Phase 2 Randomized Clinical Trial Comparing the Safety and Efficacy of PULSAR-Integrated Radiotherapy + Pembrolizumab or Nivolumab Administered With or Without STING-Agonist IMSA101 in Patients With Oligometastatic NSCLC and RCC
Phase: PHASE2
Conditions: Oligometastatic Disease
Sponsor: ImmuneSensor Therapeutics Inc.

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 1 
 
 
Clinical Study Protocol 
Phase 2 Randomized Clinical Trial Comparing the Safety 
and Efficacy of PULSAR-Integrated Radiotherapy + 
Pembrolizumab or Nivolumab Administered with or 
without STING-Agonist IMSA101 in Patients with 
Oligometastatic Non-Small Cell Lung Cancer and Renal 
Cell Carcinoma 
IMSA101-102 
Drug Development Phase: 
Phase 2 
Investigational Product: 
IMSA101 
IND Number 
142445 
Indication: 
Oligometastatic non-small cell lung cancer and 
renal cell carcinoma 
Sponsor: 
ImmuneSensor Therapeutics 
2110 Research Row #610 
Dallas, TX 75235 
Protocol Amendment: 
3 
Protocol Date and Version: 
19-OCT-2023  
Version 5.0 
 
Conduct: In accordance with the ethical principles that originate from the Declaration of Helsinki and that 
are consistent with International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use (ICH) guidelines for Good Clinical Practice (GCP) and regulatory requirements as 
applicable. 
 
CONFIDENTIAL INFORMATION 
This document is the sole property of ImmuneSensor Therapeutics (ImmuneSensor). This document and any 
and all information contained herein has to be considered and treated as strictly confidential. This document 
shall be used only for the purpose of the disclosure herein provided. No disclosure or publication shall be 
made without the prior written consent of ImmuneSensor Therapeutics. 
 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
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PRINCIPAL INVESTIGATOR’S AGREEMENT 
I have read and understand the contents of this clinical protocol for Study No. IMSA101-102 
(Protocol Amendment 3, Version 5.0) dated 19-OCT-2023, and will adhere to the study 
requirements as presented, including all statements regarding confidentiality. In addition, I 
will conduct the Study in accordance with current GCP and applicable Food and Drug 
Administration (FDA) regulatory requirements: 
Name of Principal Investigator: 
 
 
 
 
 
 
Signature 
 
Date 
 
 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 5 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
Estimate time-to-progression (TTP) for 
PULSAR-ICI + IMSA101 and 
PULSAR-ICI alone 
• Overall TTP as defined by Response 
Evaluation Criteria in Solid Tumors 
(RECIST) Version 1.1 and by 
Immune-based Response Evaluation 
Criteria in Solid Tumors (iRECIST) 
• TTP among NSCLC patients only 
• TTP among RCC patients only 
Estimate anti-tumor efficacy for 
PULSAR-ICI + IMSA101 and 
PULSAR-ICI alone using additional 
efficacy endpoints  
• Overall response rate (ORR) as defined 
by RECIST Version 1.1 and iRECIST 
• ORR per RECIST Version 1.1 and 
iRECIST for NSCLC and RCC 
subgroups 
• Duration of treatment response (DOR) 
per RECIST Version 1.1 and iRECIST 
• Progression-free survival (PFS) per 
RECIST Version 1.1 and iRECIST 
Assess quality of life (QoL) benefit 
• Patients reported outcome on QoL 
using the Functional Assessment of 
Cancer Therapy – General (FACT-G) 
questionnaire (Version 4) 
  
Methodology:  
• For all potential patients, there will be up to a 30-day screening and eligibility 
assessment period prior to enrollment. 
• Pre-treatment screening radiographic tumor assessments will be collected within 
30 days prior to the initial dose for all patients.  
• Patients shall be enrolled in 2 treatment arms as follows: 
a. Approximately 20 patients in the control arm (PULSAR-ICI alone) 
b. Approximately 20 patients in the experimental arm (PULSAR-ICI + IMSA101) 
• The study will start with a safety run-in portion for the experimental arm, followed by 
a randomized portion for both treatment arms. 
• Patients will be stratified by histology (NSCLC and RCC) in the randomized portion. 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 6 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
• PULSAR-ICI with or without IMSA101 treatment will be administered to the patients 
in Cycles 1, 2, and 3, and thereafter only standard of care ICI monotherapy will be 
administered to all patients. Each treatment cycle will be 28 days in duration for 
Cycles 1, 2 and 3, then per standard of care monotherapy thereafter based on the 
product labels of the prescribed ICI.  
• Consistent with prior monotherapy and doublet therapy safety evaluations of 
IMSA101, the experimental arm (PULSAR-ICI + IMSA101) shall employ a 3+3 
safety run-in component as follows: 
- 
The safety run-in will be conducted for the experimental arm prior to the 
randomization of patients to the 2 treatment arms. 
- 
Patients enrolled in the safety run-in period who are treated at the dose level 
selected for the experimental arm will be included in the total number of patients of 
the experimental arm. 
- 
Only two dose levels will be evaluated potentially: the previously identified 
selected Phase 2 dose of IMSA101 minus 1 dose level (800 mcg) and the 
previously identified selected Phase 2 dose of IMSA101 (1200 mcg). Dosing shall 
not continue beyond the latter dose. 
- 
3 initial patients shall be enrolled to evaluate the 800 mcg IMSA101 administered 
in combination with PULSAR-ICI. 
- 
If no dose limiting toxicities (DLTs) are observed among these initial 3 patients at 
the 800 mcg dose level, the dose level of IMSA101 will be escalated for the 
following 3 patients to 1200 mcg of IMSA101 administered in combination with 
PULSAR-ICI. 
- 
If a single DLT occurs among the initial 3 patients at an evaluated dose level, 
3 additional patients will be enrolled at the same dose level.  
- 
If ≤ 1 DLT occurs among the 6 patients at an evaluated dose level, the dose level 
shall be considered appropriate, and dose escalation continues (up to but not 
beyond the previously identified selected Ph 2 dose of 1200 mcg). If this condition 
occurs at the 1200 mcg level, subsequent patients will be enrolled at the 1200 mcg 
level. 
- 
If ≥ 2 DLTs occur among the initial 3 or 6 patients at an evaluated dose level, the 
dose level shall be considered unacceptably toxic and dose escalation will be 
discontinued.  
- 
If the 1200 mcg level is found to be unacceptably toxic, the IMSA101 dose will be 
de-escalated to the 800 mcg dose level.  
- 
If the 800 mcg dose level is found to be unacceptably toxic, additional dose levels 
of IMSA101 shall be considered and potentially recommended by a protocol 
amendment. 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 7 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
- 
No fewer than 6 total patients shall be evaluated at a given dose level prior to 
confirmation of the dose level as the Combo selected Phase 2 dose.  
Definitions: 
◦ 
Combo selected Phase 2 dose: The Combo selected Phase 2 dose is defined as 
the dose (either at MTD or below MTD) used in combination with PULSAR-
ICI that is selected for evaluation in the Phase 2 study. 
• For the experimental arm (PULSAR-ICI + IMSA101): 
- 
A single pre-defined lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) 
shall be injected throughout the study duration, if possible.  
- 
The lesion will be injected weekly for the first three weeks of Cycle 1 (Days 1, 8 
and 15) and then on Day 1 of Cycles 2 and 3. 
- 
Where the original injection site is considered by the investigator to become 
inaccessible, a second lesion/lesion site shall be selected as a replacement, and this 
shall be used henceforth so long as it is considered accessible. Subsequent injection 
sites shall be replaced when they are considered inaccessible. 
- 
Where no remaining accessible lesions are present and where benefit of IMSA101 
therapy is, in the opinion of the investigator, being derived by the patient, 
continued injections of IMSA101 into the vicinity of an inaccessible lesion or, in 
the case that a lesion can no longer be radiographically visualized, into the last 
known location of the non-visible lesion shall be recorded and allowed, if deemed 
reasonable by the investigator. 
- 
Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous 
injection only, including those lesions that are visible, palpable, or detectable by 
standard radiographic or ultrasound methods. Neither surgical procedures nor 
endoscopically guided injections including those to endobronchial, endoluminal, or 
endosinusoidal spaces shall be allowed. While no anatomic locations are required 
or disallowed, lesions selected for intra-tumoral injection must, in the opinion of 
the investigator, not be immediately adjacent to blood vasculature or other 
physiologic landmarks in such a way that will accrue undue safety risk to the 
patient.  
• All patients will be followed throughout the study for drug tolerability and safety by 
collecting clinical and laboratory data, including adverse events (AEs) using Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria, SAEs, 
concomitant medications, and vital signs. 
• A Safety Review Committee will be organized to review the safety of the administered 
treatments (PULSAR, IMSA101, and ICI) during the study and in the safety run-in 
period to determine whether dose escalation of IMSA101 should proceed. 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
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Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
• All patients will be assessed for anti-tumor efficacy at screening, prior to the end (≤ 7 
days) of Cycle 3, and at 8-week intervals (± 7 days) thereafter based on radiographic 
assessments and analysis of ORR, DOR, TTP, and PFS (all outcome measures per 
RECIST Version 1.1 and iRECIST). 
• Administration of pembrolizumab or nivolumab will follow the instructions in the 
product labels and scheduling for the products.  
• All patients will continue to receive their assigned treatment throughout the study until 
the occurrence of disease progression (based on iRECIST), death, or other 
unacceptable treatment-related toxicity, or until the study is closed by the sponsor. 
Inclusion Criteria:  
1. Male or female patients ≥ 18 years of age 
2. Signed informed consent and mental capability to understand the informed consent 
3. Histologically or cytologically documented NSCLC or RCC with radiographically 
documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of 
“oligometastatic” disease 
4. Patient’s disease must be evaluable per RECIST Version 1.1 
5. All metastatic lesions amenable to administration of radiotherapy, at the discretion of 
the investigator 
6. Must have at least one single pre-defined lesion/lesion site (longest diameter ≥ 10 mm 
and ≤ 50 mm) suitable for intra-tumoral injection  
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 
8. Electrocardiogram (ECG) without evidence of clinically significant conduction 
abnormalities or active ischemia as determined by the investigator 
9. Acceptable organ and marrow function as defined below: 
• 
Absolute neutrophil count (ANC) > 1,500 cells/μL 
• 
Platelets > 50,000 cells/μL 
• 
Total bilirubin ≤ 1.5 times (×) the upper limit of normal (ULN) 
• 
Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 × ULN. If 
liver metastases are present, AST/ALT < 5 × ULN 
• 
Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min 
using the Cockcroft-Gault formula 
• 
Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN 
10. Women of child-bearing potential (defined as a female who has experienced menarche 
and who has not undergone successful surgical sterilization [hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy]) or is not postmenopausal (defined as 
amenorrhea for at least 12 consecutive months with an appropriate clinical profile at 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 9 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
the appropriate age, eg, greater than 45 years) must have a negative serum pregnancy 
test prior to first dose of study treatment 
11. Male and female patients with reproductive potential must agree to use two forms of 
highly effective contraception throughout the study 
Exclusion Criteria:  
1. Prior disease progression through programmed cell death ligand 1 (PD-L1 or PD-1)-
targeted immunotherapy 
2. Prior receipt of stimulator of interferon genes (STING) agonist 
3. Prior receipt of therapeutic radiotherapy to the lesions intended for PULSAR treatment  
4. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or 
< 5 half-lives of the first dose of study treatment 
5. Existence of primary tumor that requires therapeutic treatment beyond the provided 
immune checkpoint inhibitor drug 
6. Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-
cancer therapy, as judged by the investigator 
7. Previous life-threatening (Grade 4) immune-related adverse event (irAE)  
8. Existence of actionable mutations that may be eligible for mutation-targeted drug that 
represents standard-of-care therapy 
9. Presence of brain metastases  
10. Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 470) 
11. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations) that in the opinion of the 
investigator would limit compliance with study requirements 
12. Women who are pregnant or breastfeeding 
13. Sponsor reserves the right to exclude any patient from the study on the basis of pre-
study medical histories, physical examination findings, clinical laboratory results, prior 
medications, or other entrance criteria 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 10 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
Test Products, Doses and Modes of Administration:  
IMSA101:  
1 mL total volume IMSA101 will be administered via intra-tumoral injection every week 
for the first 3 weeks in Cycle 1 (Days 1, 8, and 15) followed by the first week only in 
Cycles 2 and Cycle 3 (Day 1). 
ICI Immunotherapy: PD-1-targeted agents (pembrolizumab or nivolumab) will be 
administered according to the US Food and Drug Administration (FDA)-approved product 
labels of the products. The initial ICI dose will be administered on Cycle 1 Day 2, then 
dosing will be according to the product labels. 
PULSAR: 12 to 15.5 Gray (Gy) per pulse given every 4 weeks (Day 1 of Cycles 1, 2, 
and 3) for a total of 3 pulses.  
Number of Patients:  
Approximately 46 patients will be enrolled in the study: up to 12 patients in the safety run-
in portion and approximately 34 patients in the randomized portion. 
The total number of patients in each treatment arm will be as follows: 
a. Approximately 20 patients (10 NSCLC + 10 RCC) in the control arm (PULSAR-ICI) 
b. Approximately 20 patients (10 NSCLC + 10 RCC) in the experimental arm 
(PULSAR-ICI + IMSA101), including 14 randomized patients and 6 patients in the 
safety run-in who are treated at the dose level selected for the experimental arm 
Estimated Study Duration:  
The estimated total duration of the study will be approximately 3 years.  
Stopping Criteria: 
In the safety run-in period for the experimental arm, a DLT will be defined as the 
occurrence of any of the following hematologic or non-hematologic events that are 
considered at least possibly related to IMSA101 in the first 28 days (first cycle) of 
treatment. The severity of AEs will be graded according to CTCAE Version 5.0.  
Hematologic AEs 
• ≥ Grade 4 neutropenia lasting for > 7 days 
• Febrile neutropenia (defined as ANC < 1000/mm3 with a single temperature of 38.3ºC 
[101°F] or a sustained temperature of 38ºC [100.4°F] for > 1 hr) 
• ≥ Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with Grade ≥ 2 
bleeding 
• ≥ Grade 4 anemia 
 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
Page 11 
Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
Non-hematologic AEs:  
• Elevation of ALT or AST by ≥ 3 × ULN with concurrent elevation of serum total 
bilirubin ≥ 2 × ULN 
• Any ≥ Grade 3 non-hematologic AE of any duration will be considered a DLT with the 
following exceptions: 
- 
Nausea/vomiting/diarrhea: 
◦ 
≥ Grade 3 nausea/vomiting/diarrhea must be refractory to supportive care and 
last > 3 days to be considered a DLT 
◦ 
≥ Grade 3 nausea/vomiting/diarrhea that lasts ≤ 3 days is not a DLT 
- 
Fatigue: 
◦ 
≥ Grade 3 fatigue must last > 7 days to be considered a DLT 
◦ 
≥ Grade 3 fatigue that lasts ≤ 7 days is not a DLT  
 

IMSA101 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)                 Confidential 
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Sponsor: 
ImmuneSensor Therapeutics 
Investigational Product: 
IMSA101 
Developmental Phase: 
Phase 2 
Determination of Sample Size: 
The primary evaluation for efficacy is based on the proportion of patients remaining 
progression-free at 18 months after the start of the study treatment. The study is designed 
to enroll 40 patients. If the proportions of patients remaining progression-free at 18 months 
after commencement of therapy is assumed to be 20% in the control arm and 40% in the 
experimental arm, a total of 40 subjects (20 subjects per group) will provide 55% power, 
assuming a two-sided hypothesis test with a significance level of 20%. 
Statistical Considerations: 
The primary efficacy analysis will be conducted on the ITT population, using the ITT 
principle. The number and proportion of subjects remaining progression-free at 18 months 
after the start of the study treatment will be descriptively summarized by treatment group 
and be compared using Fisher’s exact test with the type I error controlled at a two-sided 
significance level of 0.2. The null and alternative hypotheses regarding the proportion of 
subjects remaining progression-free at 18 months after the start of the study treatment can 
be phrased in terms of PE and PC for experimental arm and control arm, respectively: 
  H0: PE = PC versus H1: PE ≠ PC  
If a patient withdraws from the study before disease progression or death, and the disease 
progression status at 18 month is missing, this patient will be treated as PD. 
In addition, for the descriptive purpose, the point estimate of proportion of subjects 
remaining progression-free at 18 months after the start of the study treatment and its 95% 
Clopper-Pearson confidence interval (CI) will be provided for each treatment group. 
The ORR via RECIST Version 1.1 and iRECIST will be presented with exact 2-sided 95% 
CIs using the Clopper-Pearson method. The TTP, PFS, and DOR will be estimated using 
Kaplan-Meier methods. Median event times and two-sided 95% CI for each median will 
be provided based on the Brookmeyer-Crowley method. AEs and QoL parameters will be 
described using descriptive summary statistics. 
A futility analysis for the experimental arm is planned when the tenth (10th) patient treated 
at the selected dose level has had the opportunity to reach 6 months. If 7 out of 10 patients 
have progressed or died, the study will be declared futile. 
Additional details describing the statistical analysis will be described in the Statistical 
Analysis Plan (SAP). 

IMSA101 
 
ImmuneSensor Therapeutics 
Clinical Study Protocol: IMSA101-102 
 
 
 
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Table 1 
Schedule of Assessments and Study Activities 
Procedures 
Screening1 
Days –30 to 1 
Cycle 12 
(28 days) 
Cycles 2 & 32 
(28 days) 
Cycle ≥ X18 
EOS3 
Study Day 
Day 1-2 
Day 8 
Day 15 
Day 1 
 
 
Informed Consent 
X  
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Medical History4  
X 
 
 
 
 
 
 
Concomitant Medications  
X 
X16 
X 
X 
X 
X18 
X 
Demographic data 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
Vital signs, Weight  
X 
X16 
X 
X 
X 
X18 
X 
Physical Examination5 
X 
 
 
 
 
 
X 
ECOG Performance Status  
X 
X16 
X 
X 
X 
X18 
X 
ECG6 
X 
 
 
 
  
 
X 
Hematology7 
X 
 
X 
X 
X 
X18 
X 
Coagulation7 
X 
 
 
 
 
 
 
Chemistry7 
X 
 
X 
X 
X 
X18 
X 
Thyroid function panel7 
X 
 
 
 
X17 
X17 
X17 
Urinalysis7 
X 
 
 
 
 
 
 
Pregnancy test8 
X 
 
 
 
 
 
X 
Tumor assessment using RECIST 
Version 1.1 and iRECIST9 
X 
 
 
 
X9 
X (Q8W) 
X 
PULSAR Administration10, 13 
 
X 
 
 
X 
 
 
IMSA101 Administration11, 13 
 
X 
X 
X 
X 
 
 
ICI Administration12, 13, 17 
 
X13 
 
 
X12 
X12 
 
QoL Assessment (FACT-G)14 
X 
 
 
 
X 
X (Q8W) 
X 
Assessment for AEs15 
 
X 
X 
X 
X 
X18 
X 
Abbreviations: AE: adverse event; C: cycle; CRF: case report form; D: day; ECG: electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOS: end of 
study; FACT-G: Functional Assessment of Cancer Therapy – General; Gy: Gray; hr: hour; ICI: Immune Checkpoint Inhibitor; iRECIST: immune-based 
Response Evaluation Criteria in Solid Tumors PD: pharmacodynamics; PULSAR: personalized ultra-fractionated stereotactic adaptive radiotherapy; QXW: 
every X weeks; QoL: Quality of Life; RECIST: Response Evaluation Criteria in Solid Tumors. 

