A Phase 1b/2a, Open Label Study to Evaluate Anti-tumor Efficacy and Safety of rhIL-7-hyFc (NT-I7) in Combination With Anti-PD-L1 (Atezolizumab) in Patients With Anti-PD-1/PD-L1 naïve or Relapsed/Refractory High-risk Skin Cancers
Phase: PHASE1
Conditions: Melanoma, Merkel Cell Carcinoma, Cutaneous Squamous Cell Carcinoma
Sponsor: NeoImmuneTech

A phase 1b/2a, open label study to evaluate anti-tumor efficacy and safety of rhIL-7-hyFc (NT-I7) 
in combination with anti-PD-L1 (atezolizumab) in patients with anti-PD-1/PD-L1 naïve or 
relapsed/refractory high-risk skin cancers 
NCT03901573 
19 January 2023 
Note: Signatures have been redacted from this document.

CONFIDENTIAL 
Protocol#: NIT-106 (ION-02) 
Version Date: AS vl.0 19JAN2023 
Protocol Title: A phase 1b/2a, open label study to evaluate anti-tumor efficacy and safety of 
rhIL-7-hyFc (NT-I7) in combination with anti-PD-LI (atezolizumab) in patients with anti-PD-
1/PD-Ll naive or relapsed/refracto1y high-risk skin cancers 
Protocol Number: 
Version Date: 
Products: 
Abbreviated Title: 
Study Phase: 
IND Sponsor: 
Coordinating Center: 
Principal Investigator: 
Participating Organizations: 
NIT-106 (ION-02) 
Amendment 5 vl.0 19JAN2023 
-
-
Atezolizumab (MPDL3280A; NSC 783608) 
NT-I7 (rhIL-7-hyFc) 
High-Risk Skin Cancers with Atezolizumab plus NT-I7 
Phase 1b/2a 
NeoimmuneTech, Inc. 
2400 Research Blvd, Suite 250 
Rockville, MD 20850 
info@neoimmunetech.com 
www.neoimmunetech.com 
Immune Oncology Network (ION), 
Fred Hutchinson Cancer Center 
ION - Immune Oncology Network member sites 
I 

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SPONSOR SIGNATORY 
 
I have read this protocol in its entirety and agree to conduct the study accordingly:   
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Table 1 – Document History 
Document 
Date 
Substantial 
Region 
Original Protocol (v1.0) 
06Dec2018 
- 
- 
Version 2.0 
02Jan2019 
FDA Information Request 
 
Version 3.0 
27Feb2019 
FDA recommendations and Roche 
safety notification 
 
Amendment 1, Version 1.0 09Sep2019 
- Protocol revisions per Atezolizumab 
IB v14, October 2018  
- Immunogenicity testing for 
Atezolizumab no longer required 
- Administrative corrections 
 
Amendment 2, Version 1.0 20Apr2020 
- Phase 1b Dose Level changes per 
new available data 
- Protocol revisions per Atezolizumab 
IB v15, July 2019 and Atezolizumab 
IB v15 Addendum 2, December 
2019  
- Protocol revisions per NT-I7 IB v5, 
January 29, 2020 
- Administrative corrections 
 
Amendment 3, Version 1.0 23Apr2021 
- Protocol revisions per Atezolizumab 
IB v17, September 2020 
- Protocol revisions per NT-I7 IB v6, 
February 19, 2021 
- Added 2 timepoints for Serum 
Chemistry in Study Calendar Table 
- Corrected Chemical formula and 
Structural formula for NT-I7 
- NT-I7 dosing schedule changed from 
Q3W to Q6W (every other cycle) per 
new available data 
- Pharmacokinetic draw schedule 
modified per new available data 
- Administrative corrections 
 
Amendment 4, Version 1.0 11MAR2022 
- Protocol revisions per Atezolizumab 
IB v18, July 2021 and Atezolizumab 
IB v18 Addendum 1, August 2021 
- Changed irRC to iRECIST 
- Clarification to Exclusion Criteria 
- Added notes, clarification to current 
protocol language 
- Administrative corrections 
 
Amendment 5, Version 1.0 19JAN2023 
- Updated RP2D to 1200 µg/kg 
 

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- Protocol revisions per NT-I7 IB 
v8.0, 19SEP2022 
- Protocol revisions per Atezolizumab 
IB v18, July 2021 and Addendum 1, 
August 2021 
- Protocol revisions per Dear 
Investigator Letters, dated July 27, 
2022 and November 21, 2022 
- Administrative corrections and 
additions 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS .............................................................................................................................. 6 
TABLE OF TABLES ................................................................................................................................... 8 
1. 
PROTOCOL SUMMARY .................................................................................................................... 9 
1.1 
Synopsis ........................................................................................................................................ 9 
1.2 
Schema ........................................................................................................................................ 10 
2. 
INTRODUCTION .............................................................................................................................. 12 
2.1 
Study Rationale ........................................................................................................................... 12 
2.2 
Background - Study Disease(s) ................................................................................................... 13 
2.3 
Agent(s)....................................................................................................................................... 15 
2.4 
Overall Risk/Benefit and Ethical Assessment............................................................................. 19 
3. 
OBJECTIVES AND ENDPOINTS .................................................................................................... 20 
4. 
PATIENT SELECTION ..................................................................................................................... 22 
4.1 
Inclusion Criteria ........................................................................................................................ 22 
4.2 
Exclusion Criteria ....................................................................................................................... 25 
4.3 
Inclusion of Women and Minorities ........................................................................................... 29 
5. 
STUDY DESIGN ............................................................................................................................... 30 
5.1 
Overall Design ............................................................................................................................ 30 
5.2 
Dose Escalation (Phase 1b) ........................................................................................................ 31 
5.3 
Expansion Phase (Phase 2a) ....................................................................................................... 34 
5.4 
Other Procedures: Biopsy (core needle, punch or surgical excision) ......................................... 35 
5.5 
Contraception .............................................................................................................................. 35 
6. 
STUDY TREATMENT ...................................................................................................................... 36 
6.1 
Study Treatments Administration ............................................................................................... 36 
6.2 
Dose-Limiting Toxicity............................................................................................................... 41 
6.3 
General Concomitant Medication and Supportive Care Guidelines ........................................... 43 
6.4 
Duration of Therapy .................................................................................................................... 45 
6.5 
Study Treatment beyond Disease Progression ............................................................................ 46 
6.6 
Duration of Follow-Up................................................................................................................ 47 
6.7 
Imaging Regimen ........................................................................................................................ 47 
6.8 
Patient Replacement .................................................................................................................... 48 
7. 
DOSING DELAYS/DOSE MODIFICATIONS................................................................................. 48 
7.1 
Atezolizumab (MPDL3280A)..................................................................................................... 48 
7.2 
NT-I7 (rhIL-7-hyFc) ................................................................................................................... 65 
8. 
ADVERSE EVENTS: ASSESSING AND REPORTING REQUIREMENTS ................................. 67 
8.1 
Adverse Events and Potential Risks List .................................................................................... 68 
8.2 
Adverse Event Characteristics .................................................................................................... 73 
8.3 
Expedited Adverse Event Reporting ........................................................................................... 74 
8.4 
Routine Adverse Event Reporting .............................................................................................. 77 
8.5 
Pregnancy .................................................................................................................................... 77 
8.6 
Secondary Malignancy ................................................................................................................ 78 
8.7 
Second Malignancy ..................................................................................................................... 78 

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9. 
PHARMACEUTICAL INFORMATION ........................................................................................... 78 
9.1 
Atezolizumab (NSC 783608) ...................................................................................................... 78 
9.2 
NT-I7........................................................................................................................................... 80 
9.3 
Agent Ordering and Agent Accountability ................................................................................. 82 
10. STUDY CALENDAR ........................................................................................................................ 83 
11. MEASUREMENT OF EFFECT ........................................................................................................ 85 
11.1 Antitumor Effect – Solid Tumors ............................................................................................... 85 
11.2 Correlative Studies ...................................................................................................................... 94 
12. BIOMARKER, CORRELATIVE AND SPECIAL STUDIES ........................................................ 100 
12.1 Integrated Correlative Studies ................................................................................................... 101 
12.2 Exploratory Correlative Studies ................................................................................................ 104 
12.3 Special Studies .......................................................................................................................... 107 
13. DATA REPORTING / REGULATORY REQUIREMENTS / STUDY OVERSIGHT .................. 109 
13.1 Data Reporting .......................................................................................................................... 109 
13.2 Compliance with Trial Registration and Results Posting Requirements .................................. 109 
13.3 Study Oversight ........................................................................................................................ 109 
14. SITE ACTIVATION PROCEDURES ............................................................................................. 110 
14.1 IRB Approval ............................................................................................................................ 110 
14.2 Patient Enrollment .................................................................................................................... 111 
14.3 General Guidelines .................................................................................................................... 111 
15. STATISTICAL CONSIDERATIONS ............................................................................................. 111 
15.1 Responsibility for Analyses ...................................................................................................... 111 
15.2 Study Design/Objectives ........................................................................................................... 111 
15.3 Sample Size/Accrual Rate ......................................................................................................... 112 
15.4 Stratification Factors: N/A ........................................................................................................ 114 
15.5 Analysis of Secondary Endpoints ............................................................................................. 114 
15.6 Reporting and Exclusions ......................................................................................................... 114 
16. REFERENCES ................................................................................................................................. 116 
APPENDIX A PERFORMANCE STATUS CRITERIA ....................................................................... 119 
APPENDIX B REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ...... 120 
APPENDIX C NT-I7 DILUTION AND IM INJECTION GUIDELINES ............................................. 125 
APPENDIX D SIGNATURE OF INVESTIGATOR ............................................................................. 130 
APPENDIX E ABBREVIATIONS LIST ............................................................................................... 131 

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TABLE OF TABLES 
Table 1 – Document History ...................................................................................................................... 4 
Table 2 – Study Objectives and Endpoints ............................................................................................. 21 
Table 3 – Study Treatment Details .......................................................................................................... 36 
Table 4 – Atezolizumab AE Management and Dose Interruption Guidelines .................................... 53 
Table 5 – Pharmacokinetic Timepoints ................................................................................................ 108 
Table 6 – Study Administrative Structure ............................................................................................ 122 
 

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1. 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Abbreviated Title 
High Risk Skin Cancers with Atezolizumab plus NT-I7 
Trial Phase 
Phase 1b/2a 
Clinical Indication 
Anti-programmed cell death protein 1 (PD-1)/ programmed death-
ligand 1 (PD-L1) naïve or relapsed/refractory high-risk skin cancers: 
melanoma, Merkel cell carcinoma (MCC) and cutaneous squamous 
cell carcinoma (cSCC) 
Trial Type 
Phase 1b/2a, non-randomized 2 arm, open label trial with initial NT-I7 
dose escalation phase (phase 1b) followed by a dose expansion phase 
(phase 2a) 
Primary Objective 
To evaluate the safety and tolerability of NT-I7 in combination with 
atezolizumab (Phase 1b), including estimation of the maximum 
tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) 
Phase 2a: To evaluate the Objective Response Rate (ORR) according 
to RECIST v1.1 and iRECIST, as determined by the investigator 
Secondary Objectives 
To evaluate immunogenicity of NT-I7 in combination with 
atezolizumab  
To make a preliminary assessment of the anti-tumor activity of NT-I7 
in combination with atezolizumab  
Exploratory Objectives 
To make a preliminary assessment of PK parameters of NT-I7 in 
combination with atezolizumab 
To make a preliminary assessment of biomarkers that might act as 
pharmacodynamic indicators of activity of NT-I7 in combination with 
atezolizumab 
To make a preliminary assessment of biomarkers that might act as 
predictors of anti-tumor activity of NT-I7 in combination with 
atezolizumab 
Dose Escalation Phase 
(Phase 1b) 
NT-I7 will be escalated until a plateau of peripheral T-cell level and 
tumor infiltration of T-cells is reached or unacceptable toxicities. 
End Points 
Primary endpoint of safety and tolerability of NT-I7 in combination 
with atezolizumab and estimation of MTD or RP2D for the 
combination.  
Secondary endpoints of immunogenicity of NT-I7, Objective 
Response Rate (ORR), Disease Control Rate (DCR), Duration of 
Objective Response (DOR), Progression-Free Survival (PFS) and 
Overall Survival (OS). 
Arm I (Phase 2a) 
Anti-PD-1/PD-L1 naïve cSCC and MCC 
Arm II (Phase 2a) 
Anti-PD-1/PD-L1 relapsed/refractory MCC, cSCC and melanoma 

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Number of Trial Patients 
Approximately 84 patients  
Number of Clinical Sites 
Approximately 8 clinical research sites are expected to participate in 
this study 
Duration of Participation 
Each patient will participate in the trial from the time the Informed 
Consent Form (ICF) is signed through final protocol-specified contact. 
The active study will end when the last patient completes the 90-day 
safety follow up visit, approximately 27 months after enrollment.   
Estimated Duration of Trial 
Trial is expected to be completed approximately 36 months after the 
last patient is enrolled.   
 
1.2 
Schema 
Description of Study  
This is a Phase 1b/2a, open-label, multicenter study to evaluate the safety, tolerability and anti-
tumor effect of NT-I7 (recombinant human interleukin 7 [rhIL]-7-hybrid Fc [hyFc]) in 
combination with atezolizumab (MPDL3280A) in patients with anti-PD-1/PD-L1 naïve or 
relapsed/refractory high-risk skin cancers including cSCC, MCC and melanoma.   
This study has been designed to allow for an investigation of MTD or RP2D of NT-I7 in 
combination with atezolizumab. There are two phases to this study:  
- 
Phase 1b, a NT-I7 dose-escalation phase to determine the MTD or RP2D 
- 
Phase 2a, a non-randomized parallel dose expansion phase to confirm the MTD or RP2D 
in both arms. 
Arm I:  Anti-PD-1/PD-L1 (checkpoint inhibitors [CPI]) naïve patients with cSCC and MCC  
Arm II: Anti-PD-1/PD-L1 relapsed/refractory patients with MCC, cSCC and melanoma 
 
Number of Patients  
A total of approximately 84 patients will be enrolled; up to approximately 24 patients will be 
enrolled in the Phase 1b (3 + 3 dose escalation design will be used), and approximately 60 
patients will be enrolled in the Phase 2a (24 patients in Arm I, i.e., 12 patients for each 
indication, and 36 patients in Arm II, i.e., 12 patients for each indication).  
 

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2. 
INTRODUCTION 
2.1 
Study Rationale 
Very few preclinical studies have combined interleukin 7 (IL-7) with programmed cell death 
protein 1 (PD-1), programmed death-ligand 1 (PD-L1), or CTLA-4 checkpoint blockade. One 
murine study showed the therapeutic efficacy of concomitant blockade of CTLA-4 and PD-1 
relies on interdependence of IL-7 and interferon-gamma (IFN-γ) signaling in T-cells, predicting 
the exogenous IL-7 will boost the therapeutic efficacy 1. Another study of murine sepsis showed 
that IL-7 reverses immune suppression by increasing lymphocyte proliferation, expression of 
lymphocyte adhesion molecules, IFN-γ production, and CD28 expression on splenic CD8+ T-
cells. Combined treatment with IL-7 and anti-PD-1 produced additive effects on CD28 
expression, lymphocyte proliferation, and splenic secretion of IFN-γ 2. A recent Science paper 3 
using the mouse model of chronic lymphocytic choriomeningitis virus (LCMV) infection 
explored the combined effect of IL-7 and anti-PD-L1 on the development and functionality of 
exhausted T-cells. Anti-PD-L1 treatment moderately improved IL-7 signaling by increasing 
CD127 (IL-7Rα) expression on exhausted T-cells and exploited potential pathways to improve 
checkpoint blockade efficacy by combining with IL-7. 
Anti-PD-1 and anti-PD-L1 including atezolizumab can induce remarkable responses in a subset 
of patients with cancer including skin cancers, yet very few are cured.  The mechanisms of 

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immune escape, including (1) the lack of strong, tumor-specific antigens or epitopes recognized 
by T-cells, (2) impaired or suppressed antigen presentation machinery including downregulation 
of major histocompatibility complex on cancer cells, (3) impaired or suppressed cytotoxic T-cell 
activation, (4) poor infiltration of T-cells into the tumor microenvironment (TME), and (5) 
increased immunosuppressive cytokines and cells in the TME prevent a large proportion of 
cancer patients from deriving clinical benefit from anti-PD-1/PD-L1 therapies 4. Thus, additional 
therapies to increase the frequency and depth of responses to anti-PD-1/anti-PD-L1 such as 
atezolizumab are needed.  
The current trial will determine whether: 
1. Administration of NT-I7 at a dose known to expand T-cell number and repertoire will; (a) 
increase the number of tumor-infiltrating T-cells; and (b) thereby increase the efficacy of 
atezolizumab therapy. 
2. Administration of NT-I7 with atezolizumab will result in clinically meaningful increases in 
objective response rate (ORR), disease control rate (DCR), duration of objective response 
(DOR), progression-free survival (PFS) and overall survival (OS).  
3. Assessment of serial tumor biopsies to quantify NT-I7 - induced increases in T-cell 
infiltration will explore the effect of NT-I7 in combination with atezolizumab on TME, e.g., 
persistent myeloid infiltration, or overexpression of indoleamine 2,3-dioxygenase (IDO), 
arginase and transforming growth factor β (TGF-β). 
 
2.2 
Background - Study Disease(s) 
The proposed clinical trial is a phase 1b/2a, open-label, multicenter study of the administration of 
atezolizumab (MPDL3280A) in combination with NT-I7 in patients with anti-PD-1/PD-L1 naïve 
or relapsed/refractory high-risk skin cancers: cutaneous Squamous Cell Carcinoma (cSCC), 
Merkel Cell Carcinoma (MCC) and melanoma.  
High risk melanoma, MCC and cSCC share many attributes. Biologically, as a group they have 
the highest mutational burdens from skin exposure to ultraviolet (UV) radiation and accordingly 
have amongst the highest response rates to inhibition with PD-1/PD-L1 blockade in the range of 
30-40+% ORR. Unfortunately, PD-1/PD-L1 blockade fails to induce complete responses (CRs) 
in most patients.  
Therapeutically, these are surgical diseases before dissemination and are usually treated by the 
same set of physicians (dermatologists, cutaneous surgical oncologists and cutaneous-based 
oncologists). Thus, clinical trials with all three diseases utilizing the same group disease and 
clinical trial experts are practical and can be efficient.  
Investigational trials of checkpoint inhibitors in all 3 disease groups have shown similar ORR 
(see table below).  
 
 

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Tumor Type 
Agent/Phase trial 
ORR 
cSCC 
Cemiplimab  
(Phase II) 
Two advanced cSCC 
expansion cohorts 
(Phase I) 
47%  
https://investor.regeneron.com/news-
releases/news-release-details/fda-approves-
libtayor-cemiplimab-rwlc-first-and-only-treatment 
MCC 
Pembrolizumab (Phase 
II) 
Avelumab (Phase II) 
33%-56%  
5  
6  
Melanoma 
Pembrolizumab (Phase 
III)  
Nivolumab (III) 
33%-40%  
7  
8  
Abbreviations: cSCC=cutaneous squamous cell carcinoma; MCC=Merkel cell carcinoma; ORR=objective response 
rate.  
IL-7 is a homeostatic growth factor for T-cells that normally contributes to maintaining the 
normal number of peripheral blood T-cells. IL-7-mediated signaling can induce proliferation in 
the absence of T-cell receptor (TCR) signaling 9. IL-7 signals through the IL-7 receptor (IL-7R) 
heterodimer composed of the common γ-chain (CD132) cytokine receptor and a unique IL-7Rα 
(CD127). During normal conditions, IL-7R expression is maintained on resting T-cells 10 and 
exogenous IL-7 induces expansion of most categories of T-cells.  
In clinical studies IL-7 has been shown to have numerous characteristics that could provide 
synergism with anti-PD-L1: 
1. Increase peripheral blood T-cells by several‐fold with little toxicity 11-15, 
2. Expand all categories of T-cells including CD8+, CD4+ and memory T-cells 12, 
3. Increase the total body complement of T-cells including increased size of lymph nodes, 
spleen, liver 16, 
4. Increase TCR diversity by preferentially stimulating the growth of T-cell receptor excision 
circles (TREC)-positive, naïve T-cells 16. Continuous signaling by IL-7 induces anti-
apoptotic and co-stimulatory responses that are essential for the survival of naïve T-cells. 
5. Increase tissue infiltration of T-cells into gut mucosa (other tissues including tumor have not 
been examined) 17. 
6. Reverse neutrophil lymphocyte ratios [Cancer Immunotherapy Trials Network (CITN)12-03 
(NCT01881867), manuscript submitted] 
7. Augment immune‐mediated control of both tumors and viruses 10. 
Very few preclinical studies have combined IL-7 with PD-1 or PD-L1 checkpoint blockade and 
there have been no human trials for these combinations, in large part due to a lack of availability 
of long-acting rhIL-7. However, there is sufficient inferential data to support testing the 
combination in a clinical trial setting.   

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Objectives 
Corresponding Endpoints 
To make a preliminary assessment of biomarkers 
that might act as pharmacodynamic indicators of 
activity of NT-I7 in combination with 
atezolizumab 
  
 
To make a preliminary assessment of biomarkers 
that might act as predictors of anti-tumor activity 
of NT-I7 in combination with atezolizumab  
baseline and post-baseline tumor biopsy 
comparisons of: 
- Serum concentration of NT-I7 administered in 
combination with atezolizumab at specified 
timepoints for the following parameters: Area 
under the concentration time-curve (AUC) 
Maximum serum concentration (Cmax) 
Minimum serum concentration (Cmin) 
Clearance (CL) 
- Number, distribution, and phenotype of tumor-
infiltrating cells  
- PD-L1 expression 
- Expression of Interferon γ (IFNγ) and 
associated inflammatory gene expression in the 
tumor microenvironment  
- Changes in tumor microenvironment that 
correlate with response or provide information 
on potential actionable causes for lack of 
clinical benefit   
Abbreviations: ADA=anti-drug antibodies; AUC=area under the curve; CL=clearance; Cmax=maximum serum 
concentration; Cmin=minimum serum concentration; CR=complete response; CTCAE=Common Terminology 
Criteria for Adverse Events; DCR=disease control rate; DLT=dose limiting toxicity; DOR=duration of objective 
response; IFN-γ=interferon-gamma; iRECIST=immune-related Response Evaluation Criteria in Solid Tumors; 
MTD=maximum tolerated dose; NCI=National Cancer Institute; ORR=objective response rate; OS=overall survival; 
PFS=progression-free survival; PK=pharmacokinetic; PR=partial response; RECIST=Response Evaluation Criteria 
in Solid Tumors; RP2D=recommended Phase 2 dose; SD=stable disease.  
4. 
PATIENT SELECTION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
4.1 
Inclusion Criteria  
Patients must meet all the following criteria for study entry:  
General Inclusion Criteria 
1. Patients must have the ability to understand and the willingness to sign a written 
informed consent document. 
2. Patients must be ≥18 years of age on day of signing informed consent document. 
Because no dosing or AE data are currently available on the use of NT-I7 in patients <18 
years of age, children are excluded from this study. 

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3. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%, 
see Appendix A). Exceptions, such as bilateral amputation for trauma, could be approved 
following consultation with the Protocol PI and/or ION Coordinating Center.   
4. Patients must have a life expectancy of greater or equal to 12 weeks. 
5. Patients must have adequate organ and marrow function as defined below: 
– Absolute neutrophil count 
≥1,000/mcL 
– Platelets 
≥100,000/mcL 
– Hemoglobin 
≥8.0 g/dL 
– Total bilirubin 
≤1.5 × institutional upper limit of normal (ULN) 
(however, patients with known Gilbert’s disease 
who have serum bilirubin level ≤3 × ULN may 
be enrolled.) 
– AST(SGOT)/ALT(SGPT) 
≤3 × ULN (AST and/or ALT ≤5 × ULN for 
patients with liver involvement.) 
– Alkaline phosphatase  
≤2.5 × ULN (≤5 x ULN for patients with 
documented liver involvement or bone 
metastases.) 
– Creatinine clearance 
≥30 mL/min/1.73 m2 by Cockcroft-Gault: 
 
(140 − age) × (weight in kg) × (0.85 if female) 
72 × (serum creatinine in mg/dL) 
 
At the discretion of the treating physician, a 24-
hour urine creatinine clearance could be obtained 
and utilized as the gold standard if creatinine 
clearance by Cockcroft-Gault is <30, and 
prevents patient enrollment on the trial. 
 
– INR and aPTT 
≤1.5 × ULN (This applies only to patients who 
do not receive therapeutic anticoagulation; 
patients receiving therapeutic anticoagulation, 
such as low-molecular-weight heparin or 
warfarin, should be on a stable dose.) 
6. Patients positive for HIV are allowed on study, but HIV-positive patients must have: 
a. A stable regimen of highly active antiretroviral therapy (HAART) 
b. No requirement for concurrent antibiotics or antifungal agents for the prevention 
of opportunistic infections 
c. A CD4+ count above 100 cells/mcL and an undetectable HIV viral load on 
standard polymerase chain reaction (PCR)-based tests 

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7. Female patients of childbearing potential (including women who have had a tubal 
ligation) must have a negative serum pregnancy test within 72 hours prior to Cycle 1, 
Day 1 and must agree to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive methods that result in a failure rate of < 1% per year during the study 
treatment period and for at least 150 days after the last dose of study agent(s) – refer to 
Section 5.5 for further details.  
8. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use 
contraceptive methods that result in a failure rate of < 1% per year during the study 
treatment period and for at least 150 days after the last dose of study agent(s). Men must 
agree to refrain from donating sperm during this same period – refer to Section 5.5 for 
further details. 
Cancer-Specific Inclusion Criteria 
9. Patients must have histologically or cytological documented locally advanced/inoperable 
or metastatic skin cancer including melanoma, MCC and cSCC. 
Note: Cancer must be invasive; carcinoma in situ is excluded.  
Note: Patients must have cutaneous melanoma; mucosal melanoma is excluded. 
10. Arm I: Anti-PD-1/PD-L1 naïve cSCC and MCC. 
Arm II: Anti-PD-1/PD-L1 relapsed/refractory MCC, cSCC and melanoma. 
Note: Each arm and each cancer type have different eligibility criteria (see below).  
 
Arm I – cSCC: Patients must have biopsy-proven metastatic cSCC or locoregional cSCC 
that has recurred following standard locoregional therapy with surgery and/or radiation 
therapy.  
 
Arm I – MCC: Patients must have biopsy-proven metastatic MCC or locoregional MCC 
in need of systemic therapy, including patients that have not had prior systemic therapy 
or have recurred following standard locoregional therapy with surgery and/or radiation 
therapy. Prior chemotherapy is allowed. 
 
Note: For Arm II patients, eligibility will be determined by clinical progression or 
radiographic progression. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 
will be used for patients on prior protocols that have mandated serial RECIST readings. 
In addition, the following criteria will be applied for each tumor types.  
 
Arm II – MCC: Patients must have biopsy-proven metastatic MCC or locoregional MCC 
that has recurred following anti-PD-1 or anti-PD-L1, or has stable disease (SD) following 
anti-PD-1 or anti-PD-L1, defined as a minimum of 6 weeks of SD per RECIST 1.1 
criteria. Patients may have also failed other systemic regimens, e.g., chemotherapy. 

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Note: Progression following investigational therapies is allowed. 
 
Arm II – cSCC: Patients must have biopsy-proven metastatic cSCC or locoregional cSCC 
that has recurred following anti-PD-1 or anti-PD-L1, or has SD following anti-PD-1 or 
anti-PD-L1, defined as a minimum of 6 weeks of SD per RECIST 1.1 criteria. 
Note: Progression following investigational therapies is allowed. 
 
Arm II – melanoma: Patients must have biopsy-proven metastatic melanoma or 
locoregional melanoma that has recurred following anti-PD-1, anti-PD-L1, or has SD 
following anti-PD-1 or anti-PD-L1, defined as a minimum of 6 weeks of SD per RECIST 
1.1 criteria. 
 
Note: Prior therapy with ipilimumab is allowed (subject to a 6-week washout period) but 
not required. 
 
Note: Progression following targeted therapies (e.g., BRAF inhibitor and/or MEK 
inhibitor) or other approved (e.g., talimogene laherparepvec [T-VEC]) or investigational 
therapies is allowed.  
 
11. Patients must have measurable disease per clinical exam or per RECIST 1.1 assessed by 
computed tomography (CT) scan or magnetic resonance imaging (MRI). See Section 11 
for the evaluation of measurable disease. 
12. Patients must have biopsiable disease (i.e., have at least 1 tumor lesion that is accessible 
and feasible to biopsy) as determined by the treating physician.  
13. Patients must provide tissue from an archival tumor sample (obtained after last therapy) 
or newly obtained (preferred) core biopsy, punch biopsy, or surgical excision of a 
primary or metastatic tumor lesion.  
4.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry.  
General Exclusion Criteria 
1. Inability to comply with study and follow-up procedures. 
2. Pregnancy, lactation, or breastfeeding. 
3. Significant cardiovascular disease, such as New York Heart Association cardiac disease 
(Class II or greater), myocardial infarction (within the last 3 months), uncontrolled 
hypertension, unstable arrhythmia and/or unstable angina.   
4. Poorly controlled Type 2 diabetes mellitus defined as a screening hemoglobin A1C ≥8% 
or a fasting plasma glucose ≥160 mg/dL (or 8.8 mmol/L). 

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5. Major surgical procedure, other than for diagnosis, within 28 days prior to Cycle 1, Day 
1, or anticipation of need for a major surgical procedure during the study. 
6. Any other diseases, metabolic dysfunction, physical examination finding and/or clinical 
laboratory finding giving reasonable suspicion of a disease or condition that 
contraindicates the use of an investigational drug or that may affect the interpretation of 
the results or may render the patient at high risk from treatment complications. 
7. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for 
treatment of either a psychiatric or medical (e.g., infectious) illness. 
Cancer-Specific Exclusion Criteria 
8. Patients who have had chemotherapy or radiotherapy within 2 weeks (4 weeks for 
nitrosoureas or systemic mitomycin C) prior to Cycle 1, Day 1. 
9. Patients who had prior treatment with immune CPIs, immunomodulatory monoclonal 
antibodies (mAbs), and/or mAb-derived therapies within 6 weeks before the initiation of 
study treatment, except for:  
• Prior anti-PD-L1/anti-PD-1 requires a 3-week washout period. 
• Prior anti-CTLA-4 requires a 6-week washout period. 
10. Patients 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). However, the following 
therapies are allowed: 
• 
Hormone-replacement therapy or oral contraceptives 
• 
Herbal therapy ≥1 week before initiation of study treatment (herbal therapy intended 
as anticancer therapy must be discontinued at least 2 weeks before initiation of study 
treatment) 
• 
Palliative radiotherapy for bone metastases >2 weeks prior to Cycle 1, Day 1. 
11. Patients who have received treatment with any other investigational agent within 4 weeks 
prior to Cycle 1, Day 1.  
12. Patients who have received treatment and failed therapy with checkpoint inhibition plus a 
T-cell growth factor, e.g., IL-2 (NTKR-204), IL-15 (ALT-803) or IL-7 (CYT107). 
13. Patients who have a history of an immune-related Grade 3 or 4 AE attributed to prior 
cancer immunotherapy (other than endocrinopathy managed with replacement therapy or 
asymptomatic elevation of serum amylase or lipase) that resulted in permanent 
discontinuation of the prior immunotherapeutic agent and/or occurred within 6 months 
prior to Cycle 1, Day 1.  
14. Patients who have not completely recovered from irAEs (i.e., have residual toxicities 
>Grade 1) related to prior cancer immunotherapy (other than endocrinopathy managed 

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with replacement therapy or stable vitiligo). Patients treated with corticosteroids for 
irAEs must demonstrate absence of related signs or symptoms for ≥ 4 weeks following 
discontinuation of corticosteroids.  
Note: Patients with a history of severe hypersensitivity reactions to prior immunotherapy 
are not allowed.   
15. Patients with known primary central nervous system (CNS) malignancy, untreated CNS 
metastases, or active CNS metastases (progressing or requiring corticosteroids for 
symptomatic control) are excluded, with the following exceptions: 
• 
Patients with a history of treated CNS metastases may be enrolled, provided all the 
criteria listed above are met as well as the following: 
– Measurable disease outside the CNS 
– No ongoing requirement for corticosteroids as therapy for CNS metastases, 
with corticosteroids discontinued for ≥ 2 weeks prior to initiation of study 
treatment 
– Anticonvulsants at a stable dose are allowed 
– Radiographic demonstration of improvement upon the completion of CNS-
directed therapy and no evidence of interim progression between the 
completion of CNS-directed therapy and the screening radiographic study 
– Screening CNS radiographic study ≥4 weeks from completion of 
radiotherapy.  
16. Patients who have leptomeningeal disease. 
17. Patients who have uncontrolled tumor-related pain: 
• 
Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or 
metastases causing nerve impingement) should be treated prior to enrollment 
• 
Asymptomatic metastatic lesions whose further growth would likely cause functional 
deficits or intractable pain (e.g., epidural metastasis that is not currently associated 
with spinal cord compression) should be considered for loco-regional therapy if 
appropriate prior to enrollment.  
18. Patients who have uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or calcium 
>12 mg/dL or corrected serum calcium ≥ ULN) or symptomatic hypercalcemia requiring 
continued use of bisphosphonate therapy or denosumab. 
Note: Use of bisphosphonate therapy or denosumab specifically to prevent skeletal events 
and patients who do not have a history of clinically significant hypercalcemia are 
allowed. 
Note: Patients on denosumab must be willing and eligible to receive a bisphosphonate 
instead of denosumab while on study. 

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19. Patients 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. 
Treatment-Specific Exclusion Criteria 
20. Patients in Arm I (CPI treatment naïve) with autoimmune disease history, 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-Barré syndrome, multiple 
sclerosis, vasculitis or glomerulonephritis. 
21. Patients in Arm II (CPI refractory/relapsed) with autoimmune disease history, 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, with the following caveats: 
• 
Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid-
replacement hormone may be eligible. 
• 
Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be 
eligible. 
• 
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with 
dermatologic manifestations only (e.g., no psoriatic arthritis) may be eligible 
provided all the following conditions are met: 
– Rash must cover less than 10% of body surface area (BSA) 
– Disease is well controlled at baseline and only requiring low potency topical 
steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 
0.01%, desonide 0.05%, aclometasone dipropionate 0.05%) 
– No acute exacerbations of underlying condition within the last 12 months 
(e.g., not requiring psoralen plus ultraviolet A radiation [PUVA], 
methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high 
potency or oral corticosteroids). 
22. Patients who have received treatment with systemic immunosuppressive medications 
(including, but not limited to, prednisone >10 mg/day, cyclophosphamide, azathioprine, 
methotrexate, thalidomide and antitumor necrosis factor [anti-TNF] agents) within 2 
weeks prior to Cycle 1, Day 1. 
• 
Patients who have received acute, low dose, systemic immunosuppressant 
medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled 
following consultation with the Protocol PI and/or ION Coordinating Center.  
• 
The use of inhaled corticosteroids (e.g., fluticasone for chronic obstructive pulmonary 
disease) is allowed. 
• 
The use of oral mineralocorticoids (e.g., fludrocortisone for patients with orthostatic 
hypotension) is allowed.  

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• 
Physiologic dose of corticosteroids (≤10 mg/day of prednisone or equivalent) for 
adrenal insufficiency is allowed.  
23. Patients who have a history of idiopathic pulmonary fibrosis, pneumonitis (including 
drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic 
organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest CT 
scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 
24. Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen 
[HBsAg] test at screening). 
• 
Patients with past or resolved hepatitis B infection (defined as having a negative 
HBsAg test and a positive IgG antibody to hepatitis B core antigen [anti-HBc]) are 
eligible. Hepatitis B virus (HBV) DNA must be obtained in these patients prior to 
Cycle 1, Day 1, and must demonstrate no active infection. 
• 
Patients with active hepatitis C (positive for HCV antibody) are eligible only if PCR 
is negative for HCV RNA. 
25. Patients with active tuberculosis (TB). 
26. Patients who have severe infections within 4 weeks prior to Cycle 1, Day 1, including but 
not limited to hospitalization for complications of infection, bacteremia or severe 
pneumonia. 
27. Patients who have signs or symptoms of recent infection (not meeting the above criteria 
for severe infections) within 2 weeks before initiation of study treatment, including the 
following:  
• 
Patients who have received oral or intravenous (IV) antibiotics within 2 weeks before 
initiation of study treatment. Patients receiving prophylactic antibiotics (e.g., for 
prevention of a urinary tract infection or chronic obstructive pulmonary disease) are 
eligible. 
28. Patients with prior allogeneic bone marrow transplantation or prior solid organ 
transplantation. Specific exceptions, such as past kidney transplant now on dialysis, could 
be approved following consultation with the Protocol PI and/or ION Coordinating Center.  
29. Patients who have a history of severe allergic, anaphylactic or other hypersensitivity 
reactions to chimeric or humanized antibodies or fusion proteins. 
30. Patients who have received a live, attenuated vaccine within 4 weeks prior to Cycle 1, 
Day 1 or anticipation that such a live attenuated vaccine be required during the study. 
Influenza vaccination should be given during influenza season only.  
4.3 
Inclusion of Women and Minorities 
Both men and women of all races and ethnic groups are eligible for this trial. 

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5. 
STUDY DESIGN 
5.1 
Overall Design 
This is a Phase 1b/2a, non-randomized 2 arm, open label multi-institutional trial. The dose 
escalation phase (Phase 1b) of the study will determine the MTD or RP2D of NT-I7 in 
combination with atezolizumab. The Phase 2a will be a non-randomized parallel dose expansion 
phase to confirm the MTD or RP2D in both arms.  
A total of approximately 84 patients will be enrolled; up to approximately 24 patients will be 
enrolled in the Phase 1b (a 3+3 dose escalation design will be used), and approximately 60 
patients will be enrolled in the Phase 2a (24 patients in Arm I, i.e., 12 patients for each 
indication, and 36 patients in Arm II, i.e., 12 patients for each indication).  
Arm I: Anti-PD-1/PD-L1 (CPI) naïve patients with cSCC and MCC 
Arm II: Anti-PD-1/PD-L1 relapsed/refractory patients with MCC, cSCC and melanoma 
 
 
 

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5.2 
Dose Escalation (Phase 1b) 
A 3 + 3 dose escalation design will be used to assess safety and effect on T-cell level in 
peripheral blood and tumor. The dose of NT-I7 will be escalated as shown in Section 5.2.2 
below. 
5.2.1 Treatment Plan 
Patients will have a required pre-treatment biopsy (see Section 5.4) to assess tumor micro-
environment and level of T-cell infiltration. Therapy can be started before results of the biopsy 
are reported, as it will not be used to determine therapy. 
Based on the pharmacodynamic data obtained from the GX-I7-CA-003 study (Q3W dosing) and 
preliminary data from other ongoing studies with less frequent dosing schedules, NT-I7 can be 
given less frequently than Q3W (e.g., Q6W) and will still lead to similar changes in the ALC and 
other peripheral blood T-cell subsets. 
Starting with Dose Level 4 (1200 µg/kg) of the dose escalation phase, NT-I7 will be 
administered in combination with atezolizumab every 6 weeks (Q6W). The NT-I7 dose will be 
given at the same dose level administered in Cycle 1.  

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• If none (0) of the initial 3 patients in a cohort experiences a DLT, then a new cohort 
of 3 patients will be treated at the next higher dose level. 
• If 1 of the initial 3 patients in a cohort experiences a DLT, then an additional 
3 patients will be enrolled at the same dose level. 
- 
If 0 of these 3 additional patients experiences a DLT (totaling 1/6), a new cohort 
of 3 patients will be treated at the next higher dose level.  
- 
If ≥1 of these 3 additional patients experience a DLT (totaling ≥2/6), the dose 
escalation will stop, and the next lower dose level will be declared the MTD. In 
the case this happens at the 120 µg/kg dose, a lower dose of 60 µg/kg will be 
tested. 
• If ≥2 of the initial 3 patients in a cohort experience a DLT, then the dose escalation 
will stop, and the next lower level will be declared the MTD. Three (3) additional 
patients will be entered at the next lower level if only 3 patients were treated 
previously at that dose. In the case this happens at the 120 µg/kg dose, a lower dose 
of 60 µg/kg will be tested following the same 3+3 design (see Appendix C for NT-I7 
dilution requirements at specific dose levels). 
   
Number of Patients with DLT at a 
Given Dose Level 
Escalation Decision Rule 
0 out of 3 
Enroll 3 patients at the next dose level. 
1 out of 3 
Enroll at least 3 more patients at this dose level. 
• 
If 0 of these 3 additional patients experience a DLT 
(totaling 1/6), escalate to the next dose level. 
• If ≥1 of these 3 additional patients experiences DLT 
(totaling ≥2/6 at the dose level), the dose escalation is 
stopped, and the next lower dose level will be declared the 
MTD. In the case this happens at the 120 µg/kg dose level, 
a lower dose of 60 µg/kg will be tested, and the same 3+ 3 
design followed.  
≥2 out of 3  
Dose escalation will be stopped. The next lower dose level 
will be declared the MTD. Three (3) additional patients will 
be entered at the next lower dose level if only 3 patients were 
treated previously at that dose. In the case this happens at the 
120 µg/kg dose level, a lower dose of 60 µg/kg will be tested, 
and the same 3+3 design followed. 
Abbreviations: DLT=dose-limiting toxicity; MTD=maximum tolerated dose.  
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 the clinical research 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 and Safety Monitoring Committee, which includes the ION Coordinating Center, the 
Protocol PI, clinical sites PIs and NeoImmuneTech’s Chief Medical Officer or 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 trial will proceed to the Dose Expansion Phase (Phase 2a) 
to further evaluate RP2D in a larger number of patients. 
 
5.3 
Expansion Phase (Phase 2a) 
Patients enrolled into the trial during the Expansion Phase (Phase 2a) will be treated at the RP2D 
level, determined in Phase I to be 1200 µg/kg IM Q6W, as defined in Section 5.2.2.  
The Phase 2a is designed to evaluate the anti-tumor effects of NT-I7 in combination with 
atezolizumab in a total of 60 patients. Twenty-four patients in Arm I, i.e., 12 patients for each 
indication (cSCC and MCC), and 36 patients in Arm II, i.e., 12 patients for each indication 
(MCC, cSCC and melanoma), will be enrolled. Enrolled patients will be separated into two arms 
depending on previous use of anti-PD-1/anti-PD-L1 therapy and cancer type.  
Arm I (n=24):  Anti-PD-1/PD-L1 naïve patients with cSCC (n=12) and MCC (n=12) 
Arm II (n=36): Anti-PD-1/PD-L1 relapsed/refractory patients with MCC (n=12), cSCC (n=12) 
and melanoma (n=12) 
5.3.1 Treatment Plan 
Patients will have a required pre-treatment biopsy (see Section 5.4) to assess the tumor micro-
environment and level of T-cell infiltration. Therapy can be started before results of the biopsy 
are reported, as it will not be used to determine therapy. 
On Day 1 of every other cycle (i.e., Cycle 1, Cycle 3, Cycle 5, etc.), patients will be given a dose 
of NT-I7 at the RP2D level by IM injection before receiving standard atezolizumab (1200 mg, 
intravenously). The NT-I7 dose will always be given at the RP2D level. 
On Day 1 of every cycle (21-day cycle), patients will be given a dose of Atezolizumab (1200 mg, 
intravenously). Atezolizumab will be administered every 3 weeks (Q3W).  

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PK samples will be collected on all patients during the dose expansion phase of the study (refer 
to PK timepoints tables for specific draw times, Section 12.3.2). 
CBC with differential including ALC will be checked at each cycle as standard of care. Research 
blood samples for T-cell phenotypes, CD4+ and CD8+ cell counts will be collected and tested at 
selected time points (see Sections 12.1.1 and 10). 
Starting on Cycle 3, Day 1, NT-I7 administration will be skipped when the ALC is higher than 
10,000 cells/µL. When automated and manual ALC counts are performed, manual ALC counts 
will be used if the results are conflicting. A blood draw will be performed prior to dosing on Day 
1. The results will determine if NT-I7 should be interrupted for the current cycle. Treatment with 
atezolizumab will continue every 3 weeks.  
Treatment with both study agents may continue for up to 2 years (see Section 6.4).  
Patients will have a required post-treatment biopsy (see Section 5.4) to assess changes in the 
tumor micro-environment and the level of T-cell infiltration.  
5.4 
Other Procedures: Biopsy (core needle, punch or surgical excision) 
A pre-treatment biopsy/tissue collection will be obtained within 14 days prior to the first dose of 
NT-I7 (Cycle 1, Day 1). 
Note: If an archival tumor sample (at least 0.5 × 0.5 × 0.5 cm) is available for an enrolled 
patient, the pre-treatment biopsy is not required. The tumor sample must have been obtained 
after the last therapy.  
A post-treatment tumor biopsy/tissue collection will be obtained between Cycle 2 Day 8 and 
Cycle 2 Day 21. The preference is for a biopsy/tissue collection as close to the equivalent of 
Cycle 2, Day 15.   
The biopsies will be done according to clinical site Standard Operating Procedures (SOPs). 
Tumor biopsies will be paramount. The biopsies will confirm T-cell infiltration and other 
potential actionable causes of failure.  
5.5 
Contraception  
Administration of atezolizumab may have an adverse effect on pregnancy and poses a risk to the 
human fetus, including embryo-lethality. NT-I7 has not been tested for reproductive toxicity yet 
and may expose the same risk. 
A woman is of childbearing potential if she is postmenarcheal, has not reached a postmenopausal 
state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), 
and has not undergone surgical sterilization (removal of ovaries and/or uterus).  
Women of childbearing potential (including women who have had a tubal ligation) must have a 
negative serum pregnancy test within 72 hours prior to Cycle 1, Day 1. A follow up pregnancy 
test will be performed at the 90-day Safety Follow up visit.  

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for any questions concerning a DLT. The investigator, in consultation with the ION Coordinating 
Center and the protocol PI, will make the final decision. 
6.2.1 Hematologic toxicity 
• 
Any Grade 4 event, including laboratory electrolyte abnormalities, that is not easily 
reversed without sequelae 
• 
Grade 4 neutropenia (Absolute Neutrophil Count [ANC] <500/mm3) that does not 
improve to ≤Grade 3 within 48 hours 
• 
Grade 3 febrile neutropenia  
• 
Grade 4 thrombocytopenia (<25,000/mm3) that does not improve to ≤Grade 3 within 
48 hours 
• 
Grade ≥3 thrombocytopenia (<50,000/mm3) associated with Grade ≥3 bleeding or 
that requires transfusion therapy 
• 
Grade ≥3 AST or ALT 
• 
Grade ≥2 blood bilirubin or clinical jaundice 
• 
Grade ≥2 AST or ALT and total bilirubin >2 x ULN with no initial findings of 
cholestasis (e.g., alkaline phosphatase ≤2 x ULN) and no other reason to explain the 
combination of elevated transaminases and bilirubin (e.g., viral hepatitis), i.e., Hy’s 
law 
• 
Any toxicity resulting in death (i.e., Grade 5) 
Grade 3 lymphocyte count increased (>20,000 cells/µL) will not be reported as a DLT. 
An ALC of >20,000 cells/µL is a normal physiologic response to the study treatment.  
Grade ≥3 lymphocytopenia will not be considered a DLT. 
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. 
6.2.2 Non-hematologic toxicity 
Any Grade ≥3 non-hematologic toxicity (Common Terminology Criteria for Adverse Events 
[CTCAE] v5.0) will be considered a DLT, except for the following, which will not constitute 
DLTs: 
• 
Grade ≥3 nausea, diarrhea or vomiting that resolves to Grade ≤2 in ≤72 hours with 
the use of adequate/maximal medical intervention and/or prophylaxis 
• 
Grade 3 fatigue that resolves to Grade ≤2 in ≤7 days 
• 
Grade 3 fever 
• 
Grade 3 injection site reaction (unless operative intervention is required) 
• 
Grade 3 arthralgia that can be adequately managed with supportive care or that 
resolves to Grade ≤2 within ≤72 hours 
• 
Grade 3 hyperglycemia lasting ≤72 hours with standard antidiabetic therapy 

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– The investigator must immediately notify the ION Coordinating Center in the 
event of a confirmed pregnancy in a patient participating in the study. 
• 
Termination of the study by sponsor(s), or 
• 
The drug manufacturer can no longer provide the study agent 
The reason(s) for protocol therapy discontinuation, the reason(s) for study removal and the 
corresponding dates must be documented in the CRF. 
All patients who tolerate the protocol regimen and with either CR, partial response (PR) or SD 
will be permitted to continue study treatment until confirmed disease progression or for up to 
2 years. Patients in response will have the option of continuing on atezolizumab using 
commercially purchased agent.  
Discontinuation of treatment may be considered, at the discretion of the treating physician, for 
patients who have attained a confirmed CR that have been treated for at least 24 weeks with 
study treatment and had at least 2 treatments beyond the date when the initial CR was declared. 
6.5 
Study Treatment beyond Disease Progression 
Immunotherapeutic agents such as atezolizumab 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. 
Patients who are clinically stable (without symptomatic progression) at an initial RECIST 1.1-
defined PD may continue trial treatment as long as they meet all the following criteria (following 
consultation with the Protocol PI and/or ION Coordinating Center): 
• 
Investigator-assessed clinical benefit 
• 
Tolerance of study treatment 
• 
Absence of signs and symptoms (including worsening of laboratory values) indicating 
disease progression 
• 
No decline in ECOG performance status 
• 
Absence of rapid progression of disease or threat to vital organs 
• 
Absence of progressive tumor at critical anatomical sites (e.g., cord compression) 
requiring urgent alternative medical intervention 
Patients should remain on the trial and continue to receive monitoring according to the Study 
Calendar.  
After the initial RECIST 1.1-defined PD, a follow-up scan is to be collected at the next 
scheduled imaging visit (no less than 4 weeks after the prior assessment of PD). This scan is 
evaluated using the Confirmation of Radiological Progression criteria outlined in Section 11.1.4.  
However, patients will not be permitted to continue study treatment if progression occurs after 
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(regardless of the appearance of new lesions), i.e., the response and progression events both 
occurred in the target lesions while receiving study treatment during the same treatment period.  
6.6 
Duration of Follow-Up 
The active study will end when the last patient completes the 90-day Safety Follow-up visit, 
approximately 27 months after enrollment. 
End of treatment (EOT) visit should be performed 30 (± 5) days after the last administration of 
either agent or immediately before initiation of any other cancer therapy. At the EOT visit, tumor 
assessments are only required if not performed within the past 9 weeks (for patients who are on 
the study for ≤ 18 weeks) or 12 weeks (for patients who are on the study for > 18 weeks). 
Safety Follow-up visit should be performed 60 (± 7) days and 90 (± 7) days after the last 
administration of either agent.  
Patients who permanently discontinue study treatment for reasons other than objective RECIST 
disease progression should continue to have RECIST scans performed every 12 weeks 
(± 1 week), at the investigative site or locally, up to 12 months 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, patient will be followed for 
survival every 12 weeks (±1 week) until death, loss to follow-up, withdrawal of consent or the 
end of the study, whichever occurs first. Survival follow-up can be done either by in-person visit 
or by telephone assessment. 
Patients removed from study for unacceptable AE(s) will be followed until resolution or 
stabilization of the AE; in addition, the patients will be followed for disease status and overall 
survival, as described above.  
6.7 
Imaging Regimen 
Imaging is based on standard of care practices, although the following is highly recommended.  
All patients with known disease below the head and neck will have at least a diagnostic CT scan 
of the chest, abdomen and pelvis (CAP) performed within 28 days before the initiation of study 
treatment, 9 ± 1 weeks interval for the first two timepoints after initiation of treatment, and 
subsequent imaging performed at least every 12 ± 1 weeks as per standard of care for radiologic 
and tumor measurement.  
If the patient has known disease in the head and neck, the same protocol will apply with the 
addition of a head and neck CT within 28 days before the initiation of study treatment, 9 ± 1 
weeks interval for the first two timepoints after initiation of treatment, and subsequent imaging 
performed at least every 12 ± 1 weeks as per standard of care.  

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– Definite – The AE is clearly related to the study treatment. 
– 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. 
8.3 
Expedited Adverse Event Reporting 
Expedited AE reporting for this study must be done by notifying the ION Coordinating Center, 
the study sponsor, NeoImmuneTech and IQVIA within 24 hours of the Investigator knowledge 
of the event via the study EDC system. The specific requirements are briefly outlined in the table 
below (Section 8.3.1). 
In the event that access to the EDC system is disrupted (i.e., system is down/non-functional), the 
24-hour notification is to be made to IQVIA Safety Operations via email at 
). In the rare occurrence when Internet connectivity is lost, 
and the 24-hour notification cannot be made by email, the notification is to be made by fax at 1-
 or by phone at 
. 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. 
8.3.1 Expedited Reporting Guidelines 
Use the study protocol number and the protocol-specific patient ID assigned during trial 
registration on all reports. 
Note: A death occurring within 30 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 “Neoplasms benign, malignant and 
unspecified (incl cysts and polyps) - Other (Progressive Disease)” under the system organ 
class (SOC) of the same name. 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. 
 
 
 
 
 
 

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11. 
MEASUREMENT OF EFFECT 
11.1 
Antitumor Effect – Solid Tumors 
For the purposes of this study, patients should be re-evaluated for response every 9 weeks for the 
first two timepoints, then at least every 12 weeks as per standard of care. 
Response and progression will be evaluated in this study using the new international criteria 
proposed by the revised RECIST guideline (version 1.1) 48. RECIST 1.1 will be used as the 
primary measure for assessment of tumor response, date of disease progression, and as the basis 
for all protocol guidelines related to disease status (e.g., discontinuation of study treatment). 
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the 
shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. 
This study will also evaluate response and progression using immune-related RECIST 
(iRECIST) criteria. Investigators should note the different requirements for confirmatory scans 
as well as follow up of the two criteria.  
11.1.1 Definitions 
Evaluable for toxicity. All patients will be evaluable for toxicity from the time of their first 
treatment with atezolizumab and/or NT-I7 until 30 days after the last dose of study treatment. 
Evaluable for objective response. Only those patients who have measurable disease present at 
baseline, have received at least 1 cycle of therapy and have had their disease re-evaluated will be 
considered evaluable for response. These patients will have their response classified according to 
the definitions stated below. (Note: Patients who exhibit objective disease progression before the 
end of cycle 1 will also be considered evaluable.) 
Evaluable Non-Target Disease Response. Patients who have lesions present at baseline that are 
evaluable but do not meet the definitions of measurable disease, have received at least 1 cycle of 
therapy and have had their disease re-evaluated will be considered evaluable for non-target 
disease. The response assessment is based on the presence, absence or unequivocal progression 
of the lesions. 
11.1.2 Disease Parameters 
Measurable disease. Measurable lesions are defined as those that can be accurately measured in 
at least 1 dimension (longest diameter to be recorded) as ≥20 mm (≥2 cm) by chest x-ray or as 
≥10 mm (≥1 cm) with CT scan, MRI or calipers by clinical exam. All tumor measurements must 
be recorded in millimeters (or decimal fractions of centimeters). 
Note: Tumor lesions that are situated in a previously irradiated area might or might not be 
considered measurable.  
Malignant lymph nodes. To be considered pathologically enlarged and measurable, a lymph node 
must be ≥15 mm (≥1.5 cm) in short axis when assessed by CT scan (CT scan slice thickness 

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recommended to be no greater than 5 mm [0.5 cm]). At baseline and in follow-up, only the short 
axis will be measured and followed. 
Non-measurable disease. All other lesions (or sites of disease), including small lesions (longest 
diameter <10 mm [<1 cm] or pathological lymph nodes with ≥10 to <15 mm [≥1 to <1.5 cm] 
short axis), are considered non-measurable disease. Bone lesions, leptomeningeal disease, 
ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast disease 
and abdominal masses (not followed by CT or MRI) are considered as non-measurable. 
Note: Cystic lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, by 
definition, simple cysts. 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability described above. However, if noncystic lesions are 
present in the same patient, these are preferred for selection as target lesions. 
Target lesions. All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in 
total, representative of all involved organs, should be identified as target lesions and recorded 
and measured at baseline. Target lesions should be selected on the basis of their size (lesions 
with the longest diameter), be representative of all involved organs, but in addition should be 
those that lend themselves to reproducible repeated measurements. It may be the case that, on 
occasion, the largest lesion does not lend itself to reproducible measurement in which 
circumstance the next largest lesion which can be measured reproducibly should be selected. A 
sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph nodes are to be 
included in the sum, then only the short axis is added into the sum. The baseline sum diameters 
will be used as reference to further characterize any objective tumor regression in the measurable 
dimension of the disease. 
Non-target lesions. All other lesions (or sites of disease) including any measurable lesions over 
and above the 5 target lesions should be identified as non-target lesions and should also be 
recorded at baseline. Measurements of these lesions are not required, but the presence, absence, 
or in rare cases unequivocal progression of each should be noted throughout follow-up. 
11.1.3 Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or calipers. All 
baseline evaluations should be performed as closely as possible to the beginning of treatment and 
never more than 4 weeks before the beginning of the treatment. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be 
imaged but are assessable by clinical exam. 
Clinical lesions. Clinical lesions will only be considered measurable when they are superficial 
(e.g., skin nodules and palpable lymph nodes) and ≥10 mm (≥1 cm) diameter as assessed using 

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calipers (e.g., skin nodules). In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended. 
Chest x-ray. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly 
defined and surrounded by aerated lung. However, CT is preferable. 
Conventional CT and MRI. This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm (0.5 cm) or less. If CT scans have slice 
thickness greater than 5 mm (0.5 cm), the minimum size for a measurable lesion should be twice 
the slice thickness. MRI is also acceptable in certain situations (e.g., for body scans). 
Use of MRI remains a complex issue. MRI has excellent contrast, spatial and temporal 
resolution; however, there are many image acquisition variables involved in MRI, which greatly 
impact image quality, lesion conspicuity and measurement. Furthermore, the availability of MRI 
is variable globally. As with CT, if an MRI is performed, the technical specifications of the 
scanning sequences used should be optimized for the evaluation of the type and site of disease. 
Furthermore, as with CT, the modality used at follow-up should be the same as was used at 
baseline and the lesions should be measured/assessed on the same pulse sequence. It is beyond 
the scope of the RECIST guidelines to prescribe specific MRI pulse sequence parameters for all 
scanners, body parts and diseases. Ideally, the same type of scanner should be used, and the 
image acquisition protocol should be followed as closely as possible to prior scans. Body scans 
should be performed with breath-hold scanning techniques, if possible. 
PET-CT. At present, the low dose or attenuation correction CT portion of a combined positron 
emission tomography (PET)-CT is not always of optimal diagnostic CT quality for use with 
RECIST measurements. However, if the site can document that the CT performed as part of a 
PET-CT is of identical diagnostic quality to a diagnostic CT (with IV and oral contrast), then the 
CT portion of the PET-CT can be used for RECIST measurements and can be used 
interchangeably with conventional CT in accurately measuring cancer lesions over time. Note, 
however, that the PET portion of the CT introduces additional data which may bias an 
investigator if it is not routinely or serially performed. 
Ultrasound. is not useful in assessment of lesion size and should not be used as a method of 
measurement. Ultrasound examinations cannot be reproduced in their entirety for independent 
review at a later date and, because they are operator dependent, it cannot be guaranteed that the 
same technique and measurements will be taken from one assessment to the next. If new lesions 
are identified by ultrasound in the course of the study, confirmation by CT or MRI is advised. If 
there is concern about radiation exposure at CT, MRI may be used instead of CT in selected 
instances. 
Endoscopy, Laparoscopy. The utilization of these techniques for objective tumor evaluation is 
not advised. However, such techniques may be useful to confirm complete pathological response 
when biopsies are obtained or to determine relapse in trials where recurrence after CR or surgical 
resection is an endpoint. 
Tumor markers. Tumor markers alone cannot be used to assess response. If markers are initially 
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clinical response. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) 49 
and prostate-specific antigen (PSA) response (in recurrent prostate cancer) 50,51 have been 
published. In addition, the Gynecologic Cancer Intergroup has developed CA-125 progression 
criteria which are to be integrated with objective tumor assessment for use in first-line trials in 
ovarian cancer 52. 
Cytology, Histology. These techniques can be used to differentiate between PR and CR in rare 
cases (e.g., residual lesions in tumor types, such as germ cell tumors, where known residual 
benign tumors can remain). 
The cytological confirmation of the neoplastic origin of any effusion that appears or worsens 
during treatment when the measurable tumor has met criteria for response or SD is mandatory to 
differentiate between response or SD (an effusion may be a side effect of the treatment) and PD. 
FDG-PET. While fluorodeoxyglucose (FDG)-PET response assessments need additional study, it 
is sometimes reasonable to incorporate the use of FDG-PET scanning to complement CT 
scanning in assessment of progression (particularly possible 'new' disease). New lesions on the 
basis of FDG-PET imaging can be identified according to the following algorithm: 
a. Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up: If the positive FDG-
PET at follow-up corresponds to a new site of disease confirmed by CT, this is PD. If 
the positive FDG-PET at follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is truly progression 
occurring at that site (if so, the date of PD will be the date of the initial abnormal 
FDG-PET scan). If the positive FDG-PET at follow-up corresponds to a pre-existing 
site of disease on CT that is not progressing on the basis of the anatomic images, this 
is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a manner similar to a biopsy 
in cases where a residual radiographic abnormality is thought to represent fibrosis or 
scarring. The use of FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical literature for the indication. 
However, it must be acknowledged that both approaches may lead to false positive 
CR due to limitations of FDG-PET and biopsy resolution/sensitivity. 
Note: A ‘positive’ FDG-PET scan lesion means one which is FDG avid with an uptake 
greater than twice that of the surrounding tissue on the attenuation corrected image. 
11.1.4 RECIST 1.1 Response Assessment 
11.1.4.1 
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, 
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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. 
11.1.4.2 
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 
patient 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). 
11.1.4.3 
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 patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria. 
For Patients with Measurable Disease (i.e., Target Disease) 
Target 
Lesions 
Non-Target Lesions 
New 
Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
>4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
>4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
 
PR 
Non-CR/Non-PD/not 
evaluated 
No 
PR 
 
SD 
Non-CR/Non-PD/not 
evaluated 
No 
SD 
Documented at least once 
>4 wks. from baseline** 
PD 
Any 
Yes or No 
PD 
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Any 
PD*** 
Yes or No 
PD 
 
Any 
Any 
Yes 
PD 
 
* See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** Only for non-randomized trials with response as primary endpoint. 
*** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
Note: Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration.” Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
Abbreviations: CR=complete response; PD=progressive disease; PR=partial response; RECIST=Response 
Evaluation Criteria in Solid Tumors; SD=stable disease.  
 
For Patients with Non-Measurable Disease (i.e., Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
*‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly 
used as an endpoint for assessment of efficacy in some trials so to assign this category when no lesions 
can be measured is not advised 
Abbreviations: CR=complete response; PD=progressive disease; SD=stable disease.  
11.1.5 iRECIST Response Assessment 
Overall response will also be assessed using iRECIST. Immunotherapeutics may result in 
infiltration of immune cells leading to transient increase in the size in malignant lesions, or 
undetectable lesions becoming detectable. The criteria are identical to those of RECIST 1.1 in 
many respects but have been adapted to account for instances where an increase in tumor burden, 
or the appearance of new lesions, does not reflect true tumor progression. 
Key differences are described below. All responses defined using iRECIST criteria are 
designated with a prefix. iRECIST best overall responses will be recorded separately. 
Confirming progression: Unlike RECIST 1.1, iRECIST requires the confirmation of progression 
and uses the terms iUPD (unconfirmed progression) and iCPD (confirmed progression). 
Confirmatory scans should be performed at least 4 weeks, but no longer than 8 weeks, after 
iUPD. 
iCPD is confirmed if further increase in tumor burden, compared to the last assessment, is seen 
as evidenced by one or more of the following: 
• Continued increase in tumor burden (from iUPD) where RECIST 1.1 definitions of 

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progression had been met (from nadir) in target, non-target disease, or new lesions. 
o Progression in target disease worsens with an increase of at least 5 mm in the 
absolute value of the sum. 
o Continued unequivocal progression in non-target disease with an increase in 
tumor burden. 
o Increase in size of previously identified new lesion(s) (an increase of at least 5 
mm in the absolute value of the sum of those considered to be target new lesions) 
or additional new lesions. 
• RECIST 1.1 criteria are met in lesions types (target or non-target or new lesions) where 
progression was not previously identified, including the appearance of additional new 
lesions. 
 
If iUPD is not confirmed at the next assessment, then the appropriate response will be assigned 
(iUPD if the criteria are still met, but no worsening, or iSD, iPR, or iCR if those criteria are met 
compared to baseline).  The prior documentation of iUPD does not preclude assigning iCR, iPR, 
or iSD in subsequent time-point assessments or as best overall response (BOR) providing that 
iCPD is not documented at the next assessment after iUPD (Lancet Oncol 18:e143-e152, 2017 - 
Table 2). 
 
New lesions:   
New lesions should be assessed and measured as they appear using RECIST 1.1 criteria 
(maximum of 5 lesions, no more than 2 per site, at least 10 mm in long axis [or 15 mm in short 
axis for nodal lesions]) and recorded as New Lesions - Target (NLT) and New Lesion - Non-
Target (NLNT) to allow clear differentiation from baseline target and non-target lesions. 
 
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or iCPD).  However, 
the measurements of target lesions should NOT be included in the sum of measures of original 
target lesions identified at baseline. Rather, these measurements will be collected on a separate 
table in the case record form. 
 
PD is confirmed in the New Lesion category if the next imaging assessment, conducted at least 4 
weeks (but not more than 8 weeks) after iUPD confirms further progression from iUPD with 
either an increase of at least 5 mm in the absolute value of the sum of NLT OR an increase (but 
not necessarily unequivocal increase) in the size of NLNT lesions OR the appearance of 
additional new lesions. 
Time-point (TP) iResponse 
Target 
Lesions* 
Non-Target 
Lesions* 
New 
Lesions* 
Time Point Response 
No prior 
iUPD** 
Prior iUPD**, *** 
iCR 
iCR 
No 
iCR 
iCR 
iCR 
Non-iCR/Non- 
iUPD 
No 
iPR 
iPR 

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Time-point (TP) iResponse 
Target 
Lesions* 
Non-Target 
Lesions* 
New 
Lesions* 
Time Point Response 
No prior 
iUPD** 
Prior iUPD**, *** 
iPR 
Non-iCR/Non- 
iUPD 
No 
iPR 
iPR 
iSD 
Non-iCR/Non- 
iUPD 
No 
iSD 
iSD 
iUPD with no 
change OR 
decrease 
from last TP 
iUPD with no 
change OR 
decrease from last 
TP 
Yes 
NA 
NLs confirms iCPD if NLs were 
previously identified and increase 
in size (≥5 mm in SOM for NLT or 
any increase for NLNT) or 
number. If no change in NLs (size 
or number) from last TP, remains 
iUPD. 
iSD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD 
confirmed based in further increase 
in size of NT disease (need not 
meet RECIST 1.1 criteria for 
unequivocal PD). 
iUPD 
Non-iCR/Non-
iUPD 
No 
iUPD 
Remains iUPD unless iCPD 
confirmed based on further 
increase in SOM of at least 5 mm, 
otherwise remains iUPD. 
iUPD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD 
confirmed based on further 
increase in: 
• previously identified T lesion 
iUPD SOM ≥5 mm and/or 
• NT lesion iUPD (prior 
assessment - need not be 
unequivocal PD) 
iUPD 
iUPD 
Yes 
iUPD 
Remains iUPD unless iCPD 
confirmed based on further 
increase in: 
• previously identified T lesion 
iUPD ≥5 mm and/or 
• previously identified NT lesion 
iUPD (need not be 
unequivocal) and/or 
• size or number of new lesions 
previously identified 
Non-
iUPD/PD 
Non-iUPD/PD 
Yes 
iUPD 
Remains iUPD unless iCPD 
confirmed based on increase in 
size or number of new lesions 
previously identified. 

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Time-point (TP) iResponse 
Target 
Lesions* 
Non-Target 
Lesions* 
New 
Lesions* 
Time Point Response 
No prior 
iUPD** 
Prior iUPD**, *** 
* Using RECIST 1.1 principles.  If no PSPD occurs, RECIST 1.1 and iRECIST categories for CR, PR, 
and SD would be the same.  
** in any lesion category.  
*** previously identified in assessment immediately prior to this TP. 
 
All patients will have their iBOR from the start of study treatment until the end of treatment 
classified as outlined below. 
iRECIST best overall response (iBOR) 
TPR 1 
TPR 2 
TPR 3 
TPR 4 
TPR 5 
iBOR 
iCR 
iCR, iPR, 
iUPD, NE 
iCR, iPR, 
iUPD, NE 
iUPD 
iCPD 
iCR 
iUPD 
iPR, iSD, 
NE 
iCR 
iCR, iPR, 
iSD, iUPD, 
NE 
iCR, iPR, 
iSD, iUPD, 
iCPD, NE 
iCR 
iUPD 
iPR 
iPR, iSD, 
iUPD, NE 
iPR, iSD, 
iUPD, NE, 
iCPD 
iPR, iSD, 
iUPD, NE, 
iCPD 
iPR 
iUPD 
iSD, NE 
PR 
iPR, iSD, 
iUPD, NE 
iPR, iSD, 
iUPD, 
iCPD, NE 
iPR 
iUPD 
iSD 
iSD, iUPD, 
NE 
iSD, iUPD, 
iCPD, NE 
iSD, iUPD, 
ICPD, NE 
iSD 
iUPD 
iCPD 
Anything 
Anything 
Anything 
iCPD 
iUPD 
iUPD 
iCPD 
Anything 
Anything 
iCPD 
iUPD 
NE 
NE 
NE 
NE 
iUPD 
Table assumes a randomized study where confirmation of CR or PR is not required. 
• 
NE = not evaluable that cycle. 
• 
Designation "I" for BOR can be used to indicate prior iUPD to aid in data interpretation. 
• 
For patients with non-target disease only at baseline, only CR or non-CR/non-PD can be 
assigned at each TPR but is not shown in the table for ease of presentation. 
 
11.1.6 Duration of Response 
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are met for CR/PR or iCR/iPR (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). 

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The duration of overall CR is measured from the time measurement criteria are first met for CR 
until the first date that progressive disease is objectively documented. 
 
Duration of stable disease: 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. 
11.1.7 Progression-Free Survival 
PFS is defined as the duration of time from start of treatment to time of progression or death, 
whichever occurs first. 
11.1.8 Response Review 
Radiological images will 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. 
11.2 
Correlative Studies 
11.2.1 Integrated Correlative Studies Background 
11.2.1.1 
Evaluation of Peripheral CD4+ and CD8+ T-cell Counts – Integrated Laboratory 
Correlative Study #1 
As described above, NT-I7 has been shown to double the number of peripheral blood 
lymphocytes including T-cells. Thus, CD4+ and CD8+ T-cell numbers are important biomarkers 
for the effect of NT-I7 on the peripheral T-cell populations. To assess the overall 
pharmacodynamic effect of atezolizumab plus NT-I7 and to determine whether NT-I7 in 
combination with atezolizumab results in the same, or different, level of expansion of peripheral 
lymphocytes, T-cell counts (both CD4+ and CD8+) will be evaluated in Clinical Laboratory 
Improvement Amendments (CLIA)-certified laboratories locally at each site. CD4+ and CD8+ 
T-cell counts will be evaluated at baseline, during treatment, and at end of therapy. 
Hypothesis: The combination of atezolizumab with NT-I7 will result in similar levels of 
peripheral blood T-cell expansion as with NT-I7 alone. 
11.2.1.2 
Slide-Based Immune Phenotype Panel -- Multispectral IHC – Integrated Laboratory 
Correlative Study #2 
Because tumor-infiltrating immune cells are associated with clinical outcomes, infiltrates from 
pre-treatment tumor tissue and from biopsies taken during treatment will be assessed by 
immunohistochemistry (IHC) to determine extent and the nature of T-cell infiltration and of the 
overall immune milieu of the TME. 
Paired baseline and post-baseline tumor biopsies will be evaluated using quantitative multicolor 
IHC with Perkin-Elmer’s Vectra IHC platform. This platform employs spectral deconvolution 
imaging to separate optical signals from each antibody together with state-of–the-art image 
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Vectra multispectral imaging platform (PerkinElmer), adjacent tumor sections will be stained 
and imaged with a series of 5-6 antibodies per section simultaneously to investigate the spatial 
relationship between key immunomodulatory cell types and molecules. The antibodies will 
include but are not limited to the following: pancytokeratin (AE1/AE3), CD8+, CD4+, PD-1, 
PD-L1, CD68, CD163, FOXP3, arginase, and pan- major histocompatibility complex (MHC) 
class I and class II. Data will be generated in the form of total positive cells, positive cells/mm2, 
percentage positive cells in a population, ratios of cells and molecules of interest (e.g., PD-
L1:CD8+ or FOXP3+CD4+:CD8+). Additionally, tumors may also be assayed by IHC for a 
variety of other markers including CD80, IFN-γ CD3, CD5, TIA-1, CD20, CD11b, CD137, 
CD45RO, CD301CD56 and CD16 (NK and NK T-cells), CD79a (B cells), GITR, TIM-3, 
FOXP3, LAG3. Furthermore, quantitative analysis of tumor-infiltrating lymphocyte (TIL) 
distribution (i.e., stromal and interface/invasive margin) will be performed. Anti-PD-L1 
immunohistochemical staining with the SP142 PD-L1 clone (IHC assay, HistoGeneX/CellCarta) 
kit will be performed in addition to the multispectral IHC (msIHC) to serve as both an 
independent test and control for the reproducibility of the msIHC assay. The study is intended to 
evaluate for changes in the immune profile of the TME. If sufficient archival tumor tissue 
collected before therapy is not available, a baseline biopsy will be obtained before enrolling in 
the study as part of this protocol. 
IHC studies will be performed at the Fred Hutchinson Cancer Center (Fred Hutch) 
Immunopathology Laboratory, Seattle, WA, or other agreed upon investigator. 
Hypothesis: The combination of atezolizumab with NT-I7 will alter the TME toward a pro-
inflammatory phenotype. 
11.2.1.3 
Assessment of Tumor Biopsy by Gene Expression Analysis -- Interferon γ (IFNγ) 
Gene Expression Signature - NanoString® PanCancer IO 360TM Gene Expression 
Panel and the nCounter® PanCancer Immune Profiling Panel – Integrated 
Laboratory Correlative Study #3 
To identify potential signatures correlating with tumor T-cell infiltration patterns and clinical 
response, tumor tissue will be tested for gene expression using NanoString® technology on 
unstained tissue formalin-fixed paraffin-embedded (FFPE) slide material. Specifically, slides 
will be analyzed using a 770-gene panel (nCounter® PanCancer Immune Profiling Panel), which 
contains markers for 24 different immune cell types and populations, 30 common cancer 
antigens and genes that represent immune responses including checkpoint blockade genes as well 
as the NanoString® nCounter® PanCancer IO 360TM Gene Expression Panel, which contain genes 
associated with the IFNγ Gene Expression Signature. These gene expression profiles may 
provide an additional detailed phenotype to guide correlative investigation. 
NanoString®-based gene expression analysis, specifically for the IFN γ Signature, will be used to 
test the hypothesis that the investigational study treatment regimen, NT-I7 plus atezolizumab, 
will promote a proinflammatory antitumor immune response. The IFNγ Signature, which is 
comprised of IDO1, CXCL10, CXCL9, HLA-DRA, STAT1 and IFNγ, has previously been 
shown to correlate with anti-PD-1 response and nonresponse. RNA will be extracted from all 
paraffin-embedded tumor samples and analyzed using the aforementioned NanoString® nCounter 
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those stained for mIHC to facilitate comparison between these analysis sets. Samples will consist 
of matched pre- and post-treatment FFPE biopsies. 
These analyses will be performed in coordination with NanoString® Technologies in Seattle, 
WA, and analyzed using qualified analytic tools at the Immunopathology Lab at Fred Hutch. 
Hypothesis: The combination of atezolizumab with NT-I7 will alter the TME toward a pro-
inflammatory gene expression programming (GEP) phenotype, and distinct gene expression 
patterns will be identified that may correlate with clinical outcomes. 
11.2.1.4 
T-Cell Receptor Repertoire Analysis -- TCR sequencing – Integrated Laboratory 
Correlative Study #4 
We will perform TCR sequencing where pre-treatment and post-treatment biopsies are available. 
TCR repertoire analysis will be performed on RNA extracted from FFPE biopsies and T-cells 
isolated from peripheral blood mononuclear cells (PBMCs) collected throughout study 
participation. TCR repertoire analysis has been standardized and commercialized by Adaptive 
Biosciences. The TCR sequences will also specifically be queried for sequences already known 
to encode for TCRs reactive to shared antigens in the particular tumors, such as MCC virus in 
virus positive MCC. 
Samples will be analyzed at Adaptive Bioscience in Seattle, WA, or other agreed upon vendor or 
collaborator. 
Hypothesis: The combination of atezolizumab with NT-I7 will: i) result in emergence and/or 
increased prevalence of specific TCR sequences reflecting the clonal expansion of antitumor T-
cells; and ii) expansion of those specific T-cell clones in TILs (exhibited by higher TCR 
clonality) will be associated with improved response to therapy. 
11.2.1.5 
Tumor-Associated Neo-antigen Discovery -- Whole Exome Sequencing (WES) and 
RNAseq and Antigen Prediction – Integrated Laboratory Correlative Study #5 
In order to investigate the role of T-cell–mediated immunity directed toward tumor-specific 
mutant antigens, whole exome sequencing (WES) and RNAseq of tumor cells from baseline 
tumor biopsy relative to non-tumor cells from whole blood (PBMC) will be performed to: i) 
identify tumor-associated neoantigens; and ii) identify the genomic variances that may contribute 
to response or disease progression and provide an understanding of molecular abnormalities. 
DNA and RNA will be extracted from baseline or archival FFPE tumor biopsies and then 
sequenced to identify overexpressed, known “shared” tumor-associated antigens (TAAs) and 
nonsynonymous expressed mutations using available and standard-of-practice technologies. For 
example, a computational approach (BIMAS and SYFPEITHI algorithms) can be utilized to 
analyze and prioritize these mutation-derived “virtual” antigens in terms of their likelihood to 
bind to/be presented by relevant MHC I alleles. Potential antigens can be encoded in tandem 
minigene constructs with intervening P2A viral sequences to allow for equimolar expression of 
multiple “long” (~27 amino acids) peptides centered on the putative antigenic mutational sites. 
These neoantigen libraries will be cloned into an appropriate expression vector to allow for in 
vitro-transcription of neoantigen-encoding mRNA for use in enzyme-linked immunospot 
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common “shared” antigens are also expressed. Quantitation of mutation burden may also be 
important for urothelial carcinoma, where immunogenicity and/or responses to PD-1/PD-L1 
axis-directed therapies may be associated with a high mutation burden. 
These analyses will be performed using qualified analytes and analytic tools at the 
Immunopathology Lab at Fred Hutch or at a vendor, to be determined. 
Hypothesis: Clinical outcomes will correlate with mutational burden, and tumor-associated 
neoantigens will be identified that correlate with T-cell responses and clinical outcome. 
11.2.1.6 
Antitumor Immune T-cell Responses – ELISPOT – Integrated Laboratory Correlative 
Study #6 
If there are positive clinical responses, antigen-specific T-cell responses may be assessed by 
IFNγ ELISPOT assay to provide information regarding the effect of the atezolizumab and NT-I7 
regimen on antigen-specific T-cell functional antitumor responses such as MCC virus. The 
ability of the investigational treatment to induce a tumor antigen-specific immune response will 
be assessed using ex vivo incubation of PBMC-derived T-cells with autologous PBMC either 
pulsed with peptide antigens or recombinant proteins representing MCC virus or neoantigens 
described above. Memory viral responses (influenza A, Cytomegalovirus, Epstein-Barr Virus 
and Flu [CEF]) will also be assessed as controls. We will quantitate the strength of the antigen-
specific T-cell responses and compare baseline and post-baseline T-cell responses for each 
putative antigen. The absolute change in ELISPOT responses for antigens will be compared 
between the spot-forming cells (SFC)/million PBMC at baseline (before treatment initiation) and 
at designated time points post-treatment. 
Assays will be performed in the Central Immune Monitoring Laboratory (CIML) at the Fred 
Hutch, or an agreed upon vendor or collaborator. 
Hypothesis: The combination of atezolizumab with NT-I7 will result in increased T-cell 
responses to known and/or neoantigens. 
11.2.2 Exploratory/Ancillary Correlative Studies 
11.2.2.1 
Assessment of PD-L1 Expression at Baseline and Post-treatment -- 
Immunohistochemistry (IHC) – Exploratory Laboratory Correlative Study #1 
PD-L1 has been identified as an important correlative biomarker for clinical response to anti-PD-
L1 and anti-PD-1 therapies. In particular, given that the function of atezolizumab is to block 
binding of PD-1 to PD-L1, expression of PD-L1 will be quantitated by IHC in baseline FFPE 
tumor specimens, and from biopsies obtained after treatment. This is an important part of the 
correlative studies to explore whether this marker which correlates with response in other 
circumstances also correlates with response in this protocol population. For baseline samples, 
FFPE tissue block(s) from tumor obtained before treatment will be obtained by the clinical site 
either from archival samples obtained from the relevant pathology laboratories where they were 
processed and stored, or from baseline biopsy as part of this protocol (core biopsy, punch biopsy 
or surgical excision). Post-treatment, FFPE tumor specimens will be obtained from biopsy at 
Cycle 2 (core biopsy, punch biopsy or surgical excision) as part of this protocol. 

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PD-L1 expression will be tested by IHC at HistoGeneX/CellCarta with the SP142 PD-L1 clone 
or other agreed upon vendor. 
Hypothesis: PD-L1 expression at baseline will correlate with clinical responses to atezolizumab 
and atezolizumab in combination with NT-I7. In addition, atezolizumab administration may alter 
PD-L1 expression to an unknown extent. 
11.2.2.2 
Evaluation of the Effect of Atezolizumab with and without NT-I7 on Circulating 
Lymphocyte and Monocyte Numbers and Phenotype – Exploratory Laboratory 
Correlative Study #2 
We will assess the effects of the atezolizumab with and without NT-I7 on the frequency and 
phenotypic character of PBMC subsets including dendritic cells (DCs), monocyte populations, 
T-cells, NK cells, and B cells. The effect on these immune cell subtypes of checkpoint inhibitors 
and other immune modulators is being investigated in other CITN trials and may provide 
important correlative information on the success or failure of combination immunotherapy. 
A 21-color whole blood immunophenotyping assay will quantify in 1 panel the absolute number 
and proportion of T-cells (both CD8+ and CD4+), NK cells (CD56+CD3-), NKT-cells 
(CD56+CD3+), B cells (CD19+), monocytes (CD16+), as well as both myeloid DCs 
(CD45+HLA-DR+CD11c+CD123-) and plasmacytoid DCs (CD45+HLA-DR+CD11c-CD123+). 
In addition, to further define the phenotype and activation status of T-cells, the panel includes 
memory markers (CD45RA, CD197 [CCR7]), activation and Treg markers (CD28, CD127, 
CD25, HLA-DR, CD279 [PD-1]), and markers of exhaustion (Lag-3, Tim-3, TIGIT).  
Additional whole blood immunophenotyping assays will assess the Treg population in a FoxP3 
flow assay (CD45, CD3, CD4, CD25, CD127 and FoxP3) and proliferating levels of several cell 
subsets in a Ki67 assay (CD3, CD4, CD8, CD14, CD56 and Ki67). 
For the expansion cohort, we also use a 13-color whole blood immunophenotyping assay to 
further quantify T cell differentiation subsets such as TN (CD45RA+CCR7+CD95-CD127+), 
TSCM (CD45RA+CCR7+CD95+CD127+), TCM (CD45RA- CCR7+CD95+CD127+), TEM 
(CD45RA-CCR7-CD95+CD127+/-), TTE (CD45RA+CCR7-CD95+CD127-), and “Stem-like” 
CD8 TSL (CD8+PD-1+CXCR5+TIM-3-) and exhausted TSL (CD8+ PD-1+CXCR5-TIM-3+). 
Assays will be performed in the CIML at the Fred Hutch. 
Hypothesis: The combination of atezolizumab with NT-I7 will perturb circulating lymphocyte 
and monocyte numbers and phenotypes to a yet unknown extent. 
11.2.2.3 
Multiplex Cytokines– Exploratory Laboratory Correlative Study #3 
Perturbations in cytokines, chemokines, and growth factors have been associated with cancers 
and changes in plasma cytokine concentrations of proinflammatory and immunosuppressive 
cytokines may correlate with clinical responses to therapy. Measurable changes in serum and 
plasma cytokines have been associated with checkpoint blockade therapies. Comparison of 
baseline plasma cytokines, chemokines and growth factors to longitudinal measurements during 
therapy may improve our understanding of the immunologic effects of the combination of 
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reactive changes in cytokine levels correlates with toxicity and/or efficacy of atezolizumab and 
NT-I7. Longitudinally collected plasma samples will be evaluated using commercial multiplex 
immunoassays (i.e., Luminex) or other appropriate technology (i.e., Olink primer extension 
assay) for quantitation. 
Assays will be performed at the Fred Hutch Shared Resources, or at other agreed upon vendor. 
Hypothesis: The combination of atezolizumab with NT-I7 will perturb cytokines, chemokines, 
and growth factors to a yet unknown extent. 
11.2.2.4 
Kynurenine and Tryptophan (Kyn/Trp) Ratios and Plasma Arginine Levels – 
Exploratory Laboratory Correlative Study #4 
Over expression of IDO is known to result in increases in the kynurenine and tryptophan 
(Kyn/Trp) ratio in blood and within some TMEs. Increases in Kyn/Trp ratios result in the 
subsequent suppression of T-cell responses and is a major mechanism of immune control. IDO is 
expressed by some tumors, but probably more importantly, it is expressed by lymphocytes as a 
normal mechanism and important mechanism to dampen immune responses. Expression of IDO 
(with subsequent increased Kyn/Trp ratios) may be one likely mechanism of checkpoint 
blockade and other immunotherapy failures. Thus, we will measure Kyn/Trp ratios in plasma 
taken at baseline, during treatment and at end of treatment to analyze, in patients who have failed 
clinical response to atezolizumab plus IL-7 treatment, whether failure may be associated with 
increased Kyn/Trp levels. 
In addition, another important mechanism of immune control and suppression is through 
changing concentrations of arginine (Arg) insofar as decreased levels of Arg in plasma (i.e. ARG 
depletion) is associated with decreases in CD4+ and CD8+ T-cell proliferation and decreased 
Th1 functions. Arg depletion can occur by the release by myeloid-derived suppressor cells 
(MDSCs) of arginase which converts L-Arg to ornithine. This may be another mechanism of 
tumor evasion as myeloid suppressor cells with high arginase activity are found in tumors. Thus, 
we will also measure Arg levels in the same plasma samples taken at baseline, during treatment 
and at end of treatment in this protocol to analyze, in patients who have failed clinical response 
to atezolizumab plus IL-7 treatment, whether failure may be associated with increased Arg levels 
in plasma. 
All assays will be performed at an agreed upon collaborator or vendor to be determined. 
Hypothesis: Failure to respond to atezolizumab plus NT-I7 treatment may be associated with 
increased Kyn/Trp ratios and/or increased plasma Arg levels in some patients. 
11.2.3 Special Studies 
11.2.3.1 
Assessment of Immunogenicity and Pharmacokinetics 
The known and predicted activities of these two immunotherapeutic agents in enhancing immune 
responses may, in combination, influence PK and immunogenicity. In particular, NT-I7 is 
pharmacologically targeting lymphocytes and subject to a PK-target mediated clearance (like 
many other blood growth factors). This is the case for G-CSF and other factors. We have 
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measure the presence of binding and neutralizing antibodies. We will thus measure NT-I7 blood 
levels before the first administration of NT-I7, at specified intervals after administration of NT-
I7 and at the end of treatment visit. This would enable detection of any potential significant 
interference of the concomitant immunotherapies on NT-I7 PK. Similarly, we will measure anti-
NT-I7 binding antibodies before the first NT-I7 administration and at specified intervals during 
study treatment.   
Any subject presenting with binding antibodies will be further tested for the presence of anti-NT-
I7 neutralizing antibodies. While the number of patients will be too small to draw definitive 
conclusions, this might lead to a potential interference in the combination therapy deserving a 
further exploration. 
12. 
BIOMARKER, CORRELATIVE AND SPECIAL STUDIES 
Specimens will be collected for several planned correlative studies. Many samples will be 
processed and stored to be run in batches. The CIML will provide lab kits and shipping supplies. 
Specific instructions on numbers and types of tubes required for each visit are provided in the 
ION-02 Laboratory Manual.  
In the interest of patient safety, we are including a provision to draw less blood if patients are 
anemic. A CBC will be performed as part of the safety labs each time research labs are drawn 
(safety labs drawn for screening will used for this purpose prior to the first blood draws for 
research). The results of the CBC will be reviewed, and the following blood volumes will be 
drawn based upon the patient’s hemoglobin level. 
• Hemoglobin over 10.0 g/dL, draw the full volume of blood for safety and research labs. 
• Hemoglobin between 9.0 and 10.0 g/dL, draw the full volume of blood for safety labs, CD4+ 
/CD8+ T-cell counts and full volume for plasma/serum-based studies. Limit research blood 
draws to 50 mL for cell-associated studies.  
• Hemoglobin less than 9.0 g/dL, draw the full volume of blood for safety labs and CD4+ 
/CD8+ T-cell counts. Limit research blood draws to 5 mL for plasma and 11 mL for serum-
based studies, and 30 mL for cell-associated studies. 
When blood volume or specimen material is limited, the correlative studies will be considered 
secondary to tests needed to make clinical decisions. Prioritization of secondary tests will be 
made based on technical considerations: total amount of sample from each individual subject, 
total number of samples acquired, total number of each assay performed, and information gained 
from the assays performed to date. The anticipated priority correlatives are: 
Plasma/serum-based studies and other 
1. PK and immunogenicity 
2. Multiplex Cytokines – Multiplex enzyme-linked immunosorbent assay (ELISA) 
3. Metabolites (Kyn/Trp) ratios and Arg plasma levels 
 
Cell associated studies 

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1. Evaluation of peripheral CD4+ and CD8+ T-cell counts 
2. TCR Repertoire Analysis – TCR sequencing 
3. Evaluation of the effect of atezolizumab with and without NT-I7 on circulating 
Lymphocyte and Monocyte numbers and Phenotypes 
4. Anti-Tumor Immune T-cell Responses 
Biopsy associated studies 
1. Slide-Based Immune Phenotype Panel – mIHC 
2. Assessment of tumor biopsy by gene expression analysis 
3. Assessment of PD-L1 expression at Baseline and Post-treatment – IHC 
4. Tumor-Associated Neoantigen discovery – WES and RNAseq and Antigen Prediction 
12.1 
Integrated Correlative Studies 
12.1.1 Evaluation of peripheral CD4+ and CD8+ T-cell counts – Integrated Laboratory 
Correlative Study #1 
12.1.1.1 
Collection of Specimen(s) 
Blood draws will be performed by venipuncture on study subjects in Red-Top or Gold serum-
separating tubes (SSTs) or other blood draw tubes as specified per local site SOP. 
12.1.1.2 
Handling of Specimens(s) 
Blood samples will be collected at room temperature and shipped ambient to the local clinical 
lab. 
12.1.1.3 
Shipping of Specimen(s) 
Blood collection tubes will be shipped at ambient temperature to the designated local clinical, 
CLIA-compliant laboratory the same day as the blood draw. 
12.1.1.4 
Site(s) Performing Correlative Study 
Assays will be performed at each local clinical site. Assays are to be performed at each site by a 
CLIA-compliant laboratory. The specific technique is not specified in the protocol. 
12.1.2 Slide-Based Immune Phenotype Panel – Multispectral IHC – Integrated Laboratory 
Correlative Study #2 
12.1.2.1 
Collection of Specimen(s) 
FFPE archival tissue block(s) from tumor obtained after last therapy will be identified by the 
clinical site at the relevant pathology laboratories where they were processed and stored. Tissue 
blocks are preferred, however FFPE slides can substitute if blocks are unavailable. Alternatively, 
patients will undergo a pre-treatment biopsy as part of this protocol. Patient will undergo a post-
treatment biopsy if deemed relatively safe and technically feasible as part of this protocol.  

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12.1.2.2 
Handling of Specimens(s) 
FFPE archival tumor blocks will be requested by the clinical site from the relevant pathology 
laboratory by providing the patient’s name, consent form and date of collection. Patient 
identifying information (i.e., name, initials, birthdate, etc.) will be removed from the specimen 
before shipment to the CIML. If patients undergo biopsy as part of this protocol, tissue will be 
placed in formalin for overnight shipping to the CIML. 
12.1.2.3 
Shipping of Specimen(s) 
For archival samples, clinical sites will arrange for the FFPE tumor blocks or FFPE slides to be 
shipped to the CIML. For biopsies done as part of this protocol, tissue in formalin will be 
shipped overnight at ambient temperature to the CIML. Clinical sites will utilize BSI Engage to 
communicate with the CIML. After sectioning at the CIML, the CIML will coordinate shipment 
of unstained slides to the Immunopathology Laboratory at Fred Hutch or other agreed upon 
vendor or collaborator. 
12.1.2.4 
Site(s) Performing Correlative Study 
Assays will be performed by the Immunopathology Lab at Fred Hutch or other agreed upon 
vendor or collaborator. 
12.1.3 Assessment of tumor biopsy by gene expression analysis -- Interferon γ (IFNγ) Gene 
Expression Signature - NanoString® nCounter® PanCancer IO 360TM Gene Expression 
Panel and the nCounter® PanCancer Immune Profiling Panel – Integrated Laboratory 
Correlative Study #3 
12.1.3.1 
Collection of Specimen(s) 
FFPE archival tissue block(s) from tumor obtained after last therapy will be identified by the 
clinical site at the relevant pathology laboratories where they were processed and stored. 
Alternatively, patients will undergo a pre-treatment biopsy as part of this protocol. Patients will 
undergo a post-treatment biopsy if deemed relatively safe and technically feasible as part of this 
protocol. 
12.1.3.2 
Handling of Specimens(s) 
FFPE archival tumor blocks will be requested by the clinical site from the relevant pathology 
laboratory by providing the patient’s name, consent form and date of collection. Patient 
identifying information (i.e., name, initials, birthdate, etc.) will be removed from the specimen 
before shipment to the CIML. If patients undergo biopsy as part of this protocol, tissue will be 
placed in formalin for overnight shipping to the CIML. 
12.1.3.3 
Shipping of Specimen(s) 
For archival samples, clinical sites will arrange for the FFPE tumor blocks (preferred) or FFPE 
slides (if blocks are unavailable) to be shipped to the CIML. For biopsies done as part of this 
protocol, tissue in formalin will be shipped overnight at ambient temperature to the CIML. 
Clinical sites will utilize BSI Engage to communicate with the CIML. After sectioning at the 
CIML, the CIML will coordinate shipment of unstained slides (or RNA) to NanoString® or to the 
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from FFPE slides, either at NanoString® or the CIML, using established protocols (MAN-10050-
02 Preparing Nucleic Acid from FFPE Samples for Use with nCounter® Assays). 
12.1.3.4 
Site(s) Performing Correlative Study 
Assays will be performed by NanoString® Technologies in Seattle, WA, and analyzed using 
qualified analytic tools at the Immunopathology Lab at Fred Hutch. 
12.1.4 T-Cell Receptor Repertoire Analysis – TCR sequencing – Integrated Laboratory 
Correlative Study #4 
12.1.4.1 
Collection of Specimen(s) 
Specimens will include archived and prospectively obtained tumor biopsies and blood samples. 
Blood draws will be performed by venipuncture and whole blood will be collected into 
heparinized tubes. 
12.1.4.2 
Handling of Specimens(s) 
Biopsy samples will be placed in formalin and shipped to the CIML. Blood collection tubes will 
be shipped on day of blood draw for overnight delivery to the CIML. The sample must be 
received at the CIML within 24 hours of blood draw. Whole blood will be submitted to Ficoll 
gradient centrifugation, and PBMC will be stored in aliquots of up to 20 million cells in vapor-
phase liquid nitrogen.  
12.1.4.3 
Shipping of Specimen(s) 
Whole blood and biopsies in formalin will be shipped overnight at ambient temperature to the 
CIML. Clinical sites will utilize BSI Engage to communicate with the CIML. The CIML will 
coordinate shipment of samples to Adaptive Biosciences or other agreed upon vendor or 
collaborator. 
12.1.4.4 
Site(s) Performing Correlative Study 
Samples will be analyzed at Adaptive Bioscience in Seattle, WA, or other agreed upon vendor or 
collaborator. 
12.1.5 Tumor-Associated Neoantigen discovery – Whole Exome Sequencing and RNAseq and 
Antigen Prediction – Integrated Laboratory Correlative Study #5 
12.1.5.1 
Collection of Specimen(s) 
Specimens will include archived tumor blocks (or FFPE slides) and prospectively obtained tumor 
biopsies and blood samples. Blood draws will be performed by venipuncture. 
12.1.5.2 
Handling of Specimens(s) 
For archival samples, clinical sites will arrange for the FFPE tumor specimens to be shipped to 
the CIML. Patient identifying information (i.e., name, initials, birthdate, etc.) will be removed 
from the specimen before shipment to the CIML. For biopsies done as part of this protocol, 
tissue in formalin will be shipped overnight at ambient temperature to the CIML where they will 
be embedded in paraffin. Paraffin blocks (or FFPE slides) will be stored at 4oC under desiccant.  

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Blood collection tubes will be shipped on day of blood draw for overnight delivery to the CIML. 
Blood will be processed to PBMC as described above and stored in liquid nitrogen. Nucleic acid 
will be extracted from PBMC and from biopsy specimens using vendor-specific protocols.  
12.1.5.3 
Shipping of Specimen(s) 
Whole blood, archival tumor blocks (or FFPE slides) and biopsies in formalin will be shipped to 
the CIML. Clinical sites will utilize BSI Engage to communicate with the CIML. The CIML will 
coordinate shipment of samples to the Immunopathology Lab at Fred Hutch and/or agreed upon 
vendor. 
12.1.5.4 
Site(s) Performing Correlative Study 
These analyses will be performed using qualified analytes and analytic tools at the 
Immunopathology Lab and shared resources at Fred Hutch or at a vendor to be determined. 
12.1.6 Antitumor Immune T-cell Responses -- ELISPOT – Integrated Laboratory Correlative 
Study #6 
12.1.6.1 
Collection of Specimen(s) 
Blood draws will be performed by venipuncture on study subjects just before, during, and at end 
of treatment. Whole blood will be collected into heparinized tubes. 
12.1.6.2 
Handling of Specimens(s) 
Blood collection tubes (for subsequent PBMC isolation) will be shipped on day of blood draw 
for overnight delivery to the CIML. The sample must be received at the CIML within 24 hours of 
blood draw. Whole blood will be submitted to Ficoll gradient centrifugation, and PBMC will be 
stored in aliquots of up to 20 million cells in vapor-phase liquid nitrogen. 
12.1.6.3 
Shipping of Specimen(s) 
Blood collection tubes will be shipped overnight at ambient temperature to the CIML using 
CIML-established SOPs. Clinical sites will utilize BSI Engage to communicate with the CIML. 
The CIML will coordinate shipment via liquid nitrogen dry shipper of cryopreserved PBMC in 
the event that a vendor or collaborator performs these studies. 
12.1.6.4 
Site(s) Performing Correlative Study 
Assays will be performed in the CIML at Fred Hutch or an agreed upon vendor or collaborator. 
12.2 
Exploratory Correlative Studies 
12.2.1 Assessment of PD-L1 expression at Baseline and Post-treatment -- 
Immunohistochemistry (IHC) – Exploratory Laboratory Correlative Study #1 
12.2.1.1 
Collection of Specimen(s) 
FFPE archival tissue block(s) from tumor obtained after last therapy will be identified by the 
clinical site at the relevant pathology laboratories where they were processed and stored. Tissue 
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patients will undergo a pre-treatment biopsy as part of this protocol. Patients will undergo a post-
treatment biopsy if deemed relatively safe and technically feasible as part of this protocol. 
12.2.1.2 
Handling of Specimens(s) 
FFPE archival tumor blocks will be requested by the clinical site from the relevant pathology 
laboratory by providing the patient’s name, consent form and date of collection. Patient 
identifying information (i.e., name, initials, birthdate, etc.) will be removed from the specimen 
before shipment to the CIML. If patients undergo biopsy as part of this protocol, tissue will be 
placed in formalin for overnight shipping to the CIML. 
12.2.1.3 
Shipping of Specimen(s) 
For archival samples, clinical sites will arrange for the FFPE tumor blocks (preferred) or FFPE 
slides (if blocks are unavailable) to be shipped to the CIML. For biopsies done as part of this 
protocol, tissue in formalin will be shipped overnight at ambient temperature to the CIML. 
Clinical sites will utilize BSI Engage to communicate with the CIML. After sectioning at the 
CIML, the CIML will coordinate shipment of unstained slides to HistoGeneX/CellCarta or other 
agreed upon vendor. 
12.2.1.4 
Site(s) Performing Correlative Study 
Assays will be performed by HistoGeneX/CellCarta or other agreed upon vendor. 
12.2.2 Evaluation of the effect of atezolizumab with and without NT-I7 on circulating 
Lymphocyte and Monocyte numbers and Phenotype – Exploratory Laboratory 
Correlative Study #2 
12.2.2.1 
Collection of Specimen(s) 
Blood draws will be performed by venipuncture on study subjects just before, during, and at end 
of treatment. Whole blood will be collected into heparinized tubes and ACD tubes.  
12.2.2.2 
Handling of Specimens(s) 
Blood samples will be collected at room temperature and shipped ambient to the CIML the same 
day as the blood draw. The sample must be received at the CIML within 24 hours of blood draw. 
For Whole Blood immunophenotyping, aliquots of whole blood will be immediately tested using 
multispectral immunophenotyping panels to obtain absolute cell counts for CD4+ and CD8+ T-
cell subsets and activation states, NK and NKT-cells, DC subsets, monocytes, B cells and other 
cell types using the 21c, 13c, and FoxP3 assays described in section 11.2.2.  For Ki67 assays, 
blood collection tubes (for subsequent PBMC isolation) will be shipped on day of blood draw for 
overnight delivery to the CIML. Blood will be submitted to Ficoll gradient centrifugation, and 
PBMC will be stored in aliquots of up to 20 million cells in vapor-phase liquid nitrogen for 
storage for batch analyses.  
12.2.2.3 
Shipping of Specimen(s) 
Blood collection tubes will be shipped at ambient temperature to the CIML. Clinical sites will 
utilize BSI Engage to communicate with the CIML. 

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12.2.2.4 
Site(s) Performing Correlative Study 
Flow cytometry will be performed in the CIML at Fred Hutch. Ki67 assays will be performed at 
the UW in collaboration with the CIML. 
12.2.3 Multiplex Cytokines -- Multiplex ELISA – Exploratory Laboratory Correlative Study #3 
12.2.3.1 
Collection of Specimen(s) 
Whole blood will be collected into red-top tubes by venipuncture. 
12.2.3.2 
Handling of Specimens(s) 
Blood samples will be processed to frozen serum at the local labs and stored frozen at -80°C. 
12.2.3.3 
Shipping of Specimen(s) 
Frozen serum vials will be batch-shipped quarterly from the clinical sites overnight on dry ice to 
the CIML. Clinical sites will utilize BSI Engage to communicate with the CIML. The CIML will 
coordinate shipments of serum to the Fred Hutch Shared Resource facility or other collaborator, 
as needed. 
12.2.3.4 
Site(s) Performing Correlative Study 
Assays will be performed at the Fred Hutch Shared Resource facility or other agreed upon 
collaborator or vendor. 
12.2.4 Kynurenine and tryptophan (Kyn/Trp) Ratios and Plasma Arginine levels – Exploratory 
Laboratory Correlative Study #4 
12.2.4.1 
Collection of Specimen(s) 
Blood draws will be performed by venipuncture on study subjects at time points before, during, 
and after treatment. Whole blood will be collected into heparinized tubes.  
12.2.4.2 
Handling of Specimens(s) 
Plasma will be isolated by the local laboratory and frozen at -80°C. 
12.2.4.3 
Shipping of Specimen(s) 
Plasma samples will be batch-shipped quarterly from the clinical sites overnight on dry ice to the 
CIML. Sites will utilize BSI Engage to communicate with the CIML. The CIML will coordinate 
the shipment of samples to the agreed upon collaborator or vendor. 
12.2.4.4 
Site(s) Performing Correlative Study 
Kyn/Trp and Arg levels will be assessed at an agreed upon collaborator or vendor to be 
determined.  

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12.3 
Special Studies  
12.3.1 Immunogenicity Testing (NT-I7) 
The formation of ADA and neutralizing anti-drug antibodies (NADA) to NT-I7 will be evaluated 
at: Pre-treatment with NT-I7 (Cycle 1, Day 1) and on Day 1 of each subsequent cycle. 
Immunogenicity testing will be repeated at the end of treatment visit.  
Patients who have positive ADA will be followed every 3 months for PD biomarkers including 
ALC, and serum IL-7 level until ADA level becomes undetectable.  
NeoImmuneTech has transferred and revalidated the assay method to BioAgilytix for performing 
the assays and the determination of the main ADA/NADA parameters. 
12.3.1.1 
Collection of Specimen(s) 
Whole blood will be collected in SSTs at each of the time points specified in the Study Calendar. 
Please refer to the ION-02 Laboratory Manual. 
12.3.1.2 
Handling of Specimen(s) 
Blood samples will be handled as per the draw tube manufacturer’s recommendations, processed 
at the local labs into serum aliquots, and aliquots stored frozen at -80°C until shipped to the 
CIML.  
12.3.1.3 
Shipping of Specimen(s) 
Frozen samples will be batch-shipped quarterly, or immediately upon collection of EOT visit 
from the clinical sites overnight on dry ice to the CIML. Sites will utilize BSI Engage to 
communicate with the CIML. The CIML will coordinate the shipment of samples to BioAgilytix. 
12.3.1.4 
Site(s) Performing Correlative Study 
Assays will be performed by BioAgilytix, Durham, NC. 
12.3.2 NT-I7 Pharmacokinetics 
PK samples will be collected on all patients (dose escalation and dose expansion phase). Serial 
samples will be assessed following the PK timepoints in the tables below. 
Note: The precise NT-I7 administration time and the precise PK draw time should be recorded 
accurately and prospectively to fully interpret these values. Blood draws are timed after NT-I7 
administration is complete, not completion of atezolizumab infusion. 
12.3.2.1 
Collection of Specimen(s) 
Blood draws will be performed by venipuncture on study subjects before, during, and at end of 
treatment. 

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13. 
DATA REPORTING / REGULATORY REQUIREMENTS / STUDY 
OVERSIGHT 
13.1 
Data 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 trial is granted to all persons with the appropriate roles, as listed on the Delegation 
of Duties 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 Study Procedures Manual.  
13.1.1 Responsibility for Data Submission 
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, 
protocol-specified data must be submitted accurately and in a timely manner to the data 
management organization via the EDC system. 
The data management organization, in collaboration with the ION Coordinating Center, is 
responsible for compiling and submitting data to the study sponsor for all participants and for 
providing the data to the Protocol PI for review. 
13.2 
Compliance with Trial 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 trial and its results are subject to the requirements for 
submission to the Clinical Trials Data Bank, https://www.clinicaltrials.gov. Information posted 
will allow patients to identify potentially appropriate trials for their disease conditions and 
pursue participation by calling a central contact number for further information on appropriate 
trial locations and trial site contact information.  
13.3 
Study Oversight 
This protocol will adhere to the policies and requirements listed in Appendix B. The specific 
responsibilities of the PI, the ION Coordinating Center and NeoImmuneTech and the procedures 
for auditing are presented in Appendix B. 
• The contract research organization (CRO), IQVIA, is responsible for distributing all 
Investigational New Drug Application (IND) Action Letters or Safety Reports received from 

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the study sponsor, NeoImmuneTech, to all participating institutions for submission to their 
individual Institutional Review Boards (IRBs) for action as required. 
 
• Investigational agents may be ordered by a participating site only after approved by the study 
sponsor, NeoImmuneTech, and officially activated by the ION Coordinating Center.  
14. 
SITE ACTIVATION PROCEDURES 
14.1 
IRB Approval 
Each investigator or group of investigators at a clinical site must obtain IRB approval for this 
protocol and submit all required regulatory documents (including any protocol-specific 
documents) to the CRO, IQVIA, before they can be approved to enroll patients. IQVIA uses 
extensive data to make a determination of whether a site has fulfilled all regulatory criteria 
including but not limited to: 
• 
An active Federal Wide Assurance (FWA) number 
• 
A complete Delegation of Duties Sheet (which must be maintained and kept current) 
• 
A valid IRB approval 
• 
Compliance with all protocol-specific requirements 
In addition, the site-protocol PI must meet the following criteria: 
• 
Complete Form FDA 1572 
• 
Complete Financial Disclosure 
• 
Current Curriculum Vitae  
• 
Valid Medical License 
Evidence of the following training must be provided for the site-protocol PI, sub-investigators 
and all participating clinical site staff, as reported on the Form FDA 1572 and Delegation of 
Duties Sheet: 
• 
Current GCP Training 
• 
Current Human Subject Protection (HSP) Training 
• 
Evidence of Protocol/Amendments Training 
14.1.1 Submitting Regulatory Documents 
Submit your IRB approval, model Informed Consent Form (ICF), and other protocol-specific 
regulatory documentation to IQVIA, where they will be filed and tracked.  
Regulatory Submission of Essential Documents (pre-site activation) to IQVIA by e-mail to 
NIT106EDP@iqvia.com. 

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14.2 
Patient Enrollment 
Patient 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 participants’ 
responsibility on the ION Delegation of Duties Sheet.   
Before enrolling a patient in the EDC system, registration staff should verify the following: 
• 
All eligibility criteria have been met within the protocol stated timeframes. 
• 
If applicable, all patients have signed an appropriate consent form and Health 
Insurance Portability and Accountability Act of 1996 (HIPAA) authorization form (if 
applicable). 
For further instructional information on patient enrollment; please refer to the Study Procedures 
Manual or contact the ION Coordinating Center at ion@fredhutch.org. 
14.3 
General Guidelines 
After enrollment, patients should begin protocol treatment within 3 business days. Issues that 
would cause treatment delays should be discussed with the PI. If a patient does not receive 
protocol therapy after enrollment, the patient’s enrollment on the study may be canceled. The 
Clinical Research Site (CRS) must notify the ION Coordinating Center of cancellations as soon 
as possible. 
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. No separate Statistical 
Analysis Plan (SAP) will be issued for this study. 
15.1 
Responsibility for Analyses 
The statistical analysis of the data obtained from this study will be the responsibility of Fred 
Hutch as part of the ION.  
15.2 
Study Design/Objectives 
The proposed clinical trial is a phase 1b/2a, open-label, multicenter study of the administration of 
atezolizumab (MPDL3280A) in combination with NT-I7 in patients with anti-PD-1/PD-L1 naïve 
or relapsed/refractory high-risk skin cancers: cSCC, MCC and melanoma.  
This study will evaluate the safety and anti-tumor activity of NT-I7 in combination with 
atezolizumab, including estimation of the MTD and/or the RP2D. The trial is designed to 

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determine whether NT-I7, at doses known to increase the peripheral blood T-cell level, will also 
increase the level of tumor infiltrating T-cells and thereby increases the efficacy of atezolizumab. 
15.2.1 Dose Escalation Phase 
A 3+3 dose escalation design will be utilized. Four pre-specified doses of NT-I7 (120, 360, 840, 
and 1200 µg/kg) will be tested (refer to Section 5). The initial dose level will start at 120 µg/kg. 
NT-I7 doses will be escalated according to the dose escalation scheme in Section 5.2.2, 
1200 µg/kg as the MAD. Enrollment will continue until the MTD or RP2D is identified, or up to 
the MAD.  
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 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 and Safety 
Monitoring Committee, which includes the ION Coordinating Center, the Protocol PI, clinical 
sites PIs and NeoImmuneTech’s Chief Medical Officer or 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 trial will proceed to the Dose Expansion Phase 
(Phase 2a) to further evaluate RP2D in a larger number of patients.  
 
15.2.2 Expansion Phase 
The selected RP2D will be further evaluated in the Phase 2a. 
The Phase 2a is designed to evaluate the anti-tumor effects of NT-I7 in combination with 
atezolizumab in a total of 60 patients. Twenty-four patients in Arm I, i.e., 12 patients for each 
indication (cSCC and MCC), and 36 patients in Arm II, i.e., 12 patients for each indication 
(MCC, cSCC and melanoma), will be enrolled. Enrolled patients will be separated into 2 arms 
depending on previous use of anti-PD-1/PDL-1 therapy and cancer type (see Section 5).  
15.3 
Sample Size/Accrual Rate 
During the dose escalation phase (Phase 1b), a 3+3 design will be used for identifying the MTD 
and/or the RP2D. The following design will be used:  

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Number of Patients with DLT at a 
Given Dose Level 
Escalation Decision Rule 
0 out of 3 
Enroll 3 patients at the next dose level. 
1 out of 3 
Enroll at least 3 more patients at this dose level. 
• 
If 0 of these 3 additional patients experience a DLT 
(totaling 1/6), escalate to the next dose level. 
• If ≥1 of these 3 additional patients experiences DLT 
(totaling ≥2/6 at the dose level), the dose escalation is 
stopped, and the next lower dose level will be declared the 
MTD. In the case this happens at the 120 µg/kg dose level, 
a lower dose of 60 µg/kg will be tested, and the same 3+ 3 
design followed.  
≥2 out of 3  
Dose escalation will be stopped. The next lower dose level 
will be declared the MTD. Three (3) additional patients will 
be entered at the next lower dose level if only 3 patients were 
treated previously at that dose. In the case this happens at the 
120 µg/kg dose level, a lower dose of 60 µg/kg will be tested, 
and the same 3+3 design followed. 
Abbreviations: DLT=dose-limiting toxicity; MTD=maximum tolerated dose.  
Once all patients in a cohort have completed the 3-week DLT window, all AEs will be assessed 
by the Data and Safety Monitoring Committee.  
In the dose expansion phase (Phase 2a), a total of 60 patients will be treated at the RP2D as 
defined above.  
Based on the available data provided in Section 2.2, the average historical ORR for the patients 
in this study would be 45.25% in Arm I and less than 5% in Arm II. With a total of 24 patients 
treated at the RP2D in Phase 2a of the study in Arm I, the 95% confidence interval for an 
observed ORR of 17/24 or higher would exclude 45.25%. With a total of 36 patients treated at 
the RP2D in Phase 2a of the study in Arm II, the 95% confidence interval for an observed ORR 
of 6/36 or higher would exclude 5%.  
Approximately 84 patients will be enrolled in this study; up to approximately 24 patients in the 
Phase 1b and approximately 60 evaluable patients in the Phase 2a of the study. The expected 
accrual is 4 patients per month total at approximately 8 ION sites.   
Safety Population: All patients who receive at least 1 dose of the investigational regimen will be 
considered evaluable for safety and included in the overall safety analysis. For the Phase 1b, in 
the absence of a DLT, patients must complete the full 3-week DLT window period to be 
considered evaluable for DLTs. Patients who discontinue from the study before the completion 
of the full 3-week (21 days) 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. 

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Efficacy Population: The efficacy analysis for the Phase 1b (dose escalation) portion will be 
conducted on all DLT-evaluable patients, as defined in Section 6.2.2. The efficacy analysis for 
the Phase 2a (expansion phase) portion will be conducted on all patients who received at least 
one cycle of study treatment and have at least one evaluable post baseline tumor assessments.    
15.4 
Stratification Factors: N/A 
15.5 
Analysis of Secondary Endpoints 
15.5.1 Secondary Objectives 
Statistical analyses will be conducted for the following secondary objectives: 
• 
The immunogenicity of NT-I7  
• 
A preliminary assessment of the anti-tumor activity of NT-I7 in combination with 
atezolizumab, including the ORR, as measured by RECIST v1.1 and iRECIST, the 
DCR, DOR, PFS, and OS.  
Descriptive statistics will be provided. Mean, standard deviation, median, minimum and 
maximum will be displayed for continuous variables, and numbers and percentages will be 
displayed for counts and binary variables. Kaplan-Meier estimates will be considered for time to 
event variables (DOR, PFS and OS). The analyses will be performed for each arm in Phase 2a, 
separately.   
15.5.2 Exploratory Endpoints 
Statistical analyses will be conducted to determine the immune correlates of the clinical activity 
of the investigational treatment combination. 
The endpoints will include the evaluation of the effect of the investigational treatment 
combination on the immune-bias of the TME, based upon baseline and post-baseline tumor 
biopsy comparisons of: 
• 
Serum concentration of NT-I7 administered in combination with atezolizumab at 
specified timepoints for the following parameters: Area under the concentration time-
curve (AUC), maximum serum concentration (Cmax), minimum serum concentration 
(Cmin), Clearance (CL) 
• 
Number, distribution, and phenotype of tumor-infiltrating cells 
• 
PD-L1 expression 
• 
Expression of IFNγ and associated proinflammatory gene expression in the TME 
• 
Changes in TME that correlate with response or provide information on potential 
actionable causes for lack of clinical benefit.  
15.6 
Reporting and Exclusions 
15.6.1 Evaluation of Toxicity 
All patients will be evaluable for toxicity from the time of their first treatment with atezolizumab 
and/or NT-I7 until 30 days after the last dose of study treatment. 

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15.6.2 Evaluation of Response 
All patients enrolled in the study who received at least 1 cycle of study treatment will be 
assessed for response to treatment, even if there are major protocol treatment deviations or if 
they are ineligible. Each patient will be assigned one of the following categories: (1) CR, (2) PR, 
(3) SD, (4) PD, (5) early death from malignant disease, (6) early death from toxicity, (7) early 
death because of other cause, or (9) unknown (not assessable, insufficient data). [Note: By 
arbitrary convention, category 9 usually designates the “unknown” status of any type of data in a 
clinical database.] 
All of the patients who met the eligibility criteria and received at least 1 dose of study treatment 
will be included in the main analysis of the response rate. Patients in response categories 4-9 
should be considered to have a treatment failure (disease progression). Thus, an incorrect 
treatment schedule or drug administration does not result in exclusion from the analysis of the 
response rate. Precise definitions for categories 4-9 will be protocol specific. 
All conclusions should be based on patients who received at least 1 cycle of study treatment. 
Sub-analyses may then be performed on the basis of a subset of patients, excluding those for 
whom major protocol deviations have been identified (early death due to other reasons, early 
discontinuation of treatment, major protocol violations, etc.). However, these sub-analyses may 
not serve as the basis for drawing conclusions concerning treatment efficacy, and the reasons for 
excluding patients from the analysis should be clearly reported. The 95% confidence intervals 
should also be provided. 

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Alstadhaug KB, Croughs T, Henriksen S, et al. Treatment of progressive multifocal 
leukoencephalopathy with interleukin 7. JAMA Neurol. 2014;71(8):1030-1035. 
34. 
Gasnault J, de Goer de Herve MG, Michot JM, et al. Efficacy of recombinant human interleukin 7 
in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy. Open 
Forum Infect Dis. 2014;1(2):ofu074. 
35. 
Levy Y, Sereti I, Tambussi G, et al. Effects of recombinant human interleukin 7 on T-cell 
recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a 
phase I/IIa randomized, placebo-controlled, multicenter study. Clin Infect Dis. 2012;55(2):291-
300. 
36. 
Merchant MS, Bernstein D, Amoako M, et al. Adjuvant Immunotherapy to Improve Outcome in 
High-Risk Pediatric Sarcomas. Clin Cancer Res. 2016. 
37. 
Miskin DP, Chalkias SG, Dang X, Bord E, Batson S, Koralnik IJ. Interleukin-7 treatment of PML 
in a patient with idiopathic lymphocytopenia. Neurol Neuroimmunol Neuroinflamm. 
2016;3(2):e213. 
38. 
Rosenberg SA, Sportes C, Ahmadzadeh M, et al. IL-7 administration to humans leads to 
expansion of CD8+ and CD4+ cells but a relative decrease of CD4+ T-regulatory cells. J 
Immunother. 2006;29(3):313-319. 
39. 
Sereti I, Dunham RM, Spritzler J, et al. IL-7 administration drives T cell-cycle entry and 
expansion in HIV-1 infection. Blood. 2009;113(25):6304-6314. 

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40. 
Sereti I, Estes JD, Thompson WL, et al. Decreases in colonic and systemic inflammation in 
chronic HIV infection after IL-7 administration. PLoS Pathog. 2014;10(1):e1003890. 
41. 
Sospedra M, Schippling S, Yousef S, et al. Treating progressive multifocal leukoencephalopathy 
with interleukin 7 and vaccination with JC virus capsid protein VP1. Clin Infect Dis. 
2014;59(11):1588-1592. 
42. 
Thiebaut R, Drylewicz J, Prague M, et al. Quantifying and predicting the effect of exogenous 
interleukin-7 on CD4+ T cells in HIV-1 infection. PLoS Comput Biol. 2014;10(5):e1003630. 
43. 
Thiebaut R, Jarne A, Routy JP, et al. Repeated Cycles of Recombinant Human Interleukin 7 in 
HIV-Infected Patients With Low CD4 T-Cell Reconstitution on Antiretroviral Therapy: Results 
of 2 Phase II Multicenter Studies. Clin Infect Dis. 2016;62(9):1178-1185. 
44. 
Vandergeeten C, Fromentin R, DaFonseca S, et al. Interleukin-7 promotes HIV persistence during 
antiretroviral therapy. Blood. 2013;121(21):4321-4329. 
45. 
Di Giacomo AM, Biagioli M, Maio M. The emerging toxicity profiles of anti-CTLA-4 antibodies 
across clinical indications. Semin Oncol. 2010;37(5):499-507. 
46. 
CDER C. Guidance for Industry, Drug-Induced Liver Injury: Premarketing Clinical Evaluation. 
FDA. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/drug-induced-
liver-injury-premarketing-clinical-evaluation. Published 2009. Accessed August 25, 2022. 
47. 
Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 
interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 
2007;27(1):111-122. 
48. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. 
49. 
Rustin GJ, Quinn M, Thigpen T, et al. Re: New guidelines to evaluate the response to treatment 
in solid tumors (ovarian cancer). J Natl Cancer Inst. 2004;96(6):487-488. 
50. 
Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response guidelines for phase II clinical 
trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific 
Antigen Working Group. J Clin Oncol. 1999;17(11):3461-3467. 
51. 
Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with 
progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate 
Cancer Clinical Trials Working Group. J Clin Oncol. 2008;26(7):1148-1159. 
52. 
Vergote I, Rustin GJ, Eisenhauer EA, et al. Re: new guidelines to evaluate the response to 
treatment in solid tumors [ovarian cancer]. Gynecologic Cancer Intergroup. J Natl Cancer Inst. 
2000;92(18):1534-1535. 
 
 
 

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APPENDIX A 
PERFORMANCE STATUS CRITERIA 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity.  Fully active, able to 
carry on all pre-disease performance 
without restriction. 
100 
Normal, no complaints, no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
1 
Symptoms, but ambulatory.  
Restricted in physically strenuous 
activity, but ambulatory and able to 
carry out work of a light or sedentary 
nature (e.g., light housework, office 
work). 
80 
Normal activity with effort; some signs 
or symptoms of disease. 
70 
Cares for self, unable to carry on 
normal activity or to do active work. 
2 
In bed <50% of the time.  Ambulatory 
and capable of all self-care, but 
unable to carry out any work 
activities.  Up and about more than 
50% of waking hours. 
60 
Requires occasional assistance but is 
able to care for most of his/her needs. 
50 
Requires considerable assistance and 
frequent medical care. 
3 
In bed >50% of the time.  Capable of 
only limited self-care, confined to bed 
or chair more than 50% of waking 
hours. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization 
indicated.  Death not imminent. 
4 
100% bedridden.  Completely 
disabled.  Cannot carry on any self-
care.  Totally confined to bed or chair. 
20 
Very sick, hospitalization indicated. 
Death not imminent. 
10 
Moribund, fatal processes progressing 
rapidly. 
5 
Dead. 
0 
Dead. 
 
 

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APPENDIX B 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
Regulatory and Ethical Considerations 
- 
This study will be conducted in accordance with the protocol and with the following:  
 Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
 Applicable ICH Good Clinical Practice (GCP) Guidelines. 
 Applicable laws and regulations. 
- 
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the Investigator 
and reviewed and approved by the IRB/IEC before the study is initiated. 
- 
Any amendments to the protocol will require IRB/IEC and regulatory authority approval, 
when applicable, before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to subjects. 
- 
The Investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC. 
 Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
 Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations. 
- 
After reading the protocol, each Investigator will sign the protocol signature page and 
send a copy of the signed page to IQVIA by e-mail to a contact
  
(Appendix D). The study will not start at any study center at which the Investigator has 
not signed the protocol. 
 
Adequate Resources 
The Investigator is responsible for supervising any individual or party to whom the Investigator 
delegates study-related duties and functions conducted at the study center. 
 
If the Investigator/institution retains the services of any individual or party to perform study 
related duties and functions, the Investigator/institution should ensure this individual or party 
is qualified to perform those study-related duties and functions and should implement 
procedures to ensure the integrity of the study-related duties and functions performed and any 
data generated. 
 

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Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor, via submission to IQVIA, with 
sufficient, accurate financial information as requested to allow the Sponsor to submit complete 
and accurate financial certification or disclosure statements to the appropriate regulatory 
authorities. Investigators are responsible for providing information on financial interests 
during the course of the study and for 1 year after completion of the study. 
 
Informed Consent Process 
 The Investigator or his/her representative will explain the nature of the study to the subject 
and answer all questions regarding the study. 
 Subjects must be informed that their participation is voluntary. Subjects will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
 The medical record must include a statement that written informed consent was obtained 
before the subject was entered in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the 
ICF. 
 Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
 
A copy of the ICF(s) must be provided to the subject.  
 
Data Protection 
 Subjects will be assigned a unique identifier. Any subject records or datasets that are 
transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
 The subject must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the subject. 
 The subject must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
 The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy 
legislation. 
 The Sponsor or its representative will not provide individual genotype results to subjects, 
any insurance company, any employer, their family members, general physician, or any 
other third party, unless required to do so by law. 
 Extra precautions are taken to preserve confidentiality and prevent genetic data being linked 
to the identity of the subject. In exceptional circumstances, however, certain individuals 
might see both the genetic data and the personal identifiers of a subject. For example, in 
the case of a medical emergency, the ION Coordinating Center, Sponsor or 
representative physician or an Investigator might know a subject’s identity and have 
access to his or her genetic data. Also, regulatory authorities may require access to the 

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relevant files. 
 
Administrative Structure 
The Data and Safety Monitoring committee will include, at a minimum, NeoImmuneTech’s 
Chief Medical Officer or designee, the Protocol PI, clinical site PIs and the ION 
Coordinating Center. The Principal Investigator and NeoImmuneTech, when appropriate, 
will invite other specialist individuals to participate in the review, e.g., PK scientists, 
statisticians, clinical specialists etc. 
 
Table 6 – Study Administrative Structure 
Function 
Responsible Organization 
Study Operations Management  
ION Coordinating Center 
Medical Monitoring 
ION Coordinating Center and Protocol PI 
On-site clinical monitoring 
CRO – Avance Clinical, LLC  
Study Master File 
CRO – IQVIA 
Data Management 
CRO – Cytel, Inc. 
Clinical Supply Management 
Drug Information System integrated to eDC system  
Biostatistics  
CRO – Cytel, Inc. 
Medical Writing 
ION Coordinating Center and CRO - IQVIA 
Data and Safety Monitoring Committee  
Protocol PI, clinical site PIs, ION Coordinating Center and 
NIT’s Chief Medical Officer or designee 
 
Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor, NeoImmuneTech, will submit to the Food and Drug 
Administration a summary of the results of the clinical study within 1 year from the end of the 
clinical study. It shall be accompanied by a summary written in a manner that is 
understandable to laypersons. 
 
Data Quality Assurance 
 All subject data relating to the study will be transmitted electronically. The Investigator is 
responsible for verifying that data entries are accurate and correct by electronically signing 
the eCRF. 
 The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
 The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
 The ION Coordinating Center or designee is responsible for the data management of this 
study including quality checking of the data. 
 Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized study center personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects are being protected; and that the 

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study is being conducted in accordance with the currently approved protocol and any other 
study agreements, ICH GCP, and all applicable regulatory requirements. 
 Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the Investigator for 2 years following the date a marketing application is 
approved for the drug for the indication for which it is being investigated; or, if no 
application is to be filed or if the application is not approved for such indication, until 2 years 
after the investigation is discontinued and FDA is notified. No records may be destroyed 
during the retention period without the written approval of the Sponsor. No records may be 
transferred to another location or party without written notification to the Sponsor. 
Source Documents 
The Investigator/institution should maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the study center’s subjects. Source data 
should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, should not obscure the original entry, and should be explained if 
necessary (e.g., via an audit trail). 
 
 Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s study 
center. 
 Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The Investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
 Definition of what constitutes source data can be found in the ION Study Procedures Manual. 
 
Study and Study Center Closure 
The ION Coordinating Center reserves the right to close the study center or terminate the 
study at any time for any reason at the sole discretion of the Sponsor. Study centers will be 
closed upon study completion. A study center is considered closed when all required 
documents and study supplies have been collected and a study center closure visit has been 
performed. 
 
The Investigator may initiate study center closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor, NeoImmuneTech or the 
ION Coordinating Center may include but are not limited to: 
 Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
 Inadequate recruitment of subjects by the Investigator. 
 Discontinuation of further study treatment development. 
 

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Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study center will be set forth in the Clinical Trial Agreement. 
 The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor, 
NeoImmuneTech, before submission. This allows NeoImmuneTech to protect proprietary 
information and to provide comments. 
 The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, NeoImmuneTech will generally support 
publication of multicenter studies only in their entirety and not as individual study center data. 
In this case, one of the ION Investigators will be designated, by mutual agreement, as the 
Coordinating Investigator. 
 Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
 
 
 
 
 

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Injection site 
NT-I7 will be injected by intramuscular route. The best areas for injection are the deltoid muscle 
and the muscles of the thighs and buttock; it should remain away from joints, nerves, bones, and 
other important structures. 
 
Do not use the same site for injection when the volume of injection requires several injections to 
a patient. Use the attached Injection Site Diary and the site codes below to document the 
injection site(s). 
 
 
 
 
 
 
 
 
 
Left Deltoid ‘A’ 
Right Deltoid ‘B’ 
Left Buttock ‘C’ 
Right Buttock ‘D’ 
Left Thigh ‘E’ 
Right Thigh’F’ 
 

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INJECTION SITE DIARY  
 
**To be completed by Research Nurse or Investigator** 
 
 
Patient Name 
 
Patient Study 
ID 
 
 
 
Injection  
Date (MM/DD/YYYY) 
Injection Site 
#1 
 
 A    B    C    D    E    F 
#2 
 
 A    B    C    D    E    F 
#3 
 
 A    B    C    D    E    F 
#4 
 
 A    B    C    D    E    F 
#5 
 
 A    B    C    D    E    F 
#6 
 
 A    B    C    D    E    F 
#7 
 
 A    B    C    D    E    F 

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APPENDIX D 
SIGNATURE OF INVESTIGATOR 
 
PROTOCOL TITLE:  A phase 1b/2a, open label study to evaluate anti-tumor efficacy and safety of 
rhIL-7-hyFc (NT-I7) in combination with anti-PD-L1 (atezolizumab) in patients 
with anti-PD-1/PD-L1 naïve or relapsed/refractory high-risk skin cancers 
 
PROTOCOL NUMBER:  NIT-106 (ION-02) 
 
VERSION: Amendment 5, v1.0, dated January 19, 2023 
 
This protocol is a confidential communication of NeoImmuneTech. 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 to IQVIA by e-mail to
 
 
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:  
 
 
 
 
 
 
 

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APPENDIX E 
ABBREVIATIONS LIST 
ADA  
anti-drug antibodies 
AE 
 
adverse event 
ALC  
absolute lymphocyte count 
ALT 
 
alanine aminotransferase 
AML  
acute myelocytic leukemia 
ANC  
absolute neutrophil count 
Anti-HBc 
antibody to hepatitis B core antigen 
Anti-TNF 
antitumor necrosis factor 
aPTT  
activated partial thromboplastin time 
Arg 
 
arginine 
AST 
 
aspartate aminotransferase 
AUC  
area under the concentration time-curve 
BAL  
bronchoscopic alveolar lavage 
BSA  
body surface area 
BUN  
blood urea nitrogen 
CAP  
chest, abdomen, and pelvis 
CBC  
complete blood count 
CDASH 
Clinical Data Acquisition Standards Harmonization 
CHO  
Chinese Hamster Ovary 
CIML  
Central Immune Monitoring Laboratory 
CITN  
Cancer Immunotherapy Trials Network 
CL 
 
clearance 
CLIA  
Clinical Laboratory Improvement Amendments 
CM 
 
central memory 
Cmax 
 
maximum serum concentration 
Cmin 
 
minimum serum concentration 
CNS  
central nervous system 
COPD  
chronic obstructive pulmonary disease 
CPI 
 
checkpoint Inhibitor 
CR 
 
complete response 
CRF 
 
case report form 

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CRO  
contract research organization 
CRS 
 
clinical research site 
cSCC  
cutaneous squamous cell carcinoma 
CSR 
 
clinical study report 
CT 
 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTEP  
Cancer Therapy Evaluation Program 
DC 
 
dendritic cell 
DCR  
disease control rate 
DLT 
 
dose-limiting toxicity 
DOR  
duration of objective response 
ECOG  
Eastern Cooperative Oncology Group 
eCRF  
electronic case report form 
EDC  
electronic data capture 
EKG  
electrocardiogram 
ELISA  
enzyme-linked immunosorbent assay 
ELISPOT 
enzyme-linked immunospot 
EM 
 
effector memory 
EOT 
 
end of treatment 
EU GMP 
European Union – Good Manufacturing Practice 
FDA  
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
FDAMA 
Food and Drug Administration Modernization Act 
FDG  
fluorodeoxyglucose 
FFPE  
formalin-fixed paraffin-embedded 
FIH 
 
first-in-human 
FU 
 
follow-up 
FWA  
Federal Wide Assurance 
GCP  
Good Clinical Practice 
G-CSF  
granulocyte-colony stimulating factor 
GEP 
 
gene expression programming 
HAART 
highly active antiretroviral therapy 
HBsAg 
hepatitis B surface antigen 

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HBV  
hepatitis B virus 
HCV  
hepatitis C virus 
HED  
human equivalent dose 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
 
human immunodeficiency virus 
HSP 
 
Human Subject Protection 
hyFC  
hybrid Fc 
IB 
 
Investigator’s Brochure 
IC 
 
immune cells 
ICF 
 
informed consent form 
ICH 
 
International Council for Harmonisation 
IDO 
 
indoleamine 2,3-dioxygenase 
IFN-γ(-α, etc) interferon-gamma (alpha, etc) 
IgD 
 
Immunoglobulin D 
IgG(1,2…) 
immunoglobulin G (1,2…) 
IHC 
 
immunohistochemistry 
IL-7(2, etc) 
interleukin 7 (2, etc) 
IM 
 
intramuscular 
IME 
 
important medical events 
IMP 
 
investigational medicinal product 
IND 
 
Investigational New Drug Application 
INR 
 
international normalized ratio 
ION 
 
Immune Oncology Network 
IRB 
 
Institutional Review Board 
irAE 
 
immune-related adverse event 
iRECIST 
immune-related Response Evaluation Criteria in Solid Tumors 
IV 
 
intravenous 
IVIg 
 
intravenous immunoglobulin 
Kyn/Trp 
Kynurenine and tryptophan 
LCMV  
lymphocytic choriomeningitis virus 
LDH  
lactate dehydrogenase 
LFT 
 
liver function test 
mAb  
monoclonal antibodies 

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MAD  
maximum administered dose 
MCC  
Merkel cell carcinoma 
MDS  
myelodysplastic syndrome 
MDSC  
myeloid-derived suppressor cells 
MED  
maximum effective dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC  
major histocompatibility complex 
MRI 
 
magnetic resonance imaging 
msIHC  
multispectral IHC 
MTD  
maximum tolerated dose 
NADA  
neutralizing anti-drug antibodies 
NCI 
 
National Cancer Institute 
NIT 
 
NeoImmuneTech 
NK 
 
natural killer (cells) 
NKT  
natural killer T (cells) 
NOAEL 
no observed adverse effect level 
NSCLC 
non-small cell lung cancer  
NT-I7  
rh-IL-7-hyFc ka GX-I7  
ORR  
objective response rate 
OS 
 
overall survival 
PBMC  
peripheral blood mononuclear cell 
PCR 
 
polymerase chain reaction 
PD 
 
progressive disease 
PD-1  
programmed cell death protein 1 
PD-L1  
programmed death-ligand 1 
PET 
 
positron emission tomography 
PFS 
 
progression-free survival 
Ph. EUR 
European pharmacopeia 
PI 
 
Principal Investigator 
PK 
 
pharmacokinetic(s) 
PR 
 
partial response 
PSA 
 
prostate-specific antigen 
PT 
 
prothrombin time 

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PUVA  
psoralen plus ultraviolet A radiation 
Q3W  
every 3 weeks 
RCC  
renal cell carcinoma  
RECIST 
Response Evaluation Criteria in Solid Tumors 
rhIL-7  
recombinant human IL-7 
RP-HPLC 
reverse-phase high-performance liquid chromatography 
RP2D  
recommended Phase 2 dose 
SAE 
 
serious adverse event 
SAP 
 
statistical analysis plan 
SC 
 
subcutaneous 
SD 
 
stable disease 
SE-UHPLC 
size-exclusion ultra-high-performance liquid chromatography 
SFC 
 
spot-forming cells 
SGOT  
serum glutamic oxaloacetic transaminase 
SGPT  
serum glutamic-pyruvic transaminase 
SOC  
system organ class 
SOP 
 
standard operating procedure 
SST 
 
serum-separating tube 
TAA  
tumor-associated antigen 
TB 
 
tuberculosis 
TC 
 
tumor cells 
TCR 
 
T-cell receptor 
TEAE  
treatment-emergent adverse event 
TEMRA 
terminally differentiated effector memory 
TGF-β  
transforming growth factor β 
TIL 
 
tumor-infiltrating lymphocyte 
TME  
tumor microenvironment 
TREC  
T cell receptor excision circles 
TSH 
 
thyroid-stimulating hormone 
T-VEC 
talimogene laherparepvec 
Tx 
 
treatment 
UC 
 
urothelial carcinoma  
ULN  
upper limit of normal 

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UV 
 
ultraviolet 
WES  
whole exome sequencing