A Phase 2 Clinical Study of TJ004309 in Combination With Atezolizumab (TECENTRIQ®) in Patients With Advanced or Metastatic Ovarian Cancers and Selected Advanced Solid Tumors
Phase: PHASE2
Conditions: Ovarian Cancer, Head and Neck Cancer, Non Small Cell Lung Cancer, Gastrointestinal Cancer, Triple Negative Breast Cancer, Ovarian Carcinoma
Sponsor: I-Mab Biopharma US Limited

 
Compound Name:  TJ004309 
Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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A PHASE 2 CLINICAL STUDY OF TJ004309 IN COMBINATION WITH 
ATEZOLIZUMAB (TECENTRIQ®) IN PATIENTS WITH ADVANCED OR 
METASTATIC OVARIAN CANCERS AND SELECTED ADVANCED 
SOLID TUMORS 
 
Protocol Number:  
TJ004309STM103 
Compound Name:  
TJ004309 
Study Phase:  
Phase 2 
Sponsor Name:  
I-Mab Biopharma US Limited 
Legal Registered Address:  
9801 Washingtonian Blvd, Suite 710 
Gaithersburg, MD  20878 
USA  
Regulatory Agency Identifier 
Number(s): 
IND: 156151 
Version (Approval Date): 
3.0 (30 September 2021) 
This study will be conducted in accordance with the ethical principles of Good Clinical Practice, 
according to the International Council for Harmonisation Tripartite Guideline. 
 
CONFIDENTIALITY NOTE: 
The information contained in this document is privileged and confidential. Any distribution, copying, or disclosure 
is strictly prohibited unless such disclosure is required by federal regulations or state law. Persons to whom the 
information is disclosed must know that it is confidential and that it may not be further disclosed by them. 

 
Compound Name:  TJ004309 
Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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Sponsor Signatory: 
Claire (Cong) Xu, MD, PhD 
US Site Head 
 
Date 
Sponsor Study Contact Information 
Claire (Cong) Xu, MD, PhD  
US Site Head  
I-Mab Biopharma US Limited  
Office Telephone: 240-767-9681  
Mobile Telephone:  317-755-8242  
E-mail:  Claire.Xu@i-mabbiopharma.com  
 
10/1/2021 | 11:31:40 AM EDT

 
Compound Name:  TJ004309 
Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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INVESTIGATOR AGREEMENT 
 
 
I have read the protocol and agree to conduct the study as described herein. 
 
 
 
 
 
 
Principal Investigator (Printed) 
 
 
 
 
 
 
Principal Investigator (Signature) 
Date 
 
 
 
 
Clinical Site 
 
 
By my signature, I agree to personally supervise the conduct of this study at my study site 
and to ensure its conduct is in compliance with the protocol, informed consent, Institutional 
Review Board (IRB)/Ethics Committee (EC) procedures, instructions from I-Mab Biopharma 
US Limited representatives, the Declaration of Helsinki, ICH Good Clinical Practices 
Guidelines, and local regulations governing the conduct of clinical studies. 
 
 
 

 
Compound Name:  TJ004309 
Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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STUDY IDENTIFICATION 
Sponsor 
I-Mab Biopharma US Limited 
9801 Washingtonian Blvd, Suite 710 
Gaithersburg, MD, 20878 
Sponsor’s Study Contact 
Claire (Cong) Xu, MD, PhD 
US Site Head 
I-Mab Biopharma US Limited 
9801 Washingtonian Blvd, Suite 710 
Gaithersburg, MD, 20878 
 
Sponsor’s Medical Contact  
Claire (Cong) Xu, MD, PhD 
US Site Head 
I-Mab Biopharma US Limited 
9801 Washingtonian Blvd, Suite 710 
Gaithersburg, MD, 20878 
Tel: 240-767-9681 
Tel (after hours): 317-755-8242 
 
Study Sites  
Obtain information from Form FDA 1572 
Principal Investigators 
Obtain information from Form FDA 1572 
Bioanalytical Laboratory 
Frontage Laboratory 
700 Pennsylvania Drive 
Exton, PA 19341 
 
Immunogenicity Laboratory 
Frontage Laboratory 
700 Pennsylvania Drive 
Exton, PA 19341 
 
Immunohistochemistry 
Laboratory (Tumor Analyses)  
GoPath Laboratories, LLC 
1351 Barclay Boulevard  
Buffalo Grove, IL 60089  
 
WuXi AppTec Co, Ltd 
288 Fute Middle Rd 
Pilot Free Trade Zone 
Shanghai, China 
 
 
 
 
 
 

 
Compound Name:  TJ004309 
Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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1 PROTOCOL SUMMARY 
1.1 Synopsis 
Name of Sponsor/Company: I-Mab Biopharma US Limited 
Title of Study:  
A PHASE 2 CLINICAL STUDY OF TJ004309 IN COMBINATION WITH ATEZOLIZUMAB 
(TECENTRIQ®) IN PATIENTS WITH ADVANCED OR METASTATIC OVARIAN CANCERS 
AND SELECTED ADVANCED SOLID TUMORS 
Name of Investigational Product: TJ004309 
Principal Investigators: To be determined 
Rationale:  
TJ004309 is an investigational antibody to CD73, an ectonucleotidase that converts AMP to adenosine 
and inorganic phosphate. Adenosine inhibits tumor immune surveillance by binding to the A2A and 
A2B adenosine receptors. TJ004309 non-competitively inhibits CD73-mediated conversion of AMP to 
adenosine, thereby reversing adenosine mediated immune suppression in T cells. Adenosine mediated 
by CD73 is implicated as a mechanism of resistance to PD-1/PD-L1 checkpoint inhibitors.  TJ004309 
inhibits tumor growth and complements the activity of antibody checkpoint inhibitors that target the 
PD-1/PD-L1 pathway in preclinical models. By targeting the adenosine pathway, TJ004309 has the 
potential to complement the PD-L1/PD-1 checkpoint inhibitor such as atezolizumab in cancer patients. 
Atezolizumab is a humanized monoclonal antibody to PD-L1 that is approved for the treatment of 
locally advanced or metastatic urothelial carcinoma and indicated for the treatment of several other 
indications, which will be combined with TJ004309 in this trial.  
Based on the published database and literature reports, CD73 is highly expressed in head and neck 
squamous cell carcinoma (60-80%), ovarian (50-70%), gastric (50-69%), and other cancers. To further 
test the hypothesis that the tumor types with high CD73 expression may better respond to the 
combination therapy, a tumor biomarker enriched cohort is planned to enroll patients with non-small 
cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple negative breast 
cancer (TNBC), ovarian carcinoma (OC), and gastric cancers (GC) to assess the relationship between 
antitumor activity and various tumor biomarkers. 
The enrollment of dose escalation of TJ004309 in combination with atezolizumab has been completed 
in a Phase 1 trial NCT03835949 under IND 141965. In the 3+3 dose escalation study, TJ004309 was 
administered intravenously at doses of 5, 10 or 15 mg/kg weekly (QW), or 15 or 20 mg/kg every 3 
weeks (Q3W) as a monotherapy in the first 21-day treatment cycle followed by combination therapy 
with atezolizumab (1200 mg Q3W) starting from the second cycle (week 4). No dose limiting toxicity 
(DLT) was observed and maximum tolerated dose (MTD) was not reached. Among 13 efficacy 
evaluable patients dosed ≥ 10 mg/kg, a complete response (CR = 1) and partial responses (PR = 2) were 
observed in 3 patients (ORR = 23%). A PD-(L)1 naïve patient with ovarian carcinoma achieved CR 
and remained on study for at least 15 months. In addition, higher tumor CD73 and PD-L1 co-expression 
was found in all responders compared to that in non-responders, indicating a potential correlation that 
warrants further investigation. This supports further exploration of the efficacy of TJ004309 
combination therapy in selected solid tumor types as well as the relationship between the expressions 

 
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Protocol Number (Version):  TJ004309STM103 (3.0) 
Date:  30 September 2021 
 
 
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of PD-L1 and CD73 with responses. This clinical study is designed to evaluate the efficacy and safety 
of TJ004309 combination therapy in patients with ovarian cancers and selected advanced solid tumors. 
Objectives:  
The primary objectives of the study are: 
• 
Part 1: To assess the efficacy of TJ004309 combined with atezolizumab in a cohort of 
patients with platinum-resistant IO naïve ovarian carcinoma and a separate biomarker 
enriched cohort of subjects with selected tumor types  
• 
Part 2: To further evaluate and confirm the efficacy in targeted patient population based on 
the efficacy observed in Part 1  
The secondary objectives of the study are: 
• 
To evaluate the safety and tolerability of TJ004309 when combined with the standard dose of 
atezolizumab  
• 
Part 1: To characterize the pharmacokinetic profile of TJ004309 when administered in 
combination with atezolizumab  
• 
Part 1: To determine the immunogenicity of TJ004309 when administered in combination 
with atezolizumab 
The exploratory objectives of the study are: 
• 
To investigate the expression of PD-L1, CD73, and other immune subset markers (CD8, 
CD68, CD19 and CD163) in tumor biopsies at baseline and on treatment, and their 
associations with clinical responses 
• 
To examine the CD73 enzymatic activity of tumor biopsies  
• 
To study the whole genome gene expression profiles in tumor biopsies 
 
Study design:  
This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab in 
patients with advanced or metastatic solid tumors. This clinical study will be conducted in two parts. 
Part 1 of the study will include two cohorts: Cohort 1 will include Immuno-Oncology (IO) treatment 
naïve ovarian cancer (OC) patients who have progressed on or after platinum therapy; and Cohort 2 
will include patients with head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer 
(NSCLC), gastrointestinal cancer (GC), triple negative breast cancer (TNBC), or ovarian carcinoma 
(OC) with PD-L1 expression ≥ 1% (Table 1). All subjects will be evaluated for antitumor activity on a 
regular basis as specified in the protocol and their clinical status classified according to RECIST 1.1 
and iRECIST. Treatments may continue until clinically significant disease progression, unacceptable 
toxicity, or subject/Investigator decision to withdraw. Based on the efficacy observation in Part 1, Part 
2 of the study will further evaluate the efficacy in selected targeted patient populations and will be 
initiated after reaching agreement with the regulatory agency.  
TJ004309 will be given in combination with atezolizumab 1200 mg every 3 weeks (Q3W) beginning 
with Cycle 1 Day 1 (C1D1). Premedication will be given prior to the initial infusion of TJ004309 to 
mitigate infusion related reactions. Each cycle will be 21 days in duration. 
 
 

 
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Date:  30 September 2021 
 
 
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Table 1: Study Drug Dosing Schedule – Part 1 
Cohort 
TJ004309 Q3W 
Atezolizumab Q3W 
Subjects 
Cohort 1: Platinum 
resistant or refractory 
IO naïve ovarian 
carcinoma (OC) 
20 mg/kg 
1200 mg flat dose 
N= 30 
Cohort 2: HNSCC, 
NSCLC, GC, TNBC, 
OC 
20 mg/kg 
1200 mg flat dose 
N= 30 
Up to 30 subjects will be enrolled in each cohort. If two or less responses are observed from the first 
15 subjects in Cohort 1, the enrollment may be stopped based on rules from a Simon’s 2-stage design. 
If 3 or more responses are observed from the first 15 subjects in Cohort 1 from Part 1, then Part 2 of 
the study may be initiated earlier. If any response is observed from Cohort 2, an additional cohort with 
up to 30 subjects may be opened with a specific tumor type after reviewing all other available data at 
that time. 
Safety Follow-up Period 
After the treatment periods, all subjects will enter a safety follow-up period and will be evaluated for 
safety, tolerability, and tumor response (if applicable) for at least 90 days after the last dose of study 
drug, or 30 days following cessation of study treatment if the subject initiates new anticancer therapy, 
whichever is earlier. Subjects will be required to return to the study sites for three (3) safety follow-up 
visits (approximately 30, 60 and 90 days after the last dose of study drug), except those subjects who 
withdraw consent for study participation. After treatment discontinuation, in the event of continuing 
serious adverse events (SAEs), subjects will be followed until resolution or stabilization of the SAEs 
(regardless of the relationship to the IMP). Any subject who has an ongoing non-serious AE that is 
possibly related or related to the IMP or study procedures at the 90-day post-treatment Follow-up visit 
will be followed up, where possible, until resolution or until the unresolved non-serious AE is judged 
by the Investigator (or designee) to have stabilized. Any subject who has an ongoing non-serious AE 
that is not related or unlikely related to the IMP or study procedures at the Follow-up visit, can be closed 
out as ongoing at the Investigator’s discretion. If a subject initiates a new anticancer therapy within 30 
days after the last dose of study treatment, one (1) Post-Treatment Safety Follow-Up visit should occur 
approximately 30 days after the last dose of study drug and therefore subsequent follow-up visits will 
not be required.   
Response/Survival Follow-up Period 
Subjects who do not experience progressive disease prior to treatment discontinuation will continue to 
have radiologic and clinical tumor assessments every 9 weeks for the first year and every 12 weeks 
during the second year until progression is confirmed, consent withdrawal, start of a new anti-cancer 
treatment, loss to follow-up, or death, whichever comes first. These subjects will also be followed by 
telephone every 12 weeks during the second year. The duration for response/survival follow-up is 
approximately 2 years from the first dose of study drug. 

 
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Diagnosis and Main Criteria for Inclusion:  
Inclusion Criteria: 
1. Males or females, age ≥ 18 years 
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 
3. In all cohorts, archival tumor tissue in a tissue block or biopsy specimen that allows the 
preparation of at least 20 slides prior to study entry. Tissue blocks are preferred. Archival 
tumor tissue is acceptable in either format per site’s preference.  
4. Cohort 1 - Ovarian Carcinoma (OC): 
a. Histologically confirmed epithelial ovarian cancer, fallopian tube, or primary peritoneal 
cancer subjects with any high-grade serous component, progressed on or after platinum-
containing therapy and not eligible for further platinum containing treatment (platinum-
resistant, platinum-refractory disease defined by progression of disease on a platinum-
containing regimen or recurrence of disease within 180 days of receiving the last dose of 
platinum-based treatment).  
b. Prior lines of therapy to include: 
• 
Patients must have had 1 to 3 prior lines of therapy including at least one 
bevacizumab-containing regimen or ineligible for all other available therapies;  
Or  
• 
Patients must be in the 4th or 5th line of treatment, irrespective of bevacizumab or who 
are ineligible for all therapies with demonstrated clinical benefit; 
Or 
• 
Patients with known BRCA-positive associated cancer or mutation, prior therapy 
must include PARP inhibitors (unless contraindicated) 
5. Cohort 2 - Patients with selected tumor types that have relapsed or progressed after 2 lines of 
therapy or who are ineligible for other standard of care (SOC) therapies: 
a. Histologically or cytologically confirmed metastatic NSCLC 
b. Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, 
oropharynx, hypopharynx, or larynx)  
c. Histologically or cytologically confirmed metastatic or non-resectable advanced 
metastatic gastric or gastroesophageal adenocarcinoma  
d. Histologically or cytologically confirmed unresectable, locally advanced or metastatic 
TNBC (confirmed HER2-negative, estrogen receptor-negative and progesterone receptor-
negative)  
e. Histologically confirmed ovarian cancer of all high-grade epithelial types who are IO 
treatment naïve and have progressed after 3 months on or after platinum-containing 
therapy  
f. PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% for NSCLC and Combined 
Proportion Score (CPS) ≥ 1% for all other tumor types  
g. A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1 
therapy 
h. Patients should have no more than 5 prior lines of therapies 
i. 
If the patients have progressed on treatment with prior PD-1/L1 inhibitor administered 
either as monotherapy or in combination with other therapies, additional following 
criteria must be met:  

 
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• 
have received at least 2 doses of the PD-1/L1 inhibitor; 
• 
have been on a continuous regimen of the PD-1/L1 inhibitor for at least 4 months 
without disease progression; 
• 
have demonstrated radiographic disease progression after PD-1/L1 
j. 
Patients who have had more than 1 prior PD-1/L1 inhibitor may be considered after 
discussion with the Sponsor’s Medical Monitor 
6. Cohort 2 - Pre-treatment fresh tumor biopsies and paired treatment fresh tumor biopsies will 
be collected from at least 5 patients. Biopsy must be excisional, incisional, or core. Fine 
needle aspiration is insufficient. Waiver of biopsy samples must be discussed with Sponsor’s 
Medical Monitor. NOTE: CD73 enzymatic activity and assessment of proteins in the 
adenosine pathway (e.g., CD73, A2A receptor, and whole genome gene expression profiles) 
will be assessed in fresh tumor biopsies. Samples will be collected prior to dosing and 
processed and shipped within 24 hours according to a separate laboratory manual. The fresh 
tumor biopsies require testing for the following infectious diseases: Hepatitis B, Hepatitis C, 
Tuberculosis, HIV, Syphilis, and COVID-19. Testing must be completed within 28 days of 
tumor biopsy collection and confirmed to be negative. 
7. Willingness and ability to consent for self to participate in study and the ability to comply 
with scheduled visits, treatment plan, laboratory tests, and other study procedures 
8. Patients who received prior PD-1/PD-L1 checkpoint inhibitor or prior CTLA-4 inhibitor 
therapy may enroll to Cohort 2 if they did not experience Grade 3 immune-related toxicity 
(applies to all tumor types except ovarian cancer patients)  
9. At least one measurable lesion as defined by RECIST 1.1 
10. Resolution of all acute adverse events resulting from prior cancer therapies to National 
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 
Grade ≤ 1 or baseline (except alopecia or neuropathy) 
11. Considered by the Investigator to be an appropriate candidate for a clinical study, with a life 
expectancy of ≥ 12 weeks 
12. Adequate organ function as defined by the following criteria: 
a. Absolute neutrophil count (ANC) ≥ 1500/μL 
b. Platelets ≥ 100,000/μL without transfusion support within 28 days prior to study 
treatment 
c. Hemoglobin ≥ 9.0 g/dL without transfusion support within 7 days prior to study treatment 
(erythropoietin or darbepoetin permitted) 
d. Creatinine clearance > 30 mL/min by Cockcroft-Gault formula 
e. Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) 
and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤ 3 
times upper limit of normal (ULN) or ≤ 5 times ULN in cases of liver metastases 
f. Total serum bilirubin ≤ 1.5 times the ULN, unless patient has documented Gilbert’s 
disease in which case bilirubin ≤ 3.0 times the ULN  
g. International normalized ratio (INR) from 0.8 to 1.2 unless the INR elevation is related to 
use of a Factor Xa Inhibitor 

 
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h. Activated partial thromboplastin time (aPTT) ≤ 1.5× ULN unless patient is receiving 
anticoagulant therapy if PT or PTT is within therapeutic range of intended use of 
anticoagulants 
13. No systemic anti-cancer therapy within 4 weeks of starting study treatment or at least 5 half-
lives (whichever is shorter) before study drug administration, and all AEs have either 
resolved or stabilized.  Note: Participants who have entered the follow-up phase of an 
investigational study may participate if it has been 4 weeks after the last dose of the previous 
investigational agent. 
14. Subject with a QT interval corrected for heart rate using Fridericia’s formula (QTcF) and/or 
QT interval corrected for heart rate using Bazett’s formula of ≤ 480 msec.  NOTE: If a patient 
has a prolonged QT interval and the prolongation is deemed to be due to a pacemaker upon 
Investigator evaluation (i.e., the patient otherwise has no cardiac abnormalities), the patient 
may be eligible to participate in the study following discussion with the Sponsor’s Medical 
Monitor. 
15. Women of childbearing potential (WOCBP) must: 
a. Agree to use at least 2 effective contraceptive methods (1 highly effective method in 
combination with a barrier method; oral, injectable, or implantable hormonal 
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; 
or vasectomized partner), one of which must be barrier. Use of contraceptive methods 
lasts from date of ICF signature, throughout the study, and for up to 5 months following 
the last dose of TJ004309. 
b. Have a negative serum pregnancy test (sensitive of at least 25 mIU/ml) at Screening; and 
have a negative serum or urine pregnancy test within 72 hours prior to Cycle 1 Day 1 of 
study treatment (note that the screening serum pregnancy test can be used as the test prior 
to Day 1 study treatment if it is performed within the prior 72 hours) 
c. Avoid conceiving for 5 months after the last dose of TJ004309 
d. Avoid donation of ova from date of ICF signature until 5 months after the last dose of 
TJ004309 
e. Agree to ongoing urine pregnancy testing, if clinically indicated, during the study 
16. Males must agree to use a condom (a latex condom is recommended) during sexual contact 
with a pregnant female or a female of childbearing potential, will avoid donation of sperm, or 
having a female partner conceive from date of ICF signature, while participating in the study, 
during dose interruptions, and for at least 5 months after the last dose of study treatment, even 
if he has undergone a successful vasectomy. 
Exclusion Criteria: 
1. Autoimmune disease requiring active treatment within the past twelve months (Note: vitiligo, 
type 1 diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only 
requiring hormone replacement, and conditions not expected to recur in the absence of an 
external trigger are permitted) 
2. Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone 
equivalent) or other immunosuppressive medications within 14 days prior to study treatment 