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Clinical Study Protocol: IMSA101-102 
 
 
 
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1 
All assessments and tests at the screening visit must be completed before the patients start receiving the study treatment. 
2 
A ± 3 days visit window is allowed for each visit in Cycles 1, 2, and 3 except for those assessments outlined below in footnotes 11, 12 and 13. A ±3 day 
window is allowed for Cycles 2 and 3 start date. 
3 
All patients will receive study treatment until the occurrence of disease progression (by iRECIST), death, or other unacceptable treatment-related toxicity, or 
until the study is closed by the sponsor. Before discontinuing the study, patients should make all efforts to return to the study site at the EOS visit for the 
final assessments. 
4 
Full medical history at screening. 
5 
Full physical examinations will be done at screening and EOS visit only; clinically relevant findings made after the start of study treatment, which meet the 
definition of an AE, must be recorded on the AE page of the eCRF. 
6 
ECGs will be performed at screening and at EOS visit only, or at visits where the investigator believes the assessment is indicated. 
7 
Clinical laboratory analyses will be performed by local laboratory and include hematology, coagulation, serum chemistry, thyroid function panel, and 
urinalysis. Creatinine clearance will be measured at screening. Laboratory tests at screening must be performed < 96 hr prior to C1D1. Refer to Section 6.4.5 
for details.  
8 
If the patient is a woman of childbearing potential, a serum pregnancy test must be performed at screening and at EOS.  
9 
All tumor assessment findings will be evaluated according to RECIST Version 1.1 (Appendix 13.2) and iRECIST (Appendix 13.3).  
Tumor assessments will include radiographic assessments at screening, prior to the end (≤ 7 days) of Cycle 3, and thereafter every 8 weeks (Q8W) 
(± 7 days). 
In certain circumstances, a patient experiencing RECIST progression of disease will be allowed to continue therapy on study unless confirmed progression 
by iRECIST. 
10 
PULSAR will be administered at a dose of 12-15.5 Gy on Day 1 of Cycles 1, 2 and 3 as outlined in Section 8.1. A simulation visit may be performed prior to 
each PULSAR treatment, as appropriate. 
11 
For patients randomized to the experimental arm to receive IMSA101, IMSA101 will be administered by intra-tumoral injection on Days 1 (+1 day), 8 and 
15 of Cycle 1 (ie, weekly dosing in the first 3 weeks of the 28-day/4-week cycle), and on Day 1 (+ 1 day) of Cycles 2 and 3. For Cycle 1 Day 8 and Cycle 1 
Day 15, IMSA101 doses should be administered no less than 4 days apart. 
12 
ICI (pembrolizumab or nivolumab) will be administered on Cycle 1 Day 2 (+ 1 day), and thereafter according to the product labels(nivolumab Q2W or 
Q4W, pembrolizumab Q3W or Q6W treatment schedule). 
13 
Treatment order is PULSAR first, followed by IMSA101, and then followed by ICI on applicable visits. PULSAR will be administered first on Day 1 of 
Cycles 1, 2, and 3, followed by IMSA101 on the same day or the day after. The initial ICI dose will be administered on the same day as IMSA101 or the day 
after (C1D2 [+ 1 day]), and then dosing will be according to the product labels thereafter. 
14 
FACT-G QoL assessment to be completed using FACT-G questionnaire at screening, prior to the end (≤7 days) of Cycle 3, then every 8 weeks thereafter 
(± 7 days). 
15 
AE reporting begins from the start of study treatment and continues until EOS. 
16 
C1D1 assessments prior to dosing must be performed within 96 hr prior to C1D1. 
17 
C3D1 only, and as clinically indicated for the remainder of the study. 

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18 
After Cycle 3, from Cycle X onwards, ICI will continue to be administered per product labels. The cycle duration will depend on the ICI regimen which will 
follow the product labels. Vital signs, laboratory, ECOG, concomitant medication, and AE assessments are to be completed at the ICI treatment time points. 

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Clinical Study Protocol: IMSA101-102 
 
 
 
 
 
 
Protocol Amendment 3, Version 5.0 (19-OCT-2023)               Confidential 
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TABLE OF CONTENTS 
PROTOCOL SYNOPSIS ..........................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS ..............................................................22 
1 INTRODUCTION .............................................................................................................26 
1.1 
Background ............................................................................................................26 
1.2 
Study Drug – IMSA101 .........................................................................................28 
1.3 
Nonclinical Studies ................................................................................................29 
1.4 
Clinical Experience ................................................................................................31 
1.5 
Summary of Known Risks and Benefits ................................................................32 
1.6 
Rationale for the Study ..........................................................................................35 
2 STUDY OBJECTIVES AND ENDPOINTS .....................................................................36 
3 STUDY DESIGN...............................................................................................................38 
3.1 
Study Design Overview .........................................................................................38 
3.2 
Scientific Rationale for Study Design....................................................................42 
3.3 
DLT Definitions .....................................................................................................43 
3.4 
Safety Review Committee .....................................................................................44 
3.5 
Blinding and Randomization .................................................................................44 
3.6 
Definition of Treatment Cycle and End of Study ..................................................45 
4 SELECTION OF PATIENTS ............................................................................................46 
4.1 
Number of Patients ................................................................................................46 
4.2 
Inclusion Criteria ...................................................................................................46 
4.3 
Exclusion Criteria ..................................................................................................47 
4.4 
Patients of Reproductive Potential .........................................................................48 
5 STUDY PROCEDURES AND SCHEDULE ....................................................................49 
5.1 
Description of Study Days and Study Treatments .................................................49 
5.1.1 
Screening/Baseline (Day -30 to Day 1) .....................................................49 
5.1.2 
Cycle 1 Day 1 (± 0 Day) ............................................................................50 
5.1.3 
Cycle 1 Day 2 (+ 1 Day) ............................................................................50 
5.1.4 
Cycle 1 Day 8 (± 3 Days) ..........................................................................50 
5.1.5 
Cycle 1 Day 15 (± 3 Days) ........................................................................51 
5.1.6 
Cycle 2 Day 1 / Cycle 3 Day 1 (± 3 Days) ................................................51 
5.1.7 
Cycle X and All Subsequent Cycles ..........................................................52 
5.1.8 
End of Study (EOS) Visit ..........................................................................52 
5.1.9 
Unscheduled Visits ....................................................................................53 
5.2 
Restrictions, Precautions, and Potential Adverse Effects ................................53 

IMSA101 
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6 METHODS OF ASSESSMENTS AND ENDPOINTS ....................................................55 
6.1 
Medical History .....................................................................................................55 
6.2 
Concomitant Medications ......................................................................................55 
6.3 
Demographic Data .................................................................................................55 
6.4 
Safety Assessments ................................................................................................55 
6.4.1 
Vital Signs ..................................................................................................55 
6.4.2 
Physical Examination.................................................................................56 
6.4.3 
ECOG Assessment .....................................................................................56 
6.4.4 
Electrocardiogram ......................................................................................56 
6.4.5 
Clinical Laboratory Evaluations ................................................................56 
6.4.6 
Pregnancy Test ...........................................................................................57 
6.4.7 
Adverse Events and Toxicities...................................................................57 
6.5 
Tumor Assessments ...............................................................................................57 
6.6 
Quality of Life Assessment ....................................................................................58 
7 DISCONTINUATION CRITERIA ...................................................................................59 
7.1 
Discontinuation of Study Treatment ......................................................................59 
7.1.1 
Temporary Discontinuation of Study Treatment .......................................59 
7.2 
Patient Withdrawal from the Study........................................................................59 
7.3 
Early Discontinuation of the Study ........................................................................60 
8 TREATMENT ...................................................................................................................62 
8.1 
Administration of PULSAR ...................................................................................62 
8.1.1 
Prescription Dose and Interval ...................................................................62 
8.1.2 
Treatment Concerns and Concurrent Medications ....................................62 
8.1.3 
Technical Factors and Considerations .......................................................63 
8.1.4 
Simulation and Image Guidance ................................................................63 
8.1.5 
Treatment Planning and Target Volumes ..................................................64 
8.1.6 
Dosimetry ...................................................................................................65 
8.1.7 
Normal Tissue Dose Constraints ...............................................................66 
8.2 
Dosing and Administration of IMSA101 ...............................................................67 
8.2.1 
Preparation of IMSA101 ............................................................................68 
8.2.2 
Administration of IMSA101 ......................................................................68 
8.2.3 
Storage of IMSA101 ..................................................................................69 
8.3 
Administration of ICI Drug ...................................................................................69 
8.4 
Rescue Medications and Concomitant Treatments ................................................69 
8.4.1 
COVID-19 Vaccination .............................................................................70 
8.5 
Treatment Compliance ...........................................................................................70 

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9 ADVERSE EVENTS .........................................................................................................72 
9.1 
Definitions..............................................................................................................72 
9.1.1 
Adverse Event ............................................................................................72 
9.1.2 
Serious Adverse Events .............................................................................72 
9.1.3 
Adverse Event by Severity or Intensity .....................................................73 
9.1.4 
Relationship between Adverse Events and Study Treatment ....................73 
9.1.5 
Adverse Event Follow-up ..........................................................................74 
9.1.6 
Dosing Errors .............................................................................................75 
9.1.7 
Pregnancies ................................................................................................75 
9.2 
Serious Adverse Event Reporting ..........................................................................75 
9.2.1 
Reporting Requirements ............................................................................75 
10 STATISTICAL METHODS ..............................................................................................77 
10.1 
Analysis Datasets ...................................................................................................77 
10.2 
DETERMINATION OF SAMPLE SIZE ..............................................................78 
10.3 
Data Presentation ...................................................................................................78 
10.3.1 
General Considerations ..............................................................................78 
10.3.2 
Disposition of Patients ...............................................................................79 
10.3.3 
Demographic and Baseline Characteristics ...............................................79 
10.3.4 
Prior and Concomitant Medications ..........................................................79 
10.3.5 
Safety Data .................................................................................................79 
10.3.6 
Primary Efficacy Data................................................................................80 
10.3.7 
Secondary Efficacy Data............................................................................81 
10.3.8 
Quality of Life Data ...................................................................................81 
10.3.9 
Missing Data ..............................................................................................81 
10.3.10 
Futility Analysis .........................................................................................82 
10.4 
Changes in the Conduct of the Study or Planned Analysis ...................................82 
11 REGULATORY, ETHICAL AND LEGAL OBLIGATIONS ..........................................83 
11.1 
Declaration of Helsinki ..........................................................................................83 
11.2 
Good Clinical Practice ...........................................................................................83 
11.3 
Institutional Review Boards/Ethics Committees ...................................................83 
11.4 
Regulatory Authority Approval .............................................................................83 
11.5 
Informed Consent...................................................................................................83 
11.6 
Patient Confidentiality and Disclosure ..................................................................84 
11.7 
Protocol Amendment .............................................................................................84 
11.8 
Collection, Monitoring and Auditing Study Documentation .................................85 
11.8.1 
Data Collection ..........................................................................................85 

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11.8.2 
Study Monitoring .......................................................................................86 
11.8.3 
Auditing of Study Documentation .............................................................86 
11.9 
Record Retention ...................................................................................................86 
11.10 Disclosure of Information ......................................................................................87 
11.11 Discontinuation of the Study .................................................................................87 
11.12 Study Report, Publication Policy and Archiving of Study Documentation ...........87 
11.12.1 
Data Capture ..............................................................................................87 
11.12.2 
Study Documents .......................................................................................88 
11.12.3 
Archiving of Documents ............................................................................88 
12 REFERENCES ..................................................................................................................89 
13 APPENDICES ...................................................................................................................93 
13.1 
Eastern Cooperative Oncology Group (ECOG) Performance Scale .....................93 
13.2 
RECIST Version 1.1 Guideline .............................................................................94 
13.3 
Immune-Based RECIST (iRECIST) Guideline .....................................................97 
13.4 
Creatinine Clearance ............................................................................................100 
13.5 
Contact List ..........................................................................................................101 

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LIST OF IN-TEXT FIGURES 
Figure 1 
The cGAS-cGAMP-STING Pathway ...........................................................28 
Figure 2 
Chemical Structure of IMSA101 for Injection .............................................29 
Figure 3 
Study Schema of Protocol IMSA101-102 ....................................................41 
Figure 4 
Safety Run-In for the Experimental Arm .....................................................42 
 

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LIST OF IN-TEXT TABLES 
Table 1 
Schedule of Assessments and Study Activities ............................................13 
Table 2 
Composition of IMSA101 for Injection........................................................67 
Table 3 
Definitions of Adverse Events Severity........................................................73 
Table 4 
Guidelines for Determining the Relationship (if any) Between Adverse 
Event and the Study Treatment .....................................................................74 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
3D 
three-dimensional 
AE 
adverse event 
ALT 
alanine aminotransferase  
AMP 
adenosine monophosphate 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase  
AUC0-inf 
area under the plasma concentration-time curve from time zero to infinity 
AUC0-t 
area under the plasma concentration-time curve from time zero to time t 
C1D1 
Cycle 1 Day 1 
CBC 
complete blood count 
CCL2 
chemokine (C-C motif) ligand 2 
CD 
cluster of differentiation 
CDN 
cyclic dinucleotide 
CFR 
Code of Federal Regulations 
cGAMP 
cyclic-GMP-AMP 
cGAS 
cyclic GMP-AMP synthase 
CI 
confidence interval 
cm 
centimeter 
CNS 
central nervous system 
COMPTV 
center of mass of Planning Treatment Volume 
COVID-19 
coronavirus disease 2019 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DC 
Dendritic cells 
DLT 
dose limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of treatment response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDTA 
ethylenediaminetetraacetic acid 
EOS 
End of Study 
FACT-G 
Functional Assessment of Cancer Therapy - General 
FDA 
Food and Drug Administration 

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Abbreviation 
Definition 
GCP 
Good Clinical Practice 
GMP 
guanosine monophosphate 
GTV 
Gross Tumor Volume 
Gy 
Gray 
HIPAA 
Health Insurance Portability and Accountability Act 
hr 
hour 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use  
ICI 
immune checkpoint inhibitor 
IEC 
Institutional Ethics Committee 
IFN 
interferon 
IO 
immuno-oncology 
IL 
interleukin 
IMRT 
Intensity Modulated Radiation Therapy 
INR 
international normalization ratio 
IP-10 
interferon-γ-induced protein 10 
irAE 
immune-related adverse event 
IRB 
Institutional Review Board 
iRECIST 
Immune-based Response Evaluation Criteria in Solid Tumors 
ITT 
Intention-to-Treat 
IUD 
intrauterine device 
kg 
kilogram 
kV 
kilovolt 
LC-MS/MS 
liquid chromatography–tandem mass spectrometry 
MCP-1 
monocyte chemoattractant protein 1 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOA 
mechanism of action 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MV 
megavoltage 
NHP 
non-human primate 
NSCLC 
non-small cell lung cancer 
ORR 
overall response rate 
OS 
overall survival 

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Abbreviation 
Definition 
PD 
pharmacodynamics 
PD-1 
programmed cell death 1 
PDF 
portable document format 
PD-L1 
programmed cell death ligand 1 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PTV 
Planning Treatment Volume 
PULSAR 
Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy 
QoL 
quality of life 
QTc 
corrected QT 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors  
RP2D 
recommended Phase 2 dose 
RT 
radiation therapy 
SAbR 
stereotactic ablative radiotherapy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SmPC 
Summary of Product Characteristics 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
STING 
stimulator of interferon genes 
SUSAR 
suspected unexpected serious adverse reaction 
T3 
tri-iodothyronine 
T4 
thyroxine 
TEAE 
treatment-emergent adverse event 
TILs 
tumor-infiltrating leukocytes 
TNF-α 
tumor necrosis factor-α 
TRAE 
treatment-related adverse event 
TSH 
thyroid-stimulating hormone 
TTP 
time-to-progression 
ULN 
upper limit of normal 
US 
United States 
USP 
United States Pharmacopeia 

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Abbreviation 
Definition 
WBC 
white blood cell 
WMA 
World Medical Association 

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1 
INTRODUCTION 
1.1 
BACKGROUND 
The treatment of advanced solid tumor malignancies as well as many hematologic 
malignancies continues to be defined by high unmet medical need. In most settings, 
treatments with cytotoxic chemotherapy and targeted kinase inhibitors lead to the emergence 
of drug-resistant tumor clones and subsequent tumor progression and metastasis. 
The principle of oligometastases was initially described in 1995 by Hellman and 
Weichselbaum placing cancer in an intermediate state between the localized early stage and 
the advanced metastatic stage. Lung cancer is one of the most common cancer types 
worldwide with non-small cell lung cancer (NSCLC) being the most frequently diagnosed 
subtype (Chen et al., 2022). Of the patients diagnosed with NSCLC, nearly 60% present with 
metastatic disease, while 45% of patients will ultimately develop distant metastases after 
initially presenting with localized disease. This makes NSCLC a prime disease for aggressive 
intervention (Tumati and Iyengar, 2018). A uniform definition of synchronous 
oligometastatic NSCLC does not exist. However, depending on the inclusion criteria used, 
approximately 7–50% of patients with NSCLC are categorized as presenting with 
oligometastases (Chen et al., 2022). 
Renal cell carcinoma (RCC) is the most common type of renal cancer. It accounts for 3% of 
all adult cancers and over 90% of kidney cancers. The primary treatment for early stage RCC 
is surgery. However, even with complete surgical resection and local therapy, approximately 
25% of patients may eventually develop distant metastases. Of these, only 2-20% of patients 
suffering from metastases go on to experience prolonged survival (Spyropoulou et al., 2021). 
In recent years, notable treatment success has been achieved through alternate approaches 
oriented around activation of immune-mediated tumor destruction. Immuno-oncology (IO) 
approaches, including antibodies against checkpoint proteins, have shown remarkable 
efficacy in several types of human cancers. However, existing cancer immunotherapy 
through immune checkpoint blockade is effective for only a small fraction (on average 20-
30%) of cancer patients. The patients who are refractory to immune checkpoint blockade 
often have tumors that are not inflamed, or so-called “cold” tumor cells, ie, they lack tumor-
infiltrating leukocytes (TILs), such as cluster of differentiation 8 (CD8) T cells or the tumor 
microenvironment suppresses the functions of the TILs. A major thrust of ongoing cancer 
drug development research remains focused on transforming “cold” tumor cells into “hot” 
tumor cells in order to achieve better tumor control across a wider array of patients 
(Bonaventura et al., 2019; Liu and Sun, 2021). 
Radiation therapy (RT) aims to increase tumor control while sparing healthy tissue. RT 
induces tumor-cell killing by creating deoxyribonucleic acid (DNA) lesions and it also 
induces an anti-tumor immune response by enhancing the immunogenicity of tumors and 
stimulating the accumulation and activation of CD8+ T cells. RT is able to enhance the 
immunogenicity of tumors by activating the immune system when combined with immune 
checkpoint inhibitors (ICIs). Studies combining RT with ICIs suggest a synergistic potential 
of this strategy (Boustani et al., 2021). Stereotactic ablative radiotherapy (SAbR), also known 

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as stereotactic body RT, is a modern high focus radiation technique that delivers high doses 
of radiation to small tumor targets while conforming the dose to the target tissue. Advanced 
disease progression most often occurs in original sites of disease. Early intervention with 
SAbR at the localized disease potentially improved progression-free survival (PFS) and 
overall survival (OS) compared with maintenance chemotherapy alone (Iyengar et al., 2018). 
SAbR is thought to induce a pro-immunogenic response in the tumor microenvironment and 
has the capacity to potentially turn a “cold” unresponsive tumor “hot” and receptive to 
further ICI treatment (Akanda et al., 2021). 
Studies delivering SAbR concurrently with immunotherapies have commonly shown good 
toxicity profiles. A pooled analysis of a Phase 1 and 2 trials examining single site 
SAbR + pembrolizumab vs. pembrolizumab alone demonstrated OS benefit with 
SAbR + pembrolizumab. Bauml et al. published the results from a Phase 2, single arm study 
where 45 patients with oligometastatic NSCLC (defined as less than 5 metastases) were 
previously treated with SAbR, surgical resection, chemoradiation, or radiofrequency ablation 
received pembrolizumab. This treatment with SAbR followed by ICI treatment resulted in a 
statistically significant increase in PFS to 19 months, compared to historical controls of 
6.6 months (Bauml et al., 2019). Combination therapy has been shown to be no more toxic 
than ICI monotherapy in metastatic NSCLC according to retrospective analysis and limited 
published prospective trials (Akanda et al., 2021). RCC has historically been considered 
radioresistant. However, the introduction of modern dose-escalated radiotherapy using SAbR 
has increased the utilization of radiotherapy for the treatment of RCC. A recent Phase 1/2 
clinical trial (RAPPORT) showed that the combination of SAbR and immunotherapy with 
pembrolizumab in patients with oligometastatic clear cell RCC was safe, locally effective, 
and had durable anti-tumor activity with encouraging PFS (Siva et al., 2022). 
RT (including SAbR) has been a “one-size” therapy based mostly on histology, stage, and 
tumor location. RT is historically delivered in a single course without interruption. “Booster 
cycles” are commonly used in conventional vaccines to generate long-term memory and 
immunity. The use of pulsed-RT involving repeated RT cycles has the potential to build on 
the concept of “booster cycles” by generating tumor-associated antigens with each treatment 
cycle to build cellular and humoral memory leading to the production of long-lived immune 
memory cells, which could be amplified by the addition of immunotherapy (He et al., 2021).  
Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy (PULSAR) is a variation 
of stereotactic radiotherapy with longer, infrequent intervals between treatment fractions 
compared to daily fractions in the conventional schedules. This method activates the immune 
system but avoid the potentially immunosuppressive effect from SAbR. The advantages of 
PULSAR include: 1) the interval between each pulse can be irregular, episodic, or triggered, 
depending on the response profile for each individual patient and can elicit additional tumor 
kill as well as an in situ vaccination booster, which, in combination with systemic 
immunotherapy, can synergize and improve disease control; 2) each radiotherapy pulse can 
be adapted in real time, depending on changes with the patient and disease status (eg, 
anatomy, tumor microenvironment, systemic markers, patient status); 3) radiotherapy can be 
continued as needed until the tumor is eradicated or becomes a chronic, manageable disease. 

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The innate immune system, which is the first line of defense against pathogens and cancer 
cells, is important for turning the non-inflamed tumors (“cold”) into an inflamed (“hot”) 
microenvironment. A recently discovered innate immunity pathway, the Cyclic Guanosine 
monophosphate (GMP)-Adenosine monophosphate (AMP) Synthase (cGAS)-Stimulator of 
Interferon Genes (STING) pathway plays a critical role in anti-tumor immunity. cGAS is a 
DNA sensing enzyme that activates the type 1 interferon (IFN) pathway. Upon binding 
DNA, cGAS is activated to synthesize 2’3’ cyclic-GMP-AMP (2’3’-cGAMP), which then 
functions as a secondary messenger that binds to and activates the adaptor protein STING. 
STING then activates a signal transduction cascade leading to the production of type 1 IFNs, 
cytokines, and other immune mediators, which are essential for mounting immune response 
to invading microbials, as well as malignancies (Figure 1). There is increasing evidence that 
the cGAS pathway is essential for generating anti-tumor immunity (Bose, 2017; Wang et al., 
2017). 
Figure 1 
The cGAS-cGAMP-STING Pathway  
Cytosolic DNA binds to and activates the enzyme cGAS, which then catalyzes the synthesis of 
cGAMP. cGAMP functions as a second messenger that binds to and activates the endoplasmic 
reticulum membrane protein STING, which in turn leads to the production of type 1 IFNs and 
other immune stimulatory molecules. IMSA101 is an analogue of cGAMP and directly 
stimulates STING. 
As expected, surviving tumor cells develop mechanisms to antagonize host immunity. For 
example, high expression of immune checkpoint molecules such as programmed cell death 
ligand 1 (PD-L1) on their cell surface bind programmed cell death 1 (PD-1) on T cells to 
inhibit the latter’s function. PD-L1 inhibitor therapy can reverse the inhibition of anti-tumor 
immunity and restore T cell function. However, in patients with very low anti-tumor 
immunity, the PD-L1 inhibitor will have little benefit. Instead, a positive signal is needed to 
boost intrinsic immunity. Toward this end, the administration of cGAMP directly stimulates 
STING and jump-starts anti-tumor immunity. This activity has demonstrated encouraging 
therapeutic efficacy in several mouse syngeneic tumor models (Li et al., 2016; Wang et al., 
2017). 
1.2 
STUDY DRUG – IMSA101 
IMSA101 is a small molecule analogue of cGAMP. It contains  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
  Figure 2. 
 
 
 
 
 
  
 
 
 
 
 
 
 
  

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The toxicological evaluations of IMSA101 included studies in the rat and non-human primate 
(NHP). These species were chosen based on the conservation of the STING pathway 
(Harrington et al., 2018) and on the similar immune responses to IMSA101 noted in in vitro 
studies using mouse, rat, monkey and human cells. The general findings in these studies were 
related to the mechanism of action (MOA) of IMSA101 and can be categorized as 
inflammatory responses characterized by dose-related increases in STING pathway factors 
including type 1 IFNs and proinflammatory cytokines. The findings were similar in the rat 
and NHP. The most consistent dose-related findings were increases in IFN-α, tumor necrosis 
factor-α (TNF-α), and interleukin (IL)-6 in the rat and monkey; IL-8 in the rat; IL-1ra, IFN-γ-
inducible protein 10 (IP-10), and monocyte chemoattractant protein 1 (MCP-1) in the 
monkey. The cytokine levels showed increases in the first 3-6 hours (hr) with return to 
baseline in most cases by 6-24 hr. 
The evaluations of the PK, including the absorption, protein binding, and metabolic stability 
of IMSA101 in mouse, rat, and monkey were conducted. These studies are described in detail 
in the Investigator’s Brochure (IB) (Version 4.0, 2023). 
In summary, the PK parameters of IMSA101 were estimated following administration by 
intravenous, subcutaneous, or intra-tumoral routes in mice at doses of 0.1 or 0.5 mg/kg. 
IMSA101 concentrations in plasma were measured using a qualified liquid chromatography–
tandem mass spectrometry (LC-MS/MS) method. The calculated, dose corrected area under 
the plasma concentration-time curves from time zero to time t (AUC0-t) were similar by each 
route. When administered at the dose of 0.5 mg/kg, the area under the plasma concentration-
time curve from time zero to infinity (AUC0-inf) of the intravenous dose was 494 ng·hr/mL as 
compared to the AUC0-inf of 597 ng·hr/mL of the subcutaneous dose. The calculated 
bioavailability of the subcutaneous dose was 1.21. The AUC0-inf of the intra-tumoral dose 
was 360 ng·hr/mL as compared to the AUC0-inf of 312 ng·hr/mL of the subcutaneous dose. 
The calculated relative bioavailability of the intra-tumoral dose was 1.12. The calculated 
half-life was approximately 10-15 minutes. IMSA101 showed maximal absorption at the first 
sampling point of 15 minutes following administration. 
The observed comparability of the subcutaneous and intra-tumoral dose routes provided a 
rationale for using the subcutaneous route of administration in the toxicology studies to 
approximate the intra-tumoral route that will be used in the clinical studies. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of IMSA101 is 
provided in the IB (Version 4.0, 2023). 
In addition to the monotherapy data referenced above, there now exists a growing body of 
published pre-clinical research supporting the benefit of combining radiotherapy (RT) with 
immune checkpoint inhibitors (ICI) or STING agonists in the treatment of solid tumor 
malignacies. Combinations of RT with cGAMP, the endogenous STING agonist, appear to 
synergize to completely reverse tumor growth and lead to complete survival of tested animals 
in an MC38 colorectal tumor model. Observed efficacy further appears to depend on STING 
agonism in a proportional fashion. Other published studies demonstrate that with an MC38 
model, the combination of PD-L1 antibody and RT (in a PULSAR schedule) generates more 
robust and long-lasting anti-tumor response than IO alone. In addition to these published 

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studies, our internal ImmuneSensor data with IMSA101 + RT in a B16 melanoma tumor 
model demonstrate that, in contrast to either monotherapy agent alone, the combination of 
IMSA101 and RT not only reverses growth of directly treated tumors but also generates 
considerable abscopal effect at distal tumors.  
1.4 
CLINICAL EXPERIENCE 
Clinical trials of similar STING agonists are in progress. These include MIW815 from 
Novartis/Aduro Biotech (Aduro Biotech Inc., 2016) and MK-1454 from Merck (Merck Sharp 
& Dohme Corp., 2017). Early results of these studies demonstrate agonism of the STING 
pathway by cyclic dinucleotides (CDNs) similar to IMSA101. The dose-related findings are 
consistent with the findings seen in preclinical studies and related to the MOA of a CDN 
STING agonist. These desired pharmacological effects were achieved at dose levels without 
dose-limiting toxicities (Harrington et al., 2018; Meric-Bernstam et al., 2018). 
The STING agonist IMSA101 is currently being evaluated both as monotherapy and in 
combination with ICI in an ongoing, actively enrolling first-in-human Phase 1/2a clinical 
trial at six cancer centers in the United States (US) (Protocol number: IMSA101-101, 
NCT04020185). This trial is an open-label, dose escalation (Phase 1), and dose expansion 
(Phase 2a) study of patients receiving IMSA101 alone or in combination with an ICI with the 
primary objective to establish safe recommended Phase 2 doses (RP2Ds) of IMSA101. 
Patients older than 18 years old with histologically or cytologically documented locally 
advanced or metastatic solid tumor malignancies refractory to or otherwise ineligible for 
treatment with standard of care agents/regimens are enrolled. IMSA101 at 100, 200, 400, 
800, and 1200 mcg in 1 mL total volume are administered as monotherapy to the patients by 
intra-tumoral injection every week for 3 weeks in Cycle 1 (Days 1, 8, and 15) followed by 
every other week from Cycles 2 onwards (Days 1 and 15). For combination treatment 
regimen, IMSA101 up to 800, 1200, 2400, 3600, and 4800 mcg in 1 mL total 
volume + current ICI therapy administered according to the product label is administered to 
the patients by intra-tumoral injection. Dose priming was applied in Cycle 1 Day 1 (C1D1) 
for doses of 2400-4800 mcg.  
To date, IMSA101 has been studied as a single agent and in combination with PD-1 and 
PD-L1 inhibitors for solid tumors in NSCLC, breast cancer, prostate cancer, colorectal 
cancer, cecal adenocarcinoma, head and neck cancer, pancreatic cancer, melanoma, 
mesothelioma, triple-negative breast cancer, ampullary cancer, uveal melanoma, 
neuroendocrine pheochromocytoma paraganglioma, and renal cell carcinoma.  
Based on the preliminary safety results from the Phase 1/2a study, IMSA101 in the dose 
escalation monotherapy treatment was generally safe and well tolerated. The majority of 
patients (13 patients [86.7%]) reported at least 1 treatment-emergent adverse event (TEAE). 
The most frequently reported TEAEs by preferred term across all dose levels were fatigue 
(8 patients [53.3%]), injection site pain, hyponatremia, decreased appetite, dyspnea, 
headache, and lymphocyte count decreased (each in 3 patients [20%]). All other preferred 
terms were each reported by ≤ 2 patients (13.3%). Nine serious adverse events (SAEs) have 
been reported for 6 patients, of which 3 SAEs were fatal. None of the SAEs or deaths were 

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assessed by the investigator as related to IMSA101. A detailed description of the safety 
results of the ongoing IMSA101-101 study is provided in the IB (Version 4.0, 2023).  
In the combination treatment in the Phase 1/2a study, preliminary data demonstrate favorable 
tolerability through 1200 mcg. The majority of patients reported at least 1 TEAE. The most 
frequently reported TEAEs across all dose levels was injection site pain, fatigue, chills and 
weakness. One patient experienced a dose limiting toxicity (DLT) of Grade 3 immune 
arthropathy in the 1200 mcg cohort. The event was considered to be possibly related to 
IMSA101 and possibly related to the PD-1 immune checkpoint inhibitor pembrolizumab. Six 
SAEs have been reported for 5 patients, of which none were fatal. One SAE (Grade 3 
immune arthropathy) was considered possibly related to IMSA101. Dose escalation is 
continuing in the Phase 1/2a study.  
The final efficacy and PK data are not yet available for this study at the time of the 
development of this protocol. 
In summary, IMSA101 has been evaluated at dose levels up to 1200 mcg both as 
monotherapy and in combination with PD-1 targeted immune checkpoint inhibitors. 
1200 mcg (3/4 weeks followed by bi-weekly thereafter) was identified as the provisional 
monotherapy recommended Phase 2 dose (RP2D) based on cytokine/PD and PK data. Of 
note is that both Cmax and AUC levels, as well as cytokine levels in response to dosing, 
increased across the 5 evaluated dose levels in a dose proportional manner. Accordingly, PD-
1 combo dosing was commenced at 800 mcg. In combination dosing, IMSA101 has now 
been found to be safe and well-tolerated at both the 800 mcg and 1200 mcg dose levels with 
dose escalation continuing at this time. Based on a preliminary evaluation of cytokine 
responses at the initial two combo dose levels, these elevations in response to IMSA101-
mediated STING agonism appear to be comparable to those observed following 1200 mcg 
monotherapy, again consistent with the hypothesis of a dose-dependent response trend.  
Based on the totality of monotherapy and combination therapy data evaluated to-date, triplet 
dosing of IMSA101 administered in combination with both PD-1 checkpoint inhibitor 
therapy and pulsed radiotherapy will commence in a safety run-in to this Phase 2 randomized 
clinical trial at 800 mcg. Depending on the safety data observed, either 800 mcg or 1200 mcg 
will most likely be brought into the randomized component of this study. 
1.5 
SUMMARY OF KNOWN RISKS AND BENEFITS 
A more detailed description of anticipated risks associated with IMSA101 nonclinical studies 
and clinical trials evaluating other STING agonists is provided in Section 6.6 of the IB 
(Version 4.0, 2023).  
A summary of adverse events (AEs) based on preliminary safety results from the dose 
escalation monotherapy cohorts in the ongoing trial IMSA101-101 is provided in 
Section 5.3.2 of the IB (Version 4.0, 2023). 
Briefly, the following risks may reasonably be anticipated in clinical trials evaluating the 
study treatments (PULSAR, IMSA101, and ICI): 

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Potential Risk of 
Clinical Significance 
Summary of 
Data/Rationale for Risk 
Mitigation Strategy 
Study Treatment  
PULSAR 
Complications associated 
with SAbR may include 
radiation pneumonitis, 
brachial plexopathy, gastritis, 
toxicity in the chest wall, 
skin, airway, esophagus, and 
bowel (Lo et al., 2013; Siva 
et al., 2018). The risk of 
dosing error is rare.  
PULSAR will be performed by 
qualified and trained personnel only. 
A treatment plan with dose 
calculations will be applied 
individually. The organs will be 
contoured individually. Dose 
constraint guidelines used in prior 
national protocols are included in this 
study.  
IMSA101 
• Body temperature 
increases (fever) 
• Chills 
• Alterations in serum 
chemistries 
• Altered serum 
hematology 
parameters 
• Headache 
• Injection site pain 
• Vomiting 
• Fatigue 
• Myalgia 
• Diarrhea 
• Decreased appetite 
• Dyspnea 
• Arthropathy 
 
Based on nonclinical 
findings with IMSA101 and 
toxicity events reported in 
clinical trials evaluating 
other STING agonists (IB 
Section 6.6 “Anticipated 
Clinical Risks”) 
AE assessments will be performed 
throughout the study. 
Clinical laboratory assessments will 
be performed at the same frequency 
as the study treatment. 
ICI 
Potential severe or fatal 
immune-related adverse 
events (irAE), laboratory 
abnormalities, and other 
adverse reactions 
Some patients in this study 
will be treated with a 
combination of IMSA101 
and the ICIs nivolumab or 
pembrolizumab. ICIs are 
associated with a variety of 
irAEs which arise from 
general immunologic 
enhancement. These side 
Prompt recognition and management 
will be performed throughout the 
study. The irAEs are generally 
managed through interruption of the 
ICI and temporary 
immunosuppression with 
corticosteroids and other drugs. The 
prescribing information and specific 
risks associated with particular ICIs 

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Potential Risk of 
Clinical Significance 
Summary of 
Data/Rationale for Risk 
Mitigation Strategy 
effects can include skin, 
gastrointestinal, liver, 
endocrine/hormonal, and 
other less common 
inflammatory events. 
Although extremely rare, 
fulminant and even fatal side 
effects can occur with ICIs. 
used in this study will be discussed by 
investigators with their patients and 
referenced during informed consent. 
Study Procedures 
Blood draw for clinical 
laboratory tests 
The procedure of blood draw 
involves insertion of an 
intravenous needle. This may 
cause pain, tenderness, 
bruising, bleeding, dizziness, 
vasovagal response, syncope, 
and in rare occasion, 
infection at the site where the 
needle is inserted. 
Blood draw will be performed by 
appropriately trained and qualified 
personnel. 
Intralesional (cutaneous) 
or percutaneous injection 
Complications of 
intralesional injection may 
include hematoma, 
hemorrhage, infection, 
needle tract seeding, 
systemic air embolism, and 
pneumothorax (Gillams 
2005). 
Intralesional injections will be 
performed by appropriately trained 
and qualified personnel. All invasive 
procedures will be performed at the 
study site with medical treatment 
available promptly whenever 
necessary.  
 
Benefits to individual participants receiving IMSA101 may include: 
• Receive treatment which potentially has enhanced anti-tumor activity 
• Contribute to the process of developing a new treatment for patients with advanced 
cancer and with limited therapeutic options. 
• Access to medical assessments associated with study procedures (eg, laboratory 
evaluations, quality of life [QoL], disease progression) 
 
Taking into account the measures taken to minimize risk to patients participating in this 
study, the potential risks identified in association with IMSA101 are justified by the 
anticipated benefits that may be afforded to patients with oligometastatic disease from 
NSCLC or RCC. 

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1.6 
RATIONALE FOR THE STUDY 
The immune system plays a pivotal role in defending humans and animals against cancer. 
Cancer cells accumulate mutations encoding neoantigens that are recognizable by immune 
system. In addition, they are constantly under stresses that result from chromosomal 
abnormality, genomic DNA damage, and hyperproliferation, which promotes the detection of 
their neoantigens by immune system. However, under selective pressure, cancer cells 
develop mechanisms to evade immunosurveillance. For example, tumors are able to foster an 
immunosuppressive microenvironment by hijacking the immune checkpoint signaling. ICI 
therapy has made a rapid progress recently and shown remarkable efficacies in clinics. 
Despite great successes, ICI is only effective in treating approximately 20% of cancer 
patients. Therefore, novel therapies that can better harness the immune system and benefit 
the majority of cancer patients is in urgent need. 
The purpose of this study is to compare the safety and efficacy of a novel combination 
therapy PULSAR + ICI (pembrolizumab or nivolumab) administered with or without 
IMSA101 in patients with oligometastatic NSCLC or RCC. 
 
 

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Therapy – General (FACT-G) 
questionnaire (Version 4) 
 

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3 
STUDY DESIGN 
3.1 
STUDY DESIGN OVERVIEW 
This is an open-label, multicenter, Phase 2 randomized study comparing the safety and 
efficacy of PULSAR combined with ICI immunotherapy (PULSAR-ICI) + IMSA101 and 
PULSAR-ICI alone in patients with NSCLC or RCC. 
• For all potential patients, there will be up to a 30-day screening and eligibility assessment 
period prior to enrollment. 
• Pre-treatment screening radiographic tumor assessments will be collected within 30 days 
prior to the initial dose for all patients.  
• Patients shall be enrolled in 2 treatment arms as follows: 
a. Approximately 20 patients in the control arm (PULSAR-ICI alone) 
b. Approximately 20 patients in the experimental arm (PULSAR-ICI + IMSA101)  
• The study will start with a safety run-in portion for the experimental arm, followed by a 
randomized portion for both treatment arms. 
• Patients will be stratified by histology (NSCLC and RCC) in the randomized portion. 
• PULSAR-ICI with or without IMSA101 treatment will be administered to the patients in 
Cycles 1, 2, and 3, and thereafter only standard of care ICI monotherapy will be 
administered to all patients. Each treatment cycle will be 28 days in duration for 
Cycles 1, 2 and 3, then per standard of care monotherapy thereafter based on the product 
labels of the prescribed ICI. 
- 
Consistent with prior monotherapy and doublet therapy safety evaluations of 
IMSA101, the experimental arm (PULSAR-ICI + IMSA101) shall employ a 3+3 
safety run-in component as follows: The safety run-in will be conducted for the 
experimental arm prior to the randomization of patients to the 2 treatment arms. 
- 
Patients enrolled in the safety run-in period who are treated at the dose level selected 
for the experimental arm will be included in the total number of patients of the 
experimental arm. 
- 
Only two dose levels will be evaluated potentially: the previously identified selected 
Phase 2 dose of IMSA101 minus 1 dose level (800 mcg) and the previously identified 
selected Phase 2 dose of IMSA101 (1200 mcg). Dosing shall not continue beyond the 
latter dose. 
- 
3 initial patients shall be enrolled to evaluate the 800 mcg IMSA101 administered in 
combination with PULSAR-ICI. 
- 
If no dose limiting toxicities (DLTs) are observed among these initial 3 patients at the 
800 mcg dose level, the dose level of IMSA101 will be escalated for the following 
3 patients to 1200 mcg of IMSA101 administered in combination with PULSAR-ICI. 
- 
If a single DLT occurs among the initial 3 patients at an evaluated dose level, 
3 additional patients will be enrolled at the same dose level.  

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- 
If ≤ 1 DLT occurs among the 6 patients at an evaluated dose level, the dose level shall 
be considered appropriate, and dose escalation continues (up to but not beyond the 
previously identified selected Ph 2 dose of 1200 mcg). If this condition occurs at the 
1200 mcg level, subsequent patients will be enrolled at the 1200 mcg level. 
- 
If ≥ 2 DLTs occur among the initial 3 or 6 patients at an evaluated dose level, the 
dose level shall be considered unacceptably toxic and dose escalation will be 
discontinued.  
- 
If the 1200 mcg level is found to be unacceptably toxic, the IMSA101 dose will be 
de-escalated to the 800 mcg dose level.  
- 
If the 800 mcg dose level is found to be unacceptably toxic, additional dose levels of 
IMSA101 shall be considered and potentially recommended by a protocol 
amendment. 
- 
No fewer than 6 total patients shall be evaluated at a given dose level prior to 
confirmation of the dose level as the Combo selected Phase 2 dose.  
Definitions: 
◦ 
Combo selected Phase 2 dose: The Combo selected Phase 2 dose is defined as the 
dose (either at MTD or below MTD) used in combination with PULSAR-ICI that 
is selected for evaluation in the Phase 2 study. 
• For the experimental arm (PULSAR-ICI + IMSA101): 
- 
A single pre-defined lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) shall 
be injected throughout the study duration, if possible.  
- 
The lesion will be injected weekly for the first three weeks of Cycle 1 (Days 1, 8 and 
15) and then on Day 1 of Cycles 2 and 3. 
- 
Where the original injection site is considered by the investigator to become 
inaccessible, a second lesion/lesion site shall be selected as a replacement, and this 
shall be used henceforth so long as it is considered accessible. Subsequent injection 
sites shall be replaced when they are considered inaccessible. 
- 
Where no remaining accessible lesions are present and where benefit of IMSA101 
therapy is, in the opinion of the investigator, being derived by the patient, continued 
injections of IMSA101 into the vicinity of an inaccessible lesion or, in the case that a 
lesion can no longer be radiographically visualized, into the last known location of 
the non-visible lesion shall be recorded and allowed, if deemed reasonable by the 
investigator. 
- 
Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous 
injection only, including those lesions that are visible, palpable, or detectable by 
standard radiographic or ultrasound methods. Neither surgical procedures nor 
endoscopically guided injections including those to endobronchial, endoluminal, or 
endosinusoidal spaces shall be allowed. While no anatomic locations are required or 
disallowed, lesions selected for intra-tumoral injection must, in the opinion of the 
investigator, not be immediately adjacent to blood vasculature or other physiologic 
landmarks in such a way that will accrue undue safety risk to the patient.  

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• All patients will be followed throughout the study for drug tolerability and safety by 
collecting clinical and laboratory data, including AEs using Common Terminology 
Criteria for Adverse Events (CTCAE) Version 5.0 criteria, SAEs, concomitant 
medications, and vital signs. 
• A Safety Review Committee (SRC) will be organized to review the safety of the 
administered treatments (PULSAR, IMSA101, and ICI) during the study and in the safety 
run-in period to determine whether dose escalation of IMSA101 should proceed. 
• All patients will be assessed for anti-tumor efficacy at screening, prior to the end (≤ 7 
days) of Cycle 3, and at 8-week intervals (± 7 days) thereafter based on radiographic 
assessments and analysis of ORR, DOR, TTP, and PFS (all outcome measures per 
RECIST Version 1.1 and iRECIST). 
• Administration of pembrolizumab or nivolumab will follow the instructions in the 
product labels and scheduling for the products.  
• All patients will continue to receive their assigned treatment throughout the study until 
the occurrence of disease progression (based on iRECIST), death, or other unacceptable 
treatment-related toxicity, or until the study is closed by the sponsor. 
 
A study design schema is illustrated in Figure 3, and the safety run-in procedures for the 
experimental arm is illustrated in Figure 4. 
See Schedule of Assessments and Study Activities (Table 1) for details. 
 

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Figure 3 
Study Schema of Protocol IMSA101-102 
Abbreviations: DLT: dose limiting toxicity; ICI: immune checkpoint inhibitor; MTD: maximum tolerated dose; 
PULSAR: Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy 
* The patients enrolled in the safety run-in period who are treated at the dose level selected for the experimental 
arm will be included in the total number of patients of the experimental arm. 
Combo Selected Phase 2 dose = the highest dose level of IMSA101 at which no more than 1 out of 6 patients 
experiences a DLT during the first cycle (28 days) of therapy or the dose (either at MTD or below MTD) used 
in combination with PULSAR-ICI that is selected for evaluation in the Phase 2 study. 
 

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Figure 4 
Safety Run-In for the Experimental Arm 
Abbreviations: DLT: dose limiting toxicity; ICI: immune checkpoint inhibitor; PULSAR: Personalized Ultra-
fractionated Stereotactic Adaptive Radiotherapy 
* When DLTs are observed in ≥ 2 of the initial 3 or 6 patients at the Selected Phase 2 level (1200 mcg), the 
dose level will be de-escalated to the Selected Phase 2 dose level-1 (800 mcg). The Selected Phase 2 dose level-
1 level will then be selected for the experimental arm when DLTs are observed in no more than 1 of 6 patients 
at this dose level. 
** When DLTs are observed in no more than 1 of 6 patients at the Selected dose level, the dose level will be 
selected for the experimental arm.  
 
3.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The role of cGAS-cGAMP-STING pathway in anti-tumor immunity has been demonstrated 
by independent research groups, as well as ImmuneSensor’s own preclinical studies. When 
dying tumor cells are taken up and processed by dendritic cells (DCs), DNA from these 
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promote DC maturation and tumor antigen presentation to T cells. IFNs and cytokines 
produced by DCs and other innate immune cells cooperatively stimulate T cell infiltration 
and function, leading to cytotoxic killing of tumor cells. In multiple syngeneic tumor models, 
the combination of a PD-L1 antibody with IMSA101 showed higher efficacy as compared to 
IMSA101 alone at each dose level tested. The administration of IMSA101 restored 
responsiveness to PD-L1 antibody in several types of syngeneic tumors which were 
otherwise refractory to ICIs. These studies provide a rationale for evaluating combination 
therapy in clinical settings. 
For its part, RT has been used to treat approximately 50% of all cancer patients (Begg et al., 
2011). Recent advancements in technology allow precise deposition of radiation 
simultaneously to multiple tumors with minimal leakage to surrounding healthy tissues. In 
addition to directly causing tumor cell death, radiation induces anti-tumor immune responses 
through the following mechanisms: 1) radiation causes exposure of tumor neoantigen to host 
phagocytes such as DCs and macrophage; 2) leakage of genomic or mitochondrial DNA 
activates cGAS-STING pathway, predominantly in DCs, which produces IFNs and other 
cytokines to promote antigen presentation and T cell-mediated adaptive immunity against 
tumors. However, abscopal effect from RT is extremely rare, whereas relapse of even 
directly irradiated tumors is very common, likely because immune response induced by RT is 
very weak and RT also causes upregulation of PD-L1 and recruitment of immunosuppressive 
cells into tumor (Deng et al., 2014). This can be partially overcome by optimizing the RT 
dose schedule to favor immune response and/or combining with either a STING agonist, or 
ICI, both of which have been demonstrated in pre-clinical studies (Moore et al., 2021).  
There now exists extensive experience combining ICI with SAbR for the treatment of various 
advanced solid tumor malignancies (Belluomini et al., 2019; Ko and Formenti, 2018). This 
combination appears safe and effective and is emerging as a standard-of-care in the treatment 
of oligometastatic disease. Immune checkpoint blockade is hypothesized to benefit from pre-
established anti-tumor immune response and interest focuses on the immunomodulatory 
effects of RT to induce endogenous antigen-specific immune responses. In particular, 
PULSAR is being investigated as an optimal strategy for RT delivery. Furthermore, it is now 
hypothesized that cGAS-STING-mediated stimulation of the body’s innate immune system 
can enhance RT-ICI synergy through the bridging of RT DNA damaging capacity and ICI 
activation of CD8+ cytotoxic T cell-mediated tumor destruction (Kho et al., 2021; Yum et 
al., 2020).  
Based on these findings, this Phase 2 trial will combine PULSAR-integrated RT and ICI, 
administered with or without IMSA101 in patients with oligometastatic solid tumor 
malignancies. This is an open-label, randomized clinical trial in adult patients with 
oligometastatic NSCLC or RCC. The rationale of the IMSA101 repeated dosing regimen is 
supported by the nonclinical data and the clinical data collected so far (IB, Version 4.0, 
2023).  
3.3 
DLT DEFINITIONS 
In the safety run-in period for the experimental arm of PULSAR-ICI + IMSA101, a DLT will 
be defined as the occurrence of any of the following hematologic or non-hematologic events 

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that are considered at least possibly related to IMSA101 in the first 28 days (first cycle) of 
treatment. The severity of AEs will be graded according to CTCAE Version 5.0.  
Hematologic AEs 
• ≥ Grade 4 neutropenia lasting for > 7 days 
• Febrile neutropenia (defined as absolute neutrophil count [ANC] < 1000/mm3 with a 
single temperature of 38.3ºC [101°F] or a sustained temperature of 38ºC [100.4°F] for 
> 1 hr) 
• ≥ Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with Grade ≥ 2 
bleeding 
• ≥ Grade 4 anemia 
 
Non-hematologic AEs:  
• Elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) by 
≥ 3 times (×) upper limit of normal (ULN) with concurrent elevation of serum total 
bilirubin ≥ 2 × ULN 
• Any ≥ Grade 3 non-hematologic AE of any duration will be considered a DLT with the 
following exceptions: 
- 
Nausea/vomiting/diarrhea: 
◦ 
≥ Grade 3 nausea/vomiting/diarrhea must be refractory to supportive care and last 
> 3 days to be considered a DLT 
◦ 
≥ Grade 3 nausea/vomiting/diarrhea that lasts ≤ 3 days is not a DLT 
- 
Fatigue: 
◦ 
≥ Grade 3 fatigue must last > 7 days to be considered a DLT 
◦ 
≥ Grade 3 fatigue that lasts ≤ 7 days is not a DLT 
 
For the discontinuation criteria of the study, see Section 7. 
3.4 
SAFETY REVIEW COMMITTEE  
An independent SRC will be organized to review the safety of the administered treatments 
(PULSAR, IMSA101, and ICI) during the study. The SRC will be composed of principal 
investigators (and their representatives), medical monitor, and the sponsor representatives. In 
the safety run-in period for the experimental arm, the SRC will review all available safety 
data and determine whether to proceed with dose escalation of IMSA101 or a dose level 
should be invalidated. Meeting results will be documented, and formal notification of 
decisions will be provided to all patients.  
3.5 
BLINDING AND RANDOMIZATION 
This is an open-label randomized study. No blinding will be conducted. Patients will be 
randomized to the appropriate treatment based on a pre-defined randomization list. Patients 

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will be randomized to PULSAR-ICI alone or PULSAR-ICI + IMSA101 treatments. 
Randomized patients in the experimental arm will be capped at 14. Patients enrolled in the 
experimental arm for the safety run-in will not be randomized but the patients who are 
treated at the dose level selected for the experimental arm will be counted toward the 20 total 
patients (see Section 4.1). 
In the randomized portion, patients will be stratified by histology (NSCLC and RCC). 
3.6 
DEFINITION OF TREATMENT CYCLE AND END OF STUDY 
Each treatment cycle from Cycle 1 to Cycle 3 will consist of 4 weeks (28 days) in duration. 
Details are outlined in the Schedule of Assessments and Study Activities (Table 1). 
After Cycle 3, from Cycle X onwards (see Schedule of Assessments and Study Activities 
[Table 1]), study visits will be scheduled at the ICI treatment time points per product labels; 
the duration of each cycle will depend on the ICI regimen.  
Study treatment will be administered at all scheduled visits after screening (combination 
therapy from Cycle 1 to Cycle 3, monotherapy from Cycle X onwards) except the End of 
Study (EOS) visit. 
Patients will receive treatment in the study until documented disease progression based on 
iRECIST or unacceptable toxicity.  
The estimated total duration of the study will be approximately 3 years. End of study will be 
defined as the time point when all patients permanently discontinue the treatment in the study 
due to disease progression based on iRECIST, death, or other unacceptable toxicity, or when 
the study is closed by the sponsor. 
 
 
 

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4 
SELECTION OF PATIENTS 
4.1 
NUMBER OF PATIENTS 
Approximately 46 patients will be enrolled in the study. The sample sizes in the study are not 
based on statistical criteria or calculations.  
Up to 12 patients will be enrolled in the experimental arm for the safety run-in period. Any 
patients who discontinue the study before completing the first 28 days (first cycle) of 
treatment (before receiving all 3 doses of IMSA101, PULSAR, and ICI treatments) in the 
safety run-in for reasons other than DLT will be replaced. 
Upon completion of the safety run-in, approximately 34 patients shall be randomized to 
2 treatment arms as follows: 
• 
Approximately 20 patients (10 NSCLC + 10 RCC) in the control arm (PULSAR-ICI). 
• 
Approximately 14 patients in the experimental arm (PULSAR-ICI + IMSA101).  
(The total number of patients in the experimental arm will be 20 [10 NSCLC + 10 RCC] 
after including the 6 patients in the safety run-in who are treated at the dose level selected 
for this treatment arm.) 
 
4.2 
INCLUSION CRITERIA 
Patients meeting all of the following criteria will be considered for enrollment into the study. 
1. Male or female patients ≥ 18 years of age 
2. Signed informed consent and mental capability to understand the informed consent 
3. Histologically or cytologically documented NSCLC or RCC with radiographically 
documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of 
“oligometastatic” disease 
4. Patient’s disease must be evaluable per RECIST Version 1.1 
5. All metastatic lesions amenable to administration of radiotherapy, at the discretion of the 
investigator 
6. Must have at least one single pre-defined lesion/lesion site (longest diameter ≥ 10 mm 
and ≤ 50 mm) suitable for intra-tumoral injection  
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1 
8. Electrocardiogram (ECG) without evidence of clinically significant conduction 
abnormalities or active ischemia as determined by the investigator 
9. Acceptable organ and marrow function as defined below: 
• 
ANC > 1,500 cells/μL 
• 
Platelets > 50,000 cells/μL 
• 
Total bilirubin ≤ 1.5 × ULN 

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• 
AST/ALT ≤ 2.5 × ULN. If liver metastases are present, AST/ALT < 5 × ULN 
• 
Serum creatinine < 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min 
using the Cockcroft-Gault formula 
• 
Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN 
10. Women of child-bearing potential (defined as a female who has experienced menarche 
and who has not undergone successful surgical sterilization [hysterectomy, bilateral 
salpingectomy, or bilateral oophorectomy]) or is not postmenopausal (defined as 
amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the 
appropriate age, eg, greater than 45 years) must have a negative serum pregnancy test 
prior to first dose of study treatment 
11. Male and female patients with reproductive potential must agree to use two forms of 
highly effective contraception throughout the study 
4.3 
EXCLUSION CRITERIA 
Patients are excluded from the study if any of the following criteria is met: 
1. Prior disease progression through PD-L1 or PD-1-targeted immunotherapy 
2. Prior receipt of STING agonist 
3. Prior receipt of therapeutic radiotherapy to the lesions intended for PULSAR treatment 
4. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or < 5 half-
lives of the first dose of study treatment 
5. Existence of primary tumor that requires therapeutic treatment beyond the provided 
immune checkpoint inhibitor drug 
6. Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-
cancer therapy, as judged by the investigator 
7. Previous life-threatening (Grade 4) irAE 
8. Existence of actionable mutations that may be eligible for mutation-targeted drug that 
represents standard-of-care therapy 
9. Presence of brain metastases 
10. Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval > 470) 
11. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active 
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac 
arrhythmia, or psychiatric illness/social situations) that in opinion of the investigator 
would limit compliance with study requirements 
12. Women who are pregnant or breastfeeding 
13. Sponsor reserves right to exclude any patient from the study on basis of pre-study 
medical histories, physical examination findings, clinical laboratory results, prior 
medications, or other entrance criteria 
 

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4.4 
PATIENTS OF REPRODUCTIVE POTENTIAL 
Pregnancy and breastfeeding are exclusion criteria for this study. It is important that female 
patients and the female partners of male patients do not become pregnant during the study 
treatments with PULSAR, IMSA101, and ICI.  
Female patients of childbearing potential and male patients who are partners of women of 
childbearing potential must agree to use two forms of highly effective contraception during 
the study treatments. For IMSA101, highly effective contraception should be used at least 
until 30 days following the last dose of IMSA101. Refer to the product labels (for ICI) and 
the standard practice (for PULSAR) for the recommended period of contraception for other 
components of the study treatment. 
Highly effective contraception is defined as use of one or more methods that result in a low 
failure rate (ie, less than 1%). The following are examples of acceptable methods of 
contraception: oral, injected, or implanted hormonal methods, intrauterine devices (IUDs), 
condoms with spermicide product, vasectomy, or tubal ligation or occlusion.  
A woman of childbearing or reproductive potential is defined as any female who has 
experienced menarche and who has not undergone successful surgical sterilization 
(hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or is not postmenopausal 
(defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile 
at the appropriate age, eg, greater than 45 years). 
A serum pregnancy test for all female patients of childbearing potential will be performed 
during screening. A pregnancy test will also be carried out at the EOS visit. 
Female patients who become pregnant and male patients whose female partners become 
pregnant must report to the investigator and be removed from the study immediately. The 
investigator will record pregnancy information on the appropriate form and submit it to the 
sponsor within 24 hrs of learning of the pregnancy (for female participant or female partner 
of male participant [after obtaining the necessary signed informed consent from the female 
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5 
STUDY PROCEDURES AND SCHEDULE 
Study procedures and their timing are summarized in the Schedule of Assessments and Study 
Activities (Table 1). 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
Adherence to the study design requirements, including those specified in the Schedule of 
Assessments and Study Activities, is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 
all patients screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
5.1 
DESCRIPTION OF STUDY DAYS AND STUDY TREATMENTS 
5.1.1 
Screening/Baseline (Day -30 to Day 1) 
• Obtain written informed consent before the start of any study-specific procedures 
• Review inclusion and exclusion criteria 
• Complete medical history including cancer history and all previous cancer treatments 
• Record concomitant medications including start dates, indication, dose, and frequency 
• Record demographic data including year of birth, current age, age when informed consent 
is signed, gender, race, and smoking status 
• Measure and record height in centimeters (cm) and weight in kilogram (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Perform full physical examination 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Perform a 12-lead ECG 
• Collect blood samples for hematology tests (including coagulation parameters and 
complete blood count [CBC] with differential) within 96 hr prior to C1D1 
• Collect blood samples for complete serum chemistry tests and creatinine clearance (using 
the Cockcroft-Gault formula, Appendix 13.4) within 96 hr of C1D1 
• Collect blood sample for thyroid function panel within 96 hr of C1D1 
• Perform urinalysis within 96 hr of C1D1 
• Perform a serum pregnancy test for female patients of childbearing potential 

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• Perform tumor assessment according to RECIST Version 1.1 (Appendix 13.2) and 
iRECIST (Appendix 13.3) 
• Complete QoL assessment using FACT-G questionnaire 
 
5.1.2 
Cycle 1 Day 1 (± 0 Day) 
• Record concomitant medications taken since screening including start dates, indication, 
dose, and frequency within 96 hr prior to C1D1 
• Measure and record weight (kg) within 96 hr prior to C1D1 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) within 
96 hr prior to C1D1 
• Assess and record ECOG Performance Status within 96 hr prior to C1D1 
(Appendix 13.1) 
• Administer PULSAR treatment  
• Administer IMSA101 by intra-tumoral injection (for the experimental arm only) 
following PULSAR treatment on the same day or the day after 
• Assess and record AEs 
 
5.1.3 
Cycle 1 Day 2 (+ 1 Day) 
• Administer the first ICI treatment the day after PULSAR and IMSA101 treatments, and 
according to the product label thereafter 
 
5.1.4 
Cycle 1 Day 8 (± 3 Days) 
• Record concomitant medications taken since the last visit including start dates, 
indication, dose, and frequency 
• Measure and record weight (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Collect blood samples for hematology tests (coagulation parameters are not required) 
• Collect blood samples for complete serum chemistry tests 
• Administer IMSA101 by intra-tumoral injection (for the experimental arm only) 
For Cycle 1 Day 8 and Cycle 1 Day 15, IMSA101 doses should be administered no less 
than 4 days apart. 
• Assess and record AEs 
 

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5.1.5 
Cycle 1 Day 15 (± 3 Days) 
• Record concomitant medications taken since the last visit including start dates, 
indication, dose, and frequency 
• Measure and record weight (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Collect blood samples for hematology tests (coagulation parameters are not required) 
• Collect blood samples for serum chemistry tests 
• Administer IMSA101 by intra-tumoral injection (for the experimental arm only) 
For Cycle 1 Day 8 and Cycle 1 Day 15, IMSA101 doses should be administered no less 
than 4 days apart. 
• Assess and record AEs 
 
5.1.6 
Cycle 2 Day 1 / Cycle 3 Day 1 (± 3 Days) 
• Record concomitant medications taken since the last visit including start dates, 
indication, dose, and frequency 
• Measure and record weight (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Collect blood samples for hematology tests (coagulation parameters are not required) 
• Collect blood samples for complete serum chemistry tests 
• Collect blood sample for thyroid function panel (C3D1 only) 
• Perform tumor assessment according to RECIST Version 1.1 (Appendix 13.2) and 
iRECIST (Appendix 13.3) prior to the end (≤ 7 days) of Cycle 3  
• Administer PULSAR treatment 
• Administer IMSA101 by intra-tumoral injection (for the experimental arm only) 
following PULSAR treatment on the same day or the day after 
• Administer ICI treatment according to the product label 
• Complete QoL assessment using FACT-G questionnaire prior to the end (≤7 days) of 
Cycle 3 
• Assess and record AEs 
 

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5.1.7 
Cycle X and All Subsequent Cycles 
The following assessments are to be completed at the ICI treatment time points (ICI will 
continue to be administered per product label): 
• Record concomitant medications taken since the last visit including start dates, 
indication, dose, and frequency 
• Measure and record weight (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Collect blood samples for hematology tests (coagulation parameters are not required)  
• Collect blood samples for complete serum chemistry tests 
• Collect blood samples for thyroid function panel if clinically indicated 
• Administer ICI treatment according to the product label 
• Assess and record AEs 
 
The following assessments are to be completed at the indicated intervals: 
• Perform tumor assessment according to RECIST Version 1.1 (Appendix 13.2) and 
iRECIST (Appendix 13.3) (prior to the end [≤ 7 days] of Cycle 3, and thereafter every 
8 weeks [± 7 days]) 
• Complete QoL assessment using FACT-G questionnaire (prior to the end [≤ 7 days] of 
Cycle 3, and thereafter every 8 weeks [± 7 days]) 
 
5.1.8 
End of Study (EOS) Visit  
• Record concomitant medications taken since the last visit including start dates, 
indication, dose, and frequency 
• Measure and record weight (kg) 
• Record vital signs (blood pressure, respiration rate, heart rate, body temperature) 
• Perform and record full physical examination 
• Assess and record ECOG Performance Status (Appendix 13.1) 
• Perform a 12-lead ECG 
• Collect blood samples for hematology tests (coagulation parameters are not required) 
• Collect blood samples for complete serum chemistry tests 
• Collect blood sample for thyroid function panel if clinically indicated 
• Perform a serum pregnancy test for female patients of childbearing potential 

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• Perform tumor assessment according to RECIST Version 1.1 (Appendix 13.2) and 
iRECIST (Appendix 13.3) 
• Complete QoL assessment using FACT-G questionnaire 
• Assess and record AEs 
 
5.1.9 
Unscheduled Visits 
Additional visits may be performed as appropriate and at the discretion of the investigator. 
Any of the procedures or assessments may be performed based on the reason for the visit. 
5.2 
Restrictions, Precautions, and Potential Adverse Effects 
IMSA101: 
There are no known restrictions or precautions relative to the use of nicotine, caffeine, 
alcohol, physical activity, dietary restriction, or medications for patients receiving IMSA101 
treatment. 
Based on the nonclinical findings with IMSA101 and toxicity events reported in clinical 
trials evaluating other STING adaptor protein agonists, the following risks may reasonably 
be anticipated in clinical trials evaluating IMSA101: body temperature increases (fever), 
chills, alterations in serum chemistries, altered serum hematology parameters, headache, 
injection site pain, vomiting, fatigue, myalgia, and/or diarrhea. 
Based on the preliminary safety data of the monotherapy and combination treatment in the 
ongoing Phase 1/2a study (Protocol number: IMSA101-101), the most frequently reported 
TEAEs by preferred term across all dose levels were fatigue (53.3% of patients), and 
injection site pain, hyponatremia, decreased appetite, dyspnea, headache, and lymphocyte 
count decreased (each in 20% of patients).  
ICI Treatment: 
The investigator is to refer to the prescribing information or other known sources of the 
respective ICI drugs for any specific restrictions or precautions relative to the use nicotine, 
caffeine, alcohol, physical activity, dietary restrictions, or medications for patients receiving 
ICI treatment. 
The most common adverse reactions (reported in the ≥ 20% of patients) of pembrolizumab as 
a single agent include fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, 
nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and abdominal pain 
(KEYTRUDA® [Pembrolizumab]). 
The common adverse reactions (reported in the ≥ 20% of patients) of pembrolizumab in 
combination with RT include fatigue, rash, dyspnea, cough, and flu-like symptoms (Theelen 
et al., 2019; Welsh et al., 2020).   

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The most common adverse reactions (reported in the ≥ 20% of patients) of nivolumab as a 
single agent include fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, 
cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, upper respiratory 
tract infection, pyrexia, headache, and abdominal pain (OPDIVO® [Nivolumab]). 
The reported adverse reactions of nivolumab in combination with RT include pneumonitis, 
lethargy, diarrhea, skin erythema, pancreatitis, and hearing loss (Ansari et al., 2021; Amin et 
al., 2018). 
PULSAR: 
The investigator is to follow the specific restrictions or precautions relative to food, 
medications, allergies, clothing or personal items for patients undergoing the PULSAR or 
SAbR procedure. 
Complications associated with PULSAR or SAbR may include radiation pneumonitis, 
brachial plexopathy, gastritis, toxicity in the chest wall, skin, airway, esophagus, and bowel 
(Lo et al., 2013; Siva et al., 2018). 
 
 

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6 
METHODS OF ASSESSMENTS AND ENDPOINTS 
6.1 
MEDICAL HISTORY 
At screening, a complete medical history will be obtained from each patient. Medical history 
includes baseline symptoms, cancer history, as well as a detailed history of prior procedures 
and prior cancer therapies including therapy start and stop dates, best response, disease 
progression during or after therapy, as well as discontinuations due to intolerability or 
toxicity. For female patients of child-bearing potential, the date of the last menstrual period 
should be noted. Data will be updated at subsequent visits as appropriate. 
6.2 
CONCOMITANT MEDICATIONS 
A detailed history of medications and procedures will be documented for each patient at 
screening. Concurrent medications (especially changes in medication) will be documented 
for each patient at each scheduled visit. Concomitant medications taken from Cycle X 
onwards are to be completed at the ICI treatment time points. 
Necessary supportive care such as anti-emetic, anti-diarrheal medications, and pre-infusion 
medications for ICI treatment per local guidelines will be allowed. Prophylactic pre-
treatment for headache, nausea, and vomiting is permitted (see Section 8.4). Pre-infusion 
medications for ICI treatment, when administered, should be given per local guidelines. For 
concomitant medications allowed during PULSAR, see Section 8.1.2. 
Any medication that in the opinion of the investigator will interfere with the MOA of 
IMSA101, ICI, and PULSAR is prohibited (see Section 8.4).  
6.3 
DEMOGRAPHIC DATA 
At screening, patient demographic data will be collected. These data include the year of birth, 
age, gender, race, smoking history, tumor type, molecular abnormalities if known, and other 
relevant baseline characteristics. 
6.4 
SAFETY ASSESSMENTS  
6.4.1 
Vital Signs 
Vital signs including body temperature, blood pressure (systolic and diastolic), respiration 
rate, and heart rate will be measured at each scheduled visit. From Cycle X onwards, vital 
signs are to be measured at the ICI treatment time points. 
All vital sign readings will be documented in the electronic case report form (eCRF). The 
investigator will review all vital sign values for clinical significance. Additional vital signs 
will be obtained when clinically indicated. Any clinically significant change in the vital signs 
from before the start of study treatment should be recorded as an AE. 

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6.4.2 
Physical Examination 
A full physical examination will be performed at screening and EOS visit. A full physical 
examination will include, at a minimum, assessments of the cardiovascular, respiratory, 
gastrointestinal, neurological, skin, and lymphatic systems. 
In addition, height (cm) will be measured at screening; body weight (kg) will be measured at 
screening/baseline and each scheduled visit.  
Information of the physical examination must be present in the source documentation at the 
study site. The result of the physical examination prior to the start of study treatment must be 
included in the Relevant Medical History/Current Medical Conditions page of the eCRF. 
Clinically relevant findings made after the start of study treatment, which meet the definition 
of an AE, must be recorded on the AE page of the eCRF. 
6.4.3 
ECOG Assessment 
The ECOG Performance Status Scale is a widely accepted tool in cancer clinical trials to 
measure and monitor the level of functioning in cancer patients in terms of their ability to 
care for themself, daily activity, and physical ability (Oken et al., 1982).  
The ECOG Performance Status assessments (Appendix 13.1) will be performed at each 
scheduled visit (Table 1). 
6.4.4 
Electrocardiogram 
A complete standard 12-lead ECG recording (rhythm, VR, PR interval, QRS duration, QT 
and QTc) will be performed at screening and EOS visit, or at any other visit where the 
investigator believes the assessment is indicated. The results of ECG will be reported to the 
investigator and recorded in the eCRF. 
6.4.5 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations (hematology, serum chemistry, coagulation, urinalysis) will 
be performed at the indicated visits in Table 1. Coagulation and urinalysis will be performed 
only at screening. 
All clinical laboratory evaluations will be carried out by the local laboratory and in 
accordance with the standard operating procedures or the laboratory manual. All results of 
the clinical laboratory measurements will be reported to the investigator and recorded in the 
eCRF. 
The following clinical laboratory evaluations will be performed: 
• Hematology (blood sample with ethylenediaminetetraacetic acid [EDTA]): hemoglobin, 
hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular 
hemoglobin concentration, white blood cell (WBC) count, WBC differential, red blood 
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basophils, platelets. The WBC differential may be automated or manual as per 
institutional standards. Reticulocytes should be done only when clinically indicated. 
• Serum Chemistry (blood serum sample): Complete serum chemistry will include 
sodium, potassium, chloride, bicarbonate, blood urea nitrogen, creatinine, glucose, 
calcium, phosphate, magnesium, ALT, AST, alkaline phosphatase, total bilirubin, direct 
bilirubin, lactate dehydrogenase, total protein, albumin.  
• Thyroid Function Panel (blood serum sample): a thyroid test panel will include thyroid-
stimulating hormone (TSH), tri-iodothryonine (T3) (free and total), thyroxine (T4) (free 
and total). 
• Coagulation (screening only): PT, international normalization ratio (INR), and activated 
partial thromboplastin time (aPTT).  
• Urinalysis (screening only): appearance, color, urine bilirubin, glucose, hemoglobin, 
ketones, pH, protein, specific gravity, urobilinogen, and microscopy. 
 
Any laboratory value that remains abnormal at the EOS and that is considered clinically 
significant will be followed according to accepted medical standards for up to 30 days after the 
EOS or until resolution of the abnormality. 
6.4.6 
Pregnancy Test 
A serum pregnancy test will be performed for female patients of childbearing potential at 
screening and the EOS visit to establish the absence of pregnancy. 
6.4.7 
Adverse Events and Toxicities 
Patients will be observed for 1 hr at the study site following intra-tumoral injections. All 
TEAEs will be collected and recorded in the eCRF. Toxicities and DLTs will be assessed 
using the CTCAE Version 5.0. 
See Section 3.3 for the definition of DLTs. See Section 9 for definitions and the reporting of 
AEs. 
6.5 
TUMOR ASSESSMENTS 
All known tumor sites will be documented at screening and re-assessed at each subsequent 
time point for tumor evaluation, using a single and consistent methodology throughout the 
study (see Appendix 13.2). Assessments may include the following: 
• Tumor assessment at screening and subsequent scheduled time points must include 
computed tomography (CT) scans or magnetic resonance imaging (MRI) (with 
intravenous contrast unless contraindicated and oral contrast as appropriate per 
institutional standards).  
• If a CT scan is performed in a positron emission tomography/CT scanner, the CT 
acquisition must be consistent with the standards for a full-contrast CT scan. 

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• Further investigations such as bone scans, brain MRI, etc. should be performed if there is 
any clinical suspicion of disease at any site that may not be observed using the methods 
above. 
• The same radiographic procedures used to assess disease sites at screening should be 
used throughout the study (eg, the same contract protocol for CT scans). Assessments 
should be performed by the same evaluator, if possible, to ensure internal consistency 
across visits.  
• All findings will be assessed for responses according to RECIST Version 1.1 
(Appendix 13.2) and iRECIST (Appendix 13.3) criteria and the Schedule of Assessments 
and Study Activities (Table 1). 
• In certain circumstances, a patient experiencing RECIST progression of disease will be 
allowed to continue therapy on study unless confirmed progression by iRECIST. 
• Outcome measures that will be extracted from the radiographic imaging, as defined by 
RECIST Version 1.1 and iRECIST, include TTP, ORR, DOR, and PFS. 
- 
TTP: defined as the time from the first dose of study treatment until the time of 
objective disease progression 
- 
ORR: defined as the proportion of patients with confirmed partial or complete 
response from the first dose of study treatment until disease progression 
- 
DOR: defined as the time from initial objective response (partial or complete 
response, whichever status is recorded first) until the time of disease progression or 
death from any cause 
- 
PFS: defined as the time from the first dose of study treatment until objective disease 
progression or death from any cause 
 
6.6 
QUALITY OF LIFE ASSESSMENT 
FACT-G (Cella et al., 1993) is a 27-item questionnaire using a 5-point Likert-type scale. This 
is a reliable, sensitive, and validated tool developed to measure four domains of health 
related QoL, namely physical, social, emotional, and functional well-being, in cancer 
patients. FACT-G Version 4.0 will be used in this study. 
The questionnaire will be provided to and self-administered by the patients, or performed in 
an interview if needed, at the scheduled time points in Table 1. 

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7 
DISCONTINUATION CRITERIA 
7.1 
DISCONTINUATION OF STUDY TREATMENT 
The treatment of individual patient(s) may be stopped by the investigator under the defined 
circumstances as outlined below.  
• Use of prohibited concurrent therapy 
• Non-compliance with the study treatment or study schedule 
• Abnormal clinical laboratory tests 
• Intercurrent illness warranting treatment discontinuation by the investigator 
• Disease progression warranting treatment discontinuation by the investigator 
• Pregnancy 
• Other safety criteria warranting treatment discontinuation by the investigator 
 
If, based on the investigator’s judgement, the study treatment of a patient is permanently 
discontinued, the patient will be withdrawn from the study (see Section 7.2 for procedures of 
withdrawal from the study).  
7.1.1 
Temporary Discontinuation of Study Treatment 
After the safety run-in period in the experimental arm, the administration of IMSA101 may 
need to be temporarily interrupted, if deemed appropriate by the investigator, when suspected 
toxicity of IMSA101 is observed. See Section 3.3 for the AEs that may warrant temporary 
interruption of the IMSA101. 
For the PULSAR-ICI treatment, any dose modifications or treatment interruptions should 
follow the instructions in the product labels of the prescribed ICI drugs and the standard 
guideline of the RT. 
An agreement from the sponsor and the investigator should be obtained prior to re-initiating 
treatment in a patient after an interruption in the treatment. 
Tumor assessments should continue as per protocol even if the treatment is interrupted or 
delayed. 
7.2 
PATIENT WITHDRAWAL FROM THE STUDY 
Patients are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The individual patient(s) may be 
withdrawn from the study by the investigator under the defined circumstances as outlined 
below.  
• Use of non-permitted concurrent therapy 

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• Non-compliance with the study treatment or study schedule 
• Patient lost to follow-up 
• Occurrence of AEs not compatible with the continuation of patient participation in the 
study, in the investigator’s opinion, or unacceptable to the patient to continue 
• The investigator determines that a change of therapy would be in the best interest of the 
patient 
• Intercurrent illness warranting removal by the investigator 
• Disease progression warranting removal by the investigator 
• Pregnancy 
 
The reason(s) for withdrawal (by the patient or investigator) and date will be documented in 
the eCRF.  
All patients who withdraw from the study with an ongoing AE must be followed until the 
event is resolved or deemed stable. Any patient who withdraws consent as a result of an AE, 
regardless of intensity or investigator’s opinion, must be reported as an AE leading to study 
withdrawal. Patients withdrawing from the study will be asked to complete the final 
evaluations as detailed for the EOS visit in the Schedule of Assessments (Table 1).  
If a patient refuses to complete the final evaluations upon withdrawal from the study, this 
information will be recorded in the source documentation. A patient who prematurely 
withdraws from the study for any reason will not be allowed to re-enter the study. 
If a patient withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a patient 
withdraws from the study, the patient may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
In certain circumstances, a patient experiencing RECIST progression of disease will be 
allowed to continue therapy on study unless confirmed progression by iRECIST. 
7.3 
EARLY DISCONTINUATION OF THE STUDY 
The sponsor has the right to terminate the study at any time in case of SAEs or if special 
circumstances concerning PULSAR, IMSA101, and ICI, or the company itself occur, making 
further treatment of patients impossible.  
In particular cases, the study may be terminated at a single study site at any time if it 
becomes apparent that patient enrolment or quality of the data is unsatisfactory, or the 
conduct of the study at this site is not in accordance with the protocol, the requirements of the 
Institutional Review Boards (IRB)/ Institutional Ethics Committees (IEC) or local health 
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If the study is prematurely terminated or suspended, the sponsor or delegate shall promptly 
inform the investigators, the IRB/IEC, the regulatory authorities, and any contract research 
organization(s) used in the study of the reason for termination or suspension, as specified by 
the applicable regulatory requirements. The investigator shall promptly inform the patients 
and should assure appropriate patient therapy and/or follow-up. Study materials must be 
returned, disposed of or retained as directed by the sponsor. 
 
 

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8 
TREATMENT 
8.1 
ADMINISTRATION OF PULSAR 
PULSAR is part of the combination therapy in both the control arm and experimental arm 
from Cycle 1 to Cycle 3.  
PULSAR will be administered to the patients first on Day 1 of Cycles 1, 2, and 3 (for both 
treatment arms), followed by IMSA101 on the same day or the day after (of Cycles 1, 2, and 
3; for the experimental arm only).  
PULSAR will be delivered with the targeting planning and directing of treatment fields 
guided to a target based on known three-dimensional (3D) coordinates related to reliable 
fiducial markers. This differs from conventional RT in which treatment is guided by skin or 
bony landmarks assumed to correlate to the target volume based on the initial simulation. 
Treatment will account for inter-/intra-fractional errors with careful dosimetry that delivers 
an ablative dose to the metastatic lesion(s) while respecting normal tissue constraints. 
8.1.1 
Prescription Dose and Interval 
The treating radiation oncologist will deliver 3 pulses. Each RT pulse will encompass the 
95% of the planning target volume and is considered compliant to the protocol. The 
following table lists the acceptable number of pulses and dose per pulse. Any dose delivered 
that is beyond the recommended doses will be considered an unacceptable variation. Isotoxic 
doses were calculated using the Universal Survival Model using H460 Homo sapiens lung 
carcinoma cell line data. 
Number of Pulses 
Dose Per Pulse 
Total Dose 
3 
12 – 15.5 Gy 
36 – 46.5 Gy 
 
The PULSAR “pulse” is to be delivered on Day 1 of Cycles 1, 2, and Cycle 3. PULSAR may 
be held if the patient does not have any targetable disease. Each PULSAR treatment and date 
of treatment delivery will be recorded. 
8.1.2 
Treatment Concerns and Concurrent Medications 
Corticosteroid medications for inflammatory conditions can be used at the discretion of the 
treating oncologist (in which case, its use needs to be reported as concomitant medication). 
However, the use of corticosteroid medications is generally discouraged, given its 
immunosuppressive properties. Analgesic pre-medication to avoid general discomfort during 
long treatment durations is recommended when appropriate. 

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8.1.3 
Technical Factors and Considerations 
Physical factors 
Only photon (X-ray) beams produced by linear accelerators with photon energies of 
4-15 megavoltage (MV) will be allowed. Cobalt-60 and charged particle beams (including 
electrons, protons, and heavier ions) are not allowed. Restriction of photon beam energies 
> 10 MV but less than 15 MV will be based on clinical appropriateness taking into account 
distance the beam must travel to the target. 
Dose Verification at Treatment 
In vivo dosimeter measurements (eg, diode, thermoluminescent dosimeter) may be obtained 
for surface dose verification for accessible beams. This information is not required by the 
protocol. 
Treatment Platforms 
The study allows most commercially available photon or proton producing treatment units. 
Treatment units should include image guidance. Both 3D conformal and intensity-modulated 
RT (including volumetric-modulated arc therapy [VMAT]) are allowed. Proton or other 
charged particle units are not allowed in this study. Other specialized accelerators (eg, the 
CyberKnife® or Tomotherapy) are allowed as long as they meet the technical specifications 
of the protocol. 
8.1.4 
Simulation and Image Guidance 
Patient Positioning 
Patients will be positioned in a stable position that allows accurate reproducibility of the 
target between treatments. Positions uncomfortable for the patient should be avoided so as to 
prevent uncontrolled movement during treatments. A variety of immobilization systems may 
be utilized including stereotactic frames that surround the patient on three sides and large 
rigid pillows (conforming to patients’ external contours) with reference to the stereotactic 
coordinate system. Patient immobilization must be reliable enough to ensure that the Gross 
Tumor Volume (GTV) does not deviate beyond the confines of the Planning Treatment 
Volume (PTV) with any significant probability (ie, < 5%). 
At the time of simulation for patients who will receive pulses to the lung, liver, or other 
targets likely to move greater than 0.5 cm with respiration, the movement of the dome of the 
diaphragm (superior portion of the liver) is to be observed under fluoroscopy or other 
acceptable means to estimate respiratory movement during treatment if no breathing control 
device is used. Patients will be assessed for suitability for tolerance of a respiratory control 
device using a breath-hold technique, respiratory gating, or abdominal compression to limit 
diaphragmatic excursion during respiration. Patients with severe lung disease and patients 
who cannot tolerate diaphragmatic or breathing control devices for other reasons will be 
treated without them. A larger margin to account for breathing related intra-fractional organ 
movement is required but no greater than a margin of 1.5 cm. 

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Image Guidance 
Isocenter or reference point port localization images should be obtained on the treatment unit 
immediately before treatment to ensure proper alignment of the geometric center (ie, 
isocenter) of the simulated fields. These image-guided RT images can be obtained with 
planar kilovolt (kV) imaging devices or cone-beam CT equipment. For treatment systems 
that use kV imaging but also allow electronic portal imaging device imaging using the 
treatment beam, orthogonal images verifying the isocenter also should be obtained. 
8.1.5 
Treatment Planning and Target Volumes 
Image Acquisition 
CT scans will be the primary image platform for targeting and treatment planning. The 
planning of CT scans must allow simultaneous view of the patient anatomy and fiducial 
system for stereotactic targeting. CT scan with intravenous contrast is recommended unless 
the patient has allergy to contrast or renal insufficiency. Oral gastrointestinal contrast to 
highlight the stomach and duodenum is recommended for patients with medial liver lesions 
or lesions of the caudate lobe. Axial acquisitions will be required with spacing ≤ 3.0 mm 
between scans. Images will be transferred to the treatment planning computers. 
Target Volumes 
The target lesion will be outlined by an appropriately trained physician and designated the 
GTV. The target will generally be drawn using appropriate windowing based on location of 
the metastatic lesion(s). Four-dimensional CT image guided GTV delineation to take tumor 
motion into consideration will be allowed.  
For treatment to the lung, the target will generally be drawn using CT pulmonary windows; 
however, soft tissue windows with contrast may be used to avoid inclusion of adjacent 
vessels, atelectasis, or mediastinal or chest wall structures within the GTV. This target will 
not be enlarged whatsoever for prophylactic treatment (including no “margin” for presumed 
microscopic extension); rather, include only abnormal CT signal consistent with gross tumor 
(ie, the GTV and the clinical target volume [CTV] are identical). An additional 0.5 cm in the 
axial plane and 0.5 cm in the longitudinal plane (craniocaudal) will be added to the GTV to 
constitute the PTV.  
For treatment to the liver, the following structures are contoured: entire liver, each individual 
liver GTV, each kidney, small bowel, large, bowel, duodenum, stomach, and the spinal cord. 
The PTV is constructed to account for the positional uncertainty of the GTV during treatment 
with a PTV margin of 0.5 cm is recommended. Larger margins may be used in cases where 
greater motion of the hemidiaphragm is observed in simulation despite standard maneuvers 
to diminish motion. Four-dimensional CT image acquisition is recommended to be utilized to 
evaluate for motion, and motion management techniques such as breath hold or abdominal 
compression can be utilized at the discretion of the treating physicians. Fiducial markers can 
also be utilized to facilitate image guidance if available at the institution.  

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Treatment to skeletal and paraspinous lesions may be accomplished with any 3D conformal 
radiotherapy or intensity-modulated radiotherapy technique suitable for this application with 
performance specifications adequate to provide proper tumor dose distribution and normal 
tissue sparing. 
8.1.6 
Dosimetry 
3D Conformal Planning 
3D coplanar or non-coplanar beam arrangements will be custom designed for each case to 
deliver highly conformal prescription dose distributions. Non-opposing, non-coplanar beams 
are preferable. Generally, more beams are used for larger lesion sizes. For this protocol, the 
isocenter is defined as the common point of gantry and couch rotation for the treatment unit. 
Prescription lines covering the PTV will typically be the 60-90% line (rather than 95-100%); 
however, higher isodoses (hotspots) must be manipulated to occur within the target and not 
in adjacent normal tissue. The isocenter in stereotactic coordinates will be determined from 
system fiducials (or directly from the tumor in the case of volumetric imaging) and translated 
to the treatment record.  
The treatment dose plan will be made up of multiple static beams or arcs as described above. 
The plan should be normalized to a defined point corresponding closely to the center of mass 
of the PTV (COMPTV). Typically, this point will be the isocenter of the beam rotation; 
however, it is not a protocol requirement for this point to be the isocenter. Regardless, the 
point identified as COMPTV must have defined stereotactic coordinates and receive 100% of 
the normalized dose. Because the beam apertures coincide nearly directly with the edge of 
the PTV (little or no added margin), the external border of the PTV will be covered by a 
lower isodose surface than usually used in conventional radiotherapy planning typically 
around 80% but ranging from 60-90%. The prescription dose will be delivered to the margin 
of the PTV. As such, a “hotspot” will exist within the PTV centrally at the COMPTV with a 
magnitude of prescribed dose times the reciprocal of the chosen prescription isodose line (ie, 
60-90%). 
Intensity Modulated Radiation Therapy (IMRT) 
IMRT, including volumetric-modulated arc therapy (VMAT) and modulated charged 
particles is allowed in this study. The use of IMRT in this study is at the discretion of the 
treating physician. However, IMRT should be considered only when target coverage, organ-
at-risk dose limits, or dose spillage are not achievable with 3D conformal planning. In 
addition, IMRT plans should follow the same planning principles as discussed above for 3D 
conformal planning. The number of segments (control points) and the area of each segment 
should be optimized to ensure deliverability and avoid complex beam fluences. Ideally, the 
number of segments should be minimized, and the area of each segment should be 
maximized (the aperture of one segment from each beam should correspond to the projection 
of the PTV along a beam’s eye view). 

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Dose Calculations 
For purposes of dose planning and calculation of monitor units for actual treatment, this 
protocol will require tissue density heterogeneity correction.  
Successful treatment planning will require accomplishment of all of the following criteria: 
1. Maximum dose: The treatment plan should be created such that 100% corresponds to the 
maximum dose delivered to the patient. This point must exist within the PTV. 
2. Prescription isodose: The prescription isodose surface must be ≥ 60% and < 90% of the 
maximum dose. 
3. Prescription Isodose Surface Coverage: The prescription isodose surface will be chosen 
such that 95% of the target volume (PTV) is conformally covered by the prescription 
isodose surface (PTV V95%RX = 100%) and 99% of the target volume (PTV) receives a 
minimum of 90% of the prescription dose (PTV V90%RX > 99%). 
 
8.1.7 
Normal Tissue Dose Constraints 
The following table lists the specific organ and dose fractionation constraints on normal 
tissue. Given the irregular, long intervals between each radiotherapy pulse, total dose will be 
calculated to a particular organ-at-risk to ensure safety of RT. Exceeding these dose 
tolerances by more than 2.5% constitutes a minor protocol violation. Exceeding these dose 
tolerances by more than 5% constitutes a major protocol violation. 
Three pulses 
Serial Tissue 
Volume 
(cc) 
Volume Max 
(Gy) 
Max Point Dose  
(Gy)** 
Endpoint  
(≥ Grade 3) 
Optic Pathway 
< 0.2 
15.3 
17.4 
neuritis 
Cochlea 
- 
- 
14.4 
hearing loss 
Brainstem (not medulla) 
< 0.5 
15.9 
23.1 
cranial neuropathy 
Spinal Cord and medulla 
< 0.35 
15.9 
22.5 
myelitis 
Cauda Equina 
< 5 
21.9 
25.5 
neuritis 
Sacral Plexus 
< 5 
22.5 
25.5 
neuropathy 
Esophagus* 
< 5 
27.9 
32.4 
esophagitis 
Brachial Plexus 
< 3 
22 
26 
neuropathy 
Heart/Pericardium 
< 15 
24 
30 
pericarditis 
Great vessels 
< 10 
39 
45 
aneurysm 
Trachea and Large 
Bronchus* 
< 5 
39 
43 
impairment of 
pulmonary toilet 
Bronchus- smaller 
airways 
< 0.5 
25.8 
30 
stenosis with 
atelectasis 
Rib 
< 5 
40 
50 
pain or fracture 
Skin 
< 10 
31 
33 
ulceration 
Stomach 
< 5 
22.5 
30 
ulceration/fistula 
Bile duct 
- 
- 
36 
stenosis 
Duodenum* 
< 5 
22.5 
30 
ulceration 
Jejunum/Ileum* 
< 30 
20.7 
28.5 
enteritis/obstruction 

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Colon* 
< 20 
28.8 
45 
colitis/fistula 
Rectum* 
< 3.5 
< 20 
43 
30.3 
47 
proctitis/fistula 
Ureter 
- 
- 
40 
stenosis 
Bladder wall 
< 15 
17 
33 
cystitis/fistula 
Penile bulb 
< 3 
25 
- 
impotence 
Femoral Heads  
< 10 
24 
- 
necrosis 
Renal hilum/vascular 
trunk 
15 
19.5 
- 
malignant 
hypertension 
 
Parallel Tissue 
Critical 
Volume 
(cc) 
Critical Volume 
Dose Max  
(Gy) 
Avoid 
Pneumonitis 
Endpoint  
(≥ Grade 3) 
Lung (Right & Left) 
1500 for 
males;  
950 for 
females*** 
10.8 
- 
basic lung function 
Lung (Right & Left) 
- 
- 
V-11.4 Gy < 37% 
pneumonitis 
Liver 
700*** 
17.7 
- 
basic liver function 
Renal cortex (Right & 
Left) 
200*** 
14.7 
- 
basic renal function 
* Avoid circumferential irradiation 
** “point” defined as 0.035 cc or less 
*** or one third of the “native” total organ volume (prior to any resection or volume reducing disease), 
whichever is greater 
 
8.2 
DOSING AND ADMINISTRATION OF IMSA101 
IMSA101 is a sterile, nonpyrogenic solution containing 5 mg of IMSA101 in 1.0 mL of a 
 
 
 
 
 
 
  
Composition of IMSA101 is presented in Table 2. 
Table 2 
Composition of IMSA101 for Injection 
Ingredients 
Grade 
Function 
Composition 
(1.0 mL per vial) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
NF: National Formulary; USP: United States Pharmacopeia 
 

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8.2.1 
Preparation of IMSA101 
Prior to dosing, IMSA101 will be thawed and diluted in 
 
 as detailed in a 
separate pharmacy manual in order to be delivered via intra-tumoral injection. The following 
dose levels will be administered to the patients in the study: 
Selected Phase 2 dose-1: 800 mcg 
Selected Phase 2 dose: 1200 mcg 
This drug is NOT SAFE to be administered without proper dilution. 
No dose modification of IMSA101 is allowed. 
A single pre-defined lesion/lesion site per patient will be selected and injected via intra-
tumoral injection throughout study participation. Injections of tumors that are not superficial 
will be performed under image guidance.  
8.2.2 
Administration of IMSA101 
IMSA101 will be administered to the patients in the experimental arm only. IMSA101 will 
be part of the combination therapy with PULSAR-ICI from Cycle 1 to Cycle 3. IMSA101 
will be administered to the patients on Day 1 of Cycles 1, 2, and 3 following the PULSAR 
treatment on the same day or the day after (Day 2). 
In the experimental arm, a safety run-in component will be applied to initial patients enrolled 
in the treatment arm to establish safety of the combination therapy at the dose levels of 
800 mcg and 1200 mcg (see Section 3.1). A total volume of 1 mL will be administered each 
week for 3 weeks in Cycle 1 (Days 1, 8, and 15). For Cycle 2 and Cycle 3, IMSA101 will be 
given via intra-tumoral injection on Day 1 only.  
IMSA101 is injected directly into the selected tumor. Patients will be observed for 1 hr 
following each intra-tumoral injection.   
Injectable tumors shall be accessed by intralesional (cutaneous) or percutaneous injection 
only, including those lesions that are visible, palpable, or detectable by standard radiographic 
or ultrasound methods. The administration technique and procedures for internal lesions (ie, 
whether CT or ultrasound guided) will be per institutional policy and guidelines. Neither 
surgical procedures nor endoscopically-guided injections including those to endobronchial, 
endoluminal, or endosinusoidal spaces shall be allowed. While no anatomic locations are 
required or disallowed, lesions selected for intra-tumoral injection must, in the opinion of the 
investigator: 
• Not be immediately adjacent to blood vasculature or other physiologic landmarks in such 
a way that will accrue undue safety risk to the patient  
• Have longest diameter ≥ 10 mm and ≤ 50 mm 

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• Be fully efficacy evaluable per RECIST Version 1.1 (Appendix 13.2) and iRECIST 
(Appendix 13.3) 
 
Where the original injection site is considered by the investigator to become inaccessible, a 
second lesion/lesion site shall be selected as a replacement, and this shall be used henceforth 
so long as it is considered accessible. Subsequent injection sites shall be replaced when they 
are considered inaccessible. 
Where no remaining accessible lesions are present and where benefit of IMSA101 therapy is, 
in the opinion of the investigator, being derived by the patient, continued injections of 
IMSA101 into the vicinity of an inaccessible lesion shall be allowed. In the case that a lesion 
can no longer be radiographically visualized, continued injections into the last known 
location of the non-visible lesion shall be allowed. 
8.2.3 
Storage of IMSA101 
The drug product is packaged in a container-closure system that is composed of 
pharmacopoeia-compliant components. The primary container, composed of United States 
Pharmacopeia (USP) Type 1 glass, is stoppered with a 13 mm Flurotec coated lyophilization 
stopper, and sealed with a 13 mm flip-off overseal and 13 mm cap.  
The product (IMSA101 for Injection) is stored at -20 ± 5℃. Clinical trial sites will be 
provided specific expiry and stability updates via memoranda as new data become available. 
8.3 
ADMINISTRATION OF ICI DRUG 
ICI drug (pembrolizumab or nivolumab) is part of the combination therapy in both the 
control arm and experimental arm from Cycle 1 to Cycle 3. The initial dose of the prescribed 
ICI will be administered to the patients on Cycle 1 Day 2 (following PULSAR [for both 
treatment arms] and IMSA101 [for experimental arm only] on C1D1). If IMSA101 is 
administered on C1D2, then ICI may be administered same day, or on C1D3. Thereafter, the 
ICI drug will be administered to the patients at frequencies per product labels (every 3 weeks 
or every 6 weeks for pembrolizumab; every 2 weeks or every 4 weeks for nivolumab). 
ICI drug will be administered to the patients in both treatment arms as monotherapy from 
Cycle X onwards and at frequencies according to the product labels. 
8.4 
RESCUE MEDICATIONS AND CONCOMITANT TREATMENTS 
All medications administered from the beginning of study treatment (C1D1) through EOS 
will be recorded on the eCRF. Any change in medication dosage will also be noted. 
Necessary supportive care (ie, anti-emetic and/or anti-diarrheal medications, pre-infusion 
medications for ICI treatment per local guidelines, corticosteroid and analgesic pre-
medication during PULSAR, etc.) will be allowed. Prophylactic pre-treatment for headache, 
nausea, and vomiting is permitted (Section 6.2).  

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The following medications are prohibited during the study:  
• Additional anticancer therapy, other investigational agents, and immunotherapy 
During the study treatment period, patients are not to receive any additional anticancer 
therapy, other investigational agents, or other immunotherapy not specified in this 
protocol. If the investigator determines that a patient requires any of these treatments for 
any reason, all study treatment must be discontinued. 
• Herbal therapies 
Concomitant use of herbal therapies/traditional Chinese medicine with anti-cancer 
activity included in the product label is prohibited. 
• Corticosteroids 
Corticosteroids used as an anti-cancer therapy (eg, >10 mg/day prednisone or equivalent) 
are not permitted; however, they are allowed as a pre-medication, as physiologic 
replacement, or for symptomatic management. 
- 
Systemic corticosteroids are permitted for the following purposes: 
◦ 
To modulate symptoms of an AE that is suspected to have an immunologic 
etiology 
◦ 
As needed for the prevention of emesis 
◦ 
Pre-medication for intravenous contrast allergies 
- 
In addition, the following glucocorticoid use is allowed: 
◦ 
For topical use or ocular use 
◦ 
Intra-articular joint use 
◦ 
For inhalation in the management of asthma or chronic obstructive pulmonary 
disease 
Note: Inhaled steroids are allowed for the management of asthma. 
 
The investigator should also refer to the prescribing information or other knowns sources for 
the prohibited concomitant medications that should be avoided during an ICI treatment. 
8.4.1 
COVID-19 Vaccination 
The current study will be conducted amidst the coronavirus disease 2019 (COVID-19) 
pandemic. As mass vaccination campaign of COVID-19 vaccine is ongoing worldwide, the 
patients enrolled in the study may receive COVID-19 vaccine prior to or concurrently during 
the study.  
The current COVID-19 vaccines available to the public is considered to have no interaction 
with IMSA101 that necessitate advice on vaccine timing or other precautions.  
8.5 
TREATMENT COMPLIANCE 
Patients will receive the combination therapy directly from the investigator or designee, 
under medical supervision. The investigator or other study staff will supervise each study 
treatment given at the study site. The date and time of each treatment administered at the 

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study site will be recorded in the eCRF. The dose of study drugs and patient identification 
will be confirmed at the time of dosing by the study site staff. 
The investigator and/or the study staff will administer IMSA101 only for use in patients 
enrolled in the experimental arm as described in this protocol. The study drugs are not to be 
used for reasons other than those described herein. 
Study personnel associated with the sponsor will monitor the treatment compliance of 
PULSAR, IMSA101, and ICI.  
 
 

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9 
ADVERSE EVENTS 
9.1 
DEFINITIONS 
9.1.1 
Adverse Event 
An AE is defined as any undesired medical occurrence in a patient or clinical investigation 
patient receiving a pharmaceutical product and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable sign and unintended 
sign (including an abnormal laboratory finding), symptom, or disease temporarily associated 
with the study treatment, whether or not related to the study treatment. AE reporting begins 
from the start of study treatment and continues until the EOS visit. 
9.1.2 
Serious Adverse Events 
An SAE is any untoward medical event that occurs at any dose from the start of study 
treatment until the EOS visit: 
• Results in death 
• Is life-threatening (patient is at immediate risk of death from the event as it occurred)1 
• Requires inpatient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization2 
• Results in persistent or significant disability/incapacity3 
• Results in a congenital anomaly/birth defect 
• Is an important medical event4 
 
1 “Life-threatening” means that the patient was at immediate risk of death at the time of the 
SAE; it does not refer to a SAE that hypothetically might have caused death if it were 
more severe. 
2 This means that hospital inpatient admission or prolongation of hospital stay was required 
for the treatment of the AE, or that one or the other occurred as a consequence of the 
event. Hospitalizations for elective surgery or other medical procedures that are not related 
to a TEAE are not considered SAEs.  
3 “Persistent or significant disability or incapacity” means a permanent or significant and 
substantial disruption of a person’s ability to carry out normal life functions. 
4 Important medical events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
events include allergic bronchospasm requiring intensive treatment in an emergency room 

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or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, 
or the development of drug dependency or drug abuse. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting 
is appropriate in situations where none of the outcomes listed above occurred. Important 
medical events that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the patient or may require intervention to prevent one of 
the other outcomes listed in the definition above should also usually be considered serious. 
All other AEs are considered non-serious. All non-serious AEs will be followed to 
resolution, or until the study ends, and reported to the sponsor as requested, to the IRB/IEC 
according to IRB/IEC policies (to include annual Continuing Review Reports), to the SRC as 
required, and to the US FDA as required for the annual report. 
Management of all AEs including hypersensitivity or hyperimmune reactions will be 
managed by treating physicians in conjunction with relevant institutional guidelines and with 
the consultation of the sponsor’s medical monitor. 
9.1.3 
Adverse Event by Severity or Intensity 
The assessment of severity of an AE will be rated according to the criteria in Table 3.  
Table 3 
Definitions of Adverse Events Severity 
Grade 1 (Mild) 
Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. The AE does not interfere 
with routine activities. The patient may experience slight discomfort. 
Grade 2 (Moderate) 
Moderate; minimal, local or noninvasive intervention indicated; The AE 
interferes with routine activities. The patient may experience significant 
discomfort. 
Grade 3 (Severe) 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated. The patient is 
unable to perform routine activities. The patient may experience 
intolerable discomfort or pain. 
Grade 4 (Life-Threatening) 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 (Fatal) 
Death related to AE 
Based on the CTCAE Version 5.0 
 
The term “severe” is used to describe the intensity of an AE; the event itself could be of 
relatively minor clinical significance (eg, ‘severe’ headache). This is not the same as 
“serious”. Seriousness of AEs is based on the outcome of an AE and usually associated with 
events that pose a threat to a patient’s life or functioning. 
9.1.4 
Relationship between Adverse Events and Study Treatment 
Determination of the relationship between an AE and any component of the study treatment 
will be made using the guidelines presented in Table 4. 

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Table 4 
Guidelines for Determining the Relationship (if any) Between Adverse Event 
and the Study Treatment 
Definitely Related: 
This causal relationship is assigned if the AE starts a reasonable time after the 
administration of study treatment, stops/improves when the study treatment is 
stopped, and could reasonably be explained by known characteristics of the study 
treatment. 
Probably Related: 
This causal relationship is assigned when the AE starts a reasonable time after the 
administration of study treatment, stops/improves when the study treatment is 
stopped, and could not be reasonably explained by known characteristics of the 
patient’s clinical state. 
Possibly Related: 
This causal relationship is assigned when the AE starts a reasonable time after the 
administration of study treatment, but could be produced by the patient’s clinical 
state or other modes of therapy administered to the patient. 
Unlikely Related 
This causal relationship is assigned when the time association or the patient’s 
clinical state is such that the study treatment was not likely to have had an 
association with the observed AE. 
Not Related: 
This causal relationship is assigned when there is clearly no evidence of association 
with the study treatment and the observed AE. 
 
Pregnancy or lactation is an exclusion criterion for this study. Pregnancy per se is not 
considered an AE unless there is cause to believe that the study treatment may have 
interfered with the effectiveness of a contraceptive medication. Refer to Section 4.4 for 
details. 
9.1.5 
Adverse Event Follow-up 
All AEs occurring during the study are to be followed up in accordance with good medical 
practice until they are resolved, stabilized or judged no longer clinically significant or, if a 
chronic condition, until fully characterized. Any AEs that are considered drug-related 
(possibly related, probably related, or definitely related) must be followed until resolution or 
until stabilization. 
All unresolved AEs following the study should be followed by the investigator until the 
events are resolved, the patient is lost to follow-up, or the AE is otherwise explained. At the 
last scheduled visit, the investigator should instruct each patient to report any subsequent 
event(s) that the patient, or the patient’s personal physician, believes might reasonably be 
related to participation in this study. 
Prior to the conclusion of the study at the site, the investigator should notify the sponsor, 
Safety Associate, or designee of any death or AE occurring at any time after a patient has 
discontinued or terminated study participation that may reasonably be related to this study. 
After study conclusion, the investigator should notify the sponsor of any death or AE they are 
aware of occurring at any time after a patient has discontinued or terminated study 
participation that may reasonably be related to this study.  

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9.1.6 
Dosing Errors 
Any dosing errors should be immediately reported to the sponsor. The dosing error should be 
fully documented in the patient’s source documentation/eCRF and where applicable, filed 
promptly with IRB/IEC and regulatory authorities.  
Subsequent dosing shall be discontinued until the investigator and sponsor have both 
determined that it is safe to resume treatment.  
9.1.7 
Pregnancies 
No clinical data on the effects on pregnancy or lactation are available. Precautions relative to 
patients of reproductive potential are discussed in Section 4.4. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such. 
The female patients/pregnant female partner of male patients will be followed to determine 
the outcome of the pregnancy. The investigator will collect follow-up information on the 
female patients/pregnant female partner of male patients and the neonate and the information 
will be forwarded to the sponsor. 
9.2 
SERIOUS ADVERSE EVENT REPORTING 
9.2.1 
Reporting Requirements 
Any SAE made known to the investigator during the study must be reported by the 
investigator to the sponsor, whether or not the SAE is considered to be related to any 
component of the study treatment (PULSAR/IMSA101/ICI). An SAE report consists of the 
SAE form, the AE form, and the concomitant medication form.  
A copy of these forms must be forwarded within 24 hr of awareness. Contact details will be 
provided in the study reference manual.  
The investigator should not wait to receive additional information to document fully the 
event before notification of an SAE, though additional information may be requested. Where 
applicable, information from relevant laboratory results, hospital case records, and autopsy 
reports should be obtained. 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the investigator at 
any time after cessation of study treatment and linked by the investigator to this study, should 
be reported to the sponsor’s medical monitor. 
Progression of disease by itself is not considered an AE but rather an expected outcome and a 
study endpoint and should not be reported as AEs or SAEs, unless it results in hospitalization 

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or death. AEs associated with progressive disease (such as a pleural effusion or 
gastrointestinal obstruction) and associated hospitalizations to treat the AE or SAE are 
reportable events. 
The sponsor or delegate has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC, and investigators. 
The sponsor or delegate will notify the regulatory authorities of any unexpected fatal or life-
threatening suspected adverse reaction as soon as possible, but in no case later than 
7 calendar days after sponsor’s first knowledge of the event. A complete report should be 
provided within 15 calendar days after sponsor’s first knowledge of the event and must 
include an assessment of the importance and implication of the findings and/or previous 
experience on the same or similar medical products. 
Any suspected unexpected serious adverse reaction (SUSAR) that is not fatal or life-
threatening must be filed as soon as possible but no later than 15 calendar days after 
sponsor’s first knowledge of the event. Investigator safety reports must be prepared for 
SUSARs according to local regulatory requirements and sponsor policy and forwarded to 
investigators as necessary. 
 
 

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10 STATISTICAL METHODS 
The statistical analysis plan (SAP) will be finalized prior to database lock and it will include 
a more technical and detailed description of the statistical analyses described in this section. 
10.1 ANALYSIS DATASETS 
Analysis dataset 
Description 
Enrolled 
All patients who have signed the informed 
consent. 
Full Analysis Set (FAS) 
All enrolled patients.  
Randomized patients will be classified 
according to the treatment to which they are 
randomized. 
Safety Set (SAF) 
All patients receiving at least one dose of 
study treatment. 
The patients will be analyzed according to 
the group corresponding to the treatment 
that they actually receive. 
Intention-to-Treat (ITT) 
All patients who receive at least one dose of 
study treatment.  
Randomized patients will be classified 
according to the treatment to which they are 
randomized.  
The ITT set will be used for efficacy 
analyses. 
Per Protocol Set (PPS) 
All patients who receive at least one dose of 
study treatment and either undergo at least 
one post-baseline assessment or withdraw 
due to death or disease progression before 
any evaluation and have no major protocol 
violations, as defined by the sponsor prior 
to database lock.  
The PPS will be used for efficacy analyses. 
 

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10.2 DETERMINATION OF SAMPLE SIZE 
The total number of patients in each treatment arm will be as follows: 
a. Approximately 20 patients (10 NSCLC + 10 RCC) in the control arm (PULSAR-ICI) 
b. Approximately 20 patients (10 NSCLC + 10 RCC) in the experimental arm (PULSAR 
ICI + IMSA101), including 14 randomized patients and 6 patients in the safety run-in who 
are treated at the dose level selected for the experimental arm. 
The primary evaluation for efficacy is based on the proportion of patients remaining 
progression-free at 18 months after the start of the study treatment. The study is initially 
designed to enroll 40 patients. If the proportions of patients remaining progression-free at 18 
months after commencement of therapy is assumed to be 20% in the PULSAR+ICI arm and 
40% in the PULSAR+ICI+IMSA101 arm, a total of 40 subjects will provide 55% power, 
assuming a two-sided hypothesis test with a significance level of 20%. 
This study is designed for signal detection. A sample size adaptation may be considered in 
order to acquire adequate power under the control of type I error. A larger full-powered 
randomized trial may also be considered if the provocative signal of efficacy is detected in 
this study, even if the efficacy is not statistically significant.  
10.3 DATA PRESENTATION 
10.3.1 
General Considerations 
All measured variables and derived parameters will be listed and tabulated. Summary 
descriptive statistics will be provided for all safety, efficacy, and baseline/demographic 
variables. Data of all study sites and regions will be pooled for statistical analysis. Tabulation 
of results will be displayed by visit and by treatment/dose cohort and overall. 
Continuous variables will be summarized descriptively with number of patients, mean, 
median, standard deviation (SD), Q1, Q3, minimum and maximum. Categorical variables 
will be summarized with number and percentage of patients. 
For all endpoint measurements, the last non-missing values before the first administration of 
study treatment will be used as the baseline for the respective endpoints.  
Protocol deviations, including what generally constitutes major (important) or minor protocol 
deviations, are detailed in the SAP in accordance with International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) 
guidelines. All protocol deviations will be reviewed and classified as either important or 
minor by the clinical team.  

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10.3.2 
Disposition of Patients 
A tabulation of patient disposition will be presented by treatment arm, including the number 
in each analysis set, the number that withdrew prior to completing the study, and reason(s) 
for withdrawal. 
10.3.3 
Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be summarized by treatment arm in 
appropriate tables with descriptive statistics. 
Demographic and baseline characteristics to be captured include (but not necessarily limited 
to):  
• Age, gender, race 
• Smoking history 
• Tumor type 
• Body weight 
• Height 
• ECOG performance status 
• Disease history 
 
10.3.4 
Prior and Concomitant Medications 
All medications will be classified as follows: 
• Prior use ended before the first day of study treatment 
• Concomitant use on or after the first dose of study treatment 
 
The number and percentage of patients taking prior and concomitant medication will be 
summarized by treatment arm. 
10.3.5 
Safety Data 
All safety summaries will be provided for the SAF. 
Safety will be assessed through summaries of exposure to study treatment, adverse events, 
changes in laboratory test results, and changes in vital signs and ECGs. 
All safety variables will be presented in by-patient listings. Safety data will be listed by 
patient and treatment. Listings of all AEs will contain information of seriousness, severity, 
relationship, sequelae, and onset date and resolved date. 

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Study treatment exposure (treatment duration, number of cycles, dose intensity, and dose 
adjustment) will be summarized with descriptive statistics.  
All verbatim adverse event terms will be mapped to Medical Dictionary for Regulatory 
Activities (MedDRA) thesaurus terms, and adverse event severity will be graded according 
to CTCAE v5.0. All adverse events, serious adverse events, adverse events leading to death, 
grade ≥ 3 adverse events, and adverse events leading to study treatment discontinuation or 
interruption that occur on or after the initiation of study treatment will be summarized by 
system organ class and preferred terms, and by severity grade if necessary. For events of 
varying severity, the highest grade will be used in the summaries. Deaths and cause of death 
will be summarized. 
Relevant laboratory, vital sign (pulse rate, respiratory rate, blood pressure, pulse oximetry, 
and temperature), and ECG data will be displayed by time, with grades identified where 
appropriate.  
Additional analyses may be performed as indicated.  
10.3.6 
Primary Efficacy Data 
The primary efficacy analysis will be conducted on the ITT population, using the ITT 
principle: with patients grouped according to the study arm assigned at randomization, 
regardless of whether they receive any assigned study drug, cause of treatment 
discontinuation, etc. The number and proportion of subjects remaining progression-free at 18 
months after the start of the study treatment will be descriptively summarized by treatment 
group. The difference in progression-free rate at 18 months between treatment groups will be 
compared using Fisher’s exact test with the type I error controlled at a two-sided significance 
level of 0.2. The null and alternative hypotheses regarding the proportion of subjects 
remaining progression-free at 18 months after the start of the study treatment can be phrased 
in terms of PE and PC for experimental arm and control arm, respectively: 
H0: PE = PC versus H1: PE ≠ PC  
If a patient withdraws from the study before disease progression or death, and the disease 
progression status at 18 month is missing, this patient will be treated as PD. 
In addition, for the descriptive purpose, the point estimate of proportion of subjects 
remaining progression-free at 18 months after the start of the study treatment and its 95% 
Clopper-Pearson confidence interval (CI) will be provided for each treatment group. 
For the sensitivity analysis, if a patient withdraws from the study before disease progression 
or death, or any other reason causes the disease progression status at 18 month is missing, 
this patient will be excluded from the analysis. The Fisher’s exact test will be applied using 
the similar approach mentioned above. The point estimate of the proportion and its 95% CI 
will be provided as well. 
All these analyses will also be performed on PPS. 

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10.3.7 
Secondary Efficacy Data 
All efficacy summaries will be provided for the ITT and PPS. 
The proportion of patients remaining progression-free at 8-week intervals from 6 months to 
22 months after the start of the study treatment will be summarized by treatment group and 
be analyzed using the similar approaches for the primary efficacy endpoint. 
TTP, defined as the time from commencement of therapy to progression based on RECIST 
Version 1.1 and iRECIST. Patients who are not progressed at the time of the analysis will be 
censored at the time of last tumor assessment on or prior to the clinical cutoff date. TTP will 
be estimated using Kaplan-Meier methods by treatment arm and displayed graphically. 
Median event times and two-sided 95% CI for each median will be provided based on the 
Brookmeyer-Crowley method. 
PFS is defined as the time from commencement of therapy to progression or any cause of 
death based on RECIST Version 1.1 and iRECIST. Patients who have not experienced 
progression or died at the time of analysis will be censored at the date of the last evaluable 
assessment. PFS will be estimated using Kaplan-Meier methods by treatment arm and 
displayed graphically. Median event times and two-sided 95% CI for each median will be 
provided based on the Brookmeyer-Crowley method. A two-sided log-rank test might be 
used to compare PFS between the two arms, if needed. 
DOR is defined as the time from the first occurrence of a documented objective response to 
disease progression or death from any cause (whichever occurs first), based on RECIST 
Version 1.1 and iRECIST. Patients who have not progressed and who have not died at the 
time of the analysis will be censored at the time of last tumor assessment on or prior to the 
clinical cutoff date. The analysis methods are similar to those described for TTP. 
Objective response (OR) is defined as a complete or partial response based on RECIST 
Version 1.1 and iRECIST. Patients not meeting these criteria, including patients without any 
post-baseline tumor assessment, will be considered non-responders. ORR, defined as the 
percentage of patients who have an objective response, will be estimated for each treatment 
arm. The respective 95% CIs will be calculated using the Clopper-Pearson method.  
10.3.8 
Quality of Life Data 
The QoL summary will be provided for the ITT and PPS. 
QoL data will be summarized using descriptive statistics. 
10.3.9 
Missing Data 
Missing values will be regarded as missing. No imputation method will be applied for 
missing data transformation. Analyses will be performed using the available data points. 
The missing components of incomplete dates will be assumed as the most conservative value 
possible. For example, if the start date has a missing day value, the first day of the month will 

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be imputed for study day computations. If day is missing for an end date, the last day of the 
month will be imputed. Similar logic will be assumed for missing month and year 
components. 
Missing severities of AEs will not be imputed and will be considered missing in any 
tabulations of AE severity. If an AE is missing relationship to treatment, the event will be 
considered to be related. 
Actual values, as they appear in the original eCRFs, will be presented in the patient data 
listings. 
10.3.10 Futility Analysis 
A futility analysis for the experimental arm is planned when the tenth (10th) patient treated at 
the selected dose level has had the opportunity to reach 6 months. If 7 out of 10 patients have 
progressed or died, the study will be declared futile. Additional details will be described in 
the SAP. 
10.4 CHANGES IN THE CONDUCT OF THE STUDY OR PLANNED 
ANALYSIS 
Any changes or addition to the protocol can only be made in a written protocol amendment 
that must be approved by the sponsor, the IRB/IEC, and the regulatory authorities prior to 
implementation. 
 
 

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11 REGULATORY, ETHICAL AND LEGAL OBLIGATIONS 
11.1 DECLARATION OF HELSINKI 
The principal investigator will ensure that this study is conducted in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki and applicable national 
and local laws (World Medical Association [WMA], 2013). 
11.2 GOOD CLINICAL PRACTICE 
The study will be conducted according to the study protocol and to Standard Operating 
Procedures (SOPs) that meet the guidelines provided by the ICH for GCP in clinical studies 
(ICH E6(R2), 2016). 
11.3 INSTITUTIONAL REVIEW BOARDS/ETHICS COMMITTEES 
Before implementing this study, the protocol, amendments (if any), the proposed informed 
consent forms (ICFs), patient recruitment procedures (eg, advertisements), and other 
information for the patients must be reviewed by the appropriate IRB/IEC at each study 
center in conformance with ICH E6(R2), the Code of Federal Regulations (CFR), Title 21, 
Part 56 and any other applicable local laws. The IRB/IEC written, signed approval 
letter/form must contain approval of the designated principal investigator, the protocol 
(identifying protocol title, date, and version number), and of the ICF (date, version). 
The investigator is responsible for supplying the IRB/IEC with a copy of the current IB, 
Package Insert, or Summary of Product Characteristics (SmPC) as well as any updates issued 
during the study. During the course of the study, the investigator will provide timely and 
accurate reports to the IRB/IEC on the progress of the study, at intervals not exceeding 1 year 
(or as appropriate) and will notify the IRB/IEC of SAEs or other significant safety findings, 
per the policy of the IRB/IEC. 
11.4 REGULATORY AUTHORITY APPROVAL 
Any change or addition to the protocol can only be made in a written protocol amendment 
that must be approved by the sponsor, the IRB/IEC, and/or other agency if applicable. 
11.5 INFORMED CONSENT 
The investigator must fully inform the patient (or the patient’s legal representative, if 
applicable) of all pertinent aspects of the study including the written information approved by 
the IRB/IEC. 
Prior to the start of the pre-study examination, the written ICF must be signed and personally 
dated by the patient (or by the legally authorized representatives) and by the physician who 
conducted the informed consent discussion. One copy of the written information and signed 
consent form must be given to the patient and the original copy must be retained in the 

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investigator’s study records. Patients must be reconsented to the most current version of the 
ICF(s) during their participation in the study. 
11.6 PATIENT CONFIDENTIALITY AND DISCLOSURE 
In compliance with federal regulations/ICH GCP Guidelines, it is required that the 
investigator and institution permit authorized monitors, auditors, and other authorized agents 
of the sponsor and/or its designee, the IRB/IEC approving this research, and the US FDA, as 
well as that of any other applicable agency or agencies, direct access to review the patient’s 
original medical records for verification of study-related procedures and data. The 
investigator is obligated to inform the patient that his/her study-related records will be 
reviewed by the above-named representatives without violating the confidentiality of the 
patient.  
All personal data collected and processed for the purposes of this study should be managed 
by the investigator and his/her staff with adequate precautions to ensure confidentiality of 
those data, and in accordance with the Health Insurance Portability and Accountability Act 
(HIPAA), applicable to national and/or local laws and regulations on personal data protection 
(US HHS, 2002). 
The investigator must ensure that each patient’s anonymity will be strictly maintained. On 
eCRFs or other documents submitted to the sponsor, patients must not be identified by their 
name, but by an identification code consisting of the identification number. If patients’ 
names are included on copies of documents submitted to the sponsor, the names must be 
obliterated, and the assigned identification number must be added to the documents instead. 
11.7 PROTOCOL AMENDMENT 
Before the start of the study, the study protocol, informed consent document, and any other 
appropriate documents (or amendments) will be submitted to the appropriate authorities such 
as the FDA and/or local IRB/IEC with a cover letter or a form listing the documents 
submitted, their intended dates of issue, and the site (or region or area of jurisdiction, as 
applicable) for which approval is sought. If applicable, the documents will also be submitted 
to the authorities in accordance with local legal requirements. 
The investigator should not implement any deviation from, or changes of, the protocol 
without agreement by the sponsor and prior review and documented approval from the 
IRB/IEC of an amendment. The only exceptions are where necessary to eliminate an 
immediate hazard(s) to study patients, or when the change(s) involves only logistical or 
administrative aspects of the study (eg, change in monitor[s], change of telephone 
number[s]). Non-substantial protocol amendments may or may not be required to be 
submitted for approval/notification to the appropriate authorities (ie, FDA, IRB/IEC).  
As soon as possible, the implemented deviation or change, the reasons for it, and, if 
appropriate, the proposed protocol amendment(s) should be submitted: 
• to the appropriate authorities for review and approval/favorable opinion 

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• to the sponsor for agreement 
 
The party initiating an amendment must confirm it clearly in writing and it must be signed 
and dated by the sponsor and the principal investigator. The sponsor or its designee will 
ensure that the investigators submit necessary protocol amendments to the appropriate 
IRB/IEC. 
All agreed protocol amendments must be clearly documented using standard procedures as 
defined by the sponsor and must be signed and dated by the sponsor and the investigator. 
11.8 COLLECTION, MONITORING AND AUDITING STUDY 
DOCUMENTATION 
11.8.1 
Data Collection 
The sponsor or the designee will utilize qualified monitors to review and evaluate activities 
conducted at investigator sites for Quality Assurance. 
Data for each patient will be recorded on an eCRF. Data collection must be completed for 
each patient who signs an ICF and is administered treatment. 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the sponsor (or designee). Data will be processed and analyzed 
following procedures defined by the sponsor (or designee). 
The medical monitor will review any SAEs that occur during the study.  
In accordance with ICH GCP guidelines, the study monitor will carry out source document 
verification at regular intervals to ensure that the data collected in the eCRF are accurate and 
reliable. 
Data that is not captured directly via an electronic device or instrument will be collected from 
source documents and entered into an eCRF within an electronic data capture system. 
Electronic data capture security features will include the requirement for a unique user 
identification and password for each individual who make entries, reviews, or makes changes 
to the data. 
The investigator will be responsible for ensuring data is electronically captured or that it is 
entered into the eCRF in a timely manner relative to the patient visit. The investigator will 
ensure the accuracy and completeness of all patient data specified in the protocol. Upon 
study completion, the data collected in the eCRF will be provided to each study center in 
portable document format (PDF). 

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11.8.2 
Study Monitoring 
A representative of the sponsor or the designee will meet with the investigator and his/her 
staff prior to the entrance of the first patient to review study procedures and methods of 
recording study data.  
After enrollment of the first patient, representative of the sponsor or the designee will be 
assigned to monitor at least once a year each study site for study progress and to verify that 
standards of GCP and/or ICH guidelines were followed. The investigator is expected to 
prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms, and other study-related documents are readily available for review. Source 
documents that will be reviewed include but are not limited to accuracy of eCRFs, protocol 
compliance, accuracy of entries and AE/SAE management and reporting. Documentation of 
monitoring will be maintained along with other protocol-related documents and will be 
reviewed during internal audit. 
11.8.3 
Auditing of Study Documentation 
Study centers and study documentation may be subject to a Quality Assurance audit at any 
time during or after the study. In addition, inspections may be conducted by regulatory 
authorities at their discretion.  
The investigator must permit the monitor, the IRB/IEC, the sponsor’s internal auditors, and 
representatives from regulatory authorities, direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the eCRFs. 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted, and data are generated, documented (recorded), and reported in compliance with 
the study protocol; ICH E6(R2) consolidated guidelines; and other applicable regulations. 
The extent, nature, and frequency of monitoring and/or audits will be based on such 
considerations as the study objectives and/or endpoints, the purpose of the study, study 
design complexity, and enrollment rate. At the conclusion of a program, a compliance 
statement will be generated by the sponsor (or designee) listing all audit activities performed 
during the clinical study. 
All data recordings and source documentation (including electronic health records) must be 
made available to the sponsor (or designee), FDA, IRB/IEC, and any other regulatory 
agencies that request access to study records, including source documents, for inspection and 
copying, in keeping with federal and local regulations. 
11.9 RECORD RETENTION 
According to the ICH guidelines, source documentation and other “essential documents” 
must be archived. Essential documents include those documents which individually and 
collectively permit the evaluation of the conduct of a study and the quality of the data 
produced (ICH E6(R2), 2016). This may include observations and source data contained in 
medical records (certified copies or originals are acceptable for archiving purposes), data 

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collection forms or eCRFs and research-related records held in support departments. All hard 
copies of source documents must be retained. If electronic records of documents exist, these 
must be backed up and retained with the hard copies.  
Essential documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study drug. However, these documents should 
be retained for a longer period if required by the applicable legal requirements and/or written 
agreements with the sponsor (ie, Master Service Agreement).  
The IRB/IEC should retain all relevant records (eg, written procedures, membership lists, 
lists of occupations/affiliations of members, submitted documents, minutes of meetings, and 
correspondence) for a period of at least 3 years after completion of the study and make them 
available upon request from the regulatory authorities.  
11.10 DISCLOSURE OF INFORMATION 
All information provided to the investigator by the sponsor or its designee, will be kept 
strictly confidential. No disclosure will be made except in accordance with a right of 
publication granted to the investigator. 
No information about this study or its progress will be provided to anyone not involved in the 
study other than to the sponsor or its authorized representatives, or in confidence to the IRB, 
or similar committee, except if required by law. 
11.11 DISCONTINUATION OF THE STUDY 
It is agreed that, for reasonable cause, either the investigator or sponsor may terminate the 
investigator’s participation in this study after submission of a written notice. The sponsor 
may terminate the study at any time upon immediate notice for any reason, including the 
sponsor’s belief that discontinuation of the study is necessary for the safety of patients. 
11.12 STUDY REPORT, PUBLICATION POLICY AND ARCHIVING OF 
STUDY DOCUMENTATION 
An ICH-compliant integrated clinical and statistical report will be prepared upon completion 
of the study and data analysis. The results of the study will be published in a relevant peer-
reviewed journal, with authorship status and ranking designated according to the 
acknowledged contributions of participating investigators, institutions, and the sponsor.  
11.12.1 Data Capture 
This study will use a 21 CFR Part 11 compliant electronic data capture system. An eCRF will 
be used for data recording. Any data requested on the eCRF must be entered and a reasonable 
effort should be made to retrieve any missing data.  

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The data will be checked for completeness and correctness and discrepancy reports will be 
generated accordingly and transferred to the study center for resolution by the investigator or 
his/her designee. 
Accurate and reliable data collection will be assured by verification and cross-check of the 
eCRF against the investigator’s records by the study monitor (source document verification), 
and the maintenance of a study drug accountability log by the investigator. 
11.12.2 Study Documents 
The investigator must maintain source documents for each patient in the study, including all 
demographic and medical information, laboratory data, ECGs, etc., and keep a copy of the 
signed and dated ICFs. All information on the eCRFs must be traceable to these source 
documents in the patient’s file. Data without a written or electronic record will be defined 
before study start and will be recorded directly on the eCRFs, which will be documented as 
being the source data. 
11.12.3 Archiving of Documents 
Essential documents, as listed below, must be retained by the investigator for as long as 
needed to comply with national and international regulations. The sponsor will notify the 
investigator(s)/institution(s) when the study-related records are no longer required. The 
investigator agrees to adhere to the document retention procedures by signing the protocol. 
Essential documents include: 
1. IRB/IEC/research ethics board approvals for the study protocol and all amendments 
2. All source documents and laboratory records 
3. CRF copies (electronic copies on a CDROM) 
4. Patients’ ICFs (with study number and title of trial) 
5. FDA form 1572 
6. Any other pertinent study documents 
 
 
 

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12 REFERENCES 
Aduro Biotech Inc. 2016. ClinicalTrials.gov ID#: NCT02675439. Safety and Efficacy of 
MIW815 (ADU-S100) +/- Ipilimumab in Patients with Advanced/Metastatic Solid Tumors 
or Lymphomas. Available from: https://clinicaltrials.gov/ct2/show/NCT02675439. 
Akanda ZZ, Neeson PJ, John T, et al. A narrative review of combined stereotactic ablative 
radiotherapy and immunotherapy in metastatic non-small cell lung cancer. Transl. Lung 
Cancer Res. 2021;10(6):2766-2778. 
Amin NP, Zainib M, Parker SM, Agarwal M, Mattes MD. Multi-institutional report on 
toxicities of concurrent nivolumab and radiation therapy. Adv Radiat Oncol. 2018 May 
24;3(3):399-404. doi: 10.1016/j.adro.2018.04.015. 
Ansari J, Farrag A, Ali A, et al. Concurrent use of nivolumab and radiotherapy for patients 
with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic 
disease progression on nivolumab. Mol Clin Oncol. 2021;15(4):214. doi: 
10.3892/mco.2021.2376. 
Bauml JM, Mick R, Ciunci C, et al. Pembrolizumab After Completion of Locally Ablative 
Therapy for Oligometastatic Non-Small Cell Lung Cancer: A Phase 2 Trial. JAMA Oncol. 
2019;5(9):1283-1290. doi:10.1001/jamaoncol.2019.1449. 
Begg AC, Stewart FA, Vens C. Strategies to improve radiotherapy with targeted drugs. Nat 
Rev Cancer. 2011;11(4):239-253. doi:10.1038/nrc3007. 
Belluomini L, Fiorica F, Frassoldati A. Immune Checkpoint Inhibitors and Radiotherapy in 
NSCLC Patients: Not Just a Fluke. Oncol Ther. 2019;7(1):83-91. doi:10.1007/s40487-019-
0092-z 
Bonaventura P, Shekarian T, Alcazer V, et al. Cold Tumors: A Therapeutic Challenge for 
Immunotherapy. Front Immunol. 2019;10:168. doi: 10.3389/fimmu.2019.00168. 
Bose D. cGAS/STING Pathway in Cancer: Jekyll and Hyde Story of Cancer Immune 
Response. Int J Mol Sci. 2017;18(11):2456. doi:10.3390/ijms18112456 
Boustani J, Lecoester B, Baude J, et al. Anti-PD-1/Anti-PD-L1 Drugs and Radiation 
Therapy: Combinations and Optimization Strategies. Cancers (Basel). 2021;13(19):4893. 
Cella DF, Tulsky DS, Gray G, et al.: The functional assessment of cancer therapy scale: 
development and validation of the general measure. J Clin Oncol. 1993;11:570–579. 
Chen YH, Ho UC, Kuo LT. Oligometastatic Disease in Non-Small-Cell Lung Cancer: An 
Update. Cancers (Basel). 2022;14(5):1350. doi: 10.3390/cancers14051350. 
Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. 
Nephron. 1976;16(1):31–41. 

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Deng L, Liang H, Burnette B, et al. Irradiation and anti-PD-L1 treatment synergistically 
promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687-695. 
doi:10.1172/JCI67313 
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. 
Gillams AR. Complications of percutaneous therapy. Cancer Imaging. 2005;5(1):110-3. doi: 
10.1102/1470-7330.2005.0017. 
Harrington KJ, J. Brody, M. Ingham, et al. Preliminary Results of the First-in-Human Study 
of MK-1454, an Agonist of Stimulator of Interferon Genes (STING), as Monotherapy and in 
Combination With Pembrolizumab in Patients With Advanced Solid Tumors or Lymphomas. 
In European Society for Medical Oncology Congress. 2018: Munich, Germany. 
He K, Barsoumian HB, Sezen D, et al. Pulsed Radiation Therapy to Improve Systemic 
Control of Metastatic Cancer. Front Oncol. 2021;11:737425. 
Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13(1):8-10. 
doi:10.1200/JCO.1995.13.1.8 
International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH). Integrated Addendum to ICH E6(R1): Guideline for 
Good Clinical Practice E6(R2). November 09, 2016. Accessed July 25, 2022. 
https://database.ich.org/sites/default/files/E6_R2_Addendum.pdf. 
Investigator’s Brochure of IMSA101 Version 4.0 dated 13-Sep-2023. ImmuneSensor 
Therapeutics.  
Iyengar P, Wardak Z, Gerber DE, et al. Consolidative Radiotherapy for Limited Metastatic 
Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 
2018;4(1):e173501. doi:10.1001/jamaoncol.2017.3501 
KEYTRUDA® (Pembrolizumab). Prescribing Information. Merck & Co., Inc. Accessed July 
29, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s096lbl.pdf. 
Kho VM, Mekers VE, Span PN, Bussink J, Adema GJ. Radiotherapy and cGAS/STING 
signaling: Impact on MDSCs in the tumor microenvironment. Cell Immunol. 
2021;362:104298. doi:10.1016/j.cellimm.2021.104298 
Ko EC, Formenti SC. Radiotherapy and checkpoint inhibitors: a winning new combination? 
Ther Adv Med Oncol. 2018;10:1758835918768240. Published 2018 Apr 11. 
doi:10.1177/1758835918768240 
Li T, Cheng H, Yuan H, et al. Antitumor Activity of cGAMP via Stimulation of cGAS-
cGAMP-STING-IRF3 Mediated Innate Immune Response. Sci Rep. 2016;6:19049. 
doi:10.1038/srep19049 

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Liu YT, Sun ZJ. Turning cold tumors into hot tumors by improving T-cell infiltration. 
Theranostics. 2021;11(11):5365-5386. doi: 10.7150/thno.58390. 
Lo SS, Sahgal A, Chang EL, et al. Serious complications associated with stereotactic ablative 
radiotherapy and strategies to mitigate the risk. Clin Oncol (R Coll Radiol). 2013;25(6):378-
387. doi:10.1016/j.clon.2013.01.003 
Merck Sharp & Dohme Corp. 2017. ClinicalTrials.gov ID#: NCT03010176. Study of MK-
1454 Alone or in Combination with Pembrolizumab in Participants with 
Advanced/Metastatic Solid Tumors or Lymphomas (MK-1454-001). Available from: 
https://clinicaltrials.gov/ct2/show/NCT03010176. 
Meric-Bernstam F. et al. Phase I Dose-finding Study of MIW815 (ADU-S100), an Intra-
tumoral STING Agonist, in Patients With Advanced Solid Tumors or Lymphomas, in The 
Society for Immunotherapy of Cancer. 2018: Washington DC. 
Moore C, Hsu CC, Chen WM, et al. Personalized Ultra-Fractionated Stereotactic Adaptive 
Radiotherapy (PULSAR) in Preclinical Models Enhances Single Agent Immune Checkpoint 
Blockade. Int J Radiat Oncol Biol Phys. 2021;110(5):1306–16. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-655. 
OPDIVO® (Nivolumab). Prescribing Information. Bristol-Myers Squibb Company. Accessed 
July 19, 2022. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125554s058lbl.pdf 
Seymour L, Bogaerts J, Perrone A, et al. iRECIST: guidelines for response criteria for use in 
trials testing immunotherapeutics. Lancet Oncol. 2017;18(3):e143-e152. doi: 10.1016/S1470-
2045(17)30074-8. Epub 2017 Mar 2. Erratum in: Lancet Oncol. 2019 May;20(5):e242.  
Siva S, Louie AV, Warner A, et al. Pooled analysis of stereotactic ablative radiotherapy for 
primary renal cell carcinoma: A report from the International Radiosurgery Oncology 
Consortium for Kidney (IROCK). Cancer. 2018;124(5):934-942. doi:10.1002/cncr.31156 
Siva S, Bressel M, Wood ST, et al. Stereotactic Radiotherapy and Short-course 
Pembrolizumab for Oligometastatic Renal Cell Carcinoma-The RAPPORT Trial. Eur Urol. 
2022;81(4):364-372. 
Spyropoulou D, Tsiganos P, Dimitrakopoulos FI, et al. Radiotherapy and Renal Cell 
Carcinoma: A Continuing Saga. In Vivo. 2021;35(3):1365-1377. 
Theelen WSME, Peulen HMU, Lalezari F, et al. Effect of Pembrolizumab After Stereotactic 
Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With 
Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized 
Clinical Trial. JAMA Oncol. 2019;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.  

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Tumati V, Iyengar P. The current state of oligometastatic and oligoprogressive non-small cell 
lung cancer. J Thorac Dis. 2018;10(Suppl 21):S2537-S2544. 
United States Department of Health and Human Services. Health Insurance Portability and 
Accountability (HIPAA). 5 CFR Part 160 and Subparts A and E of Part 164. August 14, 
2002. 
Wang H, Hu S, Chen X, et al. cGAS is essential for the antitumor effect of immune 
checkpoint blockade. Proc Natl Acad Sci U S A. 2017;114(7):1637-1642. 
doi:10.1073/pnas.1621363114 
Welsh J, Menon H, Chen D, et al. Pembrolizumab with or without radiation therapy for 
metastatic non-small cell lung cancer: a randomized phase I/II trial. J Immunother Cancer. 
2020;8(2):e001001. doi: 10.1136/jitc-2020-001001.  
World Medical Association (WMA). The World Medical Association Declaration of 
Helsinki - Ethical Principles for Medical Research Involving Human Patients. 2013. 
Yum S, Li M, Chen ZJ. Old dogs, new trick: classic cancer therapies activate cGAS. Cell 
Res. 2020;30(8):639-648. doi:10.1038/s41422-020-0346-1 
 

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13 APPENDICES 
13.1 EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE SCALE  
ECOG PERFORMANCE STATUS* 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, eg, light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or 
chair 
5 
Dead 
Source: Oken et al., 1982  
 

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13.2 RECIST VERSION 1.1 GUIDELINE 
All tumor assessment findings will be evaluated for response according to RECIST 
Version 1.1 (Eisenhauer et al., 2009) at the scheduled time points in Table 1.  
All patients will have their BEST RESPONSE on study classified as outlined below: 
RECIST Version 1.1 Lesion Response  
Evaluation of target lesions 
Complete response (CR):  
Disappearance of all extranodal target lesions. All 
pathological lymph nodes must have decreased to 
< 10 mm in short axis  
Partial response (PR):  
At least a 30% decrease in the sum of diameters of 
target lesions, taking as reference the Baseline sum 
of diameters  
Progressive disease (PD):  
At least a 20% increase in the sum of diameters of 
target lesions from the smallest value on trial 
(including Baseline, if that is the smallest). The sum 
of diameters must also demonstrate an absolute 
increase of at least 5 mm. Or, the appearance of one 
or more new lesions  
Stable disease (SD):  
Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD  
Evaluation of nontarget lesions  
Complete response (CR):  
Disappearance of all extranodal nontarget lesions, 
all lymph nodes must be nonpathological in size 
(< 10 mm in short axis), and normalization of tumor 
marker level  
Non-CR/Non-PD:  
Persistence of 1 or more nontarget lesion(s) or/and 
maintenance of tumor marker level above the 
normal limits  
Progressive disease (PD):  
Unequivocal progression of existing nontarget 
lesions. Or, the appearance of one or more new 
lesions  
Note: Evaluations for target, nontarget, and new lesions are to be considered together to 
assess an overall response status.  
Source: Eisenhauer et al., 2009 
Response Duration 
Response duration will be measured from the time measurement criteria for CR/PR 
(whichever is first recorded) are first met until the first date that recurrent or progressive 
disease is objectively documented, taking as reference the smallest measurements recorded 
on study (including baseline). 

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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. 
Method of Measurement 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during the study. All lesions recorded at 
baseline should have their actual measurements recorded at each subsequent evaluation, even 
when very small (eg, 2 mm). If it is the opinion of the radiologist that the lesion has likely 
disappeared, the measurement should be recorded as 0 mm. If the lesion is believed to be 
present and is faintly seen but too small to measure, a default value of 5 mm should be 
assigned. For lesions which fragment/split add together the longest diameters of the 
fragmented portions; for lesions which coalesce, measure the maximal longest diameter for 
the “merged lesion”. 
CT / MRI  
CT and MRI might be the best currently available and reproducible methods to measure 
target lesions selected for response assessment. CT and MRI should be performed with cuts 
of 5 mm or less in slice thickness contiguously.  
 

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13.3 IMMUNE-BASED RECIST (IRECIST) GUIDELINE 
All tumor assessment findings will also be evaluated for response according to iRECIST 
(reviewed in Seymour et al., 2017) at the scheduled time points in Table 1. 
Immunotherapy 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 Version 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. 
Note: “i” indicates immune responses assigned using iRECIST. 
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 Version 1.1 definitions 
of progression had been met (from nadir) in target, non-target disease or new lesions 
- 
Progression in target disease worsens with an increase of at least 5 mm in the absolute 
value of the sum 
- 
Continued unequivocal progression in non-target disease with an increase in tumor 
burden 
- 
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 Version 1.1 criteria are met in lesion 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 
providing that iCPD is not documented at the next assessment after iUPD. 
The same definitions of Response Duration and Stable Disease Duration applied for RECIST 
Version 1.1 also apply for iRECIST. 

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Time Point Response of iRECIST 
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 
iPR 
Non-iCR/Non- 
iUPD 
No 
iPR 
iPR 
iSD 
Non-iCR/Non- 
iUPD 
No 
iSD 
iSD 
iUPD 
with 
no 
change  
OR 
decrease 
from last 
time point 
iUPD with no 
change 
OR 
decrease from 
last time point 
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 time 
point, remains iUPD 
iSD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based in 
further increase in size of NT disease (need not 
meet RECIST Version 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 

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•  size or number of new lesions previously 
identified 
Abbreviations: iCPD = confirmed progression; iCR = complete response; iPR = partial response; 
iSD = stable disease; iUPD = unconfirmed progression; NA = not applicable; NL = new lesion; 
NT = non-target; SOM = sum of measures 
* Using RECIST Version 1.1 principles. If no PSPD occurs, RECIST Version 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 time point. 
Source: Seymour et al., 2017 
 
All patients will have their Best Overall Response from the start of study treatment until the 
end of treatment classified as outlined below. 
Best Overall Responses of iRECIST 
TPR1 
TPR2 
TPR3 
TPR4 
TPR5 
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. 
BOR = best overall response; NE = not evaluable in that cycle; TPR = response at that time point. 
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. 
Source: Seymour et al., 2017 
 
The same Method of Measurement applied for RECIST Version 1.1 also apply for iRECIST. 

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13.4 CREATININE CLEARANCE  
Creatinine clearance will be calculated using the Cockcroft-Gault formula (Cockcroft and 
Gault, 1976) as follows: 
Females: 
For serum creatinine concentration in mg/dL: 
CrCl = (140 – age in years) x Weight (kg) x 0.85  
72 x serum creatinine in mg/dL 
 
Males: 
For serum creatinine concentration in mg/dL: 
CrCl = (140 – age in years) x Weight (kg) x 1.00  
72 x serum creatinine in mg/dL 
 
 
 

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13.5 CONTACT LIST 
SPONSOR: 
 
  
 
Vice President, 
Clinical Operations and Project Management 
ImmuneSensor Therapeutics