nivolumab and dendritic 
cells, the best response achieved was partial response (2/7) (29).  
It is speculated that the efficacy of a single PD-1/PD-L1 blockade may be limited in PC for two 
primary reasons. First, immunosuppression caused by a high tumor burden is a reason why PC 
cannot respond to PD-1/PD-L1 blockade alone. Second, PC is intrinsically non-immunogenic 
(30). Thus, a combination strategy is the way of achieving specific anti-tumor responses in this 
aggressive tumor. 
2.1.6. 
Ovarian Cancer 
Ovarian Cancer (OC) is a potentially immunogenic tumor type that would likely benefit from 
immunotherapy since it has been shown that ovarian tumors with higher frequency of infiltrating 
lymphocytes are associated with better survival (31, 32) while higher PD-L1 expression at the 
tumor level is associated with poor prognosis (33). However, despite the high rate of tumor 
infiltrating lymphocytes (TILs), pembrolizumab monotherapy in patients with advanced recurrent 

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OC had limited efficacy with an ORR of 7.4-9.9% and a median PFS of 2.1 months ((34), 
NCT02674061), suggesting that blockade of the PD-1:PD-L1 axis is not sufficient to overcome 
the immunosuppressive tumor microenvironment (TME) in most OC patients. As a T-cell 
amplifier, NT-I7 has demonstrated its ability to expand T cells and promote tissue infiltration of 
lymphocytes in the TME of cancer patients. Thus, combination strategies including NT-I7 will 
likely increase the depth and breadth of the response to PD-1:PD-L1 blockade and thereby improve 
treatment efficacy. 
In addition, preliminary data from the Dose Escalation phase (Phase 1b) of this study, NIT-
110/KEYNOTE A60, showed significant increase of TILs in a subject with Clear Cell Ovarian 
Cancer. 
 
 
 
Altogether, OC is well positioned to benefit from combination strategies that overcome the 
immunosuppressive TME. Including OC in this study potentially addresses a high unmet medical 
need for these patients. Furthermore, using OC as a model to determine the enhanced effects of 
pembrolizumab in combination with NT-I7 will provide relevant knowledge about pan-cancer 
biomarkers that may be used as predictors of anti-tumor activity. 
Conclusion: Although immunotherapy has become new paradigm in cancer treatment, 
especially for tumors that are considered responsive to CPIs, the majority of patients fail to 
respond, and most responders eventually relapse. For tumors that are considered non-responsive 
to CPIs, such as MSS-CRC and PC, response to single-agent CPIs has been dismal. Thus, novel 
combinatorial strategies are needed to increase the depth and breadth of the response to CPIs. 
2.2. 
Background 
T-cells play a pivotal role in inducing antigen-specific immune responses to attack cancer cells, 
as they can recognize cancer antigens, destroy cancer cells and differentiate into memory T-cells 
to facilitate long term immunity. The anti-tumor efficacy of T-cells can be enhanced by 
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expressed by cancer cells, expanding T-cell clones responsive to tumor specific antigens and 
accelerating differentiation to memory T-cells to increase tumor tissue infiltration (35, 36).    
It is well recognized that T-cell lymphopenia in cancer patients is associated with lower clinical 
anti-tumor responses and lower survival rates. To date, IL-2 (Proleukin® [aldesleukin]) is the 
only Food and Drug Administration (FDA)-approved cytokine product available as a therapeutic 
option to induce the proliferation and activation of T-cells. However, the clinical application of 
IL-2 is very limited due to serious adverse effects such as capillary leak syndrome and 
compromised efficacy through the increased proliferation of regulatory T-cells that inhibit anti-
tumor immune responses (37, 38).  
IL-7 is a crucial factor for the growth and activation of T-cells, and serves as a key player in the 
differentiation, proliferation and survival of naïve and memory T-cells. Importantly, it does not 
induce proliferation of regulatory T-cells. IL-7 is also a homeostatic cytokine, produced 
constitutively by a variety of stromal cells and by keratinocytes, dendritic cells, neurons, and 
endothelial cells but is not produced by lymphocytes. Its receptor (IL-7Rα) is expressed on 
resting T cells, and then rapidly down-regulated after T cell activation or IL-7 signalling. IL-7 is 
essential for T cell development in mice and humans, as well as for T cell homeostasis, because 
it is required to maintain naïve CD4+ and CD8+ T cells in vivo. 
Recombinant human IL-7 (rhIL-7, CYT107) has been developed by Cytheris and tested in over 
300 subjects including subjects with chronic HIV or HCV infections, subjects with refractory 
solid tumors, and subjects after allogeneic stem cell transplantation. In most studies, a marked 
increase in peripheral T cells and broadening of TCR diversity were seen to be dose-dependent, 
and rhIL-7 was well tolerated. The favorable safety profile of IL-7, in contrast to the severe 
toxicities of IL-2 (e.g., hematological toxicities, capillary leak syndrome), and its ability to 
reverse lymphopenia indicate that IL-7 is a promising therapeutic target that deserves further 
clinical investigation.  
Although these combined clinical studies have demonstrated proof of mechanism in humans with 
regards to the safety, tolerability and substantial increases in T-cell count, rhIL-7 as a therapeutic 
previously faced numerous technical challenges including a short half-life of the drug, a lack of 
molecular stability of the intrinsically unstable protein, and the consequent poor production 
yield. 
NT-I7 has the potential to provide immunocompromised subjects with a breakthrough solution 
by resolving issues with previous rhIL-7 candidates. As a fusion protein with the C-terminal of 
human IL-7 fused to hyFc long-acting platform, NT-I7 has overcome the fundamental problem 
of short half-life that stalled previous rhIL-7 programs. In non-clinical studies, NT-I7 increased 
peripheral T cells, anti-tumor efficacy, and tumor infiltrating lymphocytes, either as a 
monotherapy or in combination with chemo/radiotherapy and/or CPIs. In clinical studies, NT-I7 
has demonstrated a well-tolerated safety profile and administration of NT-I7 led to a dose-
dependent increase in the peripheral CD4+ and CD8+ T cells (naïve T cells, TEM, TCM, TEMRA) 
and NK cells, but there was no dose-dependent increase in B cells. 
 

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2.3. 
Study Rationale 
Cancer patients commonly suffer from lymphopenia, stemming either from their disease or 
therapeutic interventions, such as chemotherapy and/or radiotherapy. This cancer-associated 
lymphopenia correlates with decreased overall survival (39). IL-7 has been shown to increase 
TCR repertoire in subjects by (1) expanding naïve T cell pools (40) and (2) supporting 
subdominant T cell clones and improving the survival of the CD8 memory pool (41). In addition 
to reversing lymphopenia, IL-7 has also been shown to enhance the functionality of effector T 
cells (42) and to antagonize the immunosuppressive effects of Tregs and MDSCs (43). Based on 
these various mechanisms, IL-7 administration may significantly augment PD-1/PD-L1 blockade 
by virtue of increasing the number and effector function of tumor infiltrating lymphocytes.  
Hence, based on the mechanism of action for NT-I7 and the data obtained from preclinical and 
clinical studies, adding NT-I7 to a PD-1 inhibitor, such as pembrolizumab, will potentially a) 
convert an immunologically “cold” tumor to a “hot” tumor; b) make a tumor that has developed 
resistance to a PD-1/PD-L1 inhibitor to become responsive again; and c) enhance the anti-tumor 
activity in immunologically “warm” tumors. In this clinical study, CPI treated R/R TNBC, 
NSCLC, and SCLC are selected to test the hypothesis of whether adding NT-I7 could convert 
these tumors which have developed resistance to a CPI to become responsive to a CPI again. CPI 
naïve MSS-CRC and PC are selected to test the hypothesis of whether adding NT-I7 could 
convert these immunologically “cold” tumors into “hot” tumors. In addition, CPI naïve OC is 
added to test whether NT-I7 could enhance the limited anti-tumor activity of single-agent CPI in 
these tumor types. 
Emerging data from Arms IV and V in this trial have shown promising results, comparable to 
recently presented data from MSS-CRC subjects given pembrolizumab in combination with 
favezelimab, in which ORR was 6.3% (5/80) (44).  
In the completed cohorts for Arms IV and V, ORR per iRECIST was observed in 11.1% of 
subjects in Arm IV (3/27 subjects) with 3.7% (1/27 evaluable) achieving confirmed PR per 
RECIST 1.1 (45), and in Arm V, ORR per iRECIST was achieved in 7.7% of subjects (2/26 
evaluable) and RECIST 1.1 was achieved in 3.8% of subjects (1/26 evaluable) (46). 
Previous studies in patients with CRC showed a positive relationship between tumor infiltration 
and good prognosis (47) (48). Similarly, CD8+ T cell infiltration in pancreatic cancer has been 
shown to improve sensitivity to anti-PD-1 therapy 46 (49). In the ongoing study, preliminary 
data suggests a possible role of NT-I7 in promoting tumor infiltration and increasing peripheral 
lymphocytes. 
Based on these emerging data, we will add subjects in two new arms, Arms IVa and Va, 
anticipating that this addition will help establish a clinically significant ORR, elucidate NT-I7’s 
mechanism of action in MSS-CRC and PC, and further propel the success of this trial. 
 
 
 

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2.4. 
Agents 
2.4.1. 
NT-I7 (aka efineptakin alfa, rhIL-7-hyFc) 
NT-I7 is a long-acting human IL-7 cytokine. It consists of human IL-7 fused to a hybrid Fc 
(hyFc) platform, which extends the half-life of NT-I7. HyFc is composed of the human IgD 
hinge region fused to the N-terminal region of CH2 from IgD, which is in turn fused to the C- 
terminal region of CH2 and the entire CH3 region of human IgG4. A detailed structural diagram 
of NT-I7 is shown in the NT-I7 IB. 
2.4.1.1. 
Pre-clinical Studies 
In preclinical studies, NT-I7 has demonstrated potent anti-tumor efficacy, both as a monotherapy 
and in combination with chemo/radiotherapy and immune checkpoint inhibitors (CPIs). By 
increasing peripheral and tumor infiltrating lymphocytes, and increasing T cell functionality, 
NT-I7 synergizes with therapies such as chemotherapy, radiation, and CPIs.    
In a thymectomy-induced lymphopenia model (TILP) of C57BL/6 MC-38-bearing mice, a 
combination of NT-I7 and anti-PD-1 had significant anti-tumor effects that exceeded those of 
NT-I7 or anti-PD-1 therapies alone (Figure 1).   
3
6
9
12
15
18
21
0
1000
2000
3000
***
Control
α-PD-1
IL-7-hyFc
IL-7-hyFc + α-PD-1
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Tumor volume (mm3)
***
***
*
*
3
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12
15
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21
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***
Control
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*
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Figure 1: Synergistic anti-tumor efficacy of NT-I7 with anti-PD-1 on MC38 tumor model in 
sham and TILP hosts.  
The combination treatment increased intratumoral CD4+ and CD8+ T cell infiltration compared 
to treatment with either agent alone (Figure 2). NT-I7 and anti-PD-1 combination therapy is 
further associated with a less exhausted phenotype of CD8+ TILs, where surface expression of 
co-inhibitory receptors PD-1 and TIM-3 was reduced on CD8+ TILs (Figure 3). A positive 
correlation between the number of CD8+ TILs and the suppression of tumor growth suggests that 
the combo therapy of NT-I7 with anti-PD-1 might increase tumor-specific cytotoxic CD8+ T 
cells.  

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Figure 2: Synergistic anti-tumor efficacy of NT-I7 and anti-PD-1 combination therapy is 
associated with a greater increase in CD4+ and CD8+ T cell infiltration than in 
monotherapy.   
 
Figure 3: Down-regulation of PD-1 and TIM-3 immune checkpoint expression on CD8+ 
TILs is correlated with enhanced anti-tumor activity of NT-I7 and anti-PD-1 combination 
therapy. 
A separate experiment evaluating 10mg/kg NT-I7 as a monotherapy in an MC-38 tumor model 
demonstrated that administration of NT-I7 created an immune-favorable tumor 
microenvironment (TME) by increasing the amount of tumor-infiltrating lymphocytes (TIL), the 
ratio of CD8+ Ts to regulatory Ts and MDSCs in the TME, and increasing the proliferative and 
effector capacity of CD8+ TIL (Figure 4). 

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Figure 4: NT-I7 monotherapy promotes an immune-favorable tumor microenvironment 
(TME) 
Thus, NT-I7 in combination with anti-PD-1 therapy can abrogate suppressive tumor milieu by 
inducing increased lymphocyte homing and TIL infiltration, and enhancing T cell functionality, 
thus lowering the barrier to sustained antitumor immunity.  
2.4.1.2. 
Clinical Studies  
Data from the completed studies of NT-I7 in healthy volunteers (GX-I7-HV-001) and patients 
with solid tumors (GX-I7-CA-003) showed that NT-I7 has been well tolerated with minimal 
toxicity and no treatment-related serious adverse events (SAEs). Increases in peripheral absolute 
lymphocyte count (ALC) and multiple subsets of CD4+ and CD8+ T cells have been observed 
following treatment (after an initial decrease likely due to homing to secondary lymphoid 
organs) with peak effect approximately 2 to 3 weeks after treatment. Exposure and 
pharmacodynamic effect were greater following intramuscular (IM) than subcutaneous (SC) 
administration. 
2.4.1.2.1. Completed Study GX-I7-HV-001 
GX-I7-HV-001 was a randomized, double-blind, placebo-controlled, dose-escalation, Phase 1 
study to assess safety, tolerability, pharmacokinetics (PK), and pharmacodynamics after a single 
SC or IM administration of NT-I7 in healthy volunteers. Eligible subjects randomly received 
NT-I7 or placebo in an 8:2 ratio at one of the following doses: 20 μg/kg SC, 60 μg/kg SC, or 60 
μg/kg IM.  
NT-I7 was slowly absorbed, particularly after SC administration (time to maximum 
concentration [Tmax]: 36 to 42 hours post dose) and was slowly removed from the body (T1/2: 48 
to 112 hours), resulting in a flat PK profile, typically seen in biologics. IM NT-I7 was more 

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rapidly absorbed than SC NT-I7 (median Tmax: 4 hours vs 36 hours post dose for IM vs SC, 
respectively), and exposure was ~2 times larger following IM than SC administration at the same 
dose of 60 μg/kg, although the difference was not statistically significant. The PK parameters of 
NT-I7 were more variable after IM administration than SC injection. After SC administration, 
the exposure to IL-7 was increased in a dose-proportional manner. PK parameters are 
summarized in NT-I7 IB. 
The pharmacodynamics assessments as observed by the ALC was increased in a dose-dependent 
manner after NT-I7 IM or SC administration (111.4% IM vs 75.1% SC for percent change from 
baseline at the same dose of 60 μg/kg). The increase in ALC peaked approximately 3 weeks after 
administration of NT-I7, and it lasted over several weeks. An initial 40% to 60% decrease in 
ALC was seen in all subjects within 4 days after NT-I7 administration was likely due to “homing 
effect”. Pharmacodynamic parameters are summarized in NT-I7 IB.  
Further, T-cell counts were also increased following treatment with NT-I7. Cell proliferation was 
observed for all CD4+ and CD8+ naïve T cells, effector memory T cells (TEM), central memory 
T cells (TCM), and terminally differentiated effector memory T cells (TEMRA) at 168-hour post-
dose (Day 7), and the most robust response was observed in NT-I7 60 μg/kg IM group.  
NT-I7 was well tolerated in healthy volunteers after a single SC and IM administration at 20 to 
60 μg/kg. A total of 58 treatment-emergent adverse events (TEAEs) were reported by 26 subjects 
(86.7%). No death or other SAEs were reported during the study. All TEAEs were resolved at 
follow-up. The majority of TEAEs were mild in intensity. Ten (33.3%) subjects experienced 
TEAEs of moderate intensity: injection site reaction (n=8 at 60 μg/kg SC; n=1 at 60 μg/kg IM), 
hepatic function abnormal (n=1 at 60 μg/kg SC). Injection site reactions were considered related 
to the study drug, while the relationship was unlikely for hepatic function abnormal. All other 
TEAEs were of mild intensity. 
The incidence of subjects experiencing drug related TEAEs was similar in the active treatment 
cohorts. Drug-related TEAEs are summarized in NT-I7 IB. 
All subjects had one or more out-of-range values for clinical laboratory tests, but none of these 
were considered clinically significant. No other clinically significant abnormalities were found in 
clinical laboratory tests, vital signs, 12-lead electrocardiogram, or physical examinations. 
Most subjects (n=22, 91.7%) who received NT-I7 developed anti-drug antibody (ADA) during 
the study period, while there was no ADA detected in the placebo group. Neutralizing ADAs 
(NAbs) were observed in 41.6% (10/24) of the subjects 1 month after NT-I7 administration, and 
45.8% (11/24) 2 months after NT-I7 administration, and 1 subject harbored neutralizing ADAs 5 
months after NT-I7 administration. However, the presence of ADA and NAbs did not appear to 
affect drug exposure, safety profile, or pharmacodynamic parameters of NT-I7. For more 
information, refer to NT-I7 IB. 
 

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2.4.1.2.2. Completed Study GX-I7-CA-003 
A Phase 1b trial of single-agent NT-I7 has been conducted in patients with advanced solid 
tumors in Korea (Study No. GX-I7-CA-003) utilizing a 3 + 3 dose escalation approach to 
determine the Recommended Phase 2 Dose (RP2D). The dose level ranges for this study include 
60 µg/kg, 120 µg/kg, 240 µg/kg, 480 µg/kg, 720 µg/kg, 960 µg/kg, 1200 µg/kg, and 1700 µg/kg 
given intramuscularly (IM) every 3 weeks (q3w).  
A total of 35 patients were enrolled and treated with NT-I7. There were 3 subjects who had AEs 
that resulted in death; none were considered related to NT-I7. Five subjects had 6 cases that were 
reported as SAEs. One of these SAEs was also a serious adverse drug reaction (ADR). The most 
common treatment-related AEs were injection site reactions, pyrexia, and abdominal pain. Dose-
limiting toxicity (DLT) was reported in 1 of 2 subjects in the 1700 µg/kg dose group. The RP2D 
and maximum tolerated dose (MTD) were determined to be 1200 µg/kg.  
PD data from the study showed ALC and naïve / less-differentiated memory subsets of CD4+ 
and CD8+ T cells increased in a dose-dependent manner after NT-I7 administration. The levels 
of endogenous IL-7 remained at normal levels without any significant change.  
Pharmacokinetic data show that Cmax and AUC last increased in a dose-proportional manner. The 
study confirmed that NT-I7 was safe and tolerated in patients with cancer, and that it can be 
safely administered without risk of cytokine storm when used in combination with other 
anticancer drugs. Safety data are summarized below. 
A total of 225 TEAEs occurred in 35 subjects (100.0%). By dose group, 14 TEAEs were 
reported in the NT-I7 60 µg/kg group, 30 TEAEs in the NT-I7 120 µg/kg group, 15 TEAEs in 
the NT-I7 240 µg/kg group, 21 TEAEs in the NT-I7 480 µg/kg group, 35 TEAEs in the NT-I7 
720 µg/kg group, 6 TEAEs in the NT-I7 960 µg/kg group, 88 TEAEs in the NT-I7 1200 µg/kg 
group, and 16 TEAEs in the 1700 µg/kg group. When the severity of AEs was graded using the 
NCI-CTCAE (Version 4.0), 118 TEAEs were mild (Grade 1), 84 TEAEs were moderate (Grade 
2), 16 TEAEs were severe (Grade 3), and 4 TEAEs were life-threatening or required urgent 
intervention (Grade 4). Three TEAEs were reported as death related to AEs (Grade 5). 
By preferred term (PT), the most common AEs were injection site reactions (61 TEAEs in 25 
subjects [71.4%]), pyrexia (26 TEAEs in 15 subjects [42.9%]), and abdominal pain (10 TEAEs 
in 10 subjects [28.6%]). 
There were 6 SAEs in 5 subjects (14.29%): 1 subject in the 120 μg/kg group had Grade 5 
mesenteric arterial occlusion (not related to NT-I7); 1 subject in the 480 μg/kg group had Grade 
3 ascites and Grade 5 upper gastrointestinal hemorrhage (both not related); 1 subject in the 1200 
μg/kg group had Grade 2 azotemia and Grade 5 dyspnea (both not related); and 1 subject in the 
1700 μg/kg group had Grade 3 hypersensitivity (related). The last event was also a serious ADR. 
There were 10 AEs of special interest (AESI) as specified in the protocol in 5 subjects. The AESI 
included cases of potential drug-induced liver injury, conditions suggestive of autoimmune 
disorders, Grade 2 or higher AEs suggestive of hypersensitivity or immune-mediated reaction, 
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(pneumonia) occurred in 2 subjects, all others were reported for a single subject (anaphylactic 
reaction, hypersensitivity, mesenteric arterial occlusion, pyrexia, hepatic failure, pleural effusion, 
urticaria, and hypotension). 
One of 2 subjects at 1700 µg/kg experienced DLT (hypersensitivity) as specified in the protocol. 
The RP2D and MTD of NT-I7 was determined to be 1200 µg/kg. 
Clinically significant changes in plasma and serum chemistry results after the administration of 
study drug were reported as AEs or were judged to be due to progression of the underlying 
disease. 
2.4.1.2.3. Other Studies 
ABTC-1403 (also known as NIT-104) is an ongoing Phase 1 dose-escalation and pilot study of 
the effect of NT-I7 on CD4 cell counts in subjects with high grade gliomas and severe treatment-
related CD4 lymphopenia after concurrent radiation therapy (RT) and treatment with 
temozolomide (TMZ). The NIT-104 study is closed to further enrollment. More details are 
provided in the NT-I7 IB. 
NIT-106 is a Phase 1b/2a, open-label study to evaluate anti-tumor efficacy and safety of NT-I7 
in combination with anti-PD-L1 (atezolizumab) in subjects with anti-PD-1/PD-L1 naïve or 
relapsed/refractory high-risk skin cancers. The study is ongoing in the US. 
NIT-109 is an open-label, randomized, A Multicenter, Open-label, Phase 2 Study of NT-I7 in 
Combination with Nivolumab in Subjects with Relapsed/Refractory Gastric or Gastro-
Esophageal Junction or Esophageal Adenocarcinoma who Progressed on or Intolerant to 2 or 
more Prior Lines of Systemic Therapy. The study is ongoing in the US and Poland.  
No efficacy data are available for any of the studies up to date.  
2.4.1.3. 
Benefits and Risks Conclusions 
Safety, pharmacodynamic, and PK data for NT-I7 are available from one completed study in 
healthy volunteers, four completed studies in cancer patients, and 11 ongoing studies in patients 
with cancer and COVID-19. Based on these limited data, it can be concluded that:  
• NT-I7 was well tolerated in healthy volunteers and adult subjects with cancer 
• NT-I7 was generally well tolerated in combination with CPI in adult patients with 
relapsed/refractory (R/R) solid tumors. Myocarditis has been added as a potential risk for 
NT-I7 due to two fatal events when combined with pembrolizumab and atezolizumab, 
respectively. Myocarditis has an established association with both CPIs, and both patients 
had pre-existing cardiac risk factors; these may be more likely contributors to the events, but 
a causal relationship with NT-I7 cannot be ruled out. 
• NT-I7 was slowly absorbed and eliminated, resulting in a flat PK profile, regardless of route 
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• IM administration of NT-I7 resulted in more rapid absorption and had higher exposure to 
NT-I7 than did SC administration 
• NT-I7 led to a dose-dependent increase in CD4+ and CD8+ T cells (naïve T cells, TEM, TCM, 
TEMRA) and NK cells, but there was no dose-dependent increase in B cells 
• IM administration of NT-I7 resulted in a more pronounced increase in lymphocytes over SC 
administration 
The anti-tumor activity observed with NT-I7 as monotherapy or in combination with other anti-
cancer agents, the well-tolerated safety profile seen in humans and the unique ability of NT-I7 to 
increase lymphocyte counts support further clinical investigation in patients with lymphopenia, 
including subjects with cancer who are often lymphopenic due to either the underlying diseases or 
prior anti-cancer treatments. 
Based on the evaluation of the cumulative safety data available and the anticipated efficacy/ benefit 
information for NT-I7, the benefit-risk balance for the product remains favorable. 
2.4.2. 
Pembrolizumab Background 
Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) 
with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its 
interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-
L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor 
blocking activity for PD-1. Pembrolizumab has an acceptable preclinical safety profile and is in 
clinical development as an intravenous (IV) immunotherapy for advanced malignancies. 
Keytruda® (pembrolizumab) is indicated for the treatment of subjects across a number of 
indications. For more details on specific indications refer to the Investigator’s Brochure. 
Refer to Investigator’s Brochure (IB) approved labeling for detailed background information on 
MK-3475. 
2.4.2.1. 
Pharmaceutical and Therapeutic Background 
The importance of intact immune surveillance function in controlling outgrowth of neoplastic 
transformations has been known for decades (50). Accumulating evidence shows a correlation 
between tumor-infiltrating lymphocytes in cancer tissue and favorable prognosis in various 
malignancies. In particular, the presence of CD8+ T-cells and the ratio of CD8+ effector 
T-cells/FoxP3+ regulatory T-cells (T-regs) correlates with improved prognosis and long-term 
survival in solid malignancies, such as ovarian, colorectal, and pancreatic cancer; hepatocellular 
carcinoma; malignant melanoma; and renal cell carcinoma. Tumor-infiltrating lymphocytes can 
be expanded ex vivo and reinfused, inducing durable objective tumor responses in cancers such as 
melanoma (51, 52). 
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress immune 
control. The normal function of PD-1, expressed on the cell surface of activated T-cells under 
healthy conditions, is to down-modulate unwanted or excessive immune responses, including 
autoimmune reactions. PD-1 (encoded by the gene Pdcd1) is an immunoglobulin (Ig) superfamily 
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protein 4 (CTLA-4) that has been shown to negatively regulate antigen receptor signaling upon 
engagement of its ligands (PD-L1 and/or PD-L2) (53, 54). 
The structure of murine PD-1 has been resolved (55). PD-1 and its family members are type I 
transmembrane glycoproteins containing an Ig-variable–type (IgV-type) domain responsible for 
ligand binding and a cytoplasmic tail responsible for the binding of signaling molecules. The 
cytoplasmic tail of PD-1 contains 2 tyrosine-based signaling motifs, an immunoreceptor tyrosine-
based inhibition motif, and an immunoreceptor tyrosine-based switch motif. Following T-cell 
stimulation, PD-1 recruits the tyrosine phosphatases, SHP-1 and SHP-2, to the immunoreceptor 
tyrosine-based switch motif within its cytoplasmic tail, leading to the dephosphorylation of 
effector molecules such as CD3 zeta (CD3ζ), protein kinase C-theta (PKCθ), and zeta-chain-
associated protein kinase (ZAP70), which are involved in the CD3 T-cell signaling cascade (54, 
56-58). The mechanism by which PD-1 down-modulates T-cell responses is similar to, but distinct 
from, that of CTLA-4, because both molecules regulate an overlapping set of signaling proteins 
(59, 60). As a consequence, the PD-1/PD-L1 pathway is an attractive target for therapeutic 
intervention in TNBC, NSCLC, SCLC, MSS-CRC, PC, and OC.   
2.4.2.1.1. Pre-clinical Studies 
Therapeutic studies in mouse models have shown that administration of antibodies blocking PD-
1/PD-L1 interaction enhances infiltration of tumor-specific CD8+ T cells and ultimately leads to 
tumor rejection, either as a monotherapy or in combination with other treatment modalities (61-
67). Anti-mouse PD-1 or anti-mouse PD-L1 antibodies have demonstrated antitumor responses in 
models of squamous cell carcinoma, pancreatic carcinoma, melanoma, acute myeloid leukemia 
and colorectal carcinoma (25, 64, 66-68). In such studies, tumor infiltration by CD8+ T cells and 
increased IFN-γ, granzyme B and perforin expression were observed, indicating that the 
mechanism underlying the antitumor activity of PD-1 checkpoint inhibition involved local 
infiltration and activation of effector T cell function in vivo (66) Experiments have confirmed the 
in vivo efficacy of anti-mouse PD-1 antibody as a monotherapy, as well as in combination with 
chemotherapy, in syngeneic mouse tumor models (see the IB). 
2.4.2.1.2. Justification for 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.  As outlined below, this dose is justified 
by: 
• Clinical data from 8 randomized studies in melanoma and NSCLC indications 
demonstrating flat dose- and exposure-efficacy relationships from 2 mg/kg Q3W to 10 
mg/kg every 2 weeks (Q2W) representing an approximate 5-to-7.5-fold exposure range 
(refer to the IB)  
• Population PK analysis showing that both fixed dosing and weight-based dosing provides 
similar control of PK variability with considerable overlap in the distributions of 
exposures, supporting suitability of 200 mg Q3W 
• Clinical data showing meaningful improvement in benefit-risk including overall survival 
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• Pharmacology data showing full target saturation in both systemic circulation (inferred 
from pharmacokinetic [PK] data) and tumor (inferred from physiologic-based PK [PBPK] 
analysis) at 200 mg Q3W. 
Among the 8 randomized dose-comparison studies, a total of 2262 subjects 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 subject 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 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 
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3. 
Objectives and Endpoints 
This is a multicenter, open-label Phase 1b/2a study to determine the MTD and/or RP2D, to 
assess the safety, and tolerability of NT-I7 in combination with pembrolizumab in subjects with 
CPI-treated R/R tumors (TNBC, NSCLC, SCLC), and CPI-naïve R/R tumors (MSS-CRC and  
PC), and to assess a potential correlation between tumor infiltrating lymphocytes (TILs) and 
clinical benefits in subjects with CPI-naïve R/R OC. Specific objectives and corresponding 
endpoints for the study are outlined in the following Table 1. 
 
Table 1: Objectives and endpoints 
Objectives 
Corresponding Endpoints 
Primary Objectives 
 
Phase 1b: 
• To determine the safety and tolerability, 
including determination of the Maximum 
Tolerated Dose (MTD) and/or the 
Recommended Phase 2 Dose (RP2D) of 
NT-I7 in combination with 
pembrolizumab in subjects with advanced 
solid tumors. 
 
• Incidence, nature, and severity of adverse 
events graded according to NCI CTCAE 
v5.0. 
• Incidence and nature of DLTs. 
• Potential correlation of dose levels with 
safety and efficacy parameters. 
Phase 2a:  
• To assess the preliminary anti-tumor 
activity of NT-I7 in combination with 
pembrolizumab in subjects with CPI 
treated R/R tumors (TNBC, NSCLC, 
SCLC), and CPI naïve R/R tumors (MSS-
CRC and PC), based on Objective 
Response Rate (ORR) per Response 
Evaluation Criteria in Solid Tumors by 
RECIST 1.1 and iRECIST 
 
• Objective Response Rate (ORR) for each 
individual arm, defined as the percentage 
of subjects who have at least one 
confirmed partial response (PR) or 
complete response (CR), per RECIST 1.1 
and iRECIST as determined by the 
investigator. 
 
Biomarker Cohort: 
• To assess a potential correlation between 
tumor infiltrating lymphocytes (TILs) and 
clinical benefits in subjects with CPI-
naïve R/R OC. 
 
• Number, distribution, and phenotype of 
tumor-infiltrating lymphocytes (TILs).  
CD8+ TILs in tumor biopsy samples will 
be identified using a validated IHC assay 
and properly certified by a pathologist.  
Secondary Objectives 
 
Phase 1b/2a/Biomarker Cohort: 
 
 

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• To make further assessment of the anti-
tumor activity of NT-I7 in combination 
with pembrolizumab in these patient 
populations based on ORR (for Biomarker 
Cohort only), Duration of Response 
(DoR), Disease Control Rate (DCR), 
Progression-Free Survival (PFS), and 
Overall Survival (OS) by RECIST 1.1 and 
iRECIST.  
• Objective Response Rate (ORR, 
Biomarker Cohort only) defined as the 
percentage of subjects who have at least 
one confirmed partial response (PR) or 
complete response (CR), per by RECIST 
1.1 and iRECIST as determined by the 
investigator. 
 
• Duration of response (DoR) for the 
responders in each individual arm, defined 
as the time from the first occurrence of a 
documented objective response to the time 
of the first documented disease 
progression or death from any cause, 
whichever occurs first, per RECIST 1.1 
and iRECIST as determined by the 
investigator.  
DoR will be assessed statistically via 
Kaplan-Meier methods and presented 
descriptively for the responders. 
Comparative assessments are not planned 
on this endpoint. 
• Disease Control Rate (DCR) for each 
individual arm, defined as proportion of 
subjects with a best overall response of 
CR, PR or SD, per RECIST 1.1 and 
iRECIST as determined by the 
investigator. 
 
DCR will be assessed statistically via 
Fisher Exact tests supported by Clopper-
Pearson confidence intervals; all analyses 
will be interpreted descriptively. 
Comparative assessments are not planned 
on this endpoint. 
 
• Progression Free Survival (PFS) for each 
individual arm, defined as the time from 
the first study treatment (Cycle 1, Day 1) 
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death from any cause, whichever occurs 
first, per RECIST 1.1 and iRECIST as 
determined by the investigator. 
PFS will be assessed statistically via 
Kaplan-Meier methods and presented 
descriptively for all treated subjects in 
each study arm; censoring rules and 
statistical endpoint definitions (time to 
event) will be detailed in the SAP 
prospectively. Comparative assessments 
are not planned on this endpoint. 
 
• Overall survival (OS) for each individual 
arm, defined as the time from first study 
treatment (Cycle 1, Day 1) to death from 
any cause. 
OS will be assessed statistically similarly 
to PFS (above). 
Phase 1b/2a/Biomarker Cohort: 
• To evaluate immunogenicity of NT-I7 
administered in combination with 
pembrolizumab in these patient 
populations. 
• Incidence of anti-drug antibody (ADA) to 
NT-I7 during the study relative to the 
prevalence of ADA at baseline. 
Immunogenicity to NT-I7 will be 
measured using a risk-based, tiered testing 
approach.  This includes screening and 
confirmatory assays for binding ADAs, 
epitope-specific assays to characterize 
ADA reactivity to whole NT-I7 vs IL-7 
domain, and a cell-based neutralizing 
ADA assay for IL7 bioactivity.  Subject 
samples will be obtained at baseline and 
over the course of treatment (to evaluate 
the prevalence and incidence of treatment-
emergent/boosted ADA). All 
immunogenicity assays have been 
analytically validated. 
Biomarker Cohort: 
• To assess the safety of NT-I7 in 
combination with pembrolizumab in 
subjects with CPI-naïve R/R OC 
• Incidence, nature, and severity of adverse 
events graded according to NCI CTCAE 
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Exploratory Objectives 
 
Phase 1b/2a/Biomarker Cohort: 
• To make a preliminary assessment of PK 
parameters in subjects enrolled in Phase 
1b, Phase 2a and Biomarker Cohort.  
• Serum concentration of NT-I7 
administered in combination with 
pembrolizumab at specified timepoints for 
the following parameters: Area under the 
concentration time-curve (AUC), 
maximum serum concentration (Cmax), 
minimum serum concentration (Cmin), 
and clearance (CL). 
 
ELISA-based assay to measure serum NT-
I7 levels has been analytically validated. 
In phase 1b and in the Biomarker Cohort, 
longitudinal samples will be collected 
from each subject to obtain a detailed PK 
profile. In phase 2a, a sparse sampling 
schema will be employed for population 
PK assessment. Individual PK 
measurements will be tabulated by arms 
along with descriptive statistics. Non-
compartmental PK data analysis will be 
performed from each arm with scheduled 
PK sample collection where data allow. 
Relevant descriptive statistics of non-
compartmental PK parameters will be 
provided and may include area under 
concentration-time curve, maximum 
observed concentration (Cmax), time to 
reach Cmax, clearance, volume of 
distribution, and terminal half-life. 
 
Phase 1b/2a/Biomarker Cohort: 
• To make a preliminary assessment of 
biomarkers that might act as 
pharmacodynamic indicators of NT-I7 
activity in combination with 
pembrolizumab in subjects with CPI 
treated R/R tumors (TNBC, NSCLC, 
 
 
• Number, distribution, and phenotype of 
tumor-infiltrating lymphocytes (TILs) 
(Biomarker Cohort to follow primary 
objective).  
TILs in tumor biopsy samples will be 
identified using a multi-spectral IF assay. 
Markers include, but are not limited to, 

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SCLC), and CPI naïve R/R tumors (MSS-
CRC, PC, and OC). 
 
• To make a preliminary assessment of 
biomarkers that might act as predictors of 
anti-tumor activity of NT-I7 in 
combination with pembrolizumab in 
subjects with CPI treated R/R tumors 
(TNBC, NSCLC, SCLC), and CPI naïve 
R/R tumors (MSS-CRCand PC). 
 
tCD3, CD8, Ki67, panCK, and nuclear 
stain. Image analysis will be performed 
using Halo Indica software. Descriptive 
statistics will be used to describe arm 
specific changes. 
• PD-L1 expression. 
PD-L1 expression will be performed using 
a 22C3 IHC assay in the tumor biopsy. 
PD-L1 mRNA expression by RNA 
sequencing analysis may also be explored. 
Descriptive statistics will be used to 
describe arm specific changes. 
 
• Expression of interferon γ (IFN-γ) and 
associated inflammatory gene expression 
in the tumor microenvironment.  
Based on tissue availability, gene 
expression analysis may be performed on 
tumor biopsy tissue sections. 
 
• Changes in tumor microenvironment that 
correlate with response or provide 
information on potential actionable causes 
for lack of clinical benefit. 
Exploratory analysis in pre- and on-
treatment tumor biopsy samples will be 
performed and compared between 
responders vs. non-responders to help 
elucidating the TME changes that may be 
correlated with response to treatment. 
Analysis may include, but not limited to, 
gene expression profiling and RNAseq, 
TCR repertoire diversity analysis by 
TCRseq, and immunostaining techniques 
such as multi-spectral IF. 
 
• Changes in peripheral blood biomarkers, 
including but not limited to 
immunophenotyping and inflammatory 
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with 1) the incidence of AEs and 2) as 
surrogated markers of response, TME 
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4. 
Subject Selection 
Eligibility criteria for this study have been carefully considered to ensure the safety of the study 
subjects and that the results of the study can be used. It is imperative that subjects fully meet 
entry criteria. Informed consent is withdrawn for patients who do not meet the eligibility criteria 
after screening is completed (“screen failure”).  
4.1. 
Inclusion Criteria 
Subjects must meet all the following criteria for study entry:  
1. Must be ≥18 years on the day of signing informed consent. 
2. Be willing and able to provide written informed consent/assent for the study.  
3. Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors 
who have disease progression after treatment with all available therapies for metastatic 
disease that are known to confer clinical benefit, or are intolerant to treatment, or refuse 
standard treatment. 
4. Have measurable disease per RECIST 1.1 as assessed by the enrolling physician. Lesions 
situated in a previously irradiated area are considered measurable if progression has been 
demonstrated in such lesions.  
5. Subjects enrolling in the Phase 1b and Arms I, IV, IVa, V, and Va of the Phase 2a, and 
the Biomarker Cohort must have biopsiable disease (i.e., have at least 1 tumor lesion that 
is accessible and feasible for biopsy) as determined by the enrolling physician. Willing to 
provide archival tumor tissue sample or newly obtained core or excisional biopsy of a 
tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue 
block is preferred to slide. Newly obtained biopsy is preferred to archived tissue. 
6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 
7. Subjects must have a life expectancy of greater than or equal to 12 weeks per assessment 
from the enrolling physician. 
8. Subjects must have adequate organ function as defined below: 
a. Absolute neutrophil count ≥1,500/µL 
b. Platelets ≥100,000/µL 
c. Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L (Criteria must be met without erythropoietin 
dependency and without packed red blood cell transfusion within last 2 weeks) 
d. Total bilirubin ≤1.5 × institutional upper limit of normal (ULN) OR direct bilirubin 
≤ULN for subjects with total bilirubin levels >1.5 × ULN 
e. AST(SGOT)/ALT(SGPT) ≤2.5 × ULN (AST and/or ALT ≤5 × ULN for subjects with 
liver metastasis) 
f. Alkaline phosphatase ≤2.5 × ULN (≤5 × ULN for subjects with documented liver 
involvement or bone metastases) 
g. Creatinine ≤1.5 × ULN or Creatinine clearance (CrCl) ≥30 mL/min for subjects with 
creatinine levels >1.5 × ULN. CrCl should be calculated per institutional standard.  
h. INR and aPTT ≤1.5 × ULN unless subject is receiving anticoagulant therapy as long 
as PT or aPTT is within therapeutic range of intended use of anticoagulants 
9. ECG demonstrating Fridericia's corrected QT interval (QTcF) < 470 ms. Patients with 
QTcF ≥ 470 ms will require clearance by a local cardiologist. 

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10. Female subjects who are either postmenopausal for at least 1 year, are surgically sterile for 
at least 6 weeks; female subjects of childbearing potential must agree to remain abstinent 
(refrain from heterosexual intercourse) or to use dual methods of contraception for the 
duration of study treatment and for 120 days after the last dose of study treatment 
(pembrolizumab and/or NT-I7). Female subjects of childbearing potential (including 
women who have had a tubal ligation) must have a negative serum or urine pregnancy test 
within 72 hours prior to Cycle 1, Day 1. If the urine test is positive, or cannot be 
confirmed as negative, a serum pregnancy test will be required. 
11. Non-sterile male subjects who are sexually active with female partners of childbearing 
potential must agree to remain abstinent (refrain from heterosexual intercourse) or to use 
highly effective method(s) of contraception for the duration of study treatment and for 120 
days after the last dose of study treatment (pembrolizumab and/or NT-I7). 
12. Meet the requirements for the intended stages and arms (disease specific inclusion 
criteria), as follows: 
Applicable to the Dose escalation phase (Phase 1b) only: 
a. Relapsed/refractory advanced solid tumors 
Note: Prior anti-PD-1/anti-PD-L1 requires a 4-week washout period. 
b. Willing to provide pre- and on-treatment biopsies 
Applicable to the Dose expansion phase (Phase 2a) only: 
Anti-PD-1/anti-PD-L1 refractory criteria for CPI-treated TNBC, NSCLC, and SCLC 
Subjects must have progressed on treatment with an anti-PD-1/anti-PD-L1 monoclonal 
antibody (mAb) administered either as monotherapy, or in combination with other checkpoint 
inhibitors or other therapies. PD-1/PD-L1 treatment progression is defined by meeting all of the 
following criteria: 
a. Has received at least 2 doses of an approved anti-PD-1/anti-PD-L1 mAb.  
Note: Prior anti-PD-1/anti-PD-L1 requires a 4-week washout period. 
b. Has demonstrated disease progression after anti-PD-1/anti-PD-L1 treatment as defined by 
RECIST 1.1. The initial evidence of disease progression (PD) is to be confirmed by a 
second assessment no less than four weeks from the date of the first documented PD, in the 
absence of rapid clinical progression.(1)  
Note: This determination is made by the investigator. Once PD is confirmed, the initial date 
of PD documentation will be considered the date of disease progression. 
c. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-
1/anti-PD-L1 mAb.  
Specific to Arm I: CPI-treated R/R TNBC  
a. Histopathologic or cytologic documented TNBC. Tumors must have been confirmed 
negative for ER and PR by IHC (<1% positive tumor nuclei, as per ASCO-CAP guideline 
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hybridization (FISH or CISH).  
b. Received one or more prior therapies for TNBC in the advanced or metastatic setting, and 
prior treatment (for advanced, metastatic or (neo) adjuvant) must have included a taxane 
and/or anthracycline-based therapy and anti-PD-1/anti-PD-L1.  
c. Willing to provide pre- and on-treatment biopsies. 
Specific to Arm II: CPI-treated R/R NSCLC  
a. Had prior treatment with CPI. Subjects with EGFR, BRAF, or ROS1 mutations or ALK 
translocations are required to have received prior therapy with the appropriate TKI; prior 
platinum-based chemotherapy is not required for this specific patient population.   
 
Specific to Arm III: CPI-treated R/R SCLC 
 
a. Recurrent extensive-stage SCLC. 
b. Received prior CPI therapy.  
Specific to Arm IV and IVa: CPI-naïve R/R MSS-CRC 
a. MSS-CRC (categorized as MSS by immunohistochemistry (IHC) or polymerase chain 
reaction (PCR)-based local assay at any time prior to screening or by a central laboratory). 
Note: Subjects that are MMR deficient or microsatellite instability-high (MSI-H) or 
microsatellite unstable CRC are not eligible. 
b. Previously treated with standard therapies, which must include fluoropyrimidine, 
oxaliplatin, and irinotecan; subjects treated with CPI are not eligible.  
c. Willing to provide pre- and on-treatment biopsies. 
Specific to Arm V and Va: CPI-naïve R/R Pancreatic Cancer  
a. Have documented radiographic progression to or documented intolerance of first line 
systemic chemotherapy which included either gemcitabine or Fluorouracil (5-FU) based 
regimen (including capecitabine); subjects treated previously with CPI are not eligible. 
b. Willing to provide pre- and on-treatment biopsies. 
Applicable to Biomarker Cohort only: 
a. Specific to CPI-naïve R/R Ovarian Cancer Up to 5 prior lines of treatment, including 
platinum-based treatment(s); subjects treated previously with CPI are not eligible. 
b. Willing to provide pre- and on-treatment tumor biopsies. 
4.2. 
Exclusion Criteria 
Subjects meeting any of the following criteria are not eligible for enrollment in the study: 

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1. Pregnant, lactating or breastfeeding or expecting to conceive or father children within the 
study duration from screening through 120 days after the last dose of study treatment. 
2. Receiving chemotherapy or any anti-cancer therapy with half-life <1 week within 30 days 
or 5 half-lives, whichever is shorter, prior to first dose of study treatment. Receiving 
treatment with immune CPIs, immunomodulatory monoclonal antibodies (mAbs), and/or 
mAb-derived therapies within 4 weeks prior to first dose of study treatment. Note: All AEs 
related to previous therapies, except alopecia, must be resolved to ≤Grade 1 or baseline. 
Subjects with ≤Grade 2 neuropathy may be eligible.  Subjects with endocrine-related AEs 
Grade <2 requiring treatment or hormone replacement may be eligible.   
3. Has received prior radiotherapy within 2 weeks of start of study treatment. Subjects 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. 
4. Has known active central nervous system (CNS) metastases and/or carcinomatous 
meningitis. Subjects with previously treated brain metastases may participate provided they 
are radiologically stable (without evidence of progression by repeat imaging (during 
screening) for at least 4 weeks prior to the first dose of study treatment and any neurologic 
symptoms have returned to baseline), have no evidence of new or enlarging brain 
metastases, and are not using systemic steroids for CNS symptom management for at least 
14 days prior to first dose of study treatment.  
5. Subjects who have not recovered from AEs (other than alopecia, vitiligo, neuropathy or 
endocrinopathy managed with replacement therapy) due to agents administered more than 
4 weeks earlier (i.e., have residual toxicities >Grade 1).  
6. Concurrent or previous other malignancy within 3 years of study entry, except cured basal 
or squamous cell skin cancer, transitional cell carcinoma of urothelial cancer, carcinoma in-
situ of the breast or cervix.  
7. History of severe hypersensitivity reactions to monoclonal antibodies (mAbs) or 
intravenous immunoglobulin preparations; any history of anaphylaxis; prior history of 
human anti-human antibody response; known allergy to any of the study medications, their 
analogues, or excipients in the various formulations of any agent.  
Note: Subjects with severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its 
excipients are also excluded. 
8. Subjects who have spinal cord compression not definitively treated with surgery and/or 
radiation or previously diagnosed and treated spinal cord compression without evidence 
that disease has been clinically stable for ≥2 weeks prior to screening. 
9. Subjects who have autoimmune disease history for the past 2 years, including but not 
limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, 
vascular thrombosis associated with antiphospholipid syndrome, Wegener’s 
granulomatosis, Sjögren’s syndrome, Bell’s palsy, Guillain-Barre syndrome, multiple 
sclerosis, vasculitis or glomerulonephritis.  
10. Have active and clinically relevant bacterial, fungal, viral, or TB infection, including 
known Hepatitis A, B, or C or HIV (testing not required).  
11. Clinically significant cardiac disease, including, but not limited to, any of the following: 
Congestive heart failure requiring treatment (New York Heart Association Grade ≥ 2); 
clinically significant and uncontrolled atrial fibrillation; history of acute coronary 

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syndromes including myocardial infarction, unstable angina, coronary artery bypass 
grafting, coronary angioplasty, or stenting < 6 months prior to screening; symptomatic 
chronic heart failure, history or current evidence of clinically significant cardiac arrhythmia 
and/or conduction abnormality < 6 months prior to screening except controlled atrial 
fibrillation and paroxysmal supraventricular tachycardia. 
12. Subjects who have received treatment with systemic immunosuppressive medications 
(including, but not limited to, systemic prednisone >10 mg/day or its equivalent, 
cyclophosphamide, azathioprine, methotrexate, thalidomide and antitumor necrosis factor 
[anti-TNF] agents) within 7 days prior to first dose of study treatment.  
Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid 
replacement therapy for adrenal or pituitary insufficiency) is not considered a form of 
systemic treatment and is allowed. 
13. History of allergy or intolerance (unacceptable AEs) to study drug components or 
polysorbate-80-containing infusions.  
Note: Polysorbate 80 is a buffer used to make NT-I7. 
14. Has a history of non-infectious pneumonitis that required steroids or current pneumonitis.  
15. 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 enrolling physician. 
16. Has a known psychiatric or substance abuse disorder that would interfere with the subject’s 
ability to cooperate with the requirements of the study. 
17. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples 
of live vaccines include, but are not limited to, the following:  measles, mumps, rubella, 
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and 
typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus 
vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live 
attenuated vaccines and are not allowed. 
18. Has had an allogenic tissue/solid organ transplant or bone marrow transplant.  
19. 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 (e.g., CTLA-4, OX 
40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE. 
4.3. 
Inclusion of Women and Minorities 
Men and women of all races and ethnic groups are eligible for this study. 
4.4. 
Meals and Dietary Restrictions 
Subjects should maintain a normal diet unless modifications are required to manage an AE such 
as diarrhea, nausea, or vomiting. 
4.5. 
Contraception 
NT-I7 and pembrolizumab may have adverse effects on a fetus in utero. Furthermore, it is not 
known if NT-I7 or pembrolizumab has transient adverse effects on the composition of sperm.   

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Subjects should be informed that taking the study medication may involve unknown risks to the 
fetus (unborn baby) if pregnancy were to occur during the study. In order to participate in the 
study, subjects of childbearing potential must adhere to the contraception requirement from time 
of consent (or 14 days prior to the initiation of study medication for oral contraception) throughout 
the study period up to 120 days after the last dose of study treatment.  
If there is any question that a subject of childbearing potential will not reliably comply with the 
requirements for contraception, that subject should not be entered into the study.  

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5. 
Study Design 
5.1. 
Overall Design 
 
This is a multicenter, open-label Phase 1b/2a study of NT-I7 in combination with 
pembrolizumab. The study will include a dose escalation phase (Phase 1b) followed by a dose 
expansion phase (Phase 2a) and a Biomarker cohort. 
 
The Phase 1b is designed to assess the safety and tolerability, including determination of the 
MTD and/or the RP2D, of NT-I7 in combination with pembrolizumab in subjects with 
advanced solid tumors. The Phase 1b will follow the standard 3+3 study design. Three dose 
levels of NT-I7 are planned [DL 1 (480 µg/kg IM Q6W), DL 2 (960 µg/kg IM Q6W), and DL 
3 (1200 µg/kg IM Q6W)], and up to 18 subjects will be enrolled (up to 6 subjects per dose 
level). Doses may be de-escalated to one or two levels (e.g., 360 or 240 µg/kg IM Q6W) 
depending on the pre-defined Dose-Limiting Toxicity (DLT) criteria. Pembrolizumab dose is 
fixed at 200 mg IV Q3W for all dose levels. Upon completion of Phase 1b, the MTD was not 
reached. There was 1 DLT (Grade 3 ALT increased) observed at the highest dose level tested 
(1,200 µg/kg; n=6 patients). The RP2D was determined to be NT-I7 1,200 µg/kg (IM Q6W) 
and pembrolizumab 200 mg (IV Q3W). 
 
For Phase 2a, selected arms I, II, III, IV, and V will follow the Simon’s minimax two-stage 
design which include the following indications:  CPI-treated R/R tumors (TNBC, NSCLC, 
SCLC), and CPI-naïve R/R tumors (MSS-CRC and PC). Each arm will enroll up to 17 
evaluable subjects in Stage 1 and, if the Go/No Go criterion is met, an additional 8 evaluable 
subjects in Stage 2 for a total of 25 evaluable subjects per arm. Exact 95% binomial Clopper-
Pearson confidence interval estimates of ORR from each arm is planned to support the primary 
hypothesis tests. Study enrollment will continue while the first 17 subjects are undergoing 
evaluation to confirm response. Enrolment of up to 30 subjects per arm is planned to account 
for non-evaluable subjects and dropouts. Approximately 210 subjects are planned in total for 
the Phase 2a. Subjects in the Phase 2a will be treated at the RP2D for the combination as 
determined in the Phase 1b.  
 
Arms IVa, Va, and the Biomarker Cohort will not follow the Simon’s minimax two-stage 
design. 
 
The Biomarker Cohort will enroll up to 10 evaluable subjects with CPI-naïve R/R Ovarian 
Cancer (OC). The starting dose level of NT-I7 is planned at 960 µg/kg IM Q6W to further 
evaluate the tolerability of the starting regimen. Pembrolizumab dose is fixed at 200 mg IV 
Q3W. Subjects who tolerate at least 4 cycles of treatment without Grade ≥ 3 AEs and all Grade 
2 AEs have resolved to Grade ≤ 1, the dose may be escalated to NT-I7 1200 µg/kg IM Q6W at 
Cycle 5. This cohort will test intra-patient dose escalation and collect samples for biomarker 
analyses at 2 different dosages. 
 
One treatment cycle is defined as 21 days (3 weeks) with NT-I7 administered intramuscularly 
(IM) once every 6 weeks (Q6W), and pembrolizumab administered intravenously (IV) once 

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every 3 weeks (Q3W). On days where both drugs are given, pembrolizumab will be given prior 
to NT-I7.  Completion of 35 cycles of administration (approximately 2 years) with 
pembrolizumab and NT-I7.  
5.2. 
Rationale for Dose Selection 
Completed clinical study of NT-I7 monotherapy in patients with advanced solid tumors (Study 
GX-I7-CA-003) demonstrated an increase of ALC and multiple T-cell subsets in the peripheral 
blood in a dose-dependent manner until 720 µg/kg where the increases appeared to plateau. 
However, comparative tumor infiltrating lymphocytes (TIL) data in cancer patients is not yet 
available, although it is possible that higher TIL responses may be observed at doses higher than 
720 µg/kg. Further, our preclinical data also suggested a dose-dependent increase in the 
peripheral ALC which appeared to plateau out at 2.5 mg/kg (i.e., no significant difference 
between 2.5 mg/kg and the higher dose of 10 mg/kg), but there were significantly more TILs, 
especially CD8+ T cells, at the 10 mg/kg dose. This animal dose of 10 mg/kg roughly translates 
to 810 µg/kg human dose. In addition, since 10 mg/kg was the highest dose tested in the animal 
model, it is not known whether higher doses would result in more TILs. Thus, both 960 µg/kg 
and 1200 µg/kg dose levels are selected for testing. 
The 480 µg/kg dose is chosen as the starting dose for NT-I7 based on the following rationales: 1) 
the safety profile of the combination, pembrolizumab + NT-I7, is not known; 2) based on the 
data from Study GX-I7-CA-003, 480 µg/kg dose did increase peripheral ALC and multiple 
subsets of T cells, thus can potentially provide benefit to the patients; 3) there are large 
differences between 480 µg/kg, 960 µg/kg, and 1200 µg/kg doses that may allow detection of the 
differences in pharmacodynamic parameters (e.g. peripheral ALC and TILs) between the three 
dose levels. 
Hence, based on the preclinical and clinical data, 480, 960, and 1200 µg/kg are selected for 
testing in this study. 
5.3. 
Dose Escalation (Phase 1b)  
The starting dose of NT-I7 will be 480 µg/kg.  
The 3 + 3 design will be conducted as follows. Initially, 3 subjects will be enrolled to a dose 
level; the occurrence of a single drug related DLT in one of these 3 subjects will prompt 
enrollment of up to 3 additional subjects to that same dose level. When more than 1 DLT occurs 
in ≤ 6 subjects in a dose level, dose escalation will be stopped, and this dose level will be 
identified as the non-tolerated dose. Doses between the non-tolerated dose and the preceding 
lower dose, where ≤ 1 DLT occurred, may be explored to more precisely define the MTD.  
 
The DLT is defined in Section 6.2. The DLT evaluation period is the first 21 days (3 weeks) of 
study treatment (Cycle 1, Day 1 to 21).  
The dose escalation decisions will be communicated to all study sites by regularly scheduled 
teleconferences and follow up email correspondence documenting the decision and rationale.  

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The RP2D will be selected according to the following logic, taking into account the MTD 
determination from the Dose Escalation Phase (Phase 1b) and the Maximum Effective Dose 
(MED) level which is defined as the dose level at which maximum effects on peripheral blood T-
cell levels and intratumor T-cell levels are observed. The intratumor T-cell levels will dominate 
if the peripheral blood and intratumor T-cell levels differ. The available data will be assessed by 
the Data Monitoring Committee (DMC), which will include the Protocol PI, Study Medical 
Monitor, Study statistician, and NeoImmuneTech, Inc.’s designee to select the RP2D. 
• 
If the MTD is determined AND 
• 
MTD = MED, then the RP2D = MTD = MED 
• 
MTD > MED, then the RP2D = MED 
• 
If the MTD is not reached, then the RP2D = MED 
Once the RP2D has been selected, the study will proceed to the Dose Expansion Phase (Phase 
2a) to further evaluate RP2D in a larger number of subjects and selected tumor types. 
5.4. 
Dose Expansion (Phase 2a) 
Subjects enrolled into the study during the dose expansion phase (Phase 2a) will be treated at the 
RP2D, which was determined to be 1200 µg/kg IM Q6W. Certain indications may be selected to 
expand in the expansion phase based on the emerging data. 
For Phase 2a, Arms I, II, III, IV, and V will follow the Simon’s two-stage minimax design.  
Arms IVa, Va, and the Biomarker Cohort OC will not follow the Simon’s two-stage minimax 
design. 
o Arm I 
: CPI-treated R/R TNBC 
o Arm II : CPI-treated R/R NSCLC 
o Arm III : CPI-treated R/R SCLC 
o Arm IV : CPI-naïve R/R MSS-CRC 
o Arm IVa : CPI-naïve R/R MSS-CRC 
o Arm V : CPI-naïve R/R PC 
o Arm Va : CPI-naïve R/R PC 
o Biomarker Cohort: Ovarian Cancer 
In Stage 1, up to 17 evaluable subjects per arm will be enrolled and treated. If at least one 
subject achieves objective response (complete response [CR] or partial response [PR]) in an 
arm, that arm may be expanded by enrolling up to 8 evaluable additional subjects in Stage 2. 
Study enrollment will continue while the first 17 subjects are undergoing evaluation to confirm 
response. If no objective response is observed in an arm during Stage 1, further enrollment will 
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5.5. 
Subject Expansion (Arm IVa and Va)  
The Subject Expansion Cohort is designed to further assess the clinical benefits of NT-I7 in 
combination with pembrolizumab in subjects enrolled in the 2 selected cohorts based on 
emerging data. Subjects will receive Pembrolizumab at 200 mg IV Q3W and NT-I7 1200 µg/kg 
IM Q6W. 
5.6. 
Biomarker Cohort 
The Biomarker Cohort is designed to assess the correlation between tumor infiltrating 
lymphocytes (TILs) and clinical benefits of NT-I7 in combination with pembrolizumab in 
subjects with CPI-naïve R/R Ovarian Cancer (OC). Up to 10 evaluable subjects will be enrolled 
in this cohort. The starting dose of NT-I7 will be 960 µg/kg IM Q6W. Pembrolizumab dose is 
fixed at 200 mg IV Q3W.  
Subjects who tolerate at least 4 cycles of treatment without Grade ≥ 3 AEs and all Grade 2 Aes 
have resolved to Grade ≤ 1 may be dose escalated to NT-I7 1200 µg/kg IM Q6W. 
  
 
 

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5.7. 
Study Schema 
 
 
    
 

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5.8. 
Treatment Schema 
 

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6. 
Study Treatment 
NT-I7 and Pembrolizumab  
6.1. 
Study Treatment Administration 
Reported AE and potential risks are described in Section 11.1. Appropriate dose modifications 
are described in Section 8.1 and 8.2. No investigational or commercial agents or therapies other 
than those described below may be administered with the intent to treat the subject’s malignancy. 
Treatment will be administered on an outpatient basis.  
Table 2: Study treatment details 
Study 
Treatment  
Dosage 
Formulation 
Unit Dose 
Strength 
Dosage 
Level(s) 
Route  
Regimen or 
Treatment 
Period 
Sourcing 
NT-I7 
Solution for 
injection 
25 
mg/mL 
Dose in 
µg/kga 
Q6W 
IM injection 
Day 1 of alternate 
cycle 
Provided 
centrally by 
Sponsor 
Pembrolizumab  
(MK-3475) 
Solution for 
infusion 
100 
mg/vial 
200 mg 
Q3W 
IV infusion 
Day 1 of every 
cycle 
Provided 
centrally by 
Sponsor 
Abbreviations: IM=intramuscular; IV=intravenous.  
aRefer to Sections 5.4, 5.5 and 5.6 for assigned dose level. 
6.1.1. 
NT-I7  
Chemical Formula: C4012H6350N1104O1238S42 
Structural Formula: NT-I7 is a fusion protein comprising human IL-7 fused to the human IgD 
hinge region. This in turn is fused to the N-terminal region of CH2 from IgD and two key 
regions of the antibody IgG4: C-terminal region of CH2 and the entire CH3 region. 
6.1.1.1. 
NT-I7 Pharmaceutical Information 
NT-I7 protein is produced by inserting the gene expressing rhIL-7-hyFc into the eukaryotic 
expression vector pAD15 at the Multiple Cloning Site. The CHO cell line DG44 is used to 
produce NT-I7. NT-I7 has a molecular weight of 104 KDa and is composed of 400 amino acids 
with 155 amino acids for IL-7 and 30 for the IgD hinge, 8 for IgD the CH2 domain, and 207 for 
the IgG4 region. NT-I7 contains 11 disulfide bonds, 1 O-glycosylation and 3 N-glycosylation 
sites. 
Pharmaceutical Properties: NT-I7 is supplied in a sterile, preservative-free liquid form in a 
single-use vial. One vial (1.0 mL) contains 25 mg per 1 mL of the active ingredient of the 
finished drug product. The purity of the active ingredient must be 89.0% or higher based on size-
exclusion ultra-high-performance liquid chromatography (SE-UHPLC) testing and 90.0% or 

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higher based on reverse-phase high-performance liquid chromatography (RP-HPLC) testing. The 
NT-I7 finished drug product should be a colorless, clear solution and should not contain any 
particulate matter that can be observed visually. 
Dosage Form: In addition to the active ingredient NT-I7, each vial contains sucrose, D-sorbitol, 
tri-sodium citrate dehydrates, citric acid monohydrate and Polysorbate 80 as a stabilizer and 
buffer. These ingredients meet the specification criteria of the European pharmacopeia (Ph. 
EUR). NT-I7 is supplied in a 1.0 mL vial package at a concentration of 25 mg protein/mL. The 
finished drug product solution contained in the vial is a liquid injection dosage form at pH 
5.0±0.5 and a colorless, clear solution. There should not be any floating particulates under gross 
observation. For information on the injection sites, please refer to NT-I7 Pharmacy Manual. 
Storage and Handling of NT-I7: Vials that contain NT-I7 must be kept refrigerated at 2~8℃. 
NT-I7 vials should NEVER BE FROZEN. It is recommended that vials are protected from direct 
light until the time of use.  
Route of Administration: IM injection. DO NOT SHAKE vials before injection. A vial is 
restricted to 1 subject and to 1 day of treatment.  
6.1.1.2. 
NT-I7 Dosing 
Subjects will receive NT-I7 according to the following dose escalation schedule. Dose escalation 
will proceed within each dose level as described in Section 5.3.  
The NT-I7 dose will be administered 45 (±15) minutes after Pembrolizumab on all days where 
concurrent administration is planned. NT-I7 dose administered will be determined using the 
subject’s body weight. Refer to the NT-I7 Pharmacy Manual for details. 
NT-I7 will be injected intramuscularly. Guidelines for IM injection by the research nurse or 
investigator are described in the NT-I7 Pharmacy Manual.  
On the odd-numbered cycles as pembrolizumab and NT-I7 are administered, vital signs need to 
be obtained within 60 minutes prior to the start of the pembrolizumab infusion and repeated after 
the completion of the infusion but before the NT-I7 injection. 
6.1.2. 
Pembrolizumab 
Pembrolizumab will be administered using IV infusion on Day 1 of each 3-week treatment cycle 
after all procedures and assessments have been completed. [NT-I7 to be administered 30-60 
minutes post administration of pembrolizumab on days where concurrent administration is 
planned]. 
Pembrolizumab will be administered as a dose of 200 mg using a 30-minute IV infusion. Sites 
should make every effort to target infusion timing to be as close to 30 minutes as possible.  
However, given the variability of infusion pumps from site to site, a window between -5 minutes 
and +10 minutes is permitted (i.e., infusion time is 30 minutes (-5 min/+10 min). 
On the even-numbered cycles (only pembrolizumab administered), vital signs need to be obtained 
within 60 minutes prior to the start of the pembrolizumab infusion. 

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The Pembrolizumab Pharmacy Manual contains specific instructions for the preparation of the 
pembrolizumab infusion and administration of infusion solution. 
6.2. 
Dose-Limiting Toxicity  
All toxicities will be graded using NCI CTCAE Version 5.0. For the purpose of this study, a 
DLT is any event attributed to NT-I7 and/or to pembrolizumab and occurring during the DLT 
period of first 21 days. 
Dose-limiting toxicity is defined as any AE occurring within the first 21 days (i.e., Cycle 1, Day 
1 through Day 21), that is considered to be at least possibly, probably, or definitely related to the 
study treatment (NT-I7 and/or pembrolizumab) per the investigator, and that meets at least one 
of the non-hematologic or hematologic criteria listed below.  
6.2.1. 
DLT criteria  
1. Grade 4 non-hematologic toxicity (not laboratory). 
2. Grade ≥ 3 diarrhea, nausea, or vomiting without use of anti-emetics or anti-diarrheals per 
standard of care  
3. Grade ≥ 3 rash lasting ≥ 5 days 
4. Grade 4 neutropenia lasting ≥ 5 days 
5. Febrile neutropenia Grade 3 or Grade 4: 
• Grade 3 is defined as ANC < 1000/mm3 with a single temperature of > 38.3 degrees C 
(101 degrees F) or a sustained temperature of ≥38 degrees C (100.4 degrees F) for more 
than 1 hour 
• Grade 4 is defined as ANC < 1000/mm3 with a single temperature of > 38.3 degrees C 
(101 degrees F) or a sustained temperature of ≥ 38 degrees C (100.4 degrees F) for 
more than 1 hour, with life-threatening consequences and urgent intervention indicated. 
6. Other Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia: 
• Grade 4 thrombocytopenia of any duration 
• Grade 3 thrombocytopenia associated with clinically significant bleeding 
Note: Peripheral lymphocytopenia after the first NT-I7 injection is not a sign of 
toxicity; it reflects the lymphocytes “homing effect” of NT-I7. Lymphocyte counts 
usually come back to baseline 5 to 7 days after the first injection. 
7. Any non-hematologic AE ≥ Grade 3 in severity should be considered a DLT, with the 
following exception: Grade 3 fatigue lasting ≤ 3 days.; without use of corticosteroids or 
anti-inflammatory agents per standard of care. 
8. Any Grade 3 or Grade 4 non-hematologic laboratory value if: 
• Clinically significant medical intervention is required to treat the subject, or 
• The abnormality leads to hospitalization, or 
• The abnormality persists for > 1 week, or 

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• The abnormality results in potential Drug-induced Liver Injury (DILI) as defined by 
Hy’s Law. 
Exceptions: Clinically nonsignificant, treatable, or reversible laboratory abnormalities 
including liver function tests, uric acid, etc. 
9. Other Grade ≥ 3 clinical laboratory abnormalities must be reversible to ≤ Grade 1 within 
72 hours with outpatient care and/or monitoring AND must not be considered clinically 
significant by the treating physician to be excluded from the definition of DLT. 
10. Prolonged delay (> 2 weeks) in initiating Cycle 2 due to treatment-related toxicity. 
11. Any treatment-related toxicity that causes the subject to discontinue treatment during Cycle 
1. 
12. Grade 5 toxicity. 
Once all subjects in a dose level have completed the 3-week (21 days) DLT window, the AEs 
will be assessed by the DMC, which includes the Protocol PI, Study Medical Monitor, Study 
Statistician, and Study Sponsor’s designee.  
The subjects must complete the full 3-week DLT window to be considered evaluable for DLTs. 
Subjects who discontinue from the study before completion of the full 3-week DLT window for 
reasons other than the occurrence of a DLT (e.g., withdrawal of consent, rapid tumor 
progression, death due to rapid tumor progression, AE that does not meet DLT criteria) will not 
be considered evaluable for DLTs and will be replaced. 
All subjects will be monitored for occurrence of DLT. Monitoring of all safety and toxicity data 
is done by the PIs, the study Sponsor and/or designee on a real-time basis as data are entered into 
the electronic data capture (EDC) system. All participating sites must notify the protocol PI and 
the Sponsor or designee when a DLT has occurred. 
6.3. 
Subject Replacement 
Subjects who receive at least 1 dose of the investigational treatment will be considered evaluable 
for safety and included in the overall safety analysis. 
Subjects who discontinue from the study before completion of the full 3-week DLT window for 
reasons other than the occurrence of a DLT (e.g., withdrawal of consent, rapid tumor 
progression, death due to rapid tumor progression, AE that does not meet DLT criteria) will not 
be considered evaluable for DLTs and will be replaced. 
6.4. 
Discontinuation of Study Intervention, Subject Discontinuation/Withdrawal, and 
Study Termination 
6.4.1. 
Discontinuation of Study Intervention 
In the absence of treatment delays due to AE(s), treatment with NT-I7 and pembrolizumab may 
continue for approximately 2 years or up to 35 cycles of study treatment relative to the date of 
the 1st dosing or until one of the following criteria applies: 
• Disease progression warranting alternative systemic therapy 

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Note: Subjects with RECIST-defined progressive disease (PD) who are otherwise stable without 
symptomatic progression should continue study treatment until the next radiographic imaging time 
point (at least 4 weeks after the prior assessment of PD) to assess for possible pseudo-progression. 
 
Discontinuation from treatment does not represent withdrawal from the trial.  
 
Subjects may discontinue treatment at any time for any reason or be dropped from treatment at the 
discretion of the Investigator, should any untoward effect occur.  In addition, a subject may be 
discontinued from treatment by the Investigator or the Sponsor, if treatment is inappropriate, the 
trial plan is violated, or for administrative and/or other safety reasons.  
A subject may be discontinued from treatment but continue to be monitored in the trial for any of 
the following reasons:  
• 
The subject or subject’s legally acceptable representative requests to discontinue 
treatment  
• 
The Investigator believes that for safety reasons or tolerability reasons (e.g., AE) 
it is in the best interest of the subject to discontinue study drug.  
• 
Intercurrent illness that prevents further administration of treatment  
• 
Unacceptable AEs (e.g., those meet the DLT criteria or other adverse events 
which can jeopardize patient safety per enrolling physician or considered 
unacceptable by the subject)  
• 
Progressive disease confirmed radiographically.  
• 
Note: In the case of suspected pseudoprogression, patients will be advised 
to continue treatment beyond initial RECIST 1.1-defined PD while waiting 
for confirmation of PD, provided they are clinically stable (per 
iRECIST).  Investigators are recommended to consult with the Sponsor 
designee regarding individual cases.  
• 
Treatment interruption lasting >12 weeks (see Section 8.1.1)  
• 
The patient becomes pregnant.  Refer to Section 11.8. 
• 
Noncompliance with study procedure requirements or study drug administration 
(e.g., non-compliance with study visits and miss too many drug administrations).  
• 
The subject persistently uses a disallowed medication as discussed with the 
Sponsor’s designee.  
• 
Discontinuation of treatment may be considered, at the discretion of the treating 
physician per criteria below, but continue to be monitored in the study for any of the 
following reasons:   
o Recurrent Grade 2 pneumonitis  
o Discontinuation of treatment may be considered for subjects who have 
attained a confirmed complete response (CR) and have been treated for at least 
8 cycles (at least 24 weeks), receiving 2 cycles of the combination including 2 
doses of pembrolizumab and had at least 2 treatments of NT-I7 beyond the date 
when the initial CR was declared. Completion of up to 35 treatments (or 
approximately 2 years) with pembrolizumab. Note: The number of 
administrations is calculated starting with the first dose of pembrolizumab. 

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o Any study intervention-related toxicity specified as a reason for permanent 
discontinuation as defined in the guidelines for dose modification due to AEs 
in Section 8.2. 
 
The reason(s) for protocol treatment discontinuation, the reason(s) for study removal and the 
corresponding dates must be documented in the CRF.  
  
If a subject discontinues study drug for any reason (except withdrawal of consent from the study), 
end of treatment/early withdrawal assessments should be obtained as soon as possible and follow 
up assessments should be obtained according to SOA. Subjects who permanently discontinue study 
treatment for reasons other than objective RECIST 1.1 and iRECIST disease progression should 
continue to have scans performed as scheduled, at the investigative site or locally, up to one year 
after discontinuation of study treatment. Standard of care disease assessments will be collected 
until the start of a new anticancer treatment, disease progression, pregnancy, death, withdrawal of 
consent or end of study, whichever occurs first.    
  
Subjects removed from study for unacceptable AE(s) will be followed until resolution or 
stabilization of the AE; in addition, the subjects will be followed for disease status and overall 
survival, as described above.  
 
6.4.2.  Subject Discontinuation/Withdrawal from Study 
Subjects have the right to withdraw from participation in the study at any time and any reason 
without prejudice to their future medical care by the investigator or at the institution.  If a subject 
withdraws from the trial, they will no longer receive treatment or be followed at scheduled 
protocol visits.  
A subject will be withdrawn from the study for any of the following reasons:  
• 
Subject does not meet study eligibility criteria (“screen failure”) 
• 
Withdrawal of consent by subject or subject’s legally acceptable representative  
• 
Lost to follow up  
• 
Death  
  
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the eCRF and in the source document.    
  
Withdrawal of Consent  
If the reason for withdrawal from the study is withdrawal of consent, then no additional 
assessments are allowed unless the Subject agrees to take part in the end of treatment 
visit. Subject also has the option to partially withdraw from active participation in the study and 
scheduled visits, but may allow status followup via telephone or medical record review.   
  
Lost to Follow-up  
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site.  A subject cannot be deemed lost to follow-

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up until all reasonable efforts made by the study site personnel to contact the Subject are deemed 
futile.  
• 
The study site personnel must attempt to contact the subject to reschedule the 
missed visit as soon as possible, to counsel the subject on the importance of 
maintaining the assigned visit schedule, and to ascertain whether the subject wishes to 
continue in the study.  
• 
Before a subject is deemed lost to follow-up, the Investigator or designee must 
make every reasonable effort to regain contact with the subject (where possible, 3 
telephone calls, emails, fax, and if necessary, a certified letter to the subject’s last 
known mailing address).  These contact attempts should be documented in the 
subject’s source document.  
• 
Should the subject continue to be unreachable despite every reasonable effort to 
regain contact by the site, they will be considered lost to follow-up and withdrawn 
from the study.  
6.4.3.  Study Termination 
The Sponsor reserves the right to terminate the study at any time for any reason.  If this decision 
is made, all subjects will be required to be discontinued from treatment and complete the end of 
treatment study visit.  
6.5. 
Study Treatment Beyond Progression 
Immunotherapeutic agents may produce antitumor effects by potentiating endogenous cancer-
specific immune responses. The response patterns seen with such an approach may extend 
beyond the typical time course of responses seen with cytotoxic agents and can manifest as a 
clinical response after an initial increase in tumor burden or even the appearance of new lesions. 
At the investigator’s discretion, a participant may continue on study intervention beyond 
radiological progression as defined by RECIST 1.1 if the clinical condition of the participant is 
stable or the participant is improving symptomatically, and the investigator expects continued 
clinical benefit for the participant until subsequent progression determined by iRECIST criteria 
(Appendix A – Assessment of Disease). 
In participants who have initial evidence of radiological PD by RECIST 1.1, it will be at the 
discretion of the investigator whether or not to continue a participant on study treatment until 
repeat imaging is obtained to determine whether participant’s disease is progressing or the initial 
evidence represents a ‘pseudoprogression or tumor flare’. This clinical judgment decision should 
be based on the participant’s overall clinical condition, including performance status, clinical 
symptoms, and laboratory data. Participants may continue to receive study treatment until tumor 
assessment is repeated ≥4 weeks later in order to confirm PD by iRECIST. 
Per iRECIST (Appendix A – Assessment of Disease) disease progression should be confirmed by 
the site in 4 to 8 weeks after site-assessed first radiologic evidence of PD in clinically stable 
participants. Participants who have unconfirmed disease progression may continue on treatment at 
the discretion of the investigator until progression is confirmed by the site, provided they have met 
the clinically stable definition as Appendix A – Assessment of Disease, including. absence of 

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symptoms and signs indicating clinically significant progression of disease. Subjects should 
remain on the study and continue to be monitored according to the Schedule of Assessments.  
Any participant deemed clinically unstable should be discontinued from study treatment at site-
assessed first radiologic evidence of PD, and is not required to have repeat tumor imaging for 
confirmation of PD by iRECIST.  
If repeat imaging does not confirm PD per iRECIST, as assessed by the investigator, and the 
participant continues to be clinically stable, study treatment may continue and follow the regular 
imaging schedule.  
If PD is confirmed, participants will be discontinued from study treatment. If a participant has 
iCPD as defined in Appendix A, study treatment should be discontinued; however, if the 
participant is achieving a clinically meaningful benefit, an exception to continue study treatment 
may be considered following consultation with the Sponsor. In this case, if study treatment is 
continued, tumor imaging should continue to be performed following the intervals as outlined in 
Table 6. 
6.6. 
Duration of Follow-Up and End of Study 
The active study will end when the last subject completes the 90-day Safety Follow-up visit, 
approximately 2 years after enrollment. 
End of treatment (EOT) visit should be performed within approximately 7 days after disease 
progression determination, treatment discontinuation, or immediately before initiation of any 
other cancer therapy, whichever is earlier.  
Safety Follow-up visit should be performed 30 (± 7) days and 90 (± 7) days after the last 
administration of either agent.  
Subjects who complete all 35 cycles of treatment or permanently discontinue study treatment for 
reasons other than objective disease progression confirmed by RECIST 1.1 and iRECIST should 
continue to have RECIST scans performed every 9 weeks (± 7 days), at the investigative site or 
locally, up to one year after discontinuation of study treatment. Standard of care disease 
assessments will be collected until the start of a new anticancer treatment, disease progression, 
pregnancy, death, withdrawal of consent or end of study, whichever occurs first.   
After disease progression or start of new anticancer treatment, subjects will be followed for 
survival every 90 days (± 7 days) until death, lost to follow-up, withdrawal of consent or end of 
the study, whichever occurs first. Survival follow-up can be done either by in-person visit or by 
telephone assessment. 
Subjects removed from study for unacceptable AE(s) will be followed until resolution or 
stabilization of the AE; in addition, the subjects will be followed for disease status and overall 
survival, as described above.  

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7. 
Study Procedures and Assessments  
 
7.1. 
Informed Consent 
A copy of the signed and dated ICF will be provided to the subject. The original ICF will be 
retained by the Investigator. Informed consent must be obtained prior to performing any study-
specific procedures. 
For subjects who wish to continue on study treatment beyond confirmed iRECIST-defined PD, a 
second ICF, if applicable, will be provided to the subject.  
7.2. 
Study Procedures 
Schedule of Assessments shows all procedures to be conducted at the screening visit, on-
treatment, end of treatment, and follow-up visits. Refer to Section 7.4. 
Whenever vital signs, 12-lead ECGs, and blood draws are scheduled for the same nominal time, 
the blood draws should occur last. The timing of the first 2 assessments should be such that it 
allows the blood draw (e.g., PK blood sample) to occur at the proper nominal time. 
All immediate safety concerns must be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue treatment. 
7.3. 
NT-I7 Pharmacokinetics  
PK samples will be collected from all Phase 1b and Phase 2a subjects. Serial samples will be 
assessed following the PK timepoints in Table 3. 
Note: The precise NT-I7 administration time and the precise PK draw time should be recorded 
accurately and prospectively to fully interpret these values.  
 
 
 
 
 
 
 
 
 
 
 

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Table 3: Pharmacokinetic Timepoints (All Subjects in Phase 1b and Phase 2a, and 
Biomarker Cohort) 
Treatment 
Cycle/Visit 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
 
Cycle 5 
Subsequent 
Cycles 
(Repeat up 
to 2 years) 
 
End 
of Tx 
Scheduling 
Window 
Day 1 
Day 2  
Day 8 
± 2 
days 
Day 1 
± 3 
days 
Day 1 ± 3 
days 
Day 8 
± 3 
days 
Day 1 
± 3 
days 
Day 1 
± 3 
days 
Day 1 ± 3 
days 
Hours 
0 h 
2 h 
(±15mins) 
6 h 
(±30mins) 
24 h 
(±1h) 
 
 
 
 
 
 
 
 
Pharmacokinetics* 
(Phase 1b) & 
Biomarker Cohort 
Xa 
Xb 
Xb 
Xb 
X 
Xa 
Xa 
X 
Xa 
 
 
X 
Pharmacokinetics* 
(Phase 2a) 
Xa 
Xb 
Xb 
 
X 
 
Xa 
X 
 
 
Xa 
 
Xa 
 
 
aTo be collected prior to study agent(s) administration on a dosing day.  
bBlood draws are timed after NT-I7 administration is complete, not completion of pembrolizumab infusion.  
*Details on blood collection, handling, and shipping are provided in the NT-I7 Laboratory Manual. 
 
 

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7.4. 
Schedule of Assessments 
 
 
Phase 1b and 2a 
Treatment (Tx) 
Cycle/ Visit 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 
5 
 
Cycle 6 
 
 
Subseq
uent 
Cycles 
(Repeat 
up to 2 
years) 
End of 
Tx22 
Post Tx Follow U 
Safety FU23 
Survival 
FU28 
Scheduling 
Window 
Within  
28 days 
Day 1 
Day 2   
Day 8 
±2 
days 
Day 1 
±3 
days 
Day 8 
±2 
days 
 
Day 
15 ±7 
days 
Day 1 
±3 days 
Day 8 
±3 days 
Day 1 
±3 days 
Day 1 
±3 
days 
Day 1  
±3 
days 
Day 15 
±7 
days 
Day 1 
±3 days 
30 days 
after last 
dose 
±7 days 
90 days 
after last 
dose  
±7 days 
Every 90 
days after 
last dose  
±7 days 
Pembrolizumab1 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
 
X 
 
 
 
 
NT-I72 
 
X 
 
 
 
 
 
X 
 
 
X 
 
 
Odd 
Cycles 
 
 
 
 
 
Administrative Procedures 
Informed consent3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior and 
concomitant 
medications4 
X 
X 
 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
 
 
Clinic Procedures/Assessments# 
Physical exam5 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
Performance 
Status6 
X 
X 
 
X 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Vital signs7 
X 
X 
 
X 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Height8 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
 
X 
X 
X 
 
 
Adverse events 
review9 
X 
X 
X27 
X 
X 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
 
12-lead EKG10 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
 
 
Cardiac enzymes 
(Troponin ([Tnl or 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
 
 

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Phase 1b and 2a 
Treatment (Tx) 
Cycle/ Visit 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 
5 
 
Cycle 6 
 
 
Subseq
uent 
Cycles 
(Repeat 
up to 2 
years) 
End of 
Tx22 
Post Tx Follow U 
Safety FU23 
Survival 
FU28 
Scheduling 
Window 
Within  
28 days 
Day 1 
Day 2   
Day 8 
±2 
days 
Day 1 
±3 
days 
Day 8 
±2 
days 
 
Day 
15 ±7 
days 
Day 1 
±3 days 
Day 8 
±3 days 
Day 1 
±3 days 
Day 1 
±3 
days 
Day 1  
±3 
days 
Day 15 
±7 
days 
Day 1 
±3 days 
30 days 
after last 
dose 
±7 days 
90 days 
after last 
dose  
±7 days 
Every 90 
days after 
last dose  
±7 days 
TnT]) and CK-
MB)10 
Echocardiogram30 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
 
 
Cardiologist visit30 
X 
X 
 
 
 
 
 
 
 
 
X 
 
 
X 
X 
 
 
 
CBC w/diff, 
platelets11 
X 
X 
 
X 
X 
X26 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
Serum chemistry12 
X 
X 
 
X 
X 
X26 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
PT/INR and aPTT 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Thyroid Function13 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
Odd 
cycles 
X 
 
 
 
Serum or Urine 
Pregnancy Test14 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
X 
X 
 
 
Urine Analysis15 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
 
X 
X 
 
 
 
Efficacy Measurements 
Tumor evaluation 
(CT/MRI)16 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
RECIST 1.1 and iRECIST algorithm: Every 6 
weeks (± 1 week) starting at Cycle 2, Day 1 for 
the first 6 months, then every 9 weeks (± 1 
week) until disease progression or study 
discontinuation. 
 
X 
 
 
 
 
Tumor Biopsies/Archival Tissue Collection 
Tumor Biopsy 
X17 
 
 
 
 
 
X29 
 
 
 
 
 
X24 
 
 
 
 
 
Correlative Studies# 
Immunogenicity18 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
Every 4 
cycles18 
X 
 
X 
 

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Phase 1b and 2a 
Treatment (Tx) 
Cycle/ Visit 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 
5 
 
Cycle 6 
 
 
Subseq
uent 
Cycles 
(Repeat 
up to 2 
years) 
End of 
Tx22 
Post Tx Follow U 
Safety FU23 
Survival 
FU28 
Scheduling 
Window 
Within  
28 days 
Day 1 
Day 2   
Day 8 
±2 
days 
Day 1 
±3 
days 
Day 8 
±2 
days 
 
Day 
15 ±7 
days 
Day 1 
±3 days 
Day 8 
±3 days 
Day 1 
±3 days 
Day 1 
±3 
days 
Day 1  
±3 
days 
Day 15 
±7 
days 
Day 1 
±3 days 
30 days 
after last 
dose 
±7 days 
90 days 
after last 
dose  
±7 days 
Every 90 
days after 
last dose  
±7 days 
Pharmacokinetics19 
Refer to Table 3 for PK sampling 
Immunophenotypin
g20 
 
X 
 
X 
X 
X26 
 
X 
X 
X 
 
 
X25 
 
X 
 
 
 
Cytokines 
 
X 
 
X 
 
X26 
 
X 
X 
X 
 
 
X25 
 
X 
 
 
 
TCR-Seq Analysis 
 
X21 
 
 
 
 
X21 
 
 
 
 
 
X25 
 
 
 
 
 
 
#Unless otherwise specified, all clinic procedures and sample collection are to be done prior to NT-I7 and/or pembrolizumab dosing. More details in the NT-I7 Laboratory Manual.  
 
1Pembrolizumab should be administered on Day 1 of each three-week cycle after all procedures/assessments have been completed. 
2NT-I7: Dose as assigned; once every 6 weeks, starting Cycle 1, Day 1. NT-I7 should be dosed after pembrolizumab on concurrent treatment days. 
3Written consent must be obtained prior to performing any protocol specified procedure.  
4Prior medications – Record all medications (prescription and over-the-counter [OTC]) taken within 30 days of Screening visit. Concomitant medications – Enter all medications 
(prescription and OTC) taken between 7 days prior to Cycle 1, Day 1 through the Safety Follow-up visit. 
5Full physical exam is required during Screening, Day 1 of every cycle, End of Treatment, and Safety Follow-up visits. A directed physical exam may be performed on other days as 
clinically indicated.  
6Performance status must be assessed per ECOG Performance Scale criteria. 
7Vitals (blood pressure, heart rate, respiratory rate, temperature) to be collected in a standardized manner in a sitting position after the subject has rested comfortably for ~5 minutes. On the 
odd-numbered cycles (pembrolizumab and NT-I7), vitals need to be obtained within 60 minutes prior to the start of the pembrolizumab infusion AND repeated after the completion of the 
pembrolizumab infusion, but before the NT-I7 injection. On the even-numbered cycles (pembrolizumab only), vitals need to be obtained within 60 minutes prior to the start of the 
pembrolizumab infusion. 
8Height is measured on the first visit during Screening only. 
9 All AEs, including those meeting serious criteria, from the time of consent through the 30-day safety follow-up visit, and AEs meeting serious criteria only from 30 days following 
cessation of study treatment to 90-day safety follow-up visit.  See Section 11 for additional details on reporting of AEs. 
10 Duplicate EKG, at least 5 minutes apart, and serum cardiac enzyme levels (Troponin (TnI or TnT) and CK‐MB) must be obtained at Screening, C1D1, every 4 cycles (i.e., C5D1, 
C9D1,..), and End of Treatment. A patient should be assessed by a PI or a local cardiologist to determine if the EKG and the serum cardiac enzyme levels are clinically significant. If 
either is found to be clinically significant, see footnote 30. 
11Hematology includes complete blood count (CBC) with differential, including but not limited to red blood cell (RBC) count, hemoglobin, hematocrit, white blood cell (WBC) count with 
differential (neutrophil count including lymphocyte, monocyte, eosinophil, basophil counts and bands), absolute neutrophil count (ANC), and platelet count.  

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12Chemistry includes (but is not limited to) sodium, potassium, calcium, phosphorus, chloride, magnesium, bicarbonate, blood urea nitrogen (BUN) or urea, serum creatinine, glucose, uric 
acid, albumin, total protein, alkaline phosphatase, lactate dehydrogenase, bilirubin (indirect and direct), aspartate serum glutamic oxaloacetic transaminase (AST/SGOT), alanine 
aminotransferase/serum pyruvic transaminase (ALT/SGPT). 
13Thyroid function testing: thyroid-stimulating hormone (TSH), free triiodothyronine (T3) (or total T3 for sites where free T3 is not performed), and free thyroxine (also known as free T4) 
14Serum pregnancy test to be performed at the Screening visit for all females except those surgically sterile or 2 years postmenopausal. Subsequent serum or urine pregnancy tests could be 
performed as noted or per Investigator’s discretion. If the serum screening pregnancy test is performed > 72 hours before first dose, a serum or urine pregnancy test should be repeated 
prior to dosing.  
15Urinalysis (a urine dipstick may be used) at Screening and D1 of each cycle.  
16Baseline CT/MRI tumor imaging must be performed within 28 days prior to first dose for all subjects. Scans performed as part of routine clinical management are acceptable for use as 
the baseline scan if they are of diagnostic quality and performed within the allotted screening window. The exact same image acquisition and processing parameters should be used 
throughout the study. The first on-study imaging time point will be performed 6 weeks (± 1 week) or earlier if clinically indicated, regardless of any treatment delays, for up to 6 months, 
and every 9 weeks (± 1 week) thereafter. Brain and/or bone lesions may be scanned if applicable. (Note:  Subjects do not need to undergo the next scheduled tumor imaging if it is less 
than 4 weeks after the previous scan.) See Section 13 and Appendix A – Assessment of Disease for further information. 
17Biopsy will be performed during screening for those subjects who did not have enough archival tumor tissue and are required to have pre-treatment tumor biopsy per protocol.  
18Samples for immunogenicity assays shall be collected pre-dose from all study subjects in Phase 1b, Biomarker Cohort, and in up to 10 subjects in each of the arms of Phase 2a. Samples 
shall be collected pre-dose on C1D1, C2D1, C3D1, and C5D1. Thereafter, samples shall be collected pre-dose on every 4 cycle such as C9D1, C13D1, C17D1, C21D1, and so on. Testing 
may be conducted as indicated above, and repeated at 90-day follow up visit, if positive at the end of treatment visit. 
19For sampling details of PK, please refer to Table 3.  Additional information on handling and shipping are provided in the NT-I7 Laboratory Manual. 
20Whole blood will be collected for the multispectral immunophenotyping to obtain absolute cell counts for CD4+ and CD8+ T-cell subsets and activation states, NK cells, B cells, and 
other cell types as necessary. 
21TCR-seq analysis will be performed on both whole blood (pre- and on-treatment) for all Phase 1b and selected Phase 2a arms - TNBC (Arm I), MSS-CRC (Arm IV and Arm IVa), PC 
(Arm V and Arm Va), and the Biomarker Cohort (only for subjects who have dose of NT-I7 increase to 1200 μg/kg at C5D1). TCR-seq whole blood sample should be taken pre-dose at 
C1D1 visit. On-treatment whole blood sample should be taken at the same visit (pre- or post-biopsy) as on-treatment tumor biopsy collection (C2D15±7 days).     
22End of Treatment visit will occur approximately anytime within 7 days after disease progression determination or treatment discontinuation. 
23Safety follow-up visits will be performed in clinic visit will be performed every 30 days and 90 days after last dose of treatment.  
24 Optional tumor biopsy at Cycle 6, Day 15 (± 7 days) only for CPI naïve R/R OC Biomarker Cohort (only for subjects who have dose of NT-I7 increase to 1200 μg/kg at C5D1), CPI-
naïve R/R MSS-CRC Arm IVa, and CPI-naïve R/R PC Arm Va.  
25 Applicable only for CPI naïve R/R OC Biomarker Cohort (only for subjects who have dose of NT-I7 increase to 1200 μg/kg at C5D1), CPI-naïve R/R MSS-CRC Arm IVa, and CPI-
naïve R/R PC Arm Va. 
26 Optional visit applicable only for the CPI naïve R/R MSS-CRC Arm IVa and CPI-naïve R/R PC Arm Va expansion cohorts. 
27 Visit must be performed in person during Phase 1b for PK sampling and may be performed in clinic or by telephone during Phase 2a. 
28 Survival follow-up by telephone will be performed every 90 days starting 90 days after Safety follow-up day 90 until death, lost to follow up, withdrawal of consent, or end of study, 
whichever occurs first, to find out the survival status, new anti-cancer treatments and the outcome of any ongoing adverse event(s). 
29 For all Phase 1b dose-escalation and selected Phase 2a arms - TNBC (Arm I), MSS-CRC (Arm IV and Arm IVa), PC (Arm V and Arm Va), and Biomarker Cohort, mandatory biopsies 
are required pre- and on-treatment. On treatment biopsies will be taken at C2D15 (+ 7 days).  If C3D1 (C2D15 + 7 days) is decided for the biopsy, the biopsy has to be taken before dosing 
on Cycle 3.  
30 If either the EKG or serum cardiac enzyme levels are clinically significant, an echocardiogram must be performed and the patient must be assessed by a local cardiologist to rule out the 
potential presence of myocarditis and to ensure there are no clinically significant abnormalities in the echocardiogram before enrolling in or continuing treatment. The next dosing will be 
suspended during the follow-up period until confirmation is obtained through an echocardiogram. 

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8. 
Dosing Delays/ Dose Modifications 
The National Cancer Institute (NCI) CTCAE Version 5.0 will be used to grade AEs. Subjects 
enrolled in this study will be evaluated clinically and with standard laboratory tests before and 
at regular intervals during their participation in this study as specified in this section. 
Subjects will be evaluated for AEs (all grades), SAEs, and AEs requiring study drug dose 
modification, interruption, or discontinuation at each study visit for the duration of their 
participation in the study. 
8.1. 
Dose Modification of NT-I7 
Clinical experience has demonstrated that development of autoimmune inflammatory 
conditions is a general risk with therapeutics intended to enhance anti-tumor T-cell responses. 
Such irAEs have been described for virtually all organ systems and include, but are not limited 
to, colitis, hepatitis, pneumonitis, endocrinopathy, ocular toxicity, pancreatic toxicity, and rash. 
Risks of autoimmunity associated with NT-I7 are theoretical and yet not fully evaluated in the 
clinical setting. Due to this potential risk of NT-I7 to induce autoimmune conditions, subjects 
with a history of autoimmune disease will be excluded from this study.  
The risk of development of autoimmune inflammatory condition related to NT-I7 seems 
relatively low. None of the irAEs were reported in previous clinical studies with rhIL-7, or 
with NT-I7 including the FIH study completed in normal healthy individuals, and solid tumor 
subjects (Study No. GX-I7-HV-001 and Study No. GX-I7-CA-003). 
Nevertheless, however, given the limited clinical experience with NT-I7, immune-related 
toxicities associated or possibly associated with NT-I7 should be closely monitored and 
carefully managed according to standard medical practice (e.g., thyroid hormone replacement 
for autoimmune hypothyroidism). Additional tests, such as autoimmune serology or biopsies, 
should be used to determine a possible immunogenic etiology. Although most irAEs observed 
with immune modulatory agents have been mild and self-limiting, such events should be 
recognized early and treated promptly to avoid potential major complications (69). 
Discontinuation of NT-I7 may not have an immediate therapeutic effect, and there is no 
available antidote for NT-I7. The primary approach to mild irAEs (Grades 1−2) is supportive 
and symptomatic care. In severe cases, irAEs may be acutely managed with systemic 
corticosteroids, mycophenolate or TNF-α antagonists (40, 69-85). 
Dose modifications of NT-I7 for Adverse Events: AEs from NT-I7 are expected to be mild and 
infrequent, transient and Grade 2 or less (as noted in the AE list, Section 11.1.1. If a subject 
experiences a clinically significant and/or unacceptable toxicity, dosing should be interrupted, 
or reduced or discontinued (see below for detailed guidance), and supportive therapy 
administered per standard clinical practice.   
A maximum of 2 dose reductions will be allowed for an individual subject.  If the second dose 
reduction is not tolerated, study treatment should be permanently discontinued, and the subject 
should be followed up for safety (see Section 11.3.1).  The lowest dose that may be 
administered is: 
· 
NT-I7 480 μg/kg Q6W 

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For a Grade 1 AE, no dose modification is needed. Increase monitoring of clinical 
signs/symptoms and laboratory assessments as needed and treat each of the toxicities per 
standard of care and/or institutional guidance.  For Grade 1 AE of myasthenia gravis, NT-I7 
treatment may be withheld until resolved (see Section 8.1.1 for criteria to resume treatment) or 
discontinued permanently.    
For a Grade 2 AE related to NT-I7, withhold administration of NT-I7 until the AE is resolved 
to ≤ Grade 1 (see Section 8.1.1 for criteria to resume treatment), then resume at the same dose 
level.  
For a Grade ≥3 AE related to NT-I7, if it is a 1st appearance, withhold administration of NT-I7 
until the AE is resolved to ≤ Grade 1 (see Section 8.1.1 for criteria to resume treatment), then 
decrease one dose level (e.g., to 960 μg/kg IM Q6W if the last dose level prior to the AE was 
1200 μg/kg IM Q6W, or to 480 μg/kg IM Q6W if the last dose level prior to the AE was 960 
μg/kg IM Q6W); if it is a 2nd appearance, withhold administration of NT-I7 until the AE is 
resolved to ≤ Grade 1, then decrease one dose level (e.g., to 480 μg/kg IM Q6W if the last dose 
level prior to the AE was 960 μg/kg IM Q6W).  The lowest dose that may be administered is 
480 μg/kg IM Q6W. Dose re-escalation to a higher dose level, up to 1200 μg/kg IM Q6W, is 
allowed after being discussed with and approved by the Medical Monitor and the Sponsor.   
For any grade of myocarditis, permanently discontinue NT-I7 treatment. 
8.1.1. 
Criteria to Resume for Dosing 
Subjects may resume treatment with NT-I7 when the drug-related AE(s) resolve(s) to Grade ≤ 
1 or baseline, with the following exceptions: 
• 
Subjects may resume treatment in the presence of Grade 2 fatigue. 
• 
Subjects who have not experienced a Grade 3 drug-related skin AE may resume 
treatment in the presence of Grade 2 skin toxicity. 
• 
Subjects with baseline Grade 1 AST/ALT or total bilirubin who require dose delays for 
reasons other than a 2-grade shift in AST/ALT or total bilirubin may resume treatment 
in the presence of Grade 2 AST/ALT OR total bilirubin. 
• 
Drug-related pulmonary toxicity, diarrhea, or colitis must have resolved to baseline 
before treatment is resumed. Subjects with persistent Grade 1 pneumonitis after 
completion of a steroid taper over at least 1 month may be eligible for re-initiation of 
study treatment if discussed with and approved by the Medical Monitor and the 
Sponsor. 
• 
Subjects who received systemic corticosteroids for management of any drug-related 
toxicity must be off corticosteroids or have tapered down to an equivalent dose of 
prednisone ≤ 10 mg/day. 
• 
Drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume study treatment after consultation with and approved by the 
Medical Monitor and the Sponsor. 
Prior to re-initiating study treatment in a subject with a dosing delay lasting > 12 weeks (84 
days) for NT-I7 or >6 weeks (42 days) for pembrolizumab, the NIT designee) must be 

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consulted and approves the re-initiation of study treatment. Tumor assessments should 
continue as per protocol even if dosing is delayed. Periodic study visits to assess safety and 
laboratory studies should also continue every 3 weeks or more frequently if clinically 
indicated during such dosing delays. 
8.2. 
Dose Modification of Pembrolizumab 
The toxicity of pembrolizumab could be accentuated by administration of NT-I7 and the 
component attributable to pembrolizumab and NT-I7 will be difficult if not impossible to sort 
out. Thus, the management of pembrolizumab will be used for the treatment of any AE. NT-I7 
treatment will be discontinued when pembrolizumab must be permanently discontinued. 
AEs associated with pembrolizumab exposure may represent an immune-related response. 
These irAEs may occur shortly after the first dose or several months after the last dose of 
pembrolizumab treatment and may affect more than one 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.  
Dose modification and toxicity management guidelines for irAEs associated with 
pembrolizumab are provided in Table 4. 
When study interventions are administered in combination, attribution of an adverse event to a 
single component is likely to be difficult.  Therefore, while the investigator may attribute a 
toxicity event to the combination, to NT-I7 alone, or to pembrolizumab alone, for adverse events 
listed in Table 4, both interventions must be held according to the criteria in .  
Holding Study Interventions: 
When study interventions are administered in combination, if the AE is considered immune-
related, both interventions should be held according to recommended dose modifications. 
Restarting Study Interventions: 
Subjects may not have any dose modifications (no change in dose or schedule) of 
pembrolizumab in this study, as described in Table 4.  
If the toxicity does not resolve or the criteria for resuming treatment are not met, the subject 
must be discontinued from all study interventions.  
If the toxicities do resolve and conditions are aligned with what is defined in Table 4, the 
combination of NT-I7 and pembrolizumab may be restarted at the discretion of the 
investigator. In these cases where the toxicity is attributed to the combination or to NT-I7 
alone, re-initiation of pembrolizumab as a monotherapy may be considered after 
communication with and agreement by the Sponsor. 

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Table 4:  Dose Modification and Toxicity Management Guidelines for Immune-related AEs Associated with Pembrolizumab 
General instructions: 
Severe and life-threatening irAEs should be treated with IV corticosteroids followed by oral steroids. Other systemic immunosuppressive treatment 
may be considered if the irAEs are not controlled by corticosteroids.  
The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue at least 4 weeks. 
If pembrolizumab has been withheld, pembrolizumab may resume after the irAE decreased to ≤ Grade 1 after corticosteroid taper. 
If another episode of a severe adverse reaction occurs, permanently discontinue pembrolizumab. 
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 
 
Monitor subjects for signs and symptoms of pneumonitis 
Evaluate subjects with suspected pneumonitis with radiographic 
imaging and exclude other causes. Initiate corticosteroid treatment. 
 
Recurrent 
Grade 2,  
Grade 3 or 4  
Permanently 
discontinue 
Colitis  
Grade 2 or 3 
Withhold 
Administer 
corticosteroids 
(initial dose of 
1 to 2 mg/kg 
Monitor subjects for signs and symptoms of colitis and exclude 
other causes. 

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Grade 4 
Permanently 
discontinue 
prednisone or 
equivalent) 
followed by 
taper 
 
Hepatitis 
Grade 2 
Withhold or 
discontinue based 
on severity of 
liver enzyme 
elevations. 
Administer 
corticosteroids 
(initial dose of 
0.5 to 1 mg/kg 
prednisone or 
equivalent) 
followed by 
taper 
Monitor subjects for changes in liver function (at the start of 
treatment, periodically during treatment, and as indicated based on 
clinical evaluation) and symptoms of hepatitis and exclude other 
causes.  
 
Grade 3 or 4 
Administer 
corticosteroids 
(initial dose of 
1 to 2 mg/kg 
prednisone or 
equivalent) 
followed by 
taper 
Type 1 diabetes 
mellitus (T1DM) 
or Hyperglycemia 
T1DM 
 
Initiate insulin 
replacement 
therapy for 
subjects with 
T1DM 
 
Monitor subjects for hyperglycemia or other signs and symptoms of 
diabetes 

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Severe 
hyperglycemia 
Withhold until 
metabolic control 
is achieved 
 
Adrenal 
insufficiency 
(primary and 
secondary) and 
Hypophysitis 
Grade 2 
Withhold 
Administer 
corticosteroids 
for adrenal 
insufficiency 
and initiate 
hormonal 
replacements as 
clinically 
indicated 
Monitor for signs and symptoms of adrenal insufficiency and 
hypophysitis (including hypopituitarism) and exclude other causes. 
Grade 3 or 4 
Withhold or 
discontinue 
Hyperthyroidism  
Grade 2 
Continue 
 Manage 
symptomatically 
Monitor for changes in thyroid function (at the start of treatment, 
periodically during treatment and as indicated based on clinical 
evaluation) and clinical signs and symptoms of thyroid disorders 
Grade 3 or 4 
Withhold or 
permanently 
discontinue 
Hypothyroidism 
Grade 2, 3, 4 
Continue 
May be managed 
with 
replacement 
therapy without 
corticosteroids. 
Monitor for changes in thyroid function (at the start of treatment, 
periodically during treatment and as indicated based on clinical 
evaluation) and clinical signs and symptoms of thyroid disorders 
Nephritis 
Grade 2 
Withhold 
Administer 
corticosteroids 
(prednisone 1–
2 mg/kg or 
equivalent) 
Monitor changes of renal function and exclude other causes. 
Grade 3 or 4 
Permanently 
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followed by 
taper 
Severe skin 
reactions 
 
Based on the 
severity of AE, 
withhold or 
permanently 
discontinue 
Based on 
severity of AE, 
administer 
corticosteroids 
Monitor for suspected severe skin reactions and exclude other 
causes. For signs and symptoms of SJS/TENS, refer the subject for 
specialized care for assessment and treatment.   
Severe skin 
reactions 
Suspected 
SJS, TEN, or 
DRESS 
Withhold 
Based on 
severity of AE 
administer 
corticosteroids 
 
Confirmed 
SJS, TEN, or 
DRESS 
Permanently 
discontinue 
Administer 
corticosteroids 
with specialized 
care 
 
All Other irAEs 
> Grade 1 
Withhold 
Based on 
severity of AE 
administer 
corticosteroids 
and taper upon 
improvement to 
Grade 1 or less, 
over at least one 
month. 
Administration 
of other systemic 
immunosuppress
ants can be 
Ensure adequate evaluation to confirm etiology or exclude other 
causes 
Recurrent 
Grade 3 or 
Grade 4  
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considered if 
irAEs cannot be 
controlled with 
corticosteroid 
use. 
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-irAEs will be managed as appropriate, following clinical practice recommendations. 
 
 

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8.2.1. 
Dose Modification and Toxicity Management of Infusion-reactions Related to 
Pembrolizumab 
Pembrolizumab may cause severe infusion-reactions including severe hypersensitivity or 
anaphylaxis.  Dose modification and toxicity management guidelines on pembrolizumab 
associated infusion reaction are provided in Table 5.  
 
Table 5: Pembrolizumab infusion reaction dose modification and treatment guidelines 
NCI CTCAE Grade 
Treatment 
Premedication at 
Subsequent Dosing 
Grade 1 
Mild transient reaction; 
infusion interruption 
not indicated; 
intervention not 
indicated 
Grade 2 
Therapy or infusion 
interruption indicated 
but responds promptly 
to symptomatic 
treatment (e.g., 
antihistamines, 
NSAIDs, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤24 hrs. 
• 
May continue to receive pembrolizumab with 
close monitoring 
Premedication 
with 
antipyretic or antihistamine 
may be considered 
NCI CTCAE Grade 
Treatment 
Premedication at 
Subsequent Dosing 
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; 
 
• 
Stop Infusion. 
Subject is permanently discontinued from further study 
drug treatment. 
 
No subsequent dosing 

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hospitalization 
indicated for other 
clinical sequelae  
Grade 4: 
Life-threatening 
consequences; urgent 
intervention indicated 
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 v5.0 
(CTCAE) at http://ctep.cancer.gov 
 
8.2.2. 
Other Allowed Dose Interruptions for Pembrolizumab  
Pembrolizumab may be interrupted for situations other than treatment-related AEs such as 
medical/surgical events and/or unforeseen circumstances not related to study therapy. Subjects 
should be placed back on study treatment within 3 weeks or 21 days of originally scheduled dose 
and within 42 days of previously administered dose, unless otherwise discussed with and 
approved by the Sponsor. The reason for interruption should be documented in the subject's 
study record. 
 
 
 
 
 
 

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9. 
Concomitant Therapy 
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 treatment or vaccination 
may be required.  The investigator should discuss any questions regarding this with the Sponsor 
or Sponsor’s assigned designee. The final decision on any supportive therapy or vaccination rests 
with the investigator and/or the subject's primary physician. However, the decision to continue 
the subject on study treatment requires the mutual agreement of the investigator, the Sponsor 
and the subject. 
9.1. 
Prohibited Medications/Treatment 
• Antineoplastic systemic chemotherapy or biological therapy  
• Immunotherapy not specified in this protocol 
• Chemotherapy not specified in this protocol 
• Investigational agents other than NT-I7 and pembrolizumab 
• Radiation therapy  
Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be allowed 
at the investigator’s discretion.  
• 
Live/attenuated vaccines within 30 days prior to the first dose of study treatment and while 
participating in the study up to 90 days following the last dose of study drug. 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 (e.g., FluMist®) are live attenuated vaccines and are not 
allowed. 
• Systemic glucocorticoids are permitted only for the following purposes: 
o To modulate symptoms of an AE that is suspected to have an immunologic 
etiology 
o Short-term oral or IV use in doses >10mg/day prednisone equivalent for the 
prevention of emesis is allowed after discussion with and approval by the Medical 
Monitor 
o Premedication for IV contrast allergies 
o Short-term oral or IV use in doses >10mg/day prednisone equivalent for COPD 
exacerbations 
o For chronic systemic replacement not to exceed 10 mg/day prednisone equivalent 
o In addition, the following glucocorticoid use is allowed: 
 For topical use or ocular use 
 Intra-articular joint use 
 For inhalation in the management of asthma or chronic obstructive 
pulmonary disease.  
Note: Inhaled steroids are allowed for management of asthma. 
• Immunostimulatory and immunosuppressive agents are prohibited.  

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Subjects who, in the assessment of the investigator, require the use of any of the aforementioned 
treatments for clinical management should be removed from the study.  
9.2. 
Medications Used with Caution 
 
No data exist regarding the interaction of NT-I7 with drugs known to prolong the QT/QTc 
interval. Accordingly, subjects receiving these drugs while receiving NT-I7/pembrolizumab 
therapy should be closely monitored. 
No data exist regarding the interaction of NT-I7 with commonly used vitamins, minerals, 
supplements, herbal and natural remedies. Accordingly, these drugs should be avoided, or used 
with caution at the investigator’s discretion, and closely monitored while the subject is 
receiving the study treatment. 
All treatments that the investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care. For example, subjects can continue using medically prescribed marijuana/ Marinol 
for purposes such as cancer related fatigue, nausea, vomiting, appetite improvement etc. while 
participating in the study.   
All concomitant medications will be recorded on the eCRF including all prescription, over-the-
counter (OTC) products, herbal supplements, and IV medications and fluids. If changes occur 
during the study period, documentation of drug dosage, frequency, route, and date should also 
be included on the eCRF. 
All concomitant medications received within 7 days prior to the first dose of study treatment and 
up to 30 days after the last dose of study treatment should be recorded. Concomitant medications 
administered 30 days after the last dose of study treatment should be recorded for SAEs and 
events of special interest or clinical interest (ECIs) as defined in Sections 11.4 and 11.6. 
 
10. 
 Rescue Medications and Supportive Care 
Subjects 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 8. (Table 4). 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.  
Note: If after the evaluation of the event, it is determined not to be related to pembrolizumab, 
the investigator does not need to follow the treatment guidance. Refer to Table 4 in Section 8 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.  

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11. 
Adverse Events: Assessing and Reporting Requirements 
An AE is defined as any untoward medical occurrence in a subject or clinical investigation 
subject administered a pharmaceutical product, and which does not necessarily have to have a 
causal relationship with the treatment. An AE 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 study product is also an AE. 
All AEs that occur on study, within 30 days of the last administration of the study treatment, 
must be reported. The reporting timeframe for AEs meeting the criteria of SAE is described in 
Section 11.  
AEs are reported in a routine manner during the study using the EDC system. Additionally, 
certain AEs must be reported in an expedited manner for timelier monitoring of subject safety 
and care. The following list of AEs (Sections 11.1, 11.4, and 11.6) and the characteristics of an 
observed AE will determine whether the event requires expedited reporting to the Sponsor or 
designee.   
Electronic monitoring of AEs will be done through the EDC system and/or via email reporting 
by each clinical site to the Sponsor and/or Sponsor’s safety designee. Per GCP, all sites must 
enter data in a timely manner. AEs meeting the criteria of SAE in the EDC system will trigger 
immediate review and distribution as needed and required by regulatory authorities. 
The investigator or qualified designee will assess each subject to evaluate for potential new or 
worsening AEs at the time points specified in the protocol and more frequently if clinically 
indicated.   
11.1. Adverse Events and Potential Risks List  
For a list of the adverse events and potential risks associated with NT-I7, please refer to the 
most recent version of the Investigator’s Brochure.  
11.2. Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found in the 
CTCAE version 5.0 will be utilized for AE reporting. All appropriate treatment areas should 
have access to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be 
downloaded from the Cancer Therapy Evaluation Program (CTEP) website 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
For expedited reporting purposes only: 
• AEs of Special Interest for the protocol are outlined in Sections 11.4 and 11.6. 
Attribution of the AE: 
• Definite – The AE is clearly related to the study treatment. 

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• Probable – The AE is likely related to the study treatment. 
• Possible – The AE may be related to the study treatment. 
• Unlikely – The AE is doubtfully related to the study treatment. 
• Unrelated – The AE is clearly NOT related to the study treatment. 
11.3. 
Expedited Adverse Event Reporting 
AE, SAEs, and other reportable safety events will be reported by the subject (or, when 
appropriate, by a caregiver, surrogate, or the subject's legally authorized representative).  
The investigator, who is a qualified physician, and any designees are responsible for detecting, 
assessing, documenting, and reporting events that meet the definition of an AE or SAE as well 
as other reportable safety events. Investigators remain responsible for following up of AE, 
SAEs and other reportable safety events for outcome. 
Expedited AE, including AESI, reporting for this study must be done by notifying the Sponsor 
and/or Sponsor’s safety designee within 24 hours of the investigator or investigator designee 
knowledge of the event via the study EDC system and email (CHOSafety@prahs.com and 
NIT110@neoimmunetech.com) as stipulated.  
In the rare occurrence when Internet connectivity is lost, a 24-hour notification is to be made to 
the Sponsor designated CRO, ICON Safety Helpline, by telephone at +1 888 772 2215, fax 
ICON Safety Fax Line, +1 888 772 6919 or +1 434 951 3482. Once Internet connectivity is 
restored, the 24-hour notification phoned in must be entered electronically into the data capture 
system by the original submitter at the site. 
11.3.1. 
Time Period and Frequency for Collecting AE, SAE and Other Reportable 
Safety Event Information  
 
• All AEs, SAEs and other reportable safety events that occur after the consent form is 
signed but before treatment /allocation must be reported by the investigator, if the event 
causes the subject to be excluded from the study or is the result of a protocol-specified 
intervention, including but not limited to washout or discontinuation of usual therapy, 
diet, or a procedure.  
• All AEs from the time of treatment/allocation through 30 days following cessation of 
study treatment or starting of new anticancer therapy, whichever is earlier, must be 
reported by the investigator.  
• All AEs meeting serious criteria, from the time of treatment/ allocation through 90 days 
following cessation of study treatment or initiation of new anticancer therapy, whichever 
is earlier, must be reported by the investigator.  
• All pregnancies and exposure during breastfeeding, from the time of treatment/ allocation 
through 90 days following cessation of study treatment or initiation of new anticancer 
therapy, whichever is earlier, 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 to the Sponsor if the event 
is considered to be drug-related. 

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11.3.2. 
Expedited Reporting Guidelines 
Use the study protocol number and the protocol-specific subject ID assigned during study 
registration on all reports. Progression of the cancer under study is not considered an adverse 
event unless it results in hospitalization or death.  
Note: A death occurring within 90 days of the last administration of study agent requires 
both routine and expedited reporting, regardless of causality. Attribution to treatment or 
other cause must be provided. 
Death due to PD should be reported as Grade 5 “Malignant neoplasm progression” to be 
coded under the system organ class (SOC) “Neoplasms benign, malignant and unspecified 
(incl cysts and polyps)”. Evidence that the death was a manifestation of underlying disease 
(e.g., radiological changes suggesting tumor growth or progression: clinical deterioration 
associated with a disease process) should be submitted. 
Expedited Reporting Requirements for Adverse Events that Occur on Studies under an 
IND/IDE within 30 Days of the Last Administration of the Investigational Agent/ 
Intervention 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately (within 24 hours) report ANY Serious Adverse Events, whether or 
not they are considered related to the investigational agent(s)/intervention (21 Code of Federal Regulations 
[CFR] 312.64) 
An AE is considered serious if it results in ANY of the following outcomes: 
1) Death 
2) A life-threatening AE 
3) An AE 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 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). 
11.3.3. 
Routine Adverse Event Reporting 
All AEs must be reported in routine study data submissions. AEs reported expeditiously to 
the Sponsor and/or Sponsor’s safety designee must also be reported in routine study data 
submissions. 
AE data collection and reporting, which are required as part of every clinical study, are done to 
ensure the safety of subjects enrolled in the studies as well as those who will enroll in future 
studies using similar agents. For this study the Adverse Event CRF is used for routine AE 
reporting. 
11.4. 
Adverse Events of Special Interest in NT-I7 
The following AEs are of special interest in subjects receiving NT-I7, as defined below and must 
be reported by the investigator expeditiously to the Sponsor and/or Sponsor’s Safety designee 
irrespective of regulatory seriousness criteria and the relatedness to NT-I7.   

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Immune-related adverse event (irAE) is defined as an AE associated with drug exposure that is 
consistent with an immune-mediated mechanism of action when there is no clear alternate 
etiology. For events which are potentially immune-related, additional information such as 
serologic, immunologic, and histologic (biopsy) data and use of steroids or immunosuppressants 
will be used to support an irAE diagnosis.  
 
• 
Potential drug-induced liver injury that includes an elevated ALT or AST ≥ 3 x ULN 
in combination with an elevated bilirubin ≥ 2 x ULN and, at the same time, an alkaline 
phosphatase (ALP) < 2 x ULN; no other reason can be found to explain the 
combination of increased AST or ALT, and TBL, such as viral hepatitis A, B, or C; 
preexisting or acute liver disease; or another drug capable of causing the observed 
injury. (86) 
• Conditions (regardless of grade) suggestive of an autoimmune disorder or immune-
related adverse events (irAEs), including but not limited to hepatitis, pneumonitis, 
colitis, pancreatitis, endocrinopathies (including but not limited to thyroiditis, Type 
1 diabetes mellitus, adrenal insufficiency), myocarditis, myositis/polymyositis, 
rheumatoid arthritis, vasculitis, neuritis, systemic lupus erythematosus, Sjogren’s 
syndrome, multiple sclerosis, Guillain-Barre syndrome and myasthenia gravis 
• Symptoms and signs suggestive of hypersensitivity, cytokine release, or infusion 
reaction syndromes with a different underlying pharmacological etiology   
• Grade ≥2 diarrhea  
• Grade ≥2 AST/ALT and Grade ≥2 total bilirubin elevation with constitutional 
symptoms 
• Grade ≥3 hypoxia or dyspnea  
• Grade ≥2 pleural effusion that is not due to the underlying disease (e.g., non-
malignant pleural effusion)      
11.5. Treatment of Overdose for NT-I7 
For this study, an overdose of NT-I7 will be defined as any dose > 1440 µg/kg.  
No specific information is available on the treatment of overdose of NT-I7. In the event of 
overdose, the subject should be observed closely for signs of toxicity. Appropriate supportive 
treatment should be provided if clinically indicated. 
11.6. Events of Clinical Interest (ECI) in Pembrolizumab  
Selected adverse events are also known as Events of Clinical Interest (ECI) and must be reported 
to the Sponsor within 24 hours. 
Events of clinical interest in pembrolizumab studies include:  
1. An overdose of pembrolizumab, as defined in Section 11.7– Treatment of Overdose, that 
is not associated with clinical symptoms or abnormal laboratory results. 

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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. The study site guidance for assessment and 
follow up of these criteria can be made available. It may also be appropriate to conduct 
additional evaluation for an underlying etiology in the setting of abnormalities of liver blood 
tests including AST, ALT, bilirubin, and alkaline phosphatase that do not meet the criteria 
noted above. In these cases, the decision to proceed with additional evaluation will be made 
through consultation between the study investigators and the Sponsor. However, 
abnormalities of liver blood tests that do not meet the criteria noted above are not ECIs for 
this study. 
11.7. Treatment of Overdose for Pembrolizumab 
For this study, an overdose of pembrolizumab will be defined as any dose of 1000 mg or ≥5 
times the indicated dose.  
No specific information is available on the treatment of overdose of pembrolizumab. In the event 
of overdose, the subject should be observed closely for signs of toxicity. Appropriate supportive 
treatment should be provided if clinically indicated. 
11.8. Pregnancy 
Although not an AE in and of itself, pregnancy as well as its outcome must be documented via 
the EDC system. Any pregnancy occurring in a subject or subject’s partner from the time of 
consent to 90 days after the last dose of study treatment must be reported and then followed for 
outcome. If a subject inadvertently becomes pregnant while on study drug treatment, the 
subject will be immediately discontinued from study treatment. The site will contact the 
subject at least monthly and document the subject’s status until the pregnancy has been 
completed or terminated.  
The outcome of the pregnancy will be reported to the Sponsor without delay and within 24 hours 
if the outcome is a serious adverse experience/important medical event (e.g., death, abortion, 
congenital anomaly, spontaneous abortion, missed abortion, benign hydatidiform mole, blighted 
ovum, fetal death, intrauterine death, miscarriage, stillbirth or other disabling or life-threatening 
complication to the mother or newborn). Newborn infants should be followed until 30 days old.  
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 the Sponsor and/or Sponsor’s 
safety designee within 24 hours of the investigator’s knowledge of the event via the study EDC 
system. 

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11.9. Use in Nursing Women 
It is unknown whether NT-I7 and/or pembrolizumab 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, subjects who are breastfeeding are not eligible for enrollment. 
11.10. Secondary Malignancy 
A secondary malignancy is a cancer caused by treatment for a previous malignancy (e.g., 
treatment with investigational agent/intervention, radiation or chemotherapy). A secondary 
malignancy is not considered a metastasis of the initial neoplasm. 
All secondary malignancies that occur after treatment with the study agents must be reported to 
the Sponsor and/or Sponsor’s safety designee within 24 hours of the investigator’s knowledge 
of the event via the study EDC system. Three options are available to describe the event: 
• Leukemia secondary to oncology chemotherapy (e.g., acute myelocytic leukemia 
[AML]) 
• Myelodysplastic syndrome (MDS) 
• Treatment-related secondary malignancy 
Any malignancy possibly related to cancer treatment (including AML/MDS) should also be 
reported via the routine reporting mechanisms outlined in each protocol. 
11.11. Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is NOT a 
metastasis from the initial malignancy). Second malignancies require ONLY routine AE 
reporting unless otherwise specified. 
 

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12. 
Correlative Studies and Biomarker Evaluations 
To explore the biological mechanisms and pharmacodynamic (PD) effects of the 
investigational treatment regimen, paired tumor biopsies, and peripheral blood samples will be 
utilized. Mandatory paired biopsy sampling will be obtained for all study subjects in Phase 1b, 
and study subjects in specific arms in Phase 2a. Peripheral blood will be obtained for PK, 
immunogenicity, and exploratory biomarker evaluations.  
12.1. 
Tumor Tissue for Biomarker Analyses 
A key exploratory objective of the study is to make preliminary assessment of biomarkers that 
may act as pharmacodynamic indicators or predictors of anti-tumor activity of NT-I7 in 
combination with pembrolizumab. Tumor biopsy sampling is mandatory for all study subjects 
in Phase 1b and study subjects in specific arms in Phase 2a (i.e., Arm I: CPI-treated R/R 
TNBC, Arms IV and IVa: CPI-naïve R/R MSS-CRC, Arms V and Va: CPI-naïve R/R PC), and 
the Biomarker Cohort. In these arms/cohorts, study subjects must have at least one tumor 
lesion that is accessible and feasible to biopsy and agree to provide paired biopsies in order to 
participate in this study, unless a written exemption is obtained from the Sponsor.  
Tumor biopsy samples will be obtained from each study subject where biopsy sampling is 
mandatory. The first biopsy will be obtained within 28 days prior to initiation of study drugs in 
order to establish baseline characteristics of the tumor. Archival samples may be used in place 
of a fresh biopsy for the baseline treatment sample if the archival tissue was obtained after the 
last therapy, and is within 28 days of prior to initiation of the study treatment. A second biopsy 
(on-treatment biopsy) must be obtained within 7 days of Cycle 2, Day 15 (i.e., between C2D8 
and C2D22), and before Cycle 3, Day 1 dosing in order to evaluate the effects of the study 
treatment on the tumor microenvironment. For subjects in CPI naïve R/R OC Biomarker 
Cohort, the CPI-naïve R/R MSS-CRC expansion IVa cohort and the CPI-naïve R/R PC 
expansion Va cohort, an optional tumor biopsy may be obtained at Cycle 6, Day 15 (± 7 days). 
For the Biomarker cohort, only in subjects who have dose of NT-I7 increased to 1200 µg/kg at 
C5D1. For subjects who discontinue from study early, every effort should be made to obtain 
the on-treatment biopsy. For detailed instructions on biopsy sample processing (collection, 
handling, and shipping), please refer to the NT-I7 Laboratory Manual. 
Tumor biopsy samples will be evaluated for molecular and histological changes, particularly as 
these changes pertain to the inflammatory mechanisms. Exploratory biomarker analyses may 
include, but are not limited to, characterization of PD-L1 expression, quantitation of CD4+ and 
CD8+ tumor-infiltrating lymphocyte distribution, TCR repertoire analysis, and other molecular 
assessments. 
12.2. 
Planned Peripheral Blood Biomarker Analyses 
Study subjects are required to provide peripheral blood samples for PK, immunogenicity, and 
exploratory biomarker evaluations throughout their study participation as summarized in the 
Schedule of Assessments. Whenever possible, peripheral blood samples for these evaluations 
should also be collected during the 90-day FU period. For detailed instructions on peripheral 
blood research sample processing (collection, handling, and shipping), please refer to the NT-
I7 Laboratory Manual. 

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Peripheral blood samples will be evaluated for the presence of anti-drug antibodies (ADAs) 
and neutralizing antibodies (NAbs) to NT-I7, as well as for pharmacokinetic analysis. 
Exploratory biomarker analyses on peripheral blood samples may also include, but not limited 
to, changes in circulating immune cell populations, cytokine measurements, and TCR 
repertoire analysis. 
12.3. 
Other Procedures: Biopsy (core needle, punch, or surgical excision)   
Specific details on the biopsy and its procedure, tissue collection, handling, and shipping are 
provided in the NT-I7 Laboratory Manual. 

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13. 
Tumor Imaging and Assessment of Disease 
Tumor imaging is strongly preferred to be acquired by computed tomography (CT). For the 
abdomen and pelvis, contrast-enhanced magnetic resonance imaging (MRI) may be used when 
CT with iodinated contrast is contraindicated, or when mandated by local practice. MRI is the 
strongly preferred modality for imaging the brain. The same imaging technique regarding 
modality, ideally the same scanner, and the use of contrast should be used in a subject throughout 
the study to optimize the reproducibility of the assessment of existing and new tumor burden and 
improve the accuracy of the assessment of response or progression based on imaging. Note: For 
the purposes of assessing tumor imaging, the term “investigator” refers to the local investigator 
at the site and/or the radiological reviewer located at the site or at an offsite facility. 
In general, imaging should include the chest, abdomen, and pelvis. See below for guidance 
regarding MRI Brain imaging. 
Bone scans are also required for subjects with a history of bone metastases and/or for those 
subjects with new bone pain. Any supplemental imaging done to support a positive or negative 
bone scan, such as plain X-rays, may be acquired for correlation.   
 
13.1. Initial Tumor Imaging 
Initial tumor imaging at Screening must be performed within 28 days prior to the date of 
treatment. The site study team must review screening images to confirm the subject has 
measurable disease per RECIST 1.1. 
For all subjects enrolled in Arm I (TNBC), Arm II (NSCLC), and Arm III (SCLC), a MRI brain 
imaging scan is preferred during screening. A brain scan at screening is required for any patient 
that has had brain metastasis in the past or presents with signs and/or symptoms suggestive of 
brain metastasis. 
Subjects enrolled in Arm IV (MSS-CRC), Arm IVa (MSS-CRC), Arm V (Pancreatic Cancer), 
Arm Va (Pancreatic Cancer), and Biomarker OC Cohort must have an MRI brain imaging scan 
done during screening only if: 
o The subject has known active central nervous system (CNS) metastases 
and/or carcinomatous meningitis 
o OR: the subject has sign/symptoms suggestive of brain metastasis 
Note: Subsequent MRI brain imaging is required only if: 
o The screening brain scan is positive (has tumor lesion)  
o The subject develops sign/symptoms suggestive of brain metastasis 
CT imaging is acceptable if MRI is medically contraindicated or cannot be scheduled in a timely 
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13.2. Tumor Imaging During the Study 
The first on-study imaging assessment should be performed at 6 weeks (±1 week) from the date 
of the first study treatment. Subsequent tumor imaging should be performed every 6 weeks (±1 
week) or more frequently if clinically indicated. After the first 6 months, subjects who remain 
on treatment will have imaging performed every 9 weeks (±1 week). Imaging timing should 
follow calendar days and should not be adjusted for delays in cycle start dates. Imaging should 
continue to be performed until disease progression is identified by the investigator, or 
notification by the Sponsor, whichever occurs first.  
Brain MRI is required during the study only if: 
o The screening brain scan is positive (has tumor lesion)  
o The subject develops sign/symptoms suggestive of brain metastasis 
Brain CT imaging is acceptable if MRI is medically contraindicated or cannot be scheduled in a 
timely manner. 
Objective response should be confirmed by a repeat imaging assessment. Tumor imaging to 
confirm PR or CR should be performed at least 4 weeks after the first indication of a response is 
observed. Subjects will then return to regular scheduled imaging, starting with the next scheduled 
imaging time point. Subjects who receive additional imaging for confirmation do not need to 
undergo the next scheduled tumor imaging if it is less than 4 weeks later; tumor imaging may 
resume at the subsequent scheduled imaging time point.  
Per iRECIST (Appendix A – Assessment of Disease) disease progression should be confirmed 
by the site, 4 to 8 weeks after site-assessed first radiologic evidence of PD in clinically stable 
subjects. Subjects, who have unconfirmed disease progression may continue on treatment at the 
discretion of the investigator until progression is confirmed by the site, provided they have met 
the conditions detailed in Appendix A – Assessment of Disease. Subjects who receive 
confirmatory imaging do not need to undergo the next scheduled tumor imaging if it is less than 
4 weeks later; tumor imaging may resume at the subsequent scheduled imaging time point, if 
clinically stable. Subjects, who have confirmed disease progression by iRECIST, as assessed by 
the site, will discontinue study treatment. Exceptions are detailed in Appendix A – Assessment 
of Disease, Table 6. 
13.3. 
End of Treatment and Follow-up Tumor Imaging 
For subjects who discontinue study treatment, tumor imaging should be performed at the time 
of treatment discontinuation. If previous imaging was obtained within 4 weeks prior to the date 
of discontinuation, then imaging at treatment discontinuation is not mandatory.  
For subjects who discontinue study treatment without documented disease progression, every 
effort should be made to continue monitoring disease status by tumor imaging every 90 days 
(+/- 7 days) until the start of a new anti-cancer treatment, disease progression, pregnancy, 
death, withdrawal of consent, or the end of the study, whichever occurs first.  
Details on the assessment of disease using RECIST 1.1 and iRECIST can be found within 
Appendix A – Assessment of Disease. 

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13.4. Response Criteria 
13.4.1. 
Evaluation of Target Lesions 
Complete Response (CR). Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). 
Partial Response (PR). At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (PD). At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate 
an absolute increase of at least 5 mm (0.5 cm). (Note: the appearance of 1 or more new lesions 
is also considered progressions). 
Stable Disease (SD). Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
13.4.2. 
Evaluation of Non-Target Lesions 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (<10 mm [<1 cm] short axis). 
Note: If tumor markers are initially above the upper normal limit, they must normalize for a 
subject to be considered in complete clinical response. 
Non-CR/Non-PD: Persistence of 1 or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Appearance of 1 or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally 
trump target lesion status. It must be representative of overall disease status change, not a 
single lesion increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances, and the progression status should be 
confirmed at a later time by the review panel (or PI). 
13.4.3. 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started). The subject's best response assignment 
will depend on the achievement of both measurement and confirmation criteria. 

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For Subjects with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
 
PR 
Non-CR/Non-PD/not 
evaluated 
No 
PR 
 
SD 
Non-CR/Non-PD/not 
evaluated 
No 
SD 
Documented at least once 
>4 wks. from baseline** 
PD 
Any 
Yes or No 
PD 
no prior SD, PR, or CR 
Any 
PD*** 
Yes or No 
PD 
 
Any 
Any 
Yes 
PD 
 
* See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** Only for non-randomized studies with response as primary endpoint. 
*** In exceptional circumstances, unequivocal progression in non-target lesions may be 
accepted as disease progression. 
Note: Subjects with a global deterioration of health status requiring discontinuation of 
treatment without objective evidence of disease progression at that time should be reported 
as “symptomatic deterioration.” Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; RECIST=Response 
Evaluation Criteria in Solid Tumors; SD=stable disease.  
 
For Subjects with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is 
increasingly used as an endpoint for assessment of efficacy in some studies so to assign this 
category when no lesions can be measured is not advised 
Abbreviations: CR=complete response; PD=progressive disease; SD=stable disease.  

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13.4.4. 
Duration of Response 
Duration of response: The duration of response is measured from the time measurement 
criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or 
progressive disease is objectively documented (taking as reference for progressive disease the 
smallest measurements recorded since the treatment started). 
The duration of CR is measured from the time measurement criteria are first met for CR until 
the first date that progressive disease is objectively documented. 
 
Duration of stable disease: SD is measured from the start of the treatment until the criteria for 
progression are met, taking as reference the smallest measurements recorded since the 
treatment started, including the baseline measurements. 
13.4.5. 
Progression-Free Survival (PFS) 
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first. 
 
13.4.6. Response Review 
Radiological images may be collected for a possible review of response by an expert(s) 
independent of the study. Measurement of tumor response by a trained radiologist/nuclear 
medicine physician at each clinical site will be chronicled and reported unless or until a central 
expert review takes place. 
Additional details are in the Appendix A – Assessment of Disease. 

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14. 
Data Management and Reporting 
Data collection for this study will be done exclusively through an electronic clinical data 
management system. The Data Management Organization will utilize a core set of electronic 
Case Report Forms (eCRF) that are Clinical Data Acquisition Standards Harmonization 
(CDASH)-compliant (https://www.cdisc.org/standards/foundational/cdash). Customized 
eCRFs will be included when appropriate to meet unique study requirements. The data 
management organization will prepare the eCRFs with built-in edit checks to the extent 
possible to promote data integrity.  
Access to the study is granted to all persons with the appropriate roles, as listed on the 
Delegation of Authority Sheet. Upon site activation, all persons with the appropriate roles will 
be sent a study invitation email. Site users will not be able to access the study until all required 
study specific trainings are completed. Trainings will be in the form of electronic learnings 
(eLearnings). 
For further details, please refer to the Site Operations Manual.  
14.1. 
Responsibility for Data Submission 
To provide evidence that the protocol has been followed, documentation of all procedures that 
are conducted under this protocol is required. In cases of screen failures, the following 
information must be documented within the source: demographic data (including at minimum 
sex, age and/or birth year, race/ethnicity, and informed consent date), the outcome of the 
eligibility assessment, the reason for the screening failure by criterion, and AE details. 
It is the responsibility of the PI(s) at the site to ensure that all investigators and study staff at 
the clinical site understand the procedures for data submission per the protocol. Furthermore, 
the investigator or designee is responsible for submitting protocol-specified data and queries, 
including safety case processing queries, accurately and in a timely manner to the data 
management organization via the EDC system; these must be complete and verifiable with the 
source. The clinical site must appropriately maintain the source for the required time period – 
this ensures data integrity and traceability, and protects personal information of study subjects.  
The data management organization is responsible for compiling and submitting data of all 
subjects to the study Sponsor. The EDC data and supporting documents should be available for 
the Sponsor/designee, auditors, and regulatory authorities to review/retrieve at any given time, 
as required by clinical trial agreements and GCP requirements.  
Good Documentation Practices and ALCOA+ principles for data integrity must be followed 
for all essential documents and other clinical trial-related records. The Sponsor, the delegated CRO, 
and investigators must organize and securely retain data and other study records for the 
required period of time. These must be available if requested by regulatory authorities, to 
ensure the reliability of the trial’s results. 
14.2. 
Compliance with Study Registration and Results Posting Requirements 
Under the terms of the Food and Drug Administration Modernization Act (FDAMA) and the 
Food and Drug Administration Amendments Act (FDAAA), the study Sponsor is solely 
responsible for determining whether the study and its results are subject to the requirements for 

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submission to the Clinical Trials Data Bank, https://www.clinicaltrials.gov. Information posted 
will allow subjects to identify potentially appropriate studies for their disease conditions and 
pursue participation by calling a central contact number for further information on appropriate 
study locations and study site contact information.  
14.3. 
Study Oversight 
Responsibility for monitoring the clinical trial lies with the Sponsor or the delegated CRO. The 
purpose of monitoring is to ensure protection of subjects’ human rights, safety, and well-being, 
to verify that the trial is conducted according to the current protocol and GCP, and that study 
data reported by the investigator are entered or available in a timely fashion, and are accurate, 
complete, and verifiable with source documents and other study-related records. Accordingly, 
the Sponsor or the delegated CRO will assign study monitor(s), who will monitor the study as 
detailed in planned monitoring procedures. Monitoring is scaled to data generation by sites. 
The investigator and the clinical site are required to cooperate with monitoring and auditing by 
the Sponsor or delegated CRO, as well as inspections by the IRB/IEC and regulatory 
authorities. During monitoring, auditing, and inspections, all study-related records, including 
but not limited to source documents, training records, and delegation logs, must be provided 
upon request by Sponsor monitors/auditors, IRB/IEC, or regulatory authorities. The 
investigator must be available to discuss the findings of the monitoring visit or audit. When 
source documents are directly accessed, the confidentiality of subject identities must be 
protected in accordance with local and national regulations. 
This protocol will adhere to the policies and requirements listed in the Site Operations Manual. 
Protocol waivers (documented prospective approval of requests from an investigator to deviate 
from the protocol) are prohibited for this study. For specific responsibilities of the PI, and 
NeoImmuneTech, Inc., please refer to the site-specific contract and the Form FDA1572. 
Sponsor or Sponsor’s designee is responsible for distributing all Investigational New Drug 
Application (IND) Action Letters or Safety Reports received from the study Sponsor, 
NeoImmuneTech, Inc., to all participating institutions for submission to their individual 
Institutional Review Boards (IRBs) for action as required. 
 
Study drugs may be ordered by a participating site only after approved by the study Sponsor, 
NeoImmuneTech, Inc. and officially activated.  
14.4. 
Subject Enrollment and EDC 
Subject enrollment will be facilitated using the enrollment module in the EDC system. To 
access the enrollment module, the site user must be assigned the ‘Enroll/Randomize subjects’ 
responsibility on the Delegation of Authority Sheet.   
Before enrolling a subject in the EDC system, registration staff should verify the following: 
• All eligibility criteria have been met within the protocol stated timeframes. 
• If applicable, all subjects have signed an appropriate consent form and Health 
Insurance Portability and Accountability Act of 1996 (HIPAA) authorization form 
(if applicable). 

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For further instructional information, please refer to the EDC Completion Guidelines. 
 

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15. 
Statistical Considerations 
This section outlines the statistical analysis strategy and methods for the study. If, after the 
study has begun, but before the conduct of any analysis, changes are made to primary and/or 
key secondary hypotheses or the statistical methods related to those hypotheses, then the 
protocol will be amended (consistent with ICH Guideline E-9). Changes to exploratory or other 
non-confirmatory analyses made after the protocol has been finalized, along with an 
explanation as to when and why they occurred, will be listed in the Clinical Study Report 
(CSR) for the study. Post hoc exploratory analyses will be clearly identified in the CSR.  
15.1. 
Sample Size and Power Calculation 
ORR assessed by RECIST 1.1 and iRECIST will be considered as primary efficacy endpoints 
in each Phase 2a arm and estimated using exact confidence intervals based on the binomial 
distribution (Clopper-Pearson intervals) from the evaluable subjects for selected arms. All 
subjects treated on study and with data available for the calculation of the primary endpoint 
ORR will be considered evaluable. A test from the Simon minimax design for null hypothesis 
ORR proportion in the arm population 4% vs alternative hypothesis 21% will be conducted in 
selected arms at 1-sided alpha = 0.025 and the p-value reported. 
Arms I, II, III, IV, and V of the Phase 2a study stage will follow the Simon’s two-stage 
minimax design.  Each arm will enroll 17 evaluable subjects in Stage 1 and, if the Go/No Go 
criterion is met, an additional 8 evaluable subjects in Stage 2 for a total of 25 evaluable 
subjects/arm. This will provide an estimated 80% power per selected arm in the Phase 2a stage 
of the study for the primary hypothesis test using the Simon minimax design.  Exact 95% 
binomial Clopper-Pearson confidence interval estimates of ORR from each arm is planned to 
support the primary hypothesis tests.  
Enrolment of up to 30 subjects per arm is planned to account for non-evaluable subjects and 
dropouts. Up to 238 subjects (up to 18 subjects in the Phase 1b, up to 210 subjects in all arms 
of Phase 2a and up to 10 subjects in the Biomarker Cohort) are planned to be enrolled in the 
study.   
It has been reported that approximate 7% of pseudo-progression occurred in pembrolizumab 
monotherapy in patients with melanoma while comparing ORR assessed by RECIST 1.1 vs 
iRECIST (Hodi FS, 2016). This study would explore the rate of pseudo-progression in NT-I7 
plus pembrolizumab assessed by iRECIST 1.1.  
In the phase 2a, Go/No Go decision for Arms I, II, III, IV, and V will be based on iRECIST, 
since iRECIST assessment starts after 1st PD defined by RECIST 1.1.  
15.2. 
Stratification Factors 
No stratification is planned. 
15.3. 
Interim Analyses 
In Phase 2a, Arms I, II, III, IV, and V will have a futility interim analysis per the Simon’s two-
stage minimax design at 17 evaluable subjects based on ORR assessed by RECIST 1.1 and 

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iRECIST. In Phase 1b there is a safety interim analysis after each dose level to determine the 
dosing for the next subject. 
An interim analysis will not be performed for IVa, Va, and the Biomarker Cohort Ovarian 
Cancer. 
15.4. 
Data Monitoring Committee (DMC)  
 
To provide oversight of safety, efficacy, and study conduct, a Data Monitoring Committee 
(DMC) will be instituted. The voting members of the committee are external to the 
Sponsor.   They must not be involved with the trial in any way (e.g., trial` investigators) and 
must not have competing interests that could affect their roles with respect to the trial.    
 
The DMC will monitor for subject safety and scientific integrity during the study.  The DMC 
will make a decision for dose escalation or dose-de-escalation in the Phase 1b and determine the 
RP2D; in Phase 2a and Biomarker Cohort. The DMC will monitor for subject safety and 
scientific integrity during the study. The DMC will meet to review the safety and efficacy data 
at the interim analysis for arms I, II, III, IV, and V (i.e., after the 17th evaluable subject enrolled 
into the arm has had the 1st tumor assessment).  At intervals defined by the DMC charter, the 
DMC will review and evaluate the data on clinical efficacy and safety collected during the study 
and assesses reports on cumulated SAEs. In addition to the pre-scheduled data reviews and 
planned safety monitoring, the DMC will convene additional ad hoc meetings to conduct 
emergency reviews of any event that potentially impacts safety at the request of the sponsor. 
Following each meeting, the DMC will recommend continuation, modification, or 
discontinuation of the study based on observed toxicities.  
 
Specific details regarding composition, responsibilities, and governance, including the roles and 
responsibilities of various members and the Sponsor protocol team; meeting facilitation; the trial 
governance structure; and requirements for and proper documentation of DMC reports, minutes, 
and recommendations will be described in a separate charter that is reviewed and approved by 
the DMC.  
15.5. 
Statistical Analysis Plan Summary 
 
Study Design 
Overview 
An Open-label Phase 1b/2a Study of NT-I7 (efineptakin alfa) in 
Combination with Pembrolizumab in Subjects with 
Relapsed/Refractory Advanced Solid Tumors 
Analysis 
Populations 
Safety: All-Subjects-as-Treated (ASaT) 
PK: Per-Protocol (PP) 
Efficacy: All evaluable per arm, a subset may be repeated on All-
Subjects-as-Treated (ASaT). 

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Descriptive analysis will be performed at the end of enrollment for 
Arms IVa and Va. 
Primary 
Endpoint(s) 
Phase 1b: 
• Incidence, nature, and severity of adverse events graded according 
to NCI CTCAE v5.0 
• Incidence and nature of DLTs 
• Potential correlation of dose levels with safety and efficacy 
parameters 
 Phase 2a: 
• Objective Response Rate (ORR) for each individual arm, defined 
as the percentage of subjects who have at least one confirmed 
partial response (PR) or complete response (CR), per RECIST 1.1 
and iRECIST as determined by the investigator 
Biomarker Cohort:  
• To assess a potential correlation between tumor infiltrating 
lymphocytes (TILs) and clinical benefits in subjects with CPI-
naïve R/R OC. 
Secondary 
Endpoints 
Phase 1b/2a: 
• Duration of objective response (DOR) for each individual arm, 
defined as the time from the first occurrence of a documented 
objective response to the time of the first documented disease 
progression or death from any cause, whichever occurs first, per 
RECIST 1.1 and iRECIST as determined by the investigator.  
• Disease Control Rate (DCR) for each individual arm, defined as 
proportion of subjects with a best overall response of CR, PR or 
stable disease (SD), per RECIST 1.1 as determined by the 
investigator. 
• Progression Free Survival (PFS) for each individual arm, defined 
as the time from the first study treatment (Cycle 1, Day 1) to the 
first occurrence of progression or death from any cause, 
whichever occurs first, per RECIST 1.1 as determined by the 
investigator. 
• Overall survival (OS) for each individual arm, defined as the time 
from first study treatment (Cycle 1, Day 1) to death from any 
cause 
• Incidence of anti-drug antibody (ADA) to NT-I7 during the study 
relative to the prevalence of ADA at baseline 

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Biomarker Cohort:  
• To assess the safety and tolerability of NT-I7 in combination with 
pembrolizumab in subjects with CPI-naïve R/R OC 
 
Statistical 
Methods for 
Efficacy Analysis 
  
Primary: ORR will be considered a primary efficacy endpoint and 
estimated using exact confidence intervals based on the binomial 
distribution (Clopper-Pearson intervals). A test from the Simon 
minimax design for null hypothesis ORR proportion in the arm 
population 4% vs alternative hypothesis 21% will be conducted in 
each arm at 1-sided alpha = 0.025 and the p-value reported. 
Arms I, II, III, IV, and V for the Phase 2a study stage will follow the 
Simon’s two-stage minimax design in each arm and has 5 arms. Each 
arm will enroll 17 evaluable subjects in Stage 1 and, if the Go/No Go 
criterion is met, an additional 8 evaluable subjects in Stage 2 for a 
total of 25 evaluable subjects/arm. Exact 95% binomial Clopper-
Pearson confidence interval estimates of ORR for arms I, II, III, IV, 
and V are planned to support the primary hypothesis tests. Enrolment 
of up to 30 subjects per arm is planned to account for non-evaluable 
subjects and dropouts. Approximately 210 subjects are planned for 
the Phase 2a study stage.    
Note: In addition to the primary analyses on the population of 
evaluable subjects for the primary endpoint, exploratory analyses will 
also be presented on the population of all subjects enrolled and 
treated on study.  
Secondary:  
• 
Duration of response (DoR) for the responders in each individual 
arm, is defined as the time from the first occurrence of a 
documented objective response to the time of the first documented 
disease progression or death from any cause, whichever occurs 
first, per RECIST 1.1 as determined by the investigator.  
DoR will be assessed statistically via Kaplan-Meier methods and 
presented descriptively for the responders. Comparative 
assessments are not planned on this endpoint. 
• Disease Control Rate (DCR) for each individual arm, is defined as 
proportion of subjects with a best overall response of CR, PR or 
SD, per RECIST 1.1 as determined by the investigator. 
DCR will be assessed statistically via Fisher Exact tests supported 
by Clopper-Pearson confidence intervals; all analyses will be 
interpreted descriptively. Comparative assessments are not 
planned on this endpoint. 
• Progression Free Survival (PFS) for each individual arm, is 
defined as the time from the first study treatment (Cycle 1, Day 1) 
to the first occurrence of progression or death from any cause, 

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whichever occurs first, per RECIST 1.1 as determined by the 
investigator. 
PFS will be assessed statistically via Kaplan-Meier methods and 
presented descriptively for all treated patients in each study arm; 
censoring rules and statistical endpoint definitions (time to event) 
will be detailed in the SAP prospectively. Comparative 
assessments are not planned on this endpoint. 
• Overall survival (OS) for each individual arm, is defined as the 
time from first study treatment (Cycle 1, Day 1) to death from any 
cause. 
OS will be assessed statistically similarly to PFS (above). 
• Incidence of anti-drug antibody (ADA) to NT-I7 during the study 
will be assessed, relative to the prevalence of ADA at baseline.  
Immunogenicity to NT-I7 will be measured using a risk-based, 
tiered testing approach. Additional details are provided in Table 1. 
Treatment 
Assignment 
This is not a randomized study. 
Statistical 
Methods for 
Safety Analyses 
Summary statistics will be provided for the safety endpoints as 
appropriate.  
Interim Analyses 
For Phase 2a, Arms I, II, III, IV, and V, an interim analysis for futility 
is included, per the Simon minimax design.  
An interim analysis will not be performed for Arms IVa, Va, and the 
Biomarker Cohort Ovarian Cancer. 
An interim analysis for Phase 1b will be performed. 
Multiplicity 
No multiplicity adjustment is planned. 
Sample Size and 
Power  
Up to 238 subjects (up to 18 subjects in the Phase 1b, up to 210 
subjects in the Phase 2a and up to 10 subjects in the Biomarker 
Cohort) are planned to be enrolled in the study. 
This will provide an estimated 80% power per selected arm in the 
Phase 2a stage of the study for the primary hypothesis test using the 
Simon minimax design, for 4% vs 21% ORR, at 1-sided alpha = 
0.025, as well as approximately 25 evaluable subjects per arms for 
95% exact binomial Clopper-Pearson confidence intervals for ORR 
from the design (per arm). 

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treatment of PML in a patient with idiopathic lymphocytopenia. Neurol Neuroimmunol 
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Decreases in colonic and systemic inflammation in chronic HIV infection after IL-7 
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Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. 
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progressive multifocal leukoencephalopathy with interleukin 7 and vaccination with JC virus 
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Sportes C, Babb RR, Krumlauf MC, Hakim FT, Steinberg SM, Chow CK, et al. Phase I 
study of recombinant human interleukin-7 administration in subjects with refractory 
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Thiebaut R, Drylewicz J, Prague M, Lacabaratz C, Beq S, Jarne A, et al. Quantifying 
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17. 
Abbreviations 
 
ADA 
Anti-Drug Antibody 
AEs 
Adverse Events 
AESI  
Adverse Event of Special Interest 
ALK 
Anaplastic lymphoma kinase 
ALT 
Alanine Amino Transferase 
AML 
Acute Myelocytic Leukemia 
ANC 
Absolute Neutrophil Count 
aPTT 
Activated Partial Thromboplastin Time 
ASCO-CAP 
American Society of Clinical Oncology – College of American Pathologists 
AST 
Aspartate Amino Transferase 
BCG 
Bacillus Calmette–Guérin 
BICR 
Blinded Independent Central Review 
BRAF 
Proto-oncogene B-Raf 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CD 
Cluster of Differentiation 
CDASH 
Clinical Data Acquisition Standards Harmonization 
CFR 
Code of Federal Regulation 
CHO 
Chinese Hamster Ovary 
CI 
Confidence Interval 
CISH 
Chromogenic in situ hybridization 
CNS 
Central Nervous System 
CPI 
Check Point Inhibitor 
CR 
Complete Response 
CRC  
Colorectal Cancer 
CrCl 
Creatinine Clearance 
CRF 
Case Report Form 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CTEP 
Cancer Therapy Evaluation Program 
CxDx 
Cycle x Day x 
D1 
Day 1 
DCR 
Disease Control Rate 
DILI 
Drug-Induced Liver Injury 
DL 
Dose Level 
DLT  
Dose Limiting Toxicity 
DMC 
Data Monitoring Committee 
dMMR 
deficient Mismatch Repair 
DOR  
Duration of Response 
ECI  
Events of Clinical Interest 

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ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic Data Capture 
EGFR 
Epidermal growth factor receptor 
EKG 
Electrocardiogram 
EOT 
End of Treatment 
ER 
Estrogen Receptor 
FDA 
Food and Drug Administration  
FDAAA 
Food and Drug Administration Amendments Act 
FDAMA 
Food and Drug Administration Modernization Act 
FFPE 
Formalin-fixed, paraffin embedded 
FISH 
Fluorescence in situ hybridization 
FT3/FT4 
free Triiodothyronine/ free Thyroxine 
FU 
Follow Up 
GCP 
Good Clinical Practice 
HER2 
Human epidermal growth factor receptor 2 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HR 
Hazard Ratio 
hyFC 
hybrid Fc 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization 
iCPD 
iRECIST Confirmed Progressive Disease  
iCR 
iRECIST Complete Response 
IDMC 
Independent Data Monitoring Committee 
IHC 
Immunohistochemistry 
IM 
Intramuscular 
IME 
Important Medical Events 
IND/IDE 
Investigational New Drug Application/Investigational Device Exemption 
INR 
International Normalized Ratio 
iPD 
iRECIST Progressive Disease 
iPR 
iRECIST Partial Response 
IRB 
Institutional Review Board 
iRC  
Immune-Related Response Criteria 
iRECIST 
modified Response Evaluation Criteria in Solid Tumors 
iSD 
iRECIST Stable Disease 
ITT 
Intent-To-Treat 
iUPD 
iRECIST Unconfirmed Progressive Disease  
IV 
Intravenous 
LDH 
Lactate Dehydrogenase 
LLN/ULN 
Lower Limit of Normal/Upper Limit of Normal 
mAb 
Monoclonal Antibody 
MDS 
Myelodysplastic Syndrome 
MED 
Maximum Effective Dose 

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MRI 
Magnetic Resonance Imaging 
MSI-H 
Microsatellite Instability High 
MSS-CRC  
Microsatellite Stable Colorectal Cancer 
MTD 
Maximum Tolerated Dose 
Nab 
Neutralizing Antibody 
NCI-CTCAE 
National Cancer Institute – Common Terminology Criteria for Adverse Events 
NIT 
NeoImmuneTech, Inc. 
NKT 
Natural Killer-T cells 
NSAID 
Nonsteroidal Anti-Inflammatory Drugs 
NSCLC  
Non-small Cell Lung Cancer 
NT-I7 
rh-IL-7-hyFc ka GX-I7 
OC 
Ovarian Cancer 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PC  
Pancreatic Cancer 
PCR 
Polymerase Chain Reaction 
PD 
Pharmacodynamics 
PD 
Progressive Disease 
PD-1/PD-L1 
Programmed cell death protein 1/Programmed cell death protein - Ligand 1 
PFS  
Progression Free Survival 
Ph. EUR 
European Pharmacopeia 
PI 
Principal Investigator 
PK 
Pharmacokinetics 
pMMR 
proficient Mismatch Repair 
PR 
Partial Response 
PR 
Progesterone Receptor 
Q3W 
Every 3 weeks 
Q6W 
Every 6 weeks 
QTc 
Corrected QT interval 
R/R 
Relapsed/Refractory 
RBC 
Red Blood Cells 
RECIST 
Response Evaluation Criteria in Solid Tumors 
ROS1 
ROS Proto-Oncogene 1  
RP2D 
Recommended Phase 2 Dose 
RP-HPLC 
Reverse-Phase High-Performance Liquid Chromatography 
SAEs 
Serious Adverse Events 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Stable Disease 
SE-UHPLC 
Size-Exclusion Ultra-High-Performance Liquid Chromatography 
SGOT 
Serum Glutamic-Oxaloacetic Transaminase 
SGPT 
Serum Glutamic-Pyruvate Transaminase 
SOC  
System Organ Class 

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T1DM 
Type 1 Diabetes Mellitus 
TBL 
Total bilirubin level 
TEAE 
Treatment Emergent Adverse Event 
TIL 
Tumor-infiltrating lymphocyte 
TKI 
Tyrosine Kinase Inhibitor 
TNBC 
Triple Negative Breast Cancer 
TNF 
Tumor Necrosis Factor 
TSH 
Thyroid Stimulating Hormone 
Tx 
Treatment 
VOP 
Verification of Progression 
WBC 
White Blood Cells 
 
 

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Appendix A – Assessment of Disease 
 
RECIST 1.1 Assessment of Disease 
RECIST 1.1 will be used as the primary measure for assessment of tumor response, date of 
disease progression, and as a basis for all protocol guidelines related to disease status (e.g., 
discontinuation of study treatment). RECIST 1.1 references a maximum of 5 target lesions in 
total, and 2 per organ. (87) 
iRECIST Assessment of Disease 
iRECIST is based on RECIST 1.1 but adapted to account for the unique tumor response seen 
with immunotherapeutic drugs. iRECIST will be used by the Investigator to assess tumor 
response and progression and make treatment decisions. When clinically stable, subjects may 
continue study intervention beyond RECIST 1.1 progression with continued assessment of 
response according to the rules outlined in Table 6. iRECIST reflects that some subjects can 
have a transient tumor flare in the first few months after the start of immunotherapy, and then 
experience subsequent disease response. This data will be captured in the clinical database. 
• 
If subject is clinically stable, continue study intervention per protocol  
• 
Perform scans 4 to 8 weeks after RECIST 1.1 progression 
• 
Continue investigator assessment per iRECIST 
• 
If the subject is not clinically stable, best medical practice is to be applied. 
  
For the purpose of this decision process, lack of clinical stability is defined as: 
• Unacceptable toxicity 
• Clinical signs or symptoms indicating clinically significant disease progression 
• Decline in performance status 
• Rapid disease progression or threat to vital organs or critical anatomical sites (e.g., CNS 
metastasis, respiratory failure due to tumor compression, spinal cord compression) 
requiring urgent alternative medical intervention. 
 
Any subject deemed clinically unstable should be discontinued from study treatment at site-
assessed first radiologic evidence of PD and is not required to have repeat tumor imaging for 
confirmation of PD by iRECIST. 
If the Investigator decides to continue treatment, the subject should continue to receive study 
treatment.  Regardless of the subject is on treatment or off treatment, the tumor assessment 
should be repeated 4 to 8 weeks later to confirm PD by iRECIST, per Investigator assessment.  
If repeat imaging does not confirm PD per iRECIST, as assessed by the Investigator, and the 
subject continues to be clinically stable, study treatment may continue and follow the regular 
imaging schedule. If PD is confirmed, subjects will be discontinued from study treatment. 

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If a subject has confirmed radiographic progression (iCPD) as defined in Table 6, study treatment 
should be discontinued; however, if the subject is achieving a clinically meaningful benefit, an 
exception to continue study treatment may be considered following consultation with the 
Sponsor.  In this case, if study treatment is continued, tumor imaging should continue to be 
performed following the intervals as outlined in Table 6.  
A description of the adaptations and iRECIST process is provided in the latter half of Appendix 
A – Assessment of Disease, with additional details in the iRECIST publication1. A summary of 
imaging and treatment requirements after first radiologic evidence of progression is provided in 
Table 6 and illustrated as a flowchart in Figure 5. 
 
Figure 5: Imaging and treatment for clinically stable subjects treated with NT-
I7+pembrolizumab after first radiologic evidence of PD assessed by the investigator. 
 
 
 
 
 
 
 

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Table 6: Imaging and treatment after first radiologic evidence of progressive disease 
 
Clinically Stable 
Clinically Unstable 
Imaging 
Treatment 
Imaging 
Treatment 
First radiologic 
evidence of PD by 
RECIST 1.1  
Repeat imaging at 
4 to 8 weeks to 
confirm PD. 
May continue study 
treatment at the 
Investigator’s discretion 
while awaiting 
confirmatory tumor 
imaging by site by 
iRECIST. 
Repeat imaging at 
4 to 8 weeks to 
confirm PD per 
Investigator’s 
discretion only. 
Discontinue treatment 
Repeat tumor 
imaging confirms 
PD (iCPD) by 
iRECIST per 
Investigator 
assessment 
No additional 
imaging required. 
Discontinue treatment 
(exception is possible 
upon consultation with 
Sponsor). 
No additional 
imaging required. 
Not applicable 
Repeat tumor 
imaging shows 
iUPD by iRECIST 
per Investigator 
assessment 
Repeat imaging at 
4 to 8 weeks to 
confirm PD.  May 
occur at next 
regularly scheduled 
imaging visit. 
Continue study 
treatment at the 
Investigator’s 
discretion. 
Repeat imaging at 
4 to 8 weeks to 
confirm PD per 
Investigator’s 
discretion only. 
Discontinue treatment 
Repeat tumor 
imaging shows iSD, 
iPR, or iCR by 
iRECIST per 
Investigator 
assessment. 
Continue regularly 
scheduled imaging 
assessments. 
Continue study 
treatment at the 
Investigator’s 
discretion. 
Continue regularly 
scheduled imaging 
assessments. 
May restart study 
treatment if condition has 
improved and/or clinically 
stable per Investigator’s 
discretion.  Next tumor 
imaging should occur 
according to the regular 
imaging schedule. 
iCPD = iRECIST confirmed progressive disease; iCR = iRECIST complete response; iRECIST = modified Response 
Evaluation Criteria in Solid Tumors 1.1 for immune-based therapeutics; iSD = iRECIST stable disease; iUPD = iRECIST 
unconfirmed progressive disease; PD = progressive disease; RECIST 1.1 = Response Evaluation Criteria in Solid Tumors 
1.1.; VOP=verification of progression 
 
 
 

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RECIST 1.1 and iRECIST 
 
Assessment at Screening and Prior to RECIST 1.1 Progression 
 
Until radiographic disease progression based on RECIST 1.1, there is no distinct iRECIST 
assessment. 
 
Assessment and Decision at RECIST 1.1 Progression 
 
For subjects who show evidence of radiological PD by RECIST 1.1 as determined by the 
Investigator, the Investigator will decide whether to continue a subject on study treatment until 
repeat imaging is obtained (using iRECIST for subject management (see Table 6 and Figure 5). 
This decision by the Investigator should be based on the subject’s overall clinical condition. 
Clinical stability is defined as the following:  
• Absence of symptoms and signs indicating clinically significant progression of disease 
• No decline in ECOG performance status  
• No requirements for intensified management, including increased analgesia, radiation, or 
other palliative care 
Any subject deemed clinically unstable should be discontinued from study treatment at site-
assessed first radiologic evidence of PD and is not required to have repeat tumor imaging for 
confirmation of PD by iRECIST. 
 
If the Investigator decides to continue treatment, the subject may continue to receive study 
treatment and the tumor assessment should be repeated 4 to 8 weeks later to confirm PD by 
iRECIST, per Investigator assessment.  
 
Tumor flare may manifest as any factor causing radiographic progression per RECIST 1.1, 
including: 
• Increase in the sum of diameters of target lesion(s) identified at baseline to ≥20% and 
≥5 mm from nadir 
o Note: the iRECIST publication uses the terminology “sum of measurements”, but 
“sum of diameters” will be used in this protocol, consistent with the original 
RECIST 1.1 terminology. 
• Unequivocal progression of non-target lesion(s) identified at baseline 
• Development of new lesion(s) 
 
iRECIST defines new response categories, including iUPD (unconfirmed progressive disease) 
and iCPD (confirmed progressive disease). For purposes of iRECIST assessment, the first visit 
showing progression according to RECIST 1.1 will be assigned a visit (overall) response of 
iUPD, regardless of which factors caused the progression. 
 
At this visit, target and non-target lesions identified at baseline by RECIST 1.1 will be assessed 
as usual. 
 

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New lesions will be classified as measurable or non-measurable, using the same size thresholds 
and rules as for baseline lesion assessment in RECIST 1.1. From measurable new lesions, up to 
5 lesions total (up to 2 per organ), may be selected as New Lesions – Target.  The sum of 
diameters of these lesions will be calculated and kept distinct from the sum of diameters for 
target lesions at baseline.  All other new lesions will be followed qualitatively as New Lesions – 
Non-target. 
 
Assessment at the Confirmatory Imaging 
 
On the confirmatory imaging, the subject will be classified as progression confirmed (with an 
overall response of iCPD), or as showing persistent unconfirmed progression (with an overall 
response of iUPD), or as showing disease stability or response (iSD/iPR/iCR). 
 
Confirmation of Progression 
 
Progression is considered confirmed, and the overall response will be iCPD, if ANY of the 
following occurs: 
• Any of the factors that were the basis for the initial iUPD show worsening 
o For target lesions, worsening is a further increase in the sum of diameters of ≥5 mm, 
compared to any prior iUPD time point 
o For non-target lesions, worsening is any significant growth in lesions overall, 
compared to a prior iUPD time point; this does not have to meet the “unequivocal” 
standard of RECIST 1.1 
o For new lesions, worsening is any of these: 
 An increase in the new lesion sum of diameters by ≥5 mm from a prior iUPD 
time point  
 Visible growth of new non-target lesions  
 The appearance of additional new lesions 
• Any new factor appears that would have triggered PD by RECIST 1.1 
 
Persistent iUPD 
 
Progression is considered not confirmed, and the overall response remains iUPD, if: 
• None of the progression-confirming factors identified above occurs AND 
• The target lesion sum of diameters (initial target lesions) remains above the initial PD 
threshold (by RECIST 1.1) 
 
Additional imaging for confirmation should be scheduled 4 to 8 weeks from the imaging on 
which iUPD is seen. This may correspond to the next visit in the original visit schedule.  The 
assessment of the subsequent confirmation imaging proceeds in an identical manner, with 
possible outcomes of iCPD, iUPD, and iSD/iPR/iCR. 
 
Resolution of iUPD 
 
Progression is considered not confirmed, and the overall response becomes iSD/iPR/iCR, if: 

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• None of the progression-confirming factors identified above occurs, AND 
• The target lesion sum of diameters (initial target lesions) is not above the initial PD 
threshold.  
The response is classified as iSD or iPR (depending on the sum of diameters of the target lesions), 
or iCR if all lesions resolve. 
 
In this case, the initial iUPD is considered to be pseudo-progression, and the level of suspicion 
for progression is “reset”. This means that the next visit that shows radiographic progression, 
whenever it occurs, is again classified as iUPD by iRECIST, and the confirmation process is 
repeated before a response of iCPD can be assigned. 
 
Management Following the Confirmatory Imaging 
 
If repeat imaging does not confirm PD per iRECIST, as assessed by the Investigator, and the 
subject continues to be clinically stable, study treatment may continue and follow the regular 
imaging schedule. If PD is confirmed, subjects will be discontinued from study treatment. 
Note: If a subject has confirmed radiographic progression (iCPD) as defined above, but the 
subject is achieving a clinically meaningful benefit, an exception to continue study treatment 
may be considered following consultation with the Sponsor. In this case, if study treatment is 
continued, tumor imaging should continue to be performed following the intervals as outlined in 
Section 13. 
 
Detection of Progression at Visits After Pseudo-progression Resolves 
 
After resolution of pseudo-progression (i.e., achievement of iSD/iPR/iCR), iUPD is indicated by 
any of the following events: 
• Target lesions 
o Sum of diameters reaches the PD threshold (≥20% and ≥5 mm increase from 
nadir) either for the first time, or after resolution of previous pseudo-progression. 
The nadir is always the smallest sum of diameters seen during the entire study, 
either before or after an instance of pseudo-progression. 
• Non-target lesions 
o If non-target lesions have never shown unequivocal progression, their doing so 
for the first time results in iUPD. 
o If non-target lesions have shown previous unequivocal progression, and this 
progression has not resolved, iUPD results from any significant further growth of 
non-target lesions, taken as a whole. 
• New lesions 
o New lesions appear for the first time 
o Additional new lesions appear 
o Previously identified new target lesions show an increase of ≥ 5 mm in the new 
lesion sum of diameters, from the nadir value of that sum 
o Previously identified non-target lesions show any significant growth 
 

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If any of the events above occur, the overall response for that visit is iUPD, and the iUPD 
evaluation process (see Assessment at the Confirmatory Imaging above) is repeated. Progression 
must be confirmed before iCPD can occur. 
 
The decision process is identical to the iUPD confirmation process for the initial PD, with one 
exception:  if new lesions occurred at a prior instance of iUPD, and at the confirmatory imaging 
the burden of new lesions has increased from its smallest value (for new target lesions, the sum 
of diameters is ≥5 mm increased from its nadir), then iUPD cannot resolve to iSD or iPR. It will 
remain iUPD until either a decrease in the new lesion burden allows resolution to iSD or iPR, or 
until a confirmatory factor causes iCPD. 
 
Additional details about iRECIST are provided in the iRECIST publication (Seymour, 2017).  
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Dancey J, Chen A, Hodi FS, Therasse P, Hoekstra OS, Shankar LK, Wolchok JD, Ballinger M, 
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