 
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(Note: inhaled and topical steroids, and adrenal replacement steroid doses > 10 mg daily 
prednisone equivalent, are permitted in the absence of active autoimmune disease.) 
3. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or 
has current pneumonitis/interstitial lung disease 
4. Current treatment on another therapeutic clinical trial 
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an 
agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-
lymphocyte-associated protein 4 [CTLA-4], OX 40 [Tumor necrosis factor receptor 
superfamily, member 4 (TNFRSF4)], CD137 [tumor necrosis factor receptor superfamily 
member 9 (TNFRSF9)]) (only applies to ovarian cancer patients in Cohorts 1 and 2) 
6. For ovarian patients in both cohorts: 
a. Patients who progressed during or within 3 months of first line of platinum-based therapy 
b. Patients with histologically non-epithelial tumors or ovarian tumors with low malignant 
potential (i.e., borderline tumors) or mucinous tumors 
c. Patients with evidence of bowel obstruction requiring hospitalization and decompression 
within the past 30 days 
7. Major surgical procedure or significant traumatic injury within 4 weeks prior to study 
treatment, and must have fully recovered from any such procedure; and no date of surgery (if 
applicable) or anticipated need for a major surgical procedure planned within the next 6 
months (The following situations are not considered to be major procedures and are permitted 
up to 7 days prior to study treatment: thoracentesis, paracentesis, port placement, 
laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic ultrasonographic 
procedures, mediastinoscopy, incisional biopsies, and routine dental procedures. Core biopsy 
and skin biopsy do not require a waiting period prior to dosing.) 
8. Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as > 50% of volume 
of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14 days prior to study 
treatment  
9. Pleural effusion or ascites that requires therapeutic paracentesis in the last 30 days   
10. Brain involvement with cancer, spinal cord compression, carcinomatous meningitis, or new 
evidence of brain or leptomeningeal disease; unless the lesion(s) have been radiated or 
resected, are considered fully treated and inactive, are asymptomatic, and no steroids have 
been administered for CNS disease over the 7 days prior to study treatment 
11. Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular 
accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, 
percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting 
(CABG) within 6 months prior to study treatment 
12. Thrombolytic use (except to maintain IV catheters) within 10 days prior study treatment 
13. Known active or chronic Hepatitis B or Hepatitis C, other hepatitides (non-alcohol 
steatohepatitis, alcohol or drug-related, autoimmune) serology at screening or cirrhosis  

 
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14. Any active infection requiring parenteral treatment 
15. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months prior 
to study treatment 
16. Known human immunodeficiency virus (HIV) unless CD4+ T cell count > 350 cells/μL with 
an undetectable viral load 
17. Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥ 6 weeks 
following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) or 
be postmenopausal for at least one year or must agree to use effective contraception during 
the study and for 5 months following last dose of TJ004309.  All female patients of 
reproductive potential must have a negative pregnancy test (serum or urine) within 72 hours 
prior to study treatment.  Male patients must be surgically sterile or must agree to use 
effective contraception during the study and for 5 months following last dose of TJ004309   
18. Patients with any severe infection within 4 weeks prior to initiation of study treatment, 
including, but not limited to, hospitalization for complications of infections should not be 
enrolled in the trial. Patients who required IV antibiotics or were treated with antiviral 
medications within this 4 week period should be discussed with the Sponsor Medical Monitor 
prior to enrollment 
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or may interfere with the 
interpretation of study results and, in the judgment of the Investigator, would make the patient 
inappropriate for this study 
Investigational Products, Dose and Mode of Administration:  
Each subject will be administered IV infusions of TJ004309 20 mg/kg Q3W in combination with 
atezolizumab 1200 mg Q3W. The dose of TJ004309 will be calculated based on the actual weight (kg) 
of each subject.  
TJ004309 will be supplied by the Sponsor as 150 mg/3 mL (50 mg/mL) solution in a single use vial. 
Atezolizumab will be supplied by the Sponsor as 1200 mg/20 mL (60 mg/mL) solution in a single-dose 
vial.  
All study treatments will be administered at the clinical study site. The pharmacy manual will contain 
specific instructions for the preparation of TJ004309 and administration of the infusion solution. 
Duration of Subject Participation in the Study:  
Planned screening duration: approximately 4 weeks. 
Planned treatment duration: patients are eligible for treatment until clinically significant disease 
progression, unacceptable toxicity, or subject/Investigator decision to withdraw.  
Planned follow-up safety evaluation: at least 30 days following the last dose of study drug(s). 
Response/Survival follow-up duration: approximately 2 years from the first dose of study drug. 
Total duration of study participation: approximately 120 weeks (including response/survival follow-
up). 

 
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Parameters to be Assessed/Endpoints: 
Part 1 
Efficacy: Anti-tumor activity of the combination of TJ004309 and atezolizumab will be measured by 
best of response (BOR), objective response rate (ORR), duration of response (DoR), disease control 
rate (DCR), progression free survival (PFS) and overall survival (OS) based on RECIST 1.1 and 
iRECIST. 
Safety: Treatment-emergent AEs (including serious AEs and immune-related AEs) evaluated using the 
National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) criteria (version 
5.0), changes from baseline in clinical laboratory parameters (complete blood counts [CBC] and serum 
chemistry), 12-lead electrocardiograms (ECGs), vital sign measurements, physical examinations, 
ECOG performance status, and use of concomitant medications. 
Pharmacokinetics: Serum TJ004309 concentration will be measured using validated methods at the 
time points specified in the Schedule of Assessments to determine PK parameters including Cmax and 
Ctrough. 
Immunogenicity: TJ004309 anti-drug antibodies (ADA) will be measured using validated methods at 
time points specified in the Schedule of Events. 
Exploratory biomarkers: 
o Expression of PD-L1, CD73 and other immune subset markers (CD8, CD68, CD19 and 
CD163)  
o CD73 enzymatic activity of tumor biopsies  
o Whole genome gene expression profiles in tumor biopsies 
Part 2 
Efficacy: Based on the efficacy observations in Part 1, further evaluation of anti-tumor activity of the 
combination of TJ004309 and atezolizumab in selected targeted patient population, measured by best 
of response (BOR), objective response rate (ORR), duration of response (DoR), disease control rate 
(DCR), progression free survival (PFS) and overall survival (OS) based on RECIST 1.1 and iRECIST. 
Statistical Methods: 
Details of the statistical methods will be provided in the Statistical Analysis Plan.  
Analysis Populations: 
The following populations will be considered for data summaries: 
Efficacy Evaluable Population: Population will comprise of all subjects who receive at least 1 dose of 
study drug and undergo at least 1 post-baseline tumor assessment. Subjects who die before the first 
scheduled post-baseline tumor assessment will be included in this evaluable population. 
Safety Population: Population will comprise of all subjects who receive at least 1 dose of study drug. 
Pharmacokinetic Population: Population will comprise of all subjects who receive at least 1 dose of 
study drug and at least 1 PK parameter can be derived from the collected PK data.  
Pharmacodynamic Population: Population will comprise of all subjects who receive at least 1 dose of 
TJ004309 and have paired fresh pretreatment and on-treatment tumor biopsy specimen for 
pharmacodynamic evaluation. 

 
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Biomarker Population: Population will comprise of all subjects who receive at least 1 dose of study 
drug and have baseline archival tumor biopsy specimen. 
Efficacy: 
A listing of tumor measurements will be provided by subject and time. BOR, ORR, DOR, PFS and OS 
will be listed and summarized by cohort or group if data permits. 
Safety: 
All recorded AEs will be listed and tabulated by system organ class, preferred terms, cohort/group and 
coded according to the most current version of the Medical Dictionary for Regulatory Activities 
(MedDRA). Vital signs, ECG, ECOG performance status, and clinical laboratory test results will be 
listed. Safety events will be summarized overall, and any significant physical examination findings and 
results of clinical laboratory test will be listed. No formal statistical analysis of safety data is planned. 
Pharmacokinetics: 
Summary statistics will be tabulated for each PK parameter, if feasible, and wherever applicable, by 
cohort/treatment. Mean, standard deviation, median, geometric means, and coefficients of variation will 
be presented for Cmax and Ctrough. The exposure of sparse PK samples will be combined with the PK 
data obtained from Phase 1 trial for population PK analysis and exposure-response analyses.  
Immunogenicity:  
A listing of all available immunogenicity data will be provided with the incidence of specific anti-drug 
antibodies (ADA) to TJ004309. 
Pharmacodynamics: 
Pharmacodynamics effects on CD73 enzymatic activity, immune cell profiles, and whole genome 
gene expression profiles will be evaluated in paired fresh tumor biopsies at baseline and on-treatment 
collected from a subset of subjects in Cohort 2.  
Biomarker:  
Expression of PD-L1, CD73, immune cell subsets, and whole genome gene expression profiles in 
baseline archival tumor biopsy will be evaluated for their association with clinical responses. These 
analyses are considered exploratory and will be summarized in a separate technical report. 
 
1.2 Schedule of Assessments 
The schedule of assessments (SoA) is presented in Table 2 and Table 3. 
 

 
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Table 2:  Schedule of Assessments 
Schedule of Assessments  
Cycle Number 
 
Cycle 1 
(21 days) 
Cycle 2+a 
(21 days) 
End of Treatment 
(EOT)/Early 
Termination 
Safety 
Follow-up 
(EOT + 30 
days) 
Safety 
Follow-up 
(EOT + 60 
days) 
Safety 
Follow-up 
(EOT + 90 
days) 
Cycle Day 
Screening 
1 
 
1 
Visit Window 
(≤ 28 
days) 
None 
±2 days 
Within 7 days of 
EOT/ET 
Decision 
±7 days 
±7 days 
±7 days 
Informed Consent 
X 
 
 
 
 
 
 
Medical Historyb 
X 
 
 
 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
 
 
 
Demographic Information 
X 
 
 
 
 
 
 
HBV, HCV, and HIVc 
X 
 
 
 
 
 
 
Pregnancy Testd 
X 
X 
Q4 Cycles 
X 
 
 
 
ECOG Performance Status 
X 
X 
X 
 
X 
X 
X 
Whole blood for genetic analysis (optional)e 
X 
 
 
 
 
 
 
Archival Tumor Tissue Samplef 
X 
 
 
 
 
 
 

 
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Schedule of Assessments  
Cycle Number 
 
Cycle 1 
(21 days) 
Cycle 2+a 
(21 days) 
End of Treatment 
(EOT)/Early 
Termination 
Safety 
Follow-up 
(EOT + 30 
days) 
Safety 
Follow-up 
(EOT + 60 
days) 
Safety 
Follow-up 
(EOT + 90 
days) 
Cycle Day 
Screening 
1 
 
1 
Visit Window 
(≤ 28 
days) 
None 
±2 days 
Within 7 days of 
EOT/ET 
Decision 
±7 days 
±7 days 
±7 days 
Paired Fresh Tumor Biopsyg 
X 
 
C3D1 
 
 
 
 
Study Drug Administration 
 
 
TJ004309h 
 
X 
X 
 
 
 
 
Atezolizumab 
 
X 
X 
 
 
 
 
Safety 
 
 
Adverse Eventsi 
X 
X 
X 
X 
X 
X 
X 
Prior and Concomitant Medicationsj 
X 
X 
X 
X 
X 
X 
X 
Full Physical Examinationk 
X 
X 
 
X 
 
 
 
Abbreviated Physical Examinationl 
 
 
X 
 
X 
X 
X 
Height and Body Weightm 
X 
X 
X 
X 
 
 
 

 
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Schedule of Assessments  
Cycle Number 
 
Cycle 1 
(21 days) 
Cycle 2+a 
(21 days) 
End of Treatment 
(EOT)/Early 
Termination 
Safety 
Follow-up 
(EOT + 30 
days) 
Safety 
Follow-up 
(EOT + 60 
days) 
Safety 
Follow-up 
(EOT + 90 
days) 
Cycle Day 
Screening 
1 
 
1 
Visit Window 
(≤ 28 
days) 
None 
±2 days 
Within 7 days of 
EOT/ET 
Decision 
±7 days 
±7 days 
±7 days 
Vital Signsn 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGo 
X 
 
 
X 
 
 
 
Blood Chemistryp 
X 
X 
X 
X 
X 
X 
X 
Complete Blood Count (with differential 
and platelets, reticulocytes)q 
X 
X 
X 
X 
X 
X 
X 
Coagulation Assessmentr 
X 
X 
X 
X 
X 
X 
X 
TSH, T3, T4 Testings 
X 
X 
X 
X 
X 
X 
X 
Urinalysist 
X 
X 
X 
X 
X 
X 
X 
Tumor Assessmentsu 
X 
Every 9 Weeks 
Abbreviations: ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase;; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; EOI = end of infusion; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; INR = international 
normalized ratio; NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events; PTT = partial thromboplastin time. 

 
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a) 
Treatment with TJ004309 may continue in accordance with the protocol. Subsequent study cycles should follow the same schedule of assessments as Cycle 2 unless 
otherwise specified.  
b) 
Relevant medical history including current disease state and prior treatment, including last prior therapy, best response to last prior therapy (partial response, complete 
response, stable disease, or progressive disease), and either time on last therapy or duration of response. Medical history includes all clinically significant diseases, 
cardiac history, surgeries, cancer history (which may include, but not limited to prior cancer therapies, procedures, and estrogen receptor and progesterone receptor 
status, bulky disease status), reproductive status, smoking history, use of alcohol and drugs of abuse.  
c) 
Anti-hepatitis B surface antibody, HBsAg, anti-HCV, HIV-1 and HIV-2 antibodies at Screening only.  
d) 
Serum pregnancy test at Screening, urine pregnancy at pre-dose Cycle 1 Day 1 (within 72 hours prior), Cycle 4 Day 1 and Day 1 of every subsequent 4 cycles (i.e., Cycle 
8 Day 1, Cycle 12 Day 1, etc.). The screening serum pregnancy test can be used as the test prior to Day 1 study treatment if it is performed within the prior 72 hours. 
Additional tests may be ordered at the Investigator’s discretion. Positive urine pregnancy tests should be confirmed with a serum pregnancy test. Only a Follicle-
stimulating hormone test is required for postmenopausal women. 
e) 
Samples may be collected for genetic testing (i.e., MSI/dMMR, BRCA, HRD, etc) if not previously obtained. Ovarian cancer patients only. 
f) 
Archival tissue is required for both Cohorts 1 and 2. Blocks are preferred but archival tumor tissue that allows the preparation of at least 20 slides prior to study entry is 
acceptable as well. See lab manual for further instructions. Format of archival tissue is at the site’s discretion. Sponsor may request PD-L1 testing at central laboratory. 
g) 
For Cohort 2 only: Pre-treatment and paired on-treatment fresh tumor biopsies will be collected from at least 5 patients. CD73 enzymatic activity and assessment of 
proteins in the adenosine pathway (e.g., CD73, A2A receptor, and whole genome gene expression profiles) will be assessed in fresh tumor biopsies. Biopsy must be 
excisional, incisional, or core. Fine needle aspiration is insufficient. Samples will be collected prior to dosing and processed and shipped within 24 hours according to 
separate laboratory manual. The tumor biopsy samples must complete testing for the following infectious diseases within 28 days of tumor biopsy collection: Hepatitis B, 
Hepatitis C, Tuberculosis, HIV, Syphilis, and COVID-19 and confirmed to be negative. Testing is to be performed locally.  
h) 
Initially, TJ004309 will be administered over 1 hour (±15 minutes) in Cycles 1 and 2. In the absence of IRRs in patients infused over 1 hour in Cycle 2, the infusion time 
of TJ004309 may be reduced to 30 minutes (±10 minutes) per Investigator’s discretion. Infusion timing should be close to the instructed infusion time as possible. 
i) 
Adverse events should be documented and recorded at each visit using the NCI CTCAE Version 5.0. 
j) 
All medications used by the patient including prescription drugs, over-the-counter drugs, and herbal/homeopathic remedies and therapies taken from 28 days prior to the 
first study drug dose are to be documented as prior medications. 
k) 
A full physical examination will be performed at Screening and at pre-dose of Cycle 1 Day 1, unless the screening physical examination was performed within the last 7 
days. 
l) 
Abbreviated physical examinations should be performed for all other visits. If indicated, a full physical exam may be performed instead at the Investigator’s discretion. 
m) Height will only be recorded at Screening. Doses will be calculated based on the actual weight of each subject, as measured at the Screening Visit. The weight used may 
be revised to a weight collected at a later date if it has changed by more than 10%. 
n) 
Vital signs will include body temperature, pulse rate, blood pressure, and respiratory rate after the subject has rested quietly in the seated position for ≥5 minutes. For the 
first cycle, vital signs (pulse rate, blood pressure, and respiratory rate) will be collected pre-dose, 30 minutes after the start of infusion, and 2 hours after EOI. Body 
temperature will be measured singly. At all subsequent cycles (C2+) vital signs will be performed pre-dose singly and repeated once if outside the relevant clinical 
reference ranges. On Cycle 1 Day 1, subjects should remain at the site for monitoring (with immediate access to medical resuscitation equipment) for at least 1 hour 
following the end of TJ004309 infusion. Acceptable window for collection of vital signs is ± 15 minutes. 
o) 
Triplicate ECG measurements will be obtained at Screening and as clinically indicated. The average of the 3 Screening ECGs will be used to calculate QTc to determine 
study eligibility.  Measurements should be taken after the subject has been resting quietly in the supine or reclined position for ≥ 5 minutes.  
p) 
Serum chemistry includes sodium, potassium, chloride, cholesterol, total protein, bicarbonate, albumin, calcium, magnesium, phosphorus, glucose, blood urea nitrogen, 
creatinine, uric acid, total bilirubin, AST, ALT, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, amylase, and lipase.  CA-125 testing required 
for ovarian cancer subjects only (both cohorts) and should be collected every cycle. If screening laboratory testing is performed within 72 hours of first dose of study 
treatment on Day 1, repeat testing is not required. 

 
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q) 
Complete Blood Count and Differential: white blood cells, red blood cells, absolute neutrophil count, hemoglobin, hematocrit, mean corpuscular volume, mean 
corpuscular hemoglobin, platelets, reticulocytes, and white blood cell differential. If screening laboratory testing is performed within 72 hours of first dose of study 
treatment on Day 1, repeat testing is not required 
r) 
Coagulation Tests: PT, PTT or aPTT, and INR. Any subject receiving anticoagulant therapy should continue to have coagulation factors monitored closely while on 
study. If screening laboratory testing is performed within 72 hours of first dose of study treatment on Day 1, repeat testing is not required. 
s) 
Thyroid Function Tests: TSH, free T3, and free T4. 
t) 
Dipstick is acceptable. Microscopic analyses if dipstick is abnormal. No need to repeat on Cycle 1 Day 1 if screening assessment performed within 72 hours prior to that 
date. If ≥ 2+ protein on urine dipstick, then collect spot urine sample to calculate urine protein to creatinine ratio. 
u) 
Tumor assessments will be performed at Screening, Cycle 4 Day 1, then every 9 weeks for 1 year following the first dose of study drug, and every 12 weeks for the 
second year. Scans within 28 days of Cycle 1 Day 1, prior to signing the ICF, can be used as the screening scan. On-treatment scans can be obtained +/- 7 days. The same 
modality (CT, PET/CT or MRI) should be used throughout the study for a given patient. Collection of images will be obtained for retrospective analysis. Central review 
of scans may be performed during the study. 
 

 
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Table 3: Schedule of Assessments – Pharmacokinetic, Anti-Drug Antibody, Pharmacodynamic Sampling Schedule 
Pharmacokinetic, Anti-Drug, Pharmacodynamic Antibody Testing 
Cycle Number 
  
Cycle 1 
(21 days) 
Cycle 2+ 
(21 days) 
End of Treatment 
(EOT)/Early 
Termination 
Safety 
Follow-up 
(EOT + 30 
days) 
Safety 
Follow-up 
(EOT + 60 
days) 
Safety 
Follow-up 
(EOT + 90 
days) 
Cycle Day 
Screening 
1 
1 
Visit Window 
(≤ 28 
days) 
None 
±2 days 
Within 7 days of 
EOT/ET Decision 
±7 days 
±7 days 
±7 days 
TJ004309 PK pre-dosea 
  
X 
X 
  
  
 
 
TJ004309 PK EOI (+5mins) post-doseb 
  
X 
X 
X 
X 
 
 
TJ004309 ADA pre-dosea 
  
X 
X 
X 
X 
 
 
PBMC biomarker pre-dosea 
 
X 
Cycles 2-4  
X 
 
 
 
PBMC biomarker 3 hours post-EOIb 
 
X 
Cycle 2 
 
 
 
 
Serum biomarker pre-dosea 
 
X 
Cycles 2-4 
X 
 
 
X 
Abbreviations: ADA = anti-drug antibody; EOI = end of infusion; PK = pharmacokinetic; SC = Screening.  
a) 
Acceptable window for pre-dose sampling is within 30 minutes prior to dose. 
b) 
Post-dose blood draws should be performed after TJ004309 infusion. Timepoints for post-dose blood draws should be measured from EOI. 

 
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TABLE OF CONTENTS 
Title Page ....................................................................................................................................... 1 
Study Identification ........................................................................................................................ 4 
1 
Protocol Summary ............................................................................................................. 5 
1.1 
Synopsis ................................................................................................................. 5 
1.2 
Schedule of Assessments .................................................................................... 14 
Table of Contents ......................................................................................................................... 21 
2 
Introduction ...................................................................................................................... 30 
2.1 
Overview ............................................................................................................. 30 
2.2 
Background ........................................................................................................ 30 
2.3 
Description of TJ004309 Investigational Product ........................................... 32 
2.4 
Summary of Nonclinical Data ........................................................................... 32 
2.4.1 
Nonclinical Pharmacology .................................................................... 33 
2.4.2 
Nonclinical Pharmacokinetics .............................................................. 33 
2.4.3 
Toxicology ............................................................................................ 34 
2.5 
Summary of Clinical Data ................................................................................. 34 
2.6 
Benefit/Risk Assessment .................................................................................... 35 
2.6.1 
Potential Benefit ................................................................................... 35 
2.6.2 
Potential Risk ........................................................................................ 35 
3 
Objectives and Endpoints ................................................................................................ 37 
3.1 
Objectives............................................................................................................ 37 
3.1.1 
Primary Objectives: .............................................................................. 37 
3.1.2 
Secondary Objective: ............................................................................ 37 
3.1.3 
Exploratory Objective: .......................................................................... 37 
3.2 
Endpoints ............................................................................................................ 37 
3.2.1 
Primary Endpoints ................................................................................ 37 
3.2.2 
Secondary Endpoints ............................................................................ 37 
3.2.3 
Exploratory Endpoints .......................................................................... 38 
4 
Study Design .................................................................................................................... 39 
4.1 
Overall Design .................................................................................................... 39 
4.2 
Study Rationale .................................................................................................. 40 
4.3 
Justification for Dose ......................................................................................... 40 

 
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4.4 
End of Study Definition ..................................................................................... 44 
5 
Study Population .............................................................................................................. 46 
5.1 
Inclusion Criteria ............................................................................................... 46 
5.2 
Exclusion Criteria .............................................................................................. 49 
5.3 
Lifestyle Considerations .................................................................................... 50 
5.4 
Meals and Dietary Restrictions......................................................................... 51 
5.5 
Screen Failures ................................................................................................... 51 
6 
Study Treatment ............................................................................................................... 52 
6.1 
Description, Storage, Packaging and Labeling ............................................... 52 
6.2 
Dose Preparation ................................................................................................ 52 
6.3 
Drug Accountability........................................................................................... 53 
6.4 
Treatment Administration ................................................................................ 53 
6.5 
Dose Assignment ................................................................................................ 54 
6.6 
Measures to Minimize Bias: Randomization and Blinding............................ 54 
6.7 
Study Intervention Compliance ........................................................................ 54 
6.8 
Concomitant Therapy ........................................................................................ 55 
6.8.1 
Prohibited Concomitant Medications ................................................... 55 
6.8.2 
Permitted Concomitant Medications .................................................... 56 
6.8.3 
Premedication ....................................................................................... 56 
6.9 
Dose Modification and Dose Delays ................................................................. 56 
6.10 
Treatment after Disease Progression ............................................................... 67 
6.11 
Intervention after the End of the Study ........................................................... 67 
7 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal ............................................................................................ 68 
7.1 
Discontinuation of Study Intervention ............................................................. 68 
7.1.1 
Reasons for Discontinuation of Study Intervention .............................. 68 
7.2 
Replacement of Patients .................................................................................... 68 
7.3 
Participant Withdrawal from the Study .......................................................... 68 
7.4 
Lost to Follow up ................................................................................................ 69 
8 
Study Assessments and Procedures ................................................................................. 70 
8.1 
Efficacy Assessments ......................................................................................... 70 

 
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8.2 
Baseline and Safety Assessments ...................................................................... 70 
8.2.1 
Demographics ....................................................................................... 70 
8.2.2 
Medical History, Including Cancer History .......................................... 70 
8.2.3 
Physical Examinations, Height, and Weight ........................................ 71 
8.2.4 
Vital Signs............................................................................................. 71 
8.2.5 
Performance Status ............................................................................... 72 
8.2.6 
Electrocardiograms ............................................................................... 72 
8.2.7 
Clinical Safety Laboratory Assessments .............................................. 73 
8.3 
Safety Parameters and Definitions ................................................................... 73 
8.3.1 
Definition of Adverse Events ............................................................... 73 
8.3.2 
Definition of Serious Adverse Event .................................................... 74 
8.4 
Safety Reporting Requirement ......................................................................... 76 
8.4.7 
Regulatory Reporting Requirements for SAEs ..................................... 79 
8.4.8 
Pregnancy Reporting Requirement ....................................................... 79 
8.5 
Treatment of Overdose ...................................................................................... 80 
8.6 
Safety Management Team (SMT) .................................................................... 81 
8.7 
Pharmacokinetics ............................................................................................... 81 
8.8 
Pharmacodynamics ............................................................................................ 81 
8.9 
Biomarkers ......................................................................................................... 82 
9 
Statistical Considerations ................................................................................................. 83 
9.1 
Sample Size Determination ............................................................................... 83 
9.2 
Statistical Analyses............................................................................................. 83 
9.2.1 
Disposition ............................................................................................ 83 
9.2.2 
Demographics and Baseline Characteristics ......................................... 84 
9.2.3 
Exposure ............................................................................................... 84 
9.2.4 
Efficacy Analyses ................................................................................. 84 
9.2.5 
Safety Analyses..................................................................................... 84 
9.2.6 
Pharmacokinetic Analyses .................................................................... 85 
9.2.7 
Pharmacodynamics and Biomarker Analyses....................................... 85 
9.3 
Interim Analyses ................................................................................................ 85 

 
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10 
Supporting Documentation and Operational Considerations .......................................... 86 
10.1 
Data Record and Management ......................................................................... 86 
10.2 
Protocol Deviations and Amendments ............................................................. 86 
10.3 
Record Retention ............................................................................................... 87 
10.4 
Regulatory, Ethical, and Study Oversight Considerations ............................ 87 
10.4.1 
Regulatory and Ethical Considerations................................................. 87 
10.4.2 
Financial Disclosure ............................................................................. 88 
10.4.3 
Informed Consent Process .................................................................... 88 
10.4.4 
Data Protection ..................................................................................... 89 
10.4.5 
Dissemination of Clinical Study Data .................................................. 89 
10.4.6 
Data Quality Assurance ........................................................................ 89 
10.4.7 
Source Documents ................................................................................ 90 
10.4.8 
Study and Site Closure .......................................................................... 90 
10.4.9 
Publication Policy ................................................................................. 91 
10.5 
Clinical Laboratory Tests.................................................................................. 92 
10.6 
Contraceptive Guidance .................................................................................... 94 
10.6.1 
Definitions ............................................................................................ 94 
10.6.2 
Fertile Males ......................................................................................... 94 
10.6.3 
Highly Effective Contraception ............................................................ 94 
10.6.4 
Acceptable Birth Control Methods that are not Highly 
Effective Contraception ........................................................................ 95 
10.6.5 
Unacceptable Contraception Methods .................................................. 95 
10.6.6 
Female Contraception Guidance ........................................................... 95 
10.6.7 
Male Contraception Guidance .............................................................. 95 
10.6.8 
Collection of Pregnancy Information ................................................... 96 
11 
Summary of Changes (SOC) ........................................................................................... 97 
12 
References ........................................................................................................................ 99 
13 
Appendices ..................................................................................................................... 100 
 
 

 
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LIST OF TABLES IN THE TEXT 
Table 1:  
Study Drug Dosing Schedule – Part 1 ................................................................... 7 
Table 2:   
Schedule of Assessments ..................................................................................... 15 
Table 3:  
Schedule of Assessments – Pharmacokinetic and Anti-Drug 
Antibody Sampling Schedule .............................................................................. 20 
Table 4:   
4309ST101 Most Common AEs (Excluding Symptoms of IRR) (>1 
Patient) by Preferred Term and Grade, Suspected Related to 
TJ004309 (N = 20) ............................................................................................... 41 
Table 5:  
Study Drug Treatments ........................................................................................ 52 
Table 6:   
TJ004309 Treatment Management Guidelines for Adverse Events 
(Hematological Toxicities) .................................................................................. 58 
Table 7:   
TJ004309 Treatment Management Guidelines for Adverse Events 
(Non-Hematological Toxicities) .......................................................................... 59 
Table 8:  
TJ004309 Treatment Management Guidelines for Immune-Related 
Adverse Events (irAEs) ....................................................................................... 62 
Table 9:   
Eastern Cooperative Oncology Group Performance Status Scale, 
with  Equivalent Karnofsky Performance Status Scores ..................................... 72 
Table 10:  
 Adverse Event Severity Grading ........................................................................ 77 
Table 11:   
Protocol-Required Safety Laboratory Assessments ............................................. 92 
 
 
 
 
 
 
 

 
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LIST OF FIGURES IN THE TEXT 
Figure 1:   Extracellular Adenosine Signaling Pathway .............................................................. 31 
Figure 3:  Mean Tumor Volume Change ..................................................................................... 32 
Figure 2:  Mean Tumor Volume of A375 Bearing Mice ............................................................. 32 
Figure 4:  Serum PK of TJ004309 Following a Single Dose and Multiple Doses ...................... 42 
Figure 5:  Dose Proportionality Analysis After the First Dose .................................................... 42 
Figure 6:  Sustained Decrease in Free Soluble CD73 with TJ004309 QW or Q3W 
Dosing .................................................................................................................. 43 
Figure 7:  Saturated CD73 Target Occupancy on Peripheral B Cells .......................................... 43 
 
 
 
 

 
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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ASCC 
Antibody-dependent T-cell-mediated cytotoxicity 
ADA 
Anti-drug antibodies 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AMP 
Adenosine Monophosphate 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
AUC0-∞ 
Area under the curve extrapolated to infinity 
AUC0-t 
Area under the curve from time 0 to time t 
AUCτ 
Area under the curve during a dosing interval 
BOR 
Best objective response  
C 
Cycle 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CL 
Clearance 
Cmax 
Maximum concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CR 
Complete response 
CRA 
Clinical research associate 
CRF 
Case report form 
CSR 
Clinical Study Report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
Trough concentration 
DLT 
Dose-limiting toxicity 
DOR 
Duration of response 
DRC 
Data Review Committee 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 

 
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Abbreviation 
Definition 
eCRF 
Electronic case report form 
EOS 
End-of-Study 
FFPE 
Formalin fixed, paraffin-embedded 
FOCBP 
Females of childbearing potential 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HIPAA 
Health Insurance Portability and Accountability Act 
HNSCC 
head and neck squamous cell carcinoma 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IgG 
Immunoglobulin G 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IV 
Intravenous 
kg 
kilogram 
LDH 
Lactate dehydrogenase 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mL 
milliliter 
MTD 
Maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NOAEL 
No observed adverse effect level 
NSCLC 
Non-small cell lung cancer 
OC 
Ovarian carcinoma 
ORR 
Objective response rate 
OS 
Overall survival 
PD 
Progressive disease 
PET 
Positron emission tomography 
PFS 
Progression-free survival 

 
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Abbreviation 
Definition 
PK 
Pharmacokinetic 
PR 
Partial response 
PT 
Preferred term 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended Phase 2 dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SoA 
Schedule of Activities 
SOC 
System organ class 
SUSAR 
Suspected unexpected serious adverse reactions 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
UPCR 
Urine protein-creatinine ratio 
Vss 
Volume of distribution at steady state 
Vz 
Volume of distribution 
 

 
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2 INTRODUCTION 
2.1 Overview 
Traditionally, metastatic cancer is treated with chemotherapy or other treatments that directly 
target the tumor. However, toxicities can limit the effectiveness of chemotherapy and resistance 
can develop as well. Cancer immunotherapy is one method of treatment that has been used 
successfully to treat various types of tumors by harnessing the body’s immune system to fight 
cancer. Data suggest that tumors suppress T-cell activity by activating pathways and inhibitory 
checkpoints that restrict antitumor activity. Checkpoint inhibitors are a class of immunotherapy 
treatments that inhibit checkpoints mediated by the CTLA-4 and PD-1 pathways, to re-establish 
antitumor activity1. Multiple types of cancers have responded to PD-1 checkpoint inhibitor 
therapy including non-small cell lung cancer, renal cell carcinoma, bladder cancer, and head and 
neck cancer2. However, only a minority of cancer patients respond to single agent 
immunotherapy treatment. New methods of treatment are needed to continue to improve long-
term survival for patients with metastatic cancer.  
One strategy that tumor cells employ to counter effective immune responses is the generation of 
high levels of the immunosuppressant adenosine3. Adenosine is produced at elevated levels 
within the tumor microenvironment through the CD73 ectonucleotidase and new immunotherapy 
treatments are being studied to target this antitumor pathway. 
2.2 Background 
The adenosine signaling pathway regulates tumor immune evasion. Extracellular adenosine and 
ATP levels are typically very low. However, inflammation, ischemia and tissue disruption can 
lead to the release of high levels of ATP that is enzymatically hydrolyzed to produce 
extracellular adenosine that inhibits antitumor T cell activity through binding to the A2A and 
A2B adenosine receptors expressed on immune cells4, 5, 6.  
Extracellular ATP is dephosphorylated to produce adenosine by the ectonucleotidases CD39 and 
CD73. Ectonucleotidases are highly expressed on cells within the tumor microenvironment and 
are upregulated in states of hypoxia. Ectonucleotidases are upregulated on regulatory T cells in 
response to adenosine, which establishes a positive feedback loop, causing additional increases 
in adenosine production in solid tumors and further suppression of antitumor immune 
responses3,7. . 
 
 
 
 

 
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Work has been done to explore whether the adenosine signaling pathway could be exploited to 
enhance the immune system response to cancer. Since tumors exhibit many factors that influence 
adenosine production, including hypoxia, inflammation, CD39 and CD73 upregulation, and 
tissue disruption, the adenosine pathway therefore became a prime candidate for intervention. 
Tumor growth is suppressed in CD73 deficient mice suggesting that tumor CD73-mediated 
immune suppression significantly contributes to cancer immune evasion. Zhang et al. found that 
adenosine generated by tumor CD73 in vitro and in vivo inhibited the activation phase and 
effector phase of the antitumor T cell response and promoted T cell apoptosis. Moreover, 
knockdown of CD73 on tumor cells by siRNA completely restored the efficacy of T cell therapy 
and led to long-term tumor free survival of tumor-bearing mice8. Stagg et al. additionally 
demonstrated that inhibiting CD73 with a selective monoclonal antibody significantly reduced 
the growth and metastatic capability of CD73-negative tumors9.  
Medimmune (MEDI9447) and Bristol Myers Squib have studied monoclonal antibodies that 
inhibit CD73 in early phase trials. MEDI9447 was dosed with or without the PD-1 checkpoint 
inhibitor durvalumab. The trial enrolled 42 monotherapy and 95 combination therapy patients 
without the development of dose limiting toxicity. Sustained decreases in free soluble CD73 and 
CD73 expressed on peripheral T cells was demonstrated at all dose levels. Partial responses were 
observed in 1 of 21 colorectal cancer patients and 2 of 34 pancreatic cancer patients; stable 
disease was observed in 2 of 21 colorectal cancer patients and 5 of 34 pancreatic cancer patients 
from the dose expansion phase. The most commonly reported adverse events in patients treated 
with the CD73 and PD-1 antibodies (N=71) were diarrhea (5 patients (7.0%)), fatigue (5 patients 
(7.0%)), pyrexia (4 patients (5.6%)), and increases in AST (4 patients (5.6%))7.  
The CD73 antibody BMS-986179 was tested in a phase 1/2 study as a monotherapy and in 
combination with the PD-1 checkpoint inhibitor nivolumab in patients with advanced solid 
tumors. Drug-related adverse events were observed in 30 of 52 patients (58%) who received the 
combination, without a clear dose dependent relationship. Eight patients (15%) experienced 
grade 3 drug-related adverse events, and one patient discontinued treatment due to a drug-related 
Figure 1:   Extracellular Adenosine Signaling Pathway3 

 
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adverse event of grade 3 increased ALT. Both the monotherapy and the combination treatments 
were well tolerated, without grade 4 drug-related adverse events. BMS-986179 efficiently 
inhibited CD73 enzymatic activity in tumor biopsies at all doses and produced dose dependent 
reductions in soluble CD73. Overall, 7 patients with head and neck, pancreatic, prostate, anal, 
and renal cancer achieved confirmed partial responses and 10 patients had stable disease11.  
These data suggest that CD73 could be a novel target for cancer treatment with encouraging 
signs of activity and limited toxicity. 
2.3 Description of TJ004309 Investigational Product 
TJ004309 is a humanized IgG1 to CD73 containing a N297A mutation that prevents antibody 
glycosylation. TJ004309 inhibits CD73 through a non-competitive mechanism and does not 
possess ADCC or CDC effector function. TJ004309 is formulated at 50 mg/mL in a 20 mM 
histidine buffer containing trehalose. 
2.4 Summary of Nonclinical Data 
TJ004309 is a non-competitive inhibitor of CD73 with a KD of 14 nM by Biacore testing that 
binds human and cynomolgus, but not rodent, CD73. TJ004309 binds CD73 on cell lines with an 
EC50 of 0.12-0.29 μg/mL and inhibits CD73 enzymatic activity with IC50 of 0.6-3.3 ug/ml. 
Maximal CD73 receptor occupancy reaching over 80% was observed in vitro at a mean 
concentration of 33.86 μg/mL. 
TJ004309 reversed CD73+ tumor cell mediated T cell immunosuppression that was maximal at 
30 ug/mL. TJ004309 at a dose of 5 mg/kg and 10 mg/kg increased the activity of PD-L1 
antibody in immunodeficient mice reconstituted with human PBMCs engrafted with palpable 
melanoma xenografts (Figure 2 and Figure 3). 
 
Figure 3:  Mean Tumor Volume of A375 Bearing Mice 
Figure 2:  Mean Tumor Volume Change 
of A375 Bearing Mice 

 
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2.4.1 Nonclinical Pharmacology 
Safety Pharmacology studies of TJ004309 have not been performed. 
2.4.2 Nonclinical Pharmacokinetics 
The pharmacokinetics of TJ004309 was determined in cynomolgus monkeys after bolus 
intravenous injection of single doses of 5, 25, and 50 mg/kg and after 4 weekly repeated doses of 
25 mg/kg.  
TJ004309 was administered as a single dose of 5, 25, and 50 mg/kg via bolus intravenous 
injection to cynomolgus monkeys (3 animals/sex/group). Blood samples were collected at pre-
dose and for up to 28 days post dose. Following a single intravenous injection at 5 mg/kg, 25 
mg/kg, and 50 mg/kg of TJ004309, mean peak concentrations (Cmax) of TJ004309 were 136 
µg/mL, 682 µg/mL, and 1430 µg/mL, respectively. Mean area under the concentration time 
curve from hour 0 to the time of the last measurable concentration (AUC0-last) values of 
TJ004309 were 4020 hr*µg/mL, 50400 hr*µg/mL and 135000 hr*µg/mL, respectively. Mean 
half-life (T1/2) was 44.9 hr, 61.5 hr and 104 hr, respectively. Cmax increased proportionally with 
increasing dose; while exposure increased in a non-linear manner. The elimination rate of 
TJ004309 was decreased in cynomolgus monkeys as dosage increased. The detection of antibody 
against TJ004309 did not meaningfully influence pharmacokinetics of single dose 
administration.   
Toxicokinetics of TJ004309 were also determined as part of dose-range finding (DRF), where 
the antibody was administered at doses of 0, 5, 30 and 200 mg/kg once weekly over 15 days 
(total 3 doses) via bolus intravenous injection to cynomolgus monkeys (1 animal/sex/group). 
Exposure to TJ004309, based on Cmax and AUC0-last, increased in proportion to dose level from 5 
to 200 mg/kg/day in both sexes on Days 1 and 8. The AUC0-last values on Day 8 were similar to 
those on Day 1.   
TJ004309 was also administered at doses of 0, 20, 60 and 200 mg/kg once weekly for 29 days 
(total 5 doses) via bolus intravenous injection to cynomolgus monkeys (5 animals/sex/group). 
The AUC0-last values on Day 22 were generally higher than that on Day 1 of the dosing phase, 
with mean accumulation ratios (AR) ranging from 1.65 to 2.19. Mean AR in male and female 
animals who received 20 mg/kg and 60 mg/kg were higher than 2-fold. Generally, the exposure 
of males, based on Cmax and AUC0-last, was similar to that of females, with ratios ranging from 
0.894 to 1.19.  Anti-TJ004309 antibody (ADA) were observed in 10 of 10 animals administered 
20 mg/kg, 10 of 10 animals administered 60 mg/kg, and 8 of 10 animals administered 200 
mg/kg.  
TJ004309 was also administered weekly at 25 mg/kg on days 0, 7, 14 and 21 (total 4 doses) via 
bolus intravenous injection to cynomolgus monkeys (3 animal/sex/group). Blood samples were 
collected prior to dosing and for up to 7 days following dosing for each dose. After multiple 
administrations of TJ004309 at 25 mg/kg, in week 4, mean Cmax of TJ004309 were 714 µg/mL 
and 791 µg/mL in male and female monkeys, respectively. Mean AUC0-168 of TJ004309 were 

 
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52900 hr*µg/mL and 92400 hr*µg/mL in male and female monkeys, respectively. Mean AUC0-
last of TJ004309 were 90000 hr*µg/mL and 111000 hr*µg/mL in male and female monkeys, 
respectively. Mean T1/2 calculated using data from 0 to 168 hours were 128 hr and 125 hr in male 
and female monkeys, respectively and were 69.0 hours and 112 hours, respectively, when 
extrapolated to infinity. Mean trough concentrations were approximately 254 µg/mL in week 4.   
After multiple doses of TJ004309 Cmax observed in male and female monkeys was comparable to 
single administration at the same dose level. Mean concentration-time curves were higher in 
week 4 compared to week 1 following multiple administrations at 25 mg/kg (AUC > 2-fold), 
indicating accumulation following multiple dose administration.  
Antibody against TJ004309 was observed in nearly all animals by day 14 following dosing and 
did not influence pharmacokinetics of multiple doses of TJ004309 except in a single male animal 
who demonstrated pronounced immunogenicity, whose PK data was excluded from summary 
data calculations.     
2.4.3 Toxicology  
The toxicology program to support this initial Phase 1 study included a dose range finding study 
(DRF) and a GLP 28-day repeat dose toxicology study in cynomolgus monkeys. Toxicity of 
TJ004309 was assessed in a GLP-compliant repeat-dose definitive toxicology study in 
cynomolgus monkeys that received 5 weekly doses of TJ004309 at the following dose levels: 0 
mg/kg (vehicle control), 20 mg/kg, 60 mg/kg and 200 mg/kg. Animals were dosed by IV bolus 
injection in a volume of 4 ml/kg. The vehicle was used as control. 
All animals survived to their scheduled sacrifices. TJ004309-related clinical or histopathologic 
findings were not observed at terminal or recovery sacrifices. TJ004309 related alterations in 
cytokine parameters included decreased monocyte chemoattractant protein 1 (MCP-1) observed 
on Day 1 of the dosing phase in animals administered ≥ 20 mg/kg approximately 24 hours 
following dosing, and male animals administered 20 and 60 mg/kg approximately 48 hours 
following dosing. 
Based on the collective findings, the no observed adverse effect level (NOAEL) was determined 
to be 200 mg/kg. This dose level produced to mean peak concentration (Cmax) and area under the 
concentration time curve (AUC) values of 6890 ug/mL and 594000 ug*hr/mL, respectively, in 
males and 6450 ug/mL and 501000 ug*hr/mL, respectively, in females, on Day 22 of the dosing 
phase. 
Refer to the Investigator’s Brochure for additional nonclinical data with TJ004309. 
2.5 Summary of Clinical Data 
TJ004309 was evaluated in the first-in-human (FIH) Study 4309ST101 sponsored by Tracon in 
the US, and Study TJ004309STM102 sponsored by I-Mab Biopharma in China. Study 
4309ST101, was an open label, nonrandomized, Phase 1 dose escalation study of TJ004309 in 
combination with standard dose atezolizumab in patients with advanced or metastatic solid 

 
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tumors who are refractory to or intolerant to all available therapy. Study TJ004309STM102 is a 
Phase 1/2 dose-escalation and cohort expansion study of TJ004309 in combination with 
toripalimab in patients with advanced or metastatic solid tumors to evaluate the safety, 
tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of efficacy of 
TJ004309 as a single agent and in combination with toripalimab in the Chinese patient 
population. As of 17 January 2021, 20 patients had been treated in Study 4309ST101 and 6 
patients have been treated in Study TJ004309STM102.  
In Study 4309ST101, TJ004309 was well-tolerated with no dose limiting toxicity up to 20 mg/kg 
Q3W and 15 mg/kg QW. The most common treatment-related adverse events were first dose 
infusion related reactions (65%, n=13) most commonly comprising chills/rigors, nausea, and 
vomiting (Grade 1 or 2) that resolved in subsequent infusions. One complete response and two 
partial responses were observed in 3 patients together with 3 stable disease (SD) patients. Refer 
to the Investigator’s Brochure (IB) for additional data with TJ004309. 
2.6 Benefit/Risk Assessment 
2.6.1 Potential Benefit 
TJ004309 is an investigational product, and its efficacy has not been fully established.  
Atezolizumab is approved for the treatment of appropriately selected patients who progress 
following treatment with chemotherapy. It is possible that the administration of TJ004309 and/or 
atezolizumab may result in clinical benefit (i.e., tumor response or prolonged stable disease) 
beyond that expected for treatment with atezolizumab alone. More information about the known 
and expected benefits, risks, and reasonably anticipated adverse events (AEs) associated with 
TJ004309 may be found in the Investigator’s Brochure. 
2.6.2 Potential Risk 
TJ004309 is an investigational product, and its safety profile has not been fully established. The 
occurrence of adverse events associated with TJ004309 treatment from the US dose escalation 
portion of the study (NCT04322006) includes infusion related reactions, fatigue, pruritis, and 
diarrhea.   
All therapeutic mAb used for cancer treatment have the potential to cause infusion reactions. 
Symptoms vary with a wide spectrum of severity, ranging from mild fever and chills to life- 
threatening anaphylaxis with bronchospasm, and hypotension. Typically, infusion reactions to 
mAb develop within 30 to 120 minutes after the initiation of drug infusion, although symptoms 
may not show up until 24 hours. The majority of reactions occur after the first or second 
exposure to drug, although it can also occur during subsequent treatments. The risk of an 
infusion reaction declines with each subsequent course of therapy. 
The most common symptoms of infusion-related reactions are fever/chills, nausea, vomiting, 
diarrhea, itching/flushing, rash, changes in blood pressure and pulse rate, dyspnea, chest 
discomfort, back and abdominal pain. Although the exact mechanism of infusion-related 

 
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reactions caused by mAb is not fully clear, most likely it is a result of antibody-antigen 
interactions resulting in cytokine release. 

 
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3 OBJECTIVES AND ENDPOINTS 
3.1 Objectives 
3.1.1 Primary Objectives: 
The primary objectives of the study are: 
• Part 1: To assess the efficacy of TJ004309 combined with atezolizumab in a cohort of 
patients with platinum-resistant IO naïve ovarian carcinoma and a separate biomarker 
enriched cohort of subjects with selected tumor types  
• Part 2: To further evaluate and confirm the efficacy in targeted patient population based 
on the efficacy observed in Part 1  
3.1.2 Secondary Objective: 
The secondary objectives of the study are: 
• To evaluate the safety and tolerability of TJ004309 when combined with the standard 
dose of atezolizumab  
• Part 1: To characterize the pharmacokinetic profile of TJ004309 when administered in 
combination with atezolizumab  
• Part 1: To determine the immunogenicity of TJ004309 when administered in combination 
with atezolizumab 
3.1.3 Exploratory Objective: 
The exploratory objectives of the study are: 
• To investigate the expression of PD-L1, CD73, and other immune subset markers (CD8, 
CD68, CD19 and CD163) in tumor biopsies at baseline and on treatment, and their 
associations with clinical responses 
• To examine the CD73 enzymatic activity of tumor biopsies 
• To study the whole genome gene expression profiles in tumor biopsies 
3.2 Endpoints 
3.2.1 Primary Endpoints 
Primary endpoints are: 
• Efficacy within each tumor type: ORR by RECIST v1.1 
3.2.2 Secondary Endpoints 
Secondary endpoints are: 
• The safety and tolerability of TJ004309 when combined with the standard dose of 
atezolizumab 

 
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• ORR by iRECIST 
• Duration of response (DOR) by RECIST v1.1 and iRECIST 
• Disease control rate (DCR) by RECIST v1.1 and iRECIST 
• Progression-free-survival (PFS) by RECIST v1.1 and iRECIST 
• Overall survival (OS)  
• Immunogenicity and pharmacokinetic profiles of the combination treatment 
3.2.3 Exploratory Endpoints 
The exploratory endpoints are: 
• CD73 enzymatic activity of tumor biopsies at baseline and on-treatment tumor biopsies; 
• Expression of PD-L1, CD73 and other immune subset markers (CD8, CD68, CD19 and 
CD163); 
• Whole genome gene expression profiles in tumor biopsies at baseline and on-treatment 
tumor biopsies; 

 
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4 STUDY DESIGN 
4.1 Overall Design 
This is a multicenter, open label, Phase 2 study of TJ004309 in combination with atezolizumab 
in patients with advanced or metastatic solid tumors. This clinical study will be conducted in two 
parts. Part 1 of the study will include two cohorts: Cohort 1 will include Immuno-Oncology (IO) 
treatment naïve ovarian cancer patients who have progressed on or after platinum therapy; and 
Cohort 2 will include patients with head and neck squamous cell carcinoma (HNSCC), non-small 
cell lung cancer (NSCLC), gastric cancer (GC), triple negative breast cancer (TNBC), or ovarian 
carcinoma with PD-L1 expression ≥ 1% (Table 1).  All subjects will be evaluated for antitumor 
activity on a regular basis as specified in the protocol and their clinical status classified 
according to RECIST 1.1 and iRECIST. Treatments may continue until clinically significant 
disease progression, unacceptable toxicity, or subject/Investigator decision to withdraw. Based 
on the efficacy observation in Part 1, Part 2 of the study will further evaluate the efficacy in 
selected targeted patient populations and will be initiated after reaching agreement with the 
regulatory agency. 
TJ004309 will be given in combination with atezolizumab 1200 mg every 3 weeks (Q3W) 
beginning with Cycle 1 Day 1 (C1D1). Premedication will be given prior to the initial infusion of 
TJ004309 to mitigate infusion related reactions. Each cycle will be 21 days in duration. 
Table 1: Study Drug Dosing Schedule – Part 1 
Cohort 
TJ004309 Q3W 
Atezolizumab Q3W 
Subjects 
Cohort 1: Platinum 
resistant or refractory 
IO naïve ovarian 
carcinoma (OC) 
20 mg/kg 
1200 mg flat dose 
N= 30 
Cohort 2: HNSCC, 
NSCLC, GC, TNBC, 
OC 
20 mg/kg 
1200 mg flat dose 
N= 30 
Up to 30 subjects will be enrolled in each cohort. If two or less responses are observed from the 
first 15 subjects in Cohort 1, the enrollment might be stopped based on rules from a Simon’s 2-
stage design. If 3 or more responses are observed from the first 15 subjects in Cohort 1 from Part 
1, then Part 2 of the study may be initiated earlier. If any response is observed from Cohort 2, an 
additional cohort with up to 30 subjects may be opened with a specific tumor type after 
reviewing all other available data at that time. 

 
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4.2 Study Rationale 
TJ004309 is an investigational antibody to CD73 that non-competitively inhibits CD73 mediated 
conversion of AMP to adenosine, thereby reversing adenosine mediated immune suppression on 
T cells. This mechanism of action is distinct from that inhibited by antibodies to PD-1/PD-L1, 
and CD73 is implicated as a mechanism of resistance to PD-1/PD-L1 antibody treatment. 
TJ004309 inhibited tumor growth in preclinical models and complemented the activity of 
antibodies targeting the PD-1/PD-L1 pathway. Atezolizumab is a monoclonal antibody that binds 
to PD-L1 and blocks its interactions with PD-1 and B7.1 receptors. While single agent activity of 
TJ004309 was limited, by targeting the adenosine pathway, TJ004309 has the potential to 
complement atezolizumab and improve clinical efficacy over that seen with single agent 
atezolizumab. 
4.3 Justification for Dose 
The proposed dosing regimen for the Phase 2 trial is 20 mg/kg of TJ004309 administered as a 1 
hour intravenous infusion every three weeks (Q3W) in combination with atezolizumab (1200 mg 
Q3W) starting from Cycle 1 Day 1. This dosing regimen is based on the preliminary safety, PK, 
biomarker, and antitumor activities observed in the first-in-human study 4309ST101 under IND 
141965.  
Study 4309ST101 was an open label, non-randomized, Phase 1 dose escalation study of 
TJ004309 in combination with standard dose atezolizumab in patients with advanced or 
metastatic solid tumors who are refractory to or intolerant to all available therapy. In this 3+3 
dose escalation study, TJ004309 was administered intravenously at doses of 5, 10, or 15 mg/kg 
weekly (QW), or 15 or 20 mg/kg every 3 weeks (Q3W) as a monotherapy in the first 21-day 
treatment cycle followed by combination therapy with atezolizumab (1200 mg Q3W) starting 
from the second cycle (week 4).  
At the time of 29 April 2021, the safety, PK, and PD from dose levels of 5 mg/kg, 10 mg/kg, 15 
mg/kg once weekly (QW), and 15 mg/kg and 20 mg/kg once every 3 weeks (Q3W) have been 
evaluated. Serum TJ004309 concentrations were measured using validated methods and the PK 
was analyzed by noncompartmental analysis (NCA) and population PK analysis. The 
immunogenicity was evaluated by measuring the anti-drug antibodies (ADA) to TJ004309 using 
validated methods. Furthermore, the following exploratory biomarkers were evaluated: receptor 
occupancy assessment of soluble CD73 and CD73 expression on CD19+ B cells; CD73, A2A 
receptor, and whole genome gene expression profiles in tumor specimens; CD73 enzymatic 
activity in fresh tumor biopsies. 
The proposed dosing regimen is supported by the observed clinical data, as summarized below.  
 
 
 

 
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Safety:  
In Study 4309ST101, TJ004309 was well-tolerated. No dose limiting toxicity (DLT) was 
observed and maximum tolerated dose (MTD) was not reached at dose levels up to 20 mg/kg 
Q3W and 15 mg/kg QW. The most common treatment-related adverse events (TRAE) were 
infusion related reactions (65%, n=13) following the first dose, most commonly comprising 
chills/rigors, nausea, and vomiting (Grade 1 or 2). All these TRAEs were well managed and 
resolved in subsequent infusions.  
Table 4:  4309ST101 Most Common AEs (Excluding Symptoms of IRR) (>1 Patient) by 
Preferred Term and Grade, Suspected Related to TJ004309 (N = 20) 
 
Preferred Terma 
Grade 1 
Grade 2 Grade 3 Grade 4 Grade 5 All Grades 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
Infusion related reaction 2 (10.0%) 
11 (55.0%) 
0 
0 
0 
13 (65.0%) 
Diarrhoea 
4 (20.0%) 
1 (5.0%) 
0 
0 
0 
5 (25.0%) 
Fatigue 
2 (10.0%) 
3 (15.0%) 
0 
0 
0 
5 (25.0%) 
Pruritus 
3 (15.0%) 
2 (10.0%) 
0 
0 
0 
5 (25.0%) 
Nausea 
3 (15.0%) 
0 
0 
0 
0 
3 (15.0%) 
Vomiting 
3 (15.0%) 
0 
0 
0 
0 
3 (15.0%) 
Angioedema 
2 (10.0%) 
0 
0 
0 
0 
2 (10.0%) 
Arthralgia 
2 (10.0%) 
0 
0 
0 
0 
2 (10.0%) 
Decreased appetite 
2 (10.0%) 
0 
0 
0 
0 
2 (10.0%) 
Dry skin 
1 (5.0%) 
1 (5.0%) 
0 
0 
0 
2 (10.0%) 
Hyperthyroidism 
1 (5.0%) 
1 (5.0%) 
0 
0 
0 
2 (10.0%) 
Malaise 
1 (5.0%) 
1 (5.0%) 
0 
0 
0 
2 (10.0%) 
Myalgia 
1 (5.0%) 
1 (5.0%) 
0 
0 
0 
2 (10.0%) 
Rash 
2 (10.0%) 
0 
0 
0 
0 
2 (10.0%) 
Vision blurred 
2 (10.0%) 
0 
0 
0 
0 
2 (10.0%) 
 
Antitumor activity: 
Among 13 efficacy evaluable patients dosed ≥ 10 mg/kg, complete response (CR = 1) and partial 
response (PR = 2) were observed in 3 patients (ORR = 23%). A PD-L1 naïve patient with 
ovarian carcinoma achieved CR and remained on study for at least 15 months. Refer to the 
Investigator’s Brochure (IB) for additional data with TJ004309. 
Pharmacokinetics: 

 
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Systemic exposure to TJ04309 (Cmax and AUC) increased in a dose proportional manner over a 
range from 5 mg/kg to 20 mg/kg following single dose or multiple doses. Power model tests 
suggested a slope of 0.986 and 1.00 for Cmax and AUC, respectively. The linear PK over the 
tested dosing range indicated target saturation. Following multiples doses once every three 
weeks, the accumulation ratio at the steady state over the first dose was approximately 2. 
Preliminary population PK analysis suggested that the best model was a two-compartment model 
with first order linear clearance. Body weight was found to be predictive of central volume of 
distribution, but not predictive of clearance. The population PK model estimated an effective 
half-life of 19 days (range: 11.6 to 43.9 days), which supported the dosing interval of three 
weeks.  
Figure 4:  Serum PK of TJ004309 Following a Single Dose and Multiple Doses 
Figure 5:  Dose Proportionality Analysis After the First Dose 
 
 
 

 
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Pharmacodynamic: 
Soluble CD73: Treatment of TJ004309 achieved a sustained decrease in free soluble CD73 level 
in monotherapy stage (Cycle 1) or in combination with Atezolizumab (starting at Cycle 2) at 
each of dose cohorts (5, 10, and 15 mg/kg QW; 15 mg/kg and 20 mg/kg Q3W). 
Figure 6:  Sustained Decrease in Free Soluble CD73 with TJ004309 QW or Q3W 
Dosing 
 
 
CD73 Target Occupancy on Peripheral B cells: 
 
 
 
 
Treatment of TJ004309 reached a complete saturation of receptor occupancy (RO) on peripheral 
CD19+ B cells throughout the whole dosing period at all dose levels following either QW or 
Figure 7:  Saturated CD73 Target Occupancy on Peripheral B Cells 
 
 
R O  o n  C D 1 9 +  B  c e l l s
C 1 D 1  E O I
C 2 D 1  P r e
C 3 D 1  P r e
C 4 D 1  P r e
C 5 D 1  P r e
C 6 D 1  P r e
C 7 D 1  P r e
C 8 D 1  P r e
C 9 D 1  P r e
C 1 0 D 1  P r e
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
1 0  m
g / k g ,  Q
W
 ( n = 3 )
1 5  m
g / k g ,  Q
W
 ( n = 6 )
R e c e p t o r  o c c u p a n c y  ( %
)
1 5  m
g / k g ,  Q 3 W
 ( n = 3 )
2 0  m
g / k g ,  Q 3 W
 ( n = 3 )

 
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Q3W dosing regimens, over the treatment period of monotherapy or in combination with 
atezolizumab. 
Immunogenicity: 
Three subjects were confirmed positive for anti-drug antibodies (ADA) during the treatment. No 
impacts of ADA were observed on safety or PK up to date. 
In summary, TJ004309 demonstrated a well-tolerated safety profile with only mild to moderate 
treatment-related adverse events that were managed well, promising antitumor activity with an 
ORR of 23.1% observed in three patients among 13 evaluable patients, a complete target 
saturation suggested by 100% target occupancy on the peripheral B-cells and sustained decrease 
of soluble CD73, and a linear PK with an effective half-life of approximately 19 days over the 
dosing range from 5 mg/kg to 20 mg/kg. Therefore, the proposed dosing regimen of 20 mg/kg in 
combination with atezolizumab (1200 mg/kg Q3W starting from Day 1 of Cycle 1) to be further 
tested in the Phase 2 trial is therefore supported.   
4.4 End of Study Definition 
A patient is considered to have completed the study treatment period if they complete the 
End-of-Study (EOS) visit and, as required, any further follow-up of ongoing serious adverse 
events (SAEs) regardless of relationship to study drug and/or non-serious adverse events (AEs) 
considered to be possibly, probably or definitely related to study drug until either resolution or 
determined by the Investigator to be chronic or stable.  
4.5 Safety Follow-up Period 
After the treatment periods, all subjects will enter a safety follow-up period and will be evaluated 
for safety, tolerability, and tumor response (if applicable) for at least 90 days after the last dose 
of study drug, or 30 days following cessation of study treatment if the subject initiates new 
anticancer therapy, whichever is earlier. Subjects will be required to return to the study sites for 
three (3) safety follow-up visits (approximately 30, 60 and 90 days after the last dose of study 
drug), except those subjects who withdraw consent for study participation. After treatment 
discontinuation, in the event of continuing serious adverse events (SAEs), subjects will be 
followed until resolution or stabilization of the SAEs (regardless of the relationship to the IMP). 
Any subject who has an ongoing non-serious AE that is possibly related or related to the IMP or 
study procedures at the 90-day post-treatment Follow-up visit will be followed up, where 
possible, until resolution or until the unresolved non-serious AE is judged by the Investigator (or 
designee) to have stabilized. Any subject who has an ongoing non-serious AE that is not related 
or unlikely related to the IMP or study procedures at the Follow-up visit, can be closed out as 
ongoing at the Investigator’s discretion. If a subject initiates a new anticancer therapy within 30 
days after the last dose of study treatment, one (1) Post-Treatment Safety Follow-Up visit should 
occur approximately 30 days after the last dose of study drug and therefore subsequent follow-up 
visits will not be required. 

 
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4.6 Response/Survival Follow-up Period 
Subjects who do not experience progressive disease prior to treatment discontinuation will 
continue to have radiologic and clinical tumor assessments every 9 weeks for the first year and 
every 12 weeks during the second year until progression is confirmed, consent withdrawal, start 
of a new anti-cancer treatment, loss to follow-up, or death, whichever comes first. These subjects 
will also be followed by telephone every 12 weeks during the second year. The duration for 
response/survival follow-up is approximately 2 years from the first dose of study drug. 
 

 
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5 STUDY POPULATION 
5.1 Inclusion Criteria 
Patients must meet all of the following criteria to be eligible for the study: 
1. Males or females, age ≥ 18 years 
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 
3. In all cohorts, archival tumor tissue in a tissue block or biopsy specimen that allows the 
preparation of at least 20 slides prior to study entry. Tissue blocks are preferred. Archival 
tumor tissue is acceptable in either format per site’s preference.  
4. Cohort 1 - Ovarian Carcinoma (OC): 
a. Histologically confirmed epithelial ovarian cancer, fallopian tube, or primary 
peritoneal cancer subjects with any high-grade serous component, progressed on or 
after platinum-containing therapy and not eligible for further platinum containing 
treatment (platinum-resistant, platinum-refractory disease defined by progression of 
disease on a platinum-containing regimen or recurrence of disease within 180 days of 
receiving the last dose of platinum-based treatment).  
b. Prior lines of therapy to include: 
• Patients must have had 1 to 3 prior lines of therapy including at least one 
bevacizumab-containing regimen or ineligible for all other available therapies;  
Or  
• Patients must be in the 4th or 5th line of treatment, irrespective of bevacizumab or 
who are ineligible for all therapies with demonstrated clinical benefit; 
Or 
• Patients with known BRCA-positive associated cancer or mutation, prior therapy 
must include PARP inhibitors (unless contraindicated) 
5. Cohort 2 - Patients with selected tumor types that have relapsed or progressed after 2 
lines of therapy or who are ineligible for other standard of care (SOC) therapies: 
a. Histologically or cytologically confirmed metastatic NSCLC 
b. Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, 
oropharynx, hypopharynx, or larynx)  
c. Histologically or cytologically confirmed metastatic or non-resectable advanced 
metastatic gastric or gastroesophageal adenocarcinoma  
d. Histologically or cytologically confirmed unresectable, locally advanced or metastatic 
TNBC (confirmed HER2-negative, estrogen receptor-negative and progesterone 
receptor-negative)  
e. Histologically confirmed ovarian cancer of all high-grade epithelial types who are IO 
treatment naïve and have progressed after 3 months on or after platinum-containing 
therapy  
f. PD-L1 expression Tumor Proportion Score (TPS) ≥ 1% for NSCLC and Combined 
Proportion Score (CPS) ≥ 1% for all other tumor types  

 
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g. A 28-day washout period after the completion of programmed death-1 (PD-1)/PD-L1 
therapy 
h. Patients should have no more than 5 prior lines of therapies 
i. If the patients have progressed on treatment with prior PD-1/L1 inhibitor 
administered either as monotherapy or in combination with other therapies, additional 
following criteria must be met:  
• have received at least 2 doses of the PD-1/L1 inhibitor; 
• have been on a continuous regimen of the PD-1/L1 inhibitor for at least 4 months 
without disease progression; 
• have demonstrated radiographic disease progression after PD-1/L1 
j. Patients who have had more than 1 prior PD-1/L1 inhibitor may be considered after 
discussion with the Sponsor’s Medical Monitor. 
6. Cohort 2 - Pre-treatment fresh tumor biopsies and paired treatment fresh tumor biopsies 
will be collected from at least 5 patients. Biopsy must be excisional, incisional, or core. 
Fine needle aspiration is insufficient. Waiver of biopsy samples must be discussed with 
Sponsor’s Medical Monitor. NOTE: CD73 enzymatic activity and assessment of proteins 
in the adenosine pathway (e.g., CD73, A2A receptor, and whole genome gene expression 
profiles) will be assessed in fresh tumor biopsies. Samples will be collected prior to 
dosing and processed and shipped within 24 hours according to a separate laboratory 
manual. The fresh tumor biopsies require testing for the following infectious diseases: 
Hepatitis B, Hepatitis C, Tuberculosis, HIV, Syphilis, and COVID-19. Testing must be 
completed within 28 days of tumor biopsy collection and confirmed to be negative. 
7. Willingness and ability to consent for self to participate in study and the ability to comply 
with scheduled visits, treatment plan, laboratory tests, and other study procedures 
8. Patients who received prior PD-1/PD-L1 checkpoint inhibitor or prior CTLA-4 inhibitor 
therapy may enroll to Cohort 2 if they did not experience Grade 3 immune-related 
toxicity (applies to all tumor types except ovarian cancer patients)  
9. At least one measurable lesion as defined by RECIST 1.1 
10. Resolution of all acute adverse events resulting from prior cancer therapies to National 
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 
Grade ≤ 1 or baseline (except alopecia or neuropathy) 
11. Considered by the Investigator to be an appropriate candidate for a clinical study, with a 
life expectancy of ≥ 12 weeks 
12. Adequate organ function as defined by the following criteria: 
a. Absolute neutrophil count (ANC) ≥ 1500/μL 
b. Platelets ≥ 100,000/μL without transfusion support within 28 days prior to study 
treatment 
c. Hemoglobin ≥ 9.0 g/dL without transfusion support within 7 days prior to study 
treatment (erythropoietin or darbepoetin permitted) 
d. Creatinine clearance > 30 mL/min by Cockcroft-Gault formula 

 
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e. Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase 
[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic 
transaminase [SGPT]) ≤ 3 times upper limit of normal (ULN) or ≤ 5 times ULN in 
cases of liver metastases 
f. Total serum bilirubin ≤ 1.5 times the ULN, unless patient has documented Gilbert’s 
disease in which case bilirubin ≤ 3.0 times the ULN  
g. International normalized ratio (INR) from 0.8 to 1.2 unless the INR elevation is 
related to use of a Factor Xa Inhibitor 
h. Activated partial thromboplastin time (aPTT) ≤ 1.5× ULN unless patient is receiving 
anticoagulant therapy if PT or PTT is within therapeutic range of intended use of 
anticoagulants 
13. No systemic anti-cancer therapy within 4 weeks of starting study treatment or at least 5 
half-lives (whichever is shorter) before study drug administration, and all AEs have either 
resolved or stabilized.  Note: Participants who have entered the follow-up phase of an 
investigational study may participate if it has been 4 weeks after the last dose of the 
previous investigational agent. 
14. Subject with a QT interval corrected for heart rate using Fridericia’s formula (QTcF) 
and/or QT interval corrected for heart rate using Bazett’s formula of ≤ 480 msec.  NOTE: 
If a patient has a prolonged QT interval and the prolongation is deemed to be due to a 
pacemaker upon Investigator evaluation (i.e., the patient otherwise has no cardiac 
abnormalities), the patient may be eligible to participate in the study following discussion 
with the Sponsor’s Medical Monitor. 
15. Women of childbearing potential (WOCBP) must: 
a. Agree to use at least 2 effective contraceptive methods (1 highly effective method in 
combination with a barrier method; oral, injectable, or implantable hormonal 
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with 
spermicide; or vasectomized partner), one of which must be barrier. Use of 
contraceptive methods lasts from date of ICF signature, throughout the study, and for 
up to 5 months following the last dose of TJ004309. 
b. Have a negative serum pregnancy test (sensitive of at least 25 mIU/ml) at Screening; 
and have a negative serum or urine pregnancy test within 72 hours prior to Cycle 1 
Day 1 of study treatment (note that the screening serum pregnancy test can be used as 
the test prior to Day 1 study treatment if it is performed within the prior 72 hours) 
c. Avoid conceiving for 5 months after the last dose of TJ004309 
d. Avoid donation of ova from date of ICF signature until 5 months after the last dose of 
TJ004309 
e. Agree to ongoing urine pregnancy testing, if clinically indicated, during the study 
16. Males must agree to use a condom (a latex condom is recommended) during sexual 
contact with a pregnant female or a female of childbearing potential, will avoid donation 
of sperm, or having a female partner conceive from date of ICF signature, while 
participating in the study, during dose interruptions, and for at least 5 months after the 
last dose of study treatment, even if he has undergone a successful vasectomy. 

 
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5.2 Exclusion Criteria  
Patients meeting any of the following criteria are not eligible for study participation: 
1. Autoimmune disease requiring active treatment within the past twelve months (Note: 
vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis 
only requiring hormone replacement, and conditions not expected to recur in the absence 
of an external trigger are permitted) 
2. Condition requiring systemic treatment with either corticosteroids (>10 mg daily 
prednisone equivalent) or other immunosuppressive medications within 14 days prior to 
study treatment (Note: inhaled and topical steroids, and adrenal replacement steroid doses 
> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune 
disease.) 
3. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required 
steroids or has current pneumonitis/interstitial lung disease 
4. Current treatment on another therapeutic clinical trial 
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an 
agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-
lymphocyte-associated protein 4 [CTLA-4], OX 40 [Tumor necrosis factor receptor 
superfamily, member 4 (TNFRSF4)], CD137 [tumor necrosis factor receptor superfamily 
member 9 (TNFRSF9)]) (only applies to ovarian cancer patients in Cohorts 1 and 2) 
6. For ovarian patients in both cohorts: 
a. Patients who progressed during or within 3 months of first line of platinum-based 
therapy 
b. Patients with histologically non-epithelial tumors or ovarian tumors with low 
malignant potential (i.e., borderline tumors) or mucinous tumors 
c. Patients with evidence of bowel obstruction requiring hospitalization and 
decompression within the past 30 days 
7. Major surgical procedure or significant traumatic injury within 4 weeks prior to study 
treatment, and must have fully recovered from any such procedure; and no date of 
surgery (if applicable) or anticipated need for a major surgical procedure planned within 
the next 6 months (The following situations are not considered to be major procedures 
and are permitted up to 7 days prior to study treatment: thoracentesis, paracentesis, port 
placement, laparoscopy, thorascopy, tube thoracostomy, bronchoscopy, endoscopic 
ultrasonographic procedures, mediastinoscopy, incisional biopsies, and routine dental 
procedures. Core biopsy and skin biopsy do not require a waiting period prior to dosing.) 
8. Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as > 50% of 
volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14 days 
prior to study treatment  
9. Pleural effusion or ascites that requires paracentesis in the last 30 days   

 
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10. Brain involvement with cancer, spinal cord compression, carcinomatous meningitis, or 
new evidence of brain or leptomeningeal disease; unless the lesion(s) have been radiated 
or resected, are considered fully treated and inactive, are asymptomatic, and no steroids 
have been administered for CNS disease over the 7 days prior to study treatment 
11. Angina, myocardial infarction (MI), symptomatic congestive heart failure, 
cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary 
embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery 
bypass grafting (CABG) within 6 months prior to study treatment 
12. Thrombolytic use (except to maintain IV catheters) within 10 days prior study treatment 
13. Known active or chronic Hepatitis B or Hepatitis C, other hepatitides (non-alcohol 
steatohepatitis, alcohol or drug-related, autoimmune) serology at screening or cirrhosis  
14. Any active infection requiring parenteral treatment 
15. History of hemorrhage or hemoptysis (> ½ teaspoon bright red blood) within 3 months 
prior to study treatment 
16. Known human immunodeficiency virus (HIV) unless CD4+ T cell count > 350 cells/μL 
with an undetectable viral load 
17. Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥ 6 weeks 
following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) 
or be postmenopausal for at least one year or must agree to use effective contraception 
during the study and for 5 months following last dose of TJ004309.  All female patients 
of reproductive potential must have a negative pregnancy test (serum or urine) within 72 
hours prior to study treatment.  Male patients must be surgically sterile or must agree to 
use effective contraception during the study and for 5 months following last dose of 
TJ004309   
18. Patients with any severe infection within 4 weeks prior to initiation of study treatment, 
including, but not limited to, hospitalization for complications of infections should not be 
enrolled in the trial. Patients who required IV antibiotics or were treated with antiviral 
medications within this 4 week period should be discussed with the Sponsor Medical 
Monitor prior to enrollment 
19. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality 
that may increase the risk associated with study participation or may interfere with the 
interpretation of study results and, in the judgment of the Investigator, would make the 
patient inappropriate for this study 
5.3 Lifestyle Considerations 
There are no lifestyle restrictions in this study.  

 
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5.4 Meals and Dietary Restrictions 
Participants should maintain a normal diet unless modifications are required to manage an AE 
such as diarrhea, nausea, or vomiting. 
5.5 Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently enrolled. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
One additional rescreening may be performed for individuals who initially do not meet the 
criteria for participation in this study (screen failure). Rescreened patients should be assigned the 
same participant number as for the initial screening. 

 
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6 STUDY TREATMENT 
The study drug(s) being administered in this study are TJ004309 and atezolizumab. 
6.1 Description, Storage, Packaging and Labeling 
TJ004309 is a recombinant humanized IgG1 antibody that binds to and inhibits the biologic 
activity of CD73.  TJ004309 is produced in CHO cells. TJ004309 will be supplied by the 
Sponsor as 150 mg/3 mL (50 mg/mL) solution in a sterile single-use vial.   
The study drug will be stored according to the instructions on the label or according to 
instructions provided in a separate document. TJ004309 vials are stored under refrigeration at 
2°C to 8°C (36°F to 46°F) and protected from light. Study drug will be stored at the study site in 
a location that is locked with restricted access. The Investigator or designee must confirm 
appropriate temperature conditions have been maintained during transit for all study drug 
received and any discrepancies are reported and resolved before use of the study drug. 
Only patients enrolled in the study may receive study drug and only authorized study site 
personnel may supply or administer study drug. All study drugs must be stored in a secure, 
environmentally controlled and monitored (manual or automated) area in accordance with the 
labeled storage conditions with access limited to the Investigator and authorized site staff. 
Further guidance and information for the final disposition of unused study drugs are provided in 
the Pharmacy Manual. 
The treatment to be used in this study is outlined in Table 5. 
Table 5: Study Drug Treatments 
Study 
Treatment 
Formulation 
Unit 
Dose 
Strengths 
Dose 
Levels 
Route of 
Administration 
Regimen/Treatment 
Period 
Sourcing 
TJ004039 
Solution for 
infusion 
150 mg 
vial 
20 
mg/kg 
IV infusion 
Q3W until clinically 
significant disease 
progression, 
unacceptable 
toxicity, or 
subject/Investigator 
decision to withdraw 
Provided 
by the 
Sponsor 
Atezolizumab 
(Tecentriq®) 
Solution for 
infusion 
1200 mg 
vial 
1200 
mg 
flat 
dose 
6.2 Dose Preparation 
The preparation, handling, and safe disposal of the study drug should only be prepared by 
qualified and experienced personnel. TJ004309 will be diluted using aseptic technique. The 
required dose of TJ004309 will be diluted with 0.9% sodium chloride (normal saline) and 
administered via an IV infusion pump. TJ004309 dose preparations will be administered with a 
low protein binding 0.2μm in-line filter. TJ004309 should not be administered as an IV push or 
bolus. Any unused portion in the vial should be discarded. 

 
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The physicochemical in-use stability has been demonstrated for 4 hours at ambient room 
temperature. Detailed instructions on the preparation and dispensing of TJ004309 are provided in 
the Pharmacy Manual. 
Note that the use of closed system transfer devices (CSTD) for preparation or administration of 
TJ004309 is not permitted. 
For preparation of atezolizumab, see the most recent version of the atezolizumab package insert. 
6.3 Drug Accountability 
The Investigator must maintain an accurate accounting of TJ004309 and atezolizumab supplies.  
During the study, the following information must be recorded: 
• Date of receipt, quantity, and lot number of the study drug received 
• Identification number of the patient to whom the product is dispensed 
• The date(s) and quantity of the product dispensed 
• Dates and quantity of product returned, lost, or accidentally or deliberately destroyed 
Investigational Drug Accountability Logs should be maintained by the site and must be readily 
available for inspection. 
6.4 Treatment Administration 
Intravenous hydration prior to and during therapy is left to the discretion of the Investigator but 
should be considered for patients that may be volume depleted. 
The following premedication will be administered on Cycle 1 Day 1, to be administered within 
30 minutes to 2 hours prior to the start of the initial TJ004309 infusion:   
• Antipyretic (i.e., acetaminophen 650 mg PO) 
• Antihistamine (i.e., diphenhydramine 25 to 50 mg PO/IV, cetirizine 10 mg, etc.) 
Premedication is not required for subsequent infusions unless a given patient experiences Grade 
> 2 infusion related reaction with the immediate prior dose of TJ004309. 
TJ004309 will be administered by IV utilizing an infusion pump. TJ004309 is required to be 
administered with a 0.2 micron downstream filter. The attachment of the infusion pump 
administration set to the IV bag and transport of the TJ004309 study drug to the patient will be 
performed as per standard study site procedures. Priming may be done using normal saline. 
Initially, TJ004309 will be administered over 1 hour (±15 minutes) in Cycles 1 and 2.  In the 
absence of IRRs in patients infused over 1 hour in Cycle 2, the infusion time of TJ004309 may 
be reduced to 30 minutes (± 10 min) per Investigator’s discretion.  
When the IV bag containing TJ004309 is empty, flush the IV line with sufficient normal saline 
to clear the tubing at the same infusion rate as the study drug infusion. The infusion is considered 
complete when the bag containing TJ004309 is empty including the flush. The dose level, time 

 
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of transfer to IV bag, and the infusion start and stop times must be recorded in the source 
documents. TJ004309 has been demonstrated to be compatible with polyethylene lined, non-
DEHP infusion sets and polyvinyl chloride, non-DEHP infusion sets. 
Administer atezolizumab 1200 mg IV over 60 minutes on Cycle 1 Day 1. If the patient does not 
experience any infusion related reactions, the infusion may be administered over 30 minutes 
starting with Cycle 2. Atezolizumab will be administered on Day 1 of each 21-day cycle until 
progression according to the package insert, with any dose modifications done per the package 
insert beginning with Cycle 2 Day 1. Atezolizumab should be administered at least 15 minutes 
following the completion of TJ004309 administration. 
Please refer to the Pharmacy Manual for detailed information. 
6.5 Dose Assignment 
All subjects will be given the combination treatment of TJ004309 20 mg/kg and atezolizumab 
1200 mg Q3W. All subjects will be evaluated for antitumor activity on a regular basis as 
specified in the protocol and their clinical status classified according to RECIST 1.1 and 
iRECIST. Treatments may continue until clinically significant disease progression, unacceptable 
toxicity, or subject/Investigator decision to withdraw.  
6.6 Measures to Minimize Bias: Randomization and Blinding 
Part 1 of this study is a single arm non-randomized study. 
6.7 Study Intervention Compliance 
The United States Food and Drug Administration (US FDA) and other applicable regulatory 
authorities require accounting of all investigational drug received by each study center. Records 
of drug disposition required include the date received by the center, date administered, quantity 
administered, and the patient to whom study drug was administered. The Investigator is 
responsible for the accountability of all used and unused study drug containers and unused study 
drug.  
Each study center is to use a study drug accountability log to document study drug disposition. 
All items on this form are to be completed in full. The Sponsor’s Clinical Research Associate 
(CRA) is to approve the area where study drug is to be stored and accountability records are to 
be maintained. 
The Investigator identification number and patient initials (as allowed by local regulations) and 
identification number are to be recorded on each study drug accountability log. Each time study 
personnel dispense study drug for a patient, he or she is to record the date dispensed, amount of 
study drug dispensed, and his or her initials. Study personnel are to monitor the inventory of 
clinical supplies and maintain a count of all used and unused study drug. The CRA is to review 
study drug accountability records and remaining drug supplies during routine monitoring visits. 

 
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6.8 Concomitant Therapy 
All prescription and non-prescription medications and therapies, including pharmacologic doses 
of vitamins, herbal medicines, or other non-traditional medicines, taken from 28 days prior to the 
first study drug dose are to be documented as prior medications. Medications taken from the 
time of the first study drug dose on C1D1 through 30 days after the last study drug dose are to be 
recorded as concomitant medications in the electronic case report form (eCRF). All therapies for 
primary diagnosis should be recorded regardless of when they were taken. 
6.8.1 Prohibited Concomitant Medications 
The following medications and treatments are prohibited during study participation: 
• Any commercially available or investigational anti-cancer therapy other than the study 
treatment 
• Radiation therapy is prohibited within 2 weeks prior to study Cycle 1 Day 1 and during 
study treatment. NOTE: Palliative radiation therapy to a small field outside of the target 
lesion area >1 week prior to Day 1 of the study treatment may be allowed at the 
discretion of the Investigator or palliative radiation therapy during the protocol may be 
permitted after discussion with the Sponsor’s Medical Monitor. 
• Prophylactic granulocyte colony-stimulating factor (GCSF) or GM-CSF is not permitted. 
The use of these may only be permitted after discussion with the Sponsor’s Medical 
Monitor if indicated. 
• Chronic or systemic corticosteroid use (prednisone ≥10 mg/day or dexamethasone 
≥1.5 mg/day) for supportive care is not permitted. (However, acute use to manage 
suspected immune-related AEs is allowed; however, in such cases, systemic steroid 
should be stopped at least 24 hours prior to the next dose of the study drug and the use of 
such needs to be clearly documented in the applicable source docs and CRF). Acute use 
of topical corticosteroid preparations, inhaled sprays, eye drops, or local injections of 
corticosteroids are acceptable. Use of a corticosteroid due to a confirmed allergy to IV 
contrast is also permitted. 
• Live vaccines administered within 30 days prior to the initially dose of study drug and 
while participating in the study are not permitted. Seasonal influenza vaccines for 
injection that are killed virus vaccines are allowed; live attenuated vaccines such as the 
intranasal influenza vaccine (e.g., FluMist®) are not allowed. Other types of vaccines 
(mRNA) may have exemptions, such as the SARS-CoV-2 (COVID-19) vaccine; Sponsor 
will provide up-to-date guidance based on current practices. 
• Subjects are required to refrain from donation of blood from 3 months prior to Screening, 
plasma from 2 weeks prior to Screening, and platelets from 6 weeks prior to Screening 
until 3 months after the last Follow-up visit. 

 
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6.8.2 Permitted Concomitant Medications 
Medications and treatments other than those specified in, including palliative and supportive care 
for disease-related symptoms, are permitted during the study. Patients should be closely 
monitored, and treatment is to be instituted for disease-related symptoms, as appropriate. 
• All prior medications and non-drug interventions received by subjects within 28 days (4 
weeks) prior to the initially dose of study treatment and up to 30 days after the last dose 
of study treatment will be recorded on the CRF, including the name of the procedure or 
medication, dose, route, indication and duration of treatment. Concomitant treatment 
and supportive care considered necessary for the subject’s well-being may be given at 
the discretion of the treating physician using his or her clinical judgment in consultation 
with the Sponsor. 
• Medications (antihistamines, H2-blockers, anti-pyretics, bronchodilators, 
corticosteroids, and other medically indicated medications) to treat infusion-related 
reactions are acceptable. 
• Medications to treat anemia, thrombocytopenia, and other TJ004309-related adverse 
effects are permitted. 
• Hormone replacement therapy, oral, implantable, transdermal, injectable, or 
intrauterine contraceptives are acceptable concomitant medications. 
• Antiemetic treatments may be used at the Investigator’s discretion and in accordance 
with the American Society of Clinical Oncology guidelines or equivalent after 
documented nausea or vomiting has occurred without medications having been used. 
6.8.3 Premedication 
On Cycle 1 Day 1, the following premedication will be administered within 30 minutes to 2 
hours prior to the start of the initial TJ004309 infusion:   
• Antipyretic (i.e., acetaminophen 650 mg PO) 
• Antihistamine (i.e., diphenhydramine 25 to 50 mg PO/IV, cetirizine 10 mg, etc.) 
Premedication is not required for subsequent infusions unless a given patient experiences Grade 
> 2 infusion related reaction with the immediate prior dose of TJ004309. 
6.9 Dose Modification and Dose Delays 
The treatment management guidelines including dose delay and dose modification of TJ004309 
for hematological and non-hematological toxicities are provided in Table 6 and Table 7 
respectively. Treatment management guidelines for Immune-Related Adverse Events (irAEs) are 
provided in Table 8.  

 
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Dose delay up to 4 weeks is allowed for subjects with manageable AEs at the Investigator’s 
discretion, e.g., Grade 4 or Grade 3 thrombocytopenia with Grade ≥ 2 bleeding, uncomplicated 
Grade 3 febrile neutropenia, and Grade 4 neutropenia. The Investigator can continue to withhold 
treatment for up to 12 weeks after the last dose based on the Investigator’s medical judgement. If 
the subject has recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. Dose modification or withholding of doses other than as 
described in this section is not permitted. 
If a Grade ≥ 2 toxicity recurs for the second time, the Investigator may discuss with the Sponsor 
whether resuming TJ004309 is appropriate considering the type and grade of the toxicity. If the 
agreement is to resume TJ004309, treatment can continue to be withheld for up to 12 weeks to 
allow the subject to recover to Grade ≤ 1 or baseline at the Investigator’s discretion. If the 
subject recovers to Grade ≤ 1 or baseline within 12 weeks, continue treatment of TJ004309 at the 
same dose level. If the subject does not recover within 12 weeks, permanently discontinue 
TJ004309. The Investigator should always manage their subjects according to their medical 
judgment based on the clinical circumstances. 
All dose modifications must be clearly documented in the subjects’ source notes and Case Report 
Form (CRF). 
Study treatment dose delays are permitted in the case of medical/surgical events or logistical 
reasons not related to study therapy (e.g., surgery, unrelated medical events, patient vacation, 
and/or holidays). Participants should be placed back on study therapy within 28 days of the 
scheduled interruption, unless otherwise discussed with the Sponsor. The reason for interruption 
should be documented in the patient's study record. All dose delays must be clearly documented 
in the patients’ source notes and the eCRF.

 
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Table 6:  TJ004309 Treatment Management Guidelines for Adverse Events (Hematological Toxicities) 
Adverse Event 
Grade 
Management Actions* 
Neutropenia 
Grade ≥ 4 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, continue 
treatment of TJ004309 at the same dose level. If the subject has not recovered 
within 4 weeks, the Investigator can continue to withhold for up to 12 weeks after 
the last dose based on the Investigator’s medical judgement. 
• 
Monitor absolute neutrophil count weekly until recovered or stable. 
• 
Conduct adequate evaluation to confirm etiology and/or exclude other causes. 
• 
Initiate broad spectrum antibiotics. 
• 
Consider initiating Granulocyte-colony stimulating factor (G-CSF) such as 
filgrastim or pegylated filgrastim. 
• 
If the event recurs for the second time, withhold treatment for up to 12 weeks while 
giving appropriate medical treatment at the Investigator’s discretion. If the subject 
has recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered within 12 weeks, 
permanently discontinue TJ004309. 
Febrile Neutropenia 
Grade ≥ 3 
See above 
Other hematological toxicities
1 
Grade ≥ 3 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, continue 
treatment of TJ004309 at the same dose level. If the subject has not recovered 
within 4 weeks, the Investigator can continue to withhold for up to 12 weeks after 
the last dose based on the Investigator’s medical judgement. 
• 
Monitor hematological toxicities weekly until recovered or stable. 
• 
Conduct adequate evaluation to confirm etiology and/or exclude other causes. 
• 
If the event recurs for the second time, withhold treatment for up to 12 weeks while 
giving appropriate medical treatment at the Investigator’s discretion. If the subject 
has recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered within 12 weeks, 
permanently discontinue TJ004309. 
1 With the exception of Grade 3 or 4 lymphopenia.   
*Treating physicians’ assessment and judgement are critical, and all the management actions should be taken with physician’s discretion 

 
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Table 7:  TJ004309 Treatment Management Guidelines for Adverse Events (Non-Hematological Toxicities) 
Adverse Event 
Grade 
Management Actions* 
   Infusion Related Reactions 
(IRR)
1 
Grade 2 
• 
Interrupt or slow the rate of infusion. Monitor and if the reaction worsens, stop 
infusion. 
• 
Administer institutional standard medications for hypersensitivity reaction as 
medically indicated. Monitor symptoms until stable. Re-initiate infusion if 
patient is stable at a 50% slower rate. Prophylactic medications indicated for ≤ 
24 hours. 
• 
For subsequent infusions, administer premedication with the following or per 
institutional standard: 
o H-1 antihistamine: Diphenhydramine 25-50 mg PO or IV 30 minutes prior 
to infusion 
o Acetaminophen 500-1000 mg PO 30 minutes prior to infusion 
o Corticosteroids such as dexamethasone (or equivalent) or anti- emetics 
such as ondansetron (or equivalent) may be administered based on 
clinical presentation of previous IRR 
• 
For subsequent infusions, may administer TJ004309 at a 50% slower rate. 
Grade ≥ 3 
• 
Stop infusion immediately and discontinue TJ004309. 
• 
Administer epinephrine, bronchodilators, antihistamines, glucocorticoids, IV 
fluids, vasopressors, oxygen, etc. as medically indicated. Contact sponsor to 
report SAE. 
• 
Increase monitoring of vital signs as medically indicated until stable. 
Chills 
Grade 3 
• 
Stop the infusion. 
• 
Administer aggressive symptomatic therapy per institutional standard. 
• 
After resolution of all symptoms, treatment can be resumed at slower rate, unless 
severe reaction. If severe reaction, then withhold TJ004309 per Investigator’s 
discretion of clinical presentation of the subject. 
 

 
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Diarrhea/Colitis 
Grade 2 or 3 that 
persists for 
≥ 7 days 
despite   adequate 
steroid therapy 
• 
Withhold. 
• 
Should consult with gastroenterology for Grade ≥ 2. 
• 
Administer corticosteroids starting with initial dose of 1- 2 mg/kg/day 
prednisone or equivalent. Consider hospitalization or outpatient facility for 
patients with dehydration or electrolyte imbalance. When symptoms improve 
to Grade ≤ 1, taper corticosteroids over at least 4 - 6 weeks before resuming 
treatment, although resuming treatment while on low-dose corticosteroid may 
also be an option after an evaluation of the risks and benefits. 
• 
Monitor subject for signs and symptoms of enterocolitis and/or bowel 
perforation and advise patient to increase oral fluids or IV infusion if needed. 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, and 
treatment is restarted during corticosteroid taper, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered within 4 
weeks, the Investigator can continue to withhold for up to 12 weeks after the 
last dose based on the Investigator’s medical judgement. 
• 
If recurrent Grade ≥ 3 permanently discontinue TJ004309. 
Nausea, vomiting, fatigue, or 
electrolyte abnormalities 
Grade 3 if 
persisting despite 
optimal medical 
treatment 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, continue 
treatment of TJ004309 at the same dose level. If the subject has not recovered 
within 4 weeks, the Investigator can continue to withhold for up to 12 weeks 
after the last dose based on the Investigator’s medical judgement. 
• 
Monitor toxicities weekly until recovered or stable. 
• 
Give supportive care based on Investigator discretion. 
• 
Conduct adequate evaluation to confirm etiology and/or exclude other 
causes. 
• 
If recurs for the second time, withhold treatment for up to 12 weeks while giving 
appropriate medical treatment at the Investigator’s discretion. If the subject has 
recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered up to 12 weeks, 
permanently discontinue TJ004309. 
 

 
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Grade 4 
• 
Give supportive care based on Investigator discretion. 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, continue 
treatment of TJ004309 at the same dose level. If the subject has not recovered 
within 4 weeks, the Investigator can continue to withhold for up to 12 weeks 
after the last dose based on the Investigator’s medical judgement. 
• 
If recurs for the second time, withhold treatment for up to 12 weeks while giving 
appropriate medical treatment at the Investigator’s discretion. If the subject has 
recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered up to 12 weeks, 
permanently discontinue TJ004309. 
Other non-hematological    
adverse reactions 
Grade 3 
• 
If the subject has recovered to Grade ≤ 1 or baseline within 4 weeks, continue 
treatment of TJ004309 at the same dose level. If the subject has not recovered 
within 4 weeks, the Investigator can continue to withhold for up to 12 weeks 
after the last dose based on the Investigator’s medical judgement. 
• 
Monitor toxicities weekly until recovered or stable. 
• 
Give supportive care based on Investigator discretion. 
• 
Conduct adequate evaluation to confirm etiology and/or exclude other 
causes. 
• 
If recurs for the second time, withhold treatment for up to 12 weeks while giving 
appropriate medical treatment at the Investigator’s discretion. If the subject has 
recovered to Grade ≤ 1 or baseline within 12 weeks, continue treatment of 
TJ004309 at the same dose level. If the subject has not recovered up to 12 weeks, 
permanently discontinue TJ004309. 
Grade 4 
• 
Discontinue TJ004309. 
1For further information, please refer to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) at http://ctep.cancer.gov 
*Treating physicians’ assessment and judgement are critical, and all the management actions should be taken with physician’s discretion. 
 

 
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Table 8: TJ004309 Treatment Management Guidelines for Immune-Related Adverse Events (irAEs) 
General instructions: 
1. Severe and life-threatening irAEs should be treated with IV corticosteroid followed by oral steroids. Other immunosuppressive 
treatment should begin if the irAEs are not controlled by corticosteroids. 
2. TJ004309 must be permanently discontinued if the irAE does not resolve or the corticosteroid dose is not ≤10 mg/day within 12 weeks 
of the last treatment. 
3. The corticosteroid taper should begin when the irAE is ≤ Grade 1 and continue tapering at least 4 weeks. 
4. If TJ004309 has been withheld, TJ004309 may resume after the irAE decreased to ≤ Grade 1 after corticosteroid taper. 
 

 
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irAEs 
Toxicity Grade 
(CTCAE V5.0) 
Action with 
TJ004309 
Corticosteroid 
and/or other 
therapies 
Monitoring and Follow-up 
Pneumonitis 
Grade 2 
Withhold 
Administer 
corticosteroids (initial 
dose of 1 to 2 mg/kg 
prednisone or 
equivalent) followed 
by taper 
Add prophylactic 
antibiotics for 
opportunistic 
infections 
Monitor participants for signs and symptoms of pneumonitis 
Evaluate participants with suspected pneumonitis with 
radiographic imaging and initiate corticosteroid treatment 
 
Recurrent 
Grade 2,  
Grade 3 or 4 
Permanently 
discontinue 
Diarrhea / Colitis 
Grade 2 or 3 
Withhold 
Administer 
corticosteroids (initial 
dose of 1 to 2 mg/kg 
prednisone or 
equivalent) followed 
by taper 
 
Monitor participants for signs and symptoms of enterocolitis 
(ie, diarrhea, abdominal pain, blood or mucus in stool with or 
without fever) and of bowel perforation (ie, peritoneal signs 
and ileus) 
Participants with ≥ Grade 2 diarrhea suspecting colitis should 
consider GI consultation and performing endoscopy to rule out 
colitis 
Participants with diarrhea/colitis should be advised to drink 
liberal quantities of clear fluids. If sufficient oral fluid intake 
is not feasible, fluid and electrolytes should be substituted via 
IV infusion 
Recurrent Grade 
3 or Grade 4 
Permanently 
discontinue 
AST or ALT 
elevation or 
Increased 
Bilirubin 
Grade 2 a 
Withhold 
Administer 
corticosteroids (initial 
dose of 0.5 to 1 
mg/kg prednisone or 
equivalent) followed 
by taper 
Monitor with liver function tests (consider weekly or more 
frequently until liver enzyme value returned to baseline or is 
stable) 

 
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Grade 3 b or 4 c 
Permanently 
discontinue 
Administer 
corticosteroids (initial 
dose of 1 to 2 mg/kg 
prednisone or 
equivalent) followed 
by taper 
Type 1 diabetes 
mellitus (T1DM) 
or Hyperglycemia 
New onset 
T1DM or  
Grade 3 or 4 
hyperglycemia 
associated with 
evidence of 
β-cell failure 
Withhold d 
Initiate insulin 
replacement therapy 
for participants with 
T1DM 
Administer 
antihyperglycemic in 
participants with 
hyperglycemia 
 
Monitor participants for hyperglycemia or other signs and 
symptoms of diabetes 
Hypophysitis 
Grade 2 
Withhold 
Administer 
corticosteroids and 
initiate hormonal 
replacements as 
clinically indicated 
Monitor for signs and symptoms of hypophysitis (including 
hypopituitarism and adrenal insufficiency) 
Grade 3 or 4 
Withhold or 
permanently 
discontinue d 
Hyperthyroidism 
Grade 2 
Continue 
Treat with 
nonselective beta-
blockers (e.g., 
propranolol) or 
thionamides as 
appropriate 
Monitor for signs and symptoms of thyroid disorders 
Grade 3 or 4 
Withhold or 
permanently 
discontinue d 

 
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Hypothyroidism 
Grade 2, 3 or 4 
Continue 
Initiate thyroid 
replacement 
hormones (e.g., 
levothyroxine or 
liothyronine) per 
standard of care 
Monitor for signs and symptoms of thyroid disorders 
Nephritis: 
grading according 
to increased 
creatinine or acute 
kidney injury 
Grade 2 
Withhold 
Administer 
corticosteroids 
(prednisone 
1 to 2 mg/kg or 
equivalent) followed 
by taper 
Monitor changes of renal function 
Grade 3 or 4 
Permanently 
discontinue 
Neurological 
Toxicities 
Grade 2 
Withhold 
Based on severity of 
AE administer 
corticosteroids 
Ensure adequate evaluation to confirm etiology and/or exclude 
other causes 
Grade 3 or 4 
Permanently 
discontinue 
 
Myocarditis 
Grade 2, 3 or 4 
Permanently 
discontinue 
Based on severity of 
AE administer 
corticosteroids 
 
 
 
Ensure adequate evaluation to confirm etiology and/or exclude 
other causes 
Exfoliative 
Dermatologic 
Conditions 
Suspected SJS, 
TEN, or DRESS 
Withhold 
Based on severity of 
AE administer 
corticosteroids 
Ensure adequate evaluation to confirm etiology and/or exclude 
other causes 
Confirmed SJS, 
TEN, or DRESS 
Permanently 
discontinue 
All other irAEs 
Persistent Grade 
2 
Withhold 
Ensure adequate evaluation to confirm etiology and/or exclude 
other causes 

 
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Grade 3 
Withhold or 
discontinue based 
on the event e 
Based on severity of 
AE administer 
corticosteroids 
Recurrent Grade 
3 or Grade 4 
Permanently 
discontinue 
AE(s)=adverse event(s); ALT= alanine aminotransferase; AST=aspartate aminotransferase; CTCAE=Common Terminology Criteria for Adverse Events; 
DRESS=Drug Rash with Eosinophilia and Systemic Symptom; GI=gastrointestinal; IO=immuno-oncology; ir=immune related; IV=intravenous; SJS=Stevens-
Johnson Syndrome; T1DM=type 1 diabetes mellitus; TEN=Toxic Epidermal Necrolysis; ULN=upper limit of normal. 
Note: Non-irAE will be managed as appropriate, following clinical practice recommendations. 
a AST/ALT: > 3.0 - 5.0 x ULN if baseline normal; > 3.0   5.0 x baseline, if baseline abnormal;  bilirubin: > 1.5   3.0 x ULN if baseline normal; > 1.5 - 3.0 x baseline 
if baseline abnormal 
b AST/ALT: > 5.0 to 20.0 x ULN, if baseline normal; > 5.0   20.0 x baseline, if baseline abnormal; bilirubin: > 3.0   10.0 x ULN if baseline normal; > 3.0 - 10.0 x 
baseline if baseline abnormal 
c AST/ALT: > 20.0 x ULN, if baseline normal; > 20.0 x baseline, if baseline abnormal;  bilirubin: > 10.0 x ULN if baseline normal; > 10.0 x baseline if baseline 
abnormal 
d The decision to withhold or permanently discontinue TJ004309 is at the discretion of the investigator or treating physician. If control achieved or ≤ Grade 2, 
TJ004309 may be resumed. 
e Events that require discontinuation include but are not limited to: encephalitis and other clinically important irAEs (eg. vasculitis and sclerosing cholangitis). 
 
 
 
 

 
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6.10 Treatment after Disease Progression 
A patient who is deriving clinical benefit despite radiological evidence of progressive disease, 
defined by RECIST 1.1 and iRECIST criteria, may continue study treatment at the Investigator’s 
discretion after discussion with the Sponsor.  The patient must meet all of the following criteria: 
• ECOG status of 0 or 1 
• Absence of signs/symptoms (including laboratory values) indicating unequivocal 
progression of disease. 
• Absence of tumor progression at specific anatomical sites that cannot be readily managed 
and stabilized by protocol-allowed medical interventions prior to repeat dosing.  These 
anatomical sites include the CNS, and other organs/tissues where compromised function 
secondary to tumor progression would be expected to result in severe and/or irreversible 
disability or death. 
• Must provide consent to acknowledge discussion with the Investigator of the benefit-risk 
of continuing on study beyond radiographic progression. 
6.11 Intervention after the End of the Study 
No intervention following the completion of study participation is planned. 

 
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7 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 Discontinuation of Study Intervention 
Patients will be informed that they have the right to discontinue study drug at any time for any 
reason, without prejudice to their medical care. At the time of discontinuation, all study 
procedures outlined for the EOS visit should be completed (see Table 2). The primary reason for 
study drug discontinuation is to be recorded in the eCRF.  
7.1.1 Reasons for Discontinuation of Study Intervention 
The Investigator has the right to discontinue study drug for any of the following reasons: 
• Progression of disease that, in the opinion of the Investigator, precludes further study 
treatment. (After consultation with the Study Responsible Physician, study drug may be 
continued for a patient who has met the criteria for progressive disease (PD) but, in the 
Investigator’s opinion, is receiving benefit) 
• Occurrence of an unacceptable AE per the Investigator medical judgement 
• Pregnancy (see Section 8.4.8) 
• Non-compliance 
• Lost to follow-up 
• Patient withdrawal of consent 
• Sponsor request 
7.2 Replacement of Patients 
Subjects who are withdrawn for reasons not related to study drug may be replaced following 
discussion between the Investigator and the Sponsor. 
7.3 Participant Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, 
or administrative reasons.  
At the time of withdrawal from the study, if possible, an EOS visit should be conducted, as 
shown in the SoA (Table 2). See Table 2 for data to be collected at the time of study withdrawal 
and follow-up and for any further evaluations that need to be completed. 
If the participant withdraws consent, the patient will be permanently discontinued from the study 
drug and withdrawn from the study at that time. The Sponsor may retain and continue to use any 
data collected before such a withdrawal of consent. 

 
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If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
7.4 Lost to Follow up 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study center. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit or following the site’s standard procedures: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
study. 
• Before a patient is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the patient’s 
medical record. 
• Should the patient continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole will be handled as described in 
Section 7. 

 
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8 STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Table 2 and Table 3).  
Immediate safety concerns should be discussed with the Sponsor immediately upon occurrence 
or awareness to determine if the patient should continue or discontinue study drug. 
Adherence to the study design requirements, including those specified in the SoA, is essential 
and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that a potential patient 
meets all eligibility criteria. The Investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
The patient/patient’s health proxy must provide written informed consent before the performance 
of any study-specific procedures. 
Procedures conducted as part of the patient’s routine clinical management (e.g., blood count) and 
obtained before signing of the informed consent form (ICF) may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and were 
performed within the time frame defined in the SoA (Table 2). 
8.1 Efficacy Assessments 
Tumors will be assessed for anti-tumor activity of TJ004309 at times indicated in the SoA (Table 
3). Assessments will be measured by BOR, ORR, DOR, PFS, and OS and will be based on 
RECIST 1.1 and iRECIST for solid tumors. 
8.2 Baseline and Safety Assessments 
Planned time points for all safety assessments are provided in the SoA (Table 2). 
8.2.1 Demographics 
Patient demographics, including age, sex, race, and ethnicity, are to be documented during 
Screening. 
8.2.2 Medical History, Including Cancer History 
A complete medical history is to be documented during Screening and updated at Baseline, prior 
to administration of the first study drug dose. 
The medical history is to include cancer history, including the patient’s primary diagnosis, date 
of diagnosis, method of diagnosis, and all previous treatments, including radiation therapy, and 
response to such treatment.  

 
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8.2.3 Physical Examinations, Height, and Weight 
A full physical examination will be performed at Screening and at pre-dose of Cycle 1 Day 1, 
unless the screening physical examination was performed within the last 7 days. The full 
physical examination includes general appearance, head/ears/eyes/nose/throat, lungs/chest, heart, 
abdomen, lymph nodes, musculoskeletal, extremities and neurological examinations. The 
genitourinary examination is considered optional unless indicated by medical history or report of 
current condition.  
Starting with Cycle 2, abbreviated physical examinations should be performed as appropriate at 
each visit in which completed physical examinations are not required, and on an as needed basis 
for assessment of AEs. Abbreviated physical examinations should be targeted to specific 
symptoms or complaints and be consistent with local standard of care (brief physical 
examination will be symptom-directed and include assessment of cardiac, respiratory, and 
gastrointestinal systems). 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Height (cm) is to be measured for all patients at Screening only.  
Weight (kg) is to be measured for all patients at the designated time points in the SoA (Table 2). 
The dose of each study drug will be calculated based on the actual weight of each subject, as 
measured at the screening visit. The weight used may be revised to a weight collected at a later 
date if it has changed by more than 10%. 
8.2.4 Vital Signs 
Seated blood pressure, seated pulse rate, respiratory rate, and body temperature will be assessed 
at the times indicated in the Schedule of Assessments in Table 2.  
For the first cycle, vital signs (seated blood pressure, seated pulse rate, respiratory rate) will be 
collected pre-dose, 30 minutes after the start of infusion, and 2 hours after EOI. Body 
temperature will be measured singly. The median value will be used as the baseline value in the 
data analysis. For treatment in Cycle 1, subjects should remain at the site for monitoring (with 
immediate access to medical resuscitation equipment) for at least 1 hour following the end of the 
initial infusion.  
At all subsequent cycles vital signs will be performed pre-dose singly and repeated once if 
outside the relevant clinical reference ranges. Vital signs may also be performed at other times if 
judged to be clinically appropriate or if the ongoing review of the data suggests a more detailed 
assessment of vital signs is required. 
Subjects must be seated for at least 5 minutes before blood pressure and pulse rate 
measurements. 

 
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8.2.5 Performance Status 
Performance status is to be assessed using the Eastern Cooperative Oncology Group (ECOG) 
performance status scale for all patients at the time points designated in the SoA (Table 2). The 
ECOG performance status scale, with corresponding Karnofsky performance status score 
equivalents, is presented in Table 9. 
Table 9:  Eastern Cooperative Oncology Group Performance Status Scale, with Equivalent 
Karnofsky Performance Status Scores 
ECOGa 
Karnofskyb 
Score 
Criterion 
% 
Criterion 
0 
Normal activity 
100 
Normal; no complaints; no evidence of disease 
90 
Able to carry on normal activity; minor signs or symptoms of 
disease 
1 
Symptoms but ambulatory 
80 
Normal activity with effort; some signs or symptoms of disease 
70 
Cares for self; unable to carry on normal activity or do active 
work 
2 
In bed <50% of time 
60 
Requires occasional assistance but is able to care for most of 
his/her needs 
50 
Requires considerable assistance and frequent medical care 
3 
In bed >50% of time 
40 
Disabled, requires special care and assistance 
30 
Severely disabled; hospitalization is indicated though death is 
not imminent 
4 
100% bedridden 
20 
Very sick; hospitalization is necessary 
10 
Moribund; fatal processes progressing rapidly 
5 
Dead 
0 
Dead 
a 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649-655. 
b 
Mor V, Laliberte L, Morris JN, Wiemann M.  The Karnofsky Performance Status Scale:  an examination of its reliability and 
validity in a research setting. Cancer. 1984;53:2002-2007. 
8.2.6 Electrocardiograms 
At Screening, 12-lead electrocardiograms (ECGs) are to be performed in triplicate, with each 
measurement separated by 2 minutes. The average of the 3 Screening ECGs will be used to 
calculate QTc to determine study eligibility.  The Investigator (or designee) will perform a 
clinical assessment of each 12 lead ECG.  
ECGs are to be performed at the designated time points in the SoA (Table 2). ECG 
measurements should be taken after the patient has been resting in the supine or reclined 
position. 
Additional 12 lead ECGs may be performed at other times if judged to be clinically appropriate 
or if the ongoing review of the data suggests a more detailed assessment of ECGs is required. 

 
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8.2.7 Clinical Safety Laboratory Assessments 
See Section 10.5 for the list of clinical laboratory tests to be performed and the SoA (Table 2) 
for the timing and frequency. Additional clinical laboratory evaluations will be performed at 
other times if judged to be clinically appropriate or if the ongoing review of the data suggests a 
more detailed assessment of clinical laboratory safety evaluations is required (e.g., repeat testing 
as required to confirm results). 
The Investigator must review the laboratory reports, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the patient's condition. 
If such values do not return to normal/baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified, and the Sponsor notified. 
All protocol-required laboratory assessments, as defined in Section 10.5, must be conducted in 
accordance with the laboratory manual and the SoA. 
8.3 Safety Parameters and Definitions 
Adverse events observed or discovered by the Investigator in this study, as well as information 
on AEs reported by the patient, whether or not there is a suspicious causal association with the 
study medication, are required to be reported in accordance with the following requirement.  
8.3.1 Definition of Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment.  
An AE can therefore be any of the following:  
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the medical 
and scientific judgment of the Investigator (i.e., but not related to progression of 
underlying disease). 
• Worsening of signs and symptoms of the malignancy under study drug treatment. 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study drug administration even though it may 
have been present before the start of the study. 

 
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• Related to a protocol-mandated intervention, including those that occur prior to 
assignment of study treatment (e.g., screening invasive procedures such as biopsies). 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study drug or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is 
an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses 
should be reported regardless of sequelae. 
Events NOT meeting the AEs definition: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments associated with the underlying disease, unless judged by the Investigator to 
be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or its progression, signs, or symptoms, unless more 
severe than expected for the participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy). The condition that leads 
to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen overall. 
8.3.2 Definition of Serious Adverse Event 
An SAE is defined as any untoward medical occurrence that at any dose meets any of the 
following criteria: 
• Results in death 
• Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the patient 
was at risk of death at the time of the event. It does not refer to an event which hypothetically 
might have caused death, if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the patient has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalization” occurred or was necessary, the AE should be considered serious. 

 
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• Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a patient’s ability to conduct normal life 
functions. 
• Is a congenital anomaly/birth defect 
• Is a significant medical event in the Investigator’s judgement  
Medical or scientific judgment should be exercised in deciding whether SAE reporting 
is appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These events should usually be considered serious. 
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias, or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse. 
The terms "severe" and "serious" are not synonymous. Severity refers to the intensity of an AE 
(e.g., rated as mild, moderate, or severe, or according to the NCI CTCAE, version 5.0.  
Severity and seriousness need to be independently assessed for each AE recorded on the eCRF. 
8.3.2.1 Hospitalization 
Some events that require inpatient hospital care or prolongation of existing hospitalization may 
not be considered as SAE. When hospitalization is not associated with an AE as supported by 
evidence, the hospitalization will not be considered as SAE, the following “hospitalizations” 
should not per se constitute a SAE: 
• Inpatient hospital care or prolongation of existing hospitalization is a result of other 
factors rather than an SAE (e.g., pre-existing conditions)  
• Inpatient hospital care appointed or scheduled prior to the study (e.g., hospitalization for 
routine physical examination, patient education and planned medical operations, social 
causes etc.). 
The causes of the above hospitalization events must be clearly documented in the medical 
records. 
8.3.2.2 Disease Progression 
Progression of the malignancy under study (including signs and symptoms of progression) 
should not be recorded as an AE or SAE. If the Investigator believes that the progression of 
malignancy under study is related to the study drug or the progression of the malignancy led to 
death, the progression should be reported as an SAE. 

 
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8.4 Safety Reporting Requirement 
The Investigator is responsible for ensuring that all AEs are detected, documented, and recorded 
on the Adverse Event eCRF.  
Each study patient will be questioned about AEs at each clinic visit following initiation of 
treatment. Open-ended and non-leading verbal questioning of the patient/patient’s legal guardian 
is the preferred method to inquire about AE information. Examples of non-directive questions 
include the following: 
"How have you felt since your last clinic visit?" 
"Have you had any new or changed health problems since you were last here?"  
For each AE recorded on the Adverse Event eCRF, the Investigator will make an assessment for 
seriousness, severity and causality (see Section 8.4.2). 
8.4.1 Adverse Event Reporting Time Period 
All AEs, whether reported by the subject voluntarily or upon questioning, or noted on physical 
examination, will be recorded from the time the ICF is signed until study completion, 30 days 
after the last dose of study drug or 30 days following cessation of study treatment if the subject 
initiates new anti-cancer therapy, whichever is earlier. The event name, date of onset, duration, 
and severity will be documented, together with an Investigator’s (or designee’s) opinion of the 
relationship to study drug.  
Before initiation of study drug, only the AEs which regarded as have relationship to study 
procedure will be collected as AE.  
All SAEs (regardless of relationship to study drug) and/or non-serious AE considered to be 
possibly, probably or definitely related to study drug recorded during the course of the study will 
be followed up, where possible, until resolution or until the unresolved AEs are judged by the 
Investigator (or designee) to have stabilized. This will be completed at the Investigator’s (or 
designee’s) discretion. Medical occurrences that begin before the start of study drug, but after 
obtaining informed consent, will be recorded on the Medical History/Current Medical Conditions 
section of the eCRF rather than in the Adverse Event section. 
8.4.2 Assessment of Severity of Adverse Event 
To report AEs on the CRFs, the Investigator will use the severity grading as described in NCI 
CTCAE, version 5.0. Every effort should be made by the Investigator to assess the AE according 
to CTCAE criteria. If the Investigator is unable to assess severity because the term is not 
described in NCI CTCAE, version 5.0, then severity of mild, moderate, severe, life-threatening, 
or fatal may be used to describe the maximum intensity of the AE, as guided by Table 10. Note 
that the selection of the most appropriate verbatim term for AEs is not restricted to only those 
toxicities represented in NCI CTCAE. For purposes of consistency, these intensity grades are 
defined in Table 10. 

 
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Table 10:  Adverse Event Severity Grading 
Grade 
Non-CTCAE Severity 
Definition 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic 
observations only; or intervention not indicated 
2 
Moderate 
Minimal, local, or non-invasive intervention indicated; or 
limiting age-appropriate instrumental ADLb 
3 
Severe 
Medically significant, but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; 
disabling; or limiting self-care ADLc 
4 
Life-Threatening 
Urgent intervention indicated 
5 
Fatal 
Results in patient’s death 
    NCI CTCAE = National Cancer Institute Common Terminology Criteria for Adverse Events. 
ADL= Activities of Daily Living 
b Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
c Self -care ADL refer to bathing, dressing, and undressing, feeding self, using the toilet, taking medications, and not bedridden 
8.4.3 Assessment of Causality of Adverse Event 
The Investigator is obligated to assess the relationship between study drug(s) and each 
occurrence of each AE. A “reasonable possibility” of a relationship conveys that there are facts, 
evidence, and/or arguments to suggest a causal relationship, and not that a relationship cannot be 
ruled out. The Investigator (or designee) will determine the relationship of AE to the study and 
use 5-category system according to the following guidelines, the “definitely related, probably 
related, and possibly related” are classified into related to the study drug, and “unlikely related, 
definitely unrelated” are classified into unrelated to the study drug: 
• Definitely unrelated: there is no temporal relationship; there is reasonable evidence to 
suggest that AE is caused by other factors such as concomitant medications or 
concomitant diseases. 
• Unlikely Related: AE is more likely to be caused by other factors such as concomitant 
medications or concomitant diseases; the temporal relationship indicates that is unlikely 
to be causally related to the study drug. 
• Possibly Related: There is a reasonable temporal relationship but could have been 
caused by other factors such as concomitant medications or concomitant diseases. 
• Probably Related: There is a reasonable temporal relationship and unlikely to be 
caused by other factors such as concomitant medications or concomitant diseases; there 
is indicative de-challenge information. 

 
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• Definitely related: There is an obvious reasonable temporal relationship; the AE is a 
possible adverse reaction and cannot be explained by other factors such as concomitant 
medications or concomitant diseases; there is indicative information of de-challenge 
and re-challenge. 
For patients receiving combination therapy, causality will be assessed individually for each 
protocol-mandated therapy. 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that 
the Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to the Sponsor. 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
8.4.4 Procedure for Recording Adverse Event 
When an AE occurs, it is the responsibility of the Investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The Investigators should use correct medical terminology/concepts when recording AEs in the 
eCRF.  
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE term. Only one AE term should be recorded in 
the event field on the AE eCRF. 
8.4.5 Reporting of Serious Adverse Event 
Certain events require immediate reporting to allow the Sponsor to take appropriate measures to 
address potential new risks in a clinical study. The Investigator must report such events to the 
Sponsor immediately (no later than 24 hours). The Investigator must report all SAEs to the 
Sponsor no later than 24 hours after awareness of the event, regardless of relationship to study 
drug. 
The Investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the information).  
Investigators must also comply with local requirements for reporting SAEs to the Institutional 
Review Board (IRB). 
Report SAEs to the Sponsor’s PV service vendor, dMed Biopharma via email: 
• On discovery, all SAEs should be immediately reported (no later than 24 hours after 
awareness of the event) to dMed Biopharma by completing the SAE reporting form and 
email the documents to dMed Biopharma Drug Safety:  

 
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DrugSafety-imab@dmedglobal.com 
• Please note that this email address is for the reporting of SAE and pregnancy 
information only. 
8.4.6 Follow-up of AE and SAE 
Every reasonable effort will be made to follow up with subjects who have AEs. Any subject who 
has an ongoing SAE (regardless of relationship to study drug) and/or non-serious AE that is 
possibly, probably or definitely related to the IMP or study procedures at the 30-day post-
treatment, follow-up visit or last study visit will be followed up, where possible, until resolution 
or until the unresolved AE is judged by the Investigator (or designee) to have stabilized. This 
will be completed at the Investigator’s (or designee’s) discretion. Any subject who has an 
ongoing non-serious AE that is not related or unlikely related to the IMP or study procedures at 
the Follow up visit or last study visit, can be closed out as ongoing at the Investigator’s 
discretion. If a subject initiates new anti-cancer therapy during the follow-up period, new AEs 
are not required to be reported.  
New or updated information will be recorded in the originally completed eCRF. 
8.4.7 Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
drug under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
applicable regulatory agencies about the safety of a study drug under clinical investigation. 
The Sponsor will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it along with the Investigator’s Brochure and will notify the IRB, if appropriate according to 
local requirements. 
8.4.8 Pregnancy Reporting Requirement 
A pregnancy event refers to a pregnancy of a female subject or a maternal pregnancy of a male 
patient during a clinical study or within 5 months after the patient’s last dose of study drug. The 
Investigator will collect pregnancy information via the Pregnancy Reporting Form within 24 hours 
after becoming aware of the information.  

 
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Study drug must be discontinued immediately in the event of a pregnancy in a patient. 
The patient should be referred to an obstetrician/gynecologist experienced in reproductive 
toxicity for further evaluation and counseling. 
The Investigator will follow the patient /patient’s partner until completion of the pregnancy 
and provide this follow-up information using the same procedures as the initial reporting. 
Generally, the follow-up will be within 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence of 
anomalies) or indication for the procedure.  
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(Section 8.3.2), then the Investigator should report it as such, and the Investigator needs to fill 
out an SAE reporting form and report to the Sponsor within 24 hours. Furthermore, all neonatal 
deaths that occurs within 30 days of birth should be reported, without regard to causality, as 
SAEs. In addition, any infant death after 30 days that the Investigator suspects is related to the 
in-utero exposure to the study drug should also be reported. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. 
Any post-study pregnancy related SAE considered reasonably related to the study drug by the 
Investigator will be reported to the Sponsor or designee. While the Investigator is not obligated 
to actively seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting. 
8.5 Treatment of Overdose 
There is no defined overdose of TJ004309. Signs and symptoms of an overdose should be 
reported as AEs. Overdoses will not be considered SAEs unless the outcome of the overdose 
meets seriousness criteria (see Section 8.3.2). 
In the event of an overdose, the Investigator should: 
1. Contact the Study Responsible Physician immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
drug can no longer be detected systemically (at least 3 days). 
3. Obtain a plasma sample for PK analysis if requested by the Study Responsible Physician 
(determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
No specific information is available on the treatment of overdose of TJ004039. In the event of 
overdose, the subject should have immediate interruption of their infusion and be observed 
closely for signs of toxicity. Decisions regarding dose interruptions or modifications will be 
made by the Investigator in consultation with the Study Responsible Physician based on the 

 
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clinical evaluation of the patient. Appropriate supportive treatment should be provided if 
clinically indicated. 
8.6 Safety Management Team (SMT) 
A dedicated internal Safety Management Team (SMT) for TJ004309 will be formed for 
continuous safety monitoring. According to the safety management charter, the dedicated 
TJ004309 SMT is a cross functional team, composed of a safety physician, clinical physician, 
regulatory representative, biostatistician, and ad hoc members. From the program level, the team 
will review and evaluate the safety data mentioned above during the lifecycle of TJ004309, 
periodically and/or ad hoc. The charter guides the team to review all safety data including all lab 
tests, nonserious AEs, SAEs, nonclinical data, and the published same class drug safety data. 
Based on the nature of the safety issue with the team consensus, the team will provide the 
appropriate recommendations as well as communications to the appropriate stakeholders, 
including but not limited to health authorities, Investigators, subjects, and ethical committees. 
8.7 Pharmacokinetics 
Blood samples of approximately 5 mL each will be collected for measurement of serum 
concentrations of study drug as specified in the SoA (Table 3).  Serum samples will be prepared 
per lab manual. 
The following pharmacokinetic parameters of TJ004309 will be obtained by direct measurement 
of PK samples or derived by population PK modeling and simulations: 
• Cmax (maximum observed concentration) 
• Tmax (time of the maximum observed concentration) 
• AUC0-t (from time zero to the time of the last quantifiable concentration), AUCτ (AUC 
over a dosing interval), AUC0-∞ (AUC from time zero to infinity), t1/2 (terminal 
elimination half-life) 
• Ctrough (trough concentration) 
• CL (clearance) 
• Vss (volume of distribution at steady-state) 
• Vz (volume of distribution associated with terminal phase) 
8.8 Pharmacodynamics  
Paired fresh pre-treatment and on-treatment tumor biopsy specimens will be collected from at 
least 5 subjects in Cohort 2, for the measurement of CD73 enzymatic activity with enzyme-
histochemistry, infiltrating immune cells using multiplex-immunohistochemistry and the whole 
genome gene expression profiles using RNA sequencing. Samples will be processed, stored, and 
shipped according to a separate laboratory manual. 

 
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8.9 Biomarkers 
For both cohorts, baseline archival tumor biopsy specimens will be collected for the expression 
of PD-L1 and CD73 by immunohistochemistry, measurement of infiltrating immune cells using 
multiplex-immunohistochemistry and whole genome gene expression profiles using RNA 
sequencing to explore the predictive biomarkers. 
For Cohort 2, PD-L1 expression at baseline archival tumor biopsy will be used to pre-select the 
patients for the inclusion criteria. Archival tumor biopsy samples are preferred in block format 
but archival tumor tissue that allows the preparation of at least 20 slides prior to study entry is 
acceptable. 
For both cohorts, approximately 15 mL and 5 mL of blood will be collected as specified in the 
SoA (Table 3), for peripheral blood mononuclear cell (PBMC) and serum preparation, 
respectively. After processing the PBMC and serum samples will be cryopreserved for future 
immunophenotyping, gene expression and protein expression analysis. PBMC and serum 
samples will be processed, stored, and shipped according to a separate lab manual.  
 

 
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9 STATISTICAL CONSIDERATIONS 
9.1 Sample Size Determination 
For Part 1 of the study, the sample size is not based on formal statistical considerations. Rather, it 
is based on a desire to obtain sufficient safety, tolerability, PK, pharmacodynamic, and 
preliminary efficacy information while exposing as few patients as possible to the investigational 
treatment. With up to 30 patients per cohort, Part 1 of the study provides an opportunity to 
further investigate the safety profile and explore tumor activities in a more selective patient 
population and helps to make decision for the Part 2 design.  
For purposes of analysis, the following populations are defined: 
Population 
Description 
Efficacy Evaluable 
The efficacy evaluable population will comprise all subjects who receive at 
least 1 dose of study drug and undergo at least 1 post-baseline tumor 
assessment. Subjects who die before the initially scheduled post-baseline 
tumor assessment will be included in this evaluable population. 
Safety 
The safety population will include all subjects who receive at least 1 dose of 
study drug. 
Pharmacokinetics 
The PK population will include all subjects who receive at least 1 dose of 
study drug and have sufficient information to estimate at least 1 of the PK 
parameters of interest (Cmax or AUC). 
Pharmacodynamic 
The pharmacodynamic population will include all subjects who receive at 
least 1 dose of TJ004309 and have sufficient information for 
pharmacodynamic evaluation. 
Biomarker 
The biomarker population will include all subjects who receive at least 1 dose 
of study drug and have baseline archival tumor biopsy specimen. 
9.2 Statistical Analyses 
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a Statistical Analysis Plan (SAP).  
In general, summary tabulations will be presented that display the number of observations, mean, 
standard deviation, median, minimum, and maximum for continuous variables, and the number 
and percent (of non-missing values) per category for categorical data. The 95% CI for the 
estimates will be calculated when applicable. The statistical analyses will be performed using 
SAS® version 9.4 or later (SAS Institute Inc, Cary NC).  
9.2.1 Disposition 
The number of patients included in each analysis set will be summarized, along with the reason 
for any exclusions. Patients discontinuing from study treatment and/or withdrawing from study 
participation the primary reason for discontinuation will be summarized. 

 
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9.2.2 Demographics and Baseline Characteristics 
Descriptive summaries of demographic and baseline characteristics will be tabulated. No 
statistical tests will be performed on these characteristics. 
9.2.3 Exposure 
The overall duration of study treatment administration and number of cycles initiated will be 
summarized. For each patient, the cumulative administered dose of study drug will be calculated. 
These data will be further summarized for each cohort by calculating the mean, standard 
deviation, median, and range of these values. The number and proportion of patients with 
1 or more dose modifications (i.e., dose reduction) will be tabulated along with the reason for 
modification. 
9.2.4 Efficacy Analyses 
A listing of tumor measurements will be provided by subject and time. BOR, ORR, DOR, PFS 
and OS will be listed and summarized by cohort/group based on efficacy evaluable population if 
data permits. 
9.2.5 Safety Analyses 
All safety analyses will be performed on the Safety Analysis Population. The safety assessment 
will be based on the frequency of AEs, on the observation of clinically significant abnormalities 
of laboratory values, concomitant medication use, vital signs, ECGs, ECOG performance status, 
and physical examination data in the Safety Analysis Population. 
AEs will be coded using the standard Medical Dictionary for Regulatory Activities (MedDRA), 
Version 23.0 or higher. Adverse events will be graded by the Investigator according to the 
CTCAE, version 5.0.  
Analyses of AEs will be based on the principle of treatment emergence. Treatment-emergent 
AEs are defined as having onset after study drug dosing or a sign, symptom, or diagnosis that 
worsens after study drug dosing. Henceforth, whenever an analysis or summary of AEs is 
mentioned, it is intended that this is in reference to treatment-emergent adverse events (TEAEs), 
unless it is stated otherwise. 
TEAEs will be summarized based on the number and percentage of patients experiencing the 
event by system organ class (SOC) and preferred term (PT). The causal relationship between the 
occurrence of an AE and study drug will be judged by the Investigator on the basis of his or her 
clinical judgment (i.e., Related, Possibly Related, Probably Related, Unlikely Related, and Not 
Related). In the event a patient experiences repeat episodes of the same AE, then the event with 
the highest severity grade and strongest causal relationship to study drug will be used for 
purposes of incidence tabulations. 

 
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9.2.6 Pharmacokinetic Analyses 
Summary statistics will be tabulated for each PK parameter, if feasible, and wherever applicable, 
by cohort/treatment. Mean, standard deviation, median, geometric means, and coefficients of 
variation will be presented for Cmax and Ctrough. The exposure of sparse PK samples will be 
combined with the PK data obtained from Phase 1 trial for population PK analysis and exposure-
response analyses.  
9.2.7 Pharmacodynamics and Biomarker Analyses 
Pharmacodynamics effects on CD73 enzymatic activity, immune cell profiles, and whole 
genome gene expression profiles will be evaluated in paired fresh tumor biopsies at baseline and 
on-treatment collected from a subset of subjects in Cohort 2. 
Expression of PD-L1, CD73, immune cell subsets, and whole genome gene expression profiles 
in baseline archival tumor biopsy will be evaluated for their association with clinical responses. 
These analyses are considered exploratory and will be summarized in a separate technical report. 
9.3 Interim Analyses 
A futility analysis with 15 patients based on rules from a Simon’s 2-stage design for Cohort 1 is 
planned for this study. In addition, analyses of the data may be performed for publication and 
regulatory reporting purposes. 

 
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10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 Data Record and Management 
Standard clinical monitoring and data management practices will be used to ensure the integrity 
of the data. As used in this protocol, the term CRF should be understood to refer to either a paper 
form or an electronic data record or both, depending on the data collection method used in this 
study. 
A CRF is required and should be completed for each subject. The completed original CRFs are 
the sole property of I-Mab and should not be made available in any form to third parties, except 
for authorized representatives of I-Mab or appropriate regulatory authorities, without written 
permission from I-Mab. 
The Investigator has ultimate responsibility for the collection and reporting of all clinical, safety, 
and laboratory data entered on the CRFs and any other data collection forms (source documents) 
and ensuring that they are accurate, authentic/original, attributable, complete, consistent, legible, 
timely (contemporaneous), enduring, and available when required. The CRFs must be signed by 
the Investigator or by an authorized staff member to attest that the data contained on the CRFs 
are true. Any corrections to entries made in the CRFs or source documents must be dated, 
initialed, and explained (if necessary) and should not obscure the original entry. In most cases, 
the source documents are the hospital's or the physician's patient chart. In these cases, data 
collected on the CRFs must match the data in those charts. Discrepancies in the data will be 
brought to the attention of the clinical team, and investigational site personnel, if necessary. 
Resolutions to these issues will be reflected in the database. An audit trail within the system will 
track all changes made to the data. 
Data will be entered into a validated database. Data Management will be responsible for data 
review and processing, in accordance with the Sponsor’s data management procedures. Database 
lock will occur once quality control procedure, and quality assurance procedures (if applicable) 
have been completed. PDF files of the eCRFs will be provided to the Investigators at the 
completion of the study. 
10.2 Protocol Deviations and Amendments 
The Investigator must adhere to the protocol as detailed in this document. The Investigator will 
be responsible for enrolling only those subjects who have met protocol eligibility criteria. The 
Investigators will be required to sign an Investigator Agreement to confirm acceptance and 
willingness to comply with the study protocol. The Investigator should document and explain 
any protocol deviations in source. The Investigator should promptly report any deviations to the 
Sponsor or designee, and to the IRB/EC in accordance with established IRB/EC policies and 
procedures. The Sponsor or designee will review all protocol deviations and conduct impact 
assessments as needed. As per the Sponsor's standard operating procedures, prospective requests 

 
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to deviate from the protocol, including requests to waive protocol eligibility criteria, are not 
allowed and will not be granted.  
All protocol revisions (amendments) must originate with and be documented by the Sponsor. 
The Investigator must submit all amendments to his/her IRB for review and approval prior to 
implementation; documentation of approval signed by the chairperson or designee must be sent 
to the Sponsor. 
10.3 Record Retention 
Essential documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an International Council for Harmonisation (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 investigational product. 
However, these documents should be retained for a longer period if required by the applicable 
local requirements. Essential documents include, but are not limited to, the following: signed 
informed consent documents for all subjects; subject identification code list, screening log (if 
applicable), and enrollment log; record of all communications between the Investigator and the 
IRB; composition of the IRB; record of all communications between the Investigator, Sponsor, 
and their authorized representative(s); list of Sub-Investigators and other appropriately qualified 
persons to whom the Investigator has delegated significant study-related duties, together with 
their roles in the study, curriculum vitae, and their signatures; copies of CRFs (if paper) and of 
documentation of corrections for all subjects; investigational product accountability records; 
record of any body fluids or tissue samples retained; and all other source documents (subject 
records, hospital records, laboratory records, etc.). 
ICH requires that patient identification codes be retained for at least 15 years after the 
completion or discontinuation of the study. 
10.4 Regulatory, Ethical, and Study Oversight Considerations 
10.4.1 Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical Sciences 
(CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
The Protocol, Protocol Amendments, ICF, Investigator’s Brochure, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB by the Investigator and reviewed and 
approved by the IRB before the study is initiated. 

 
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Any amendments to the protocol will require IRB approval before implementation of changes 
made to the study design, except for changes necessary to eliminate an immediate hazard to 
study participants. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB. 
• Notifying the IRB of SAEs or other significant safety findings as required by IRB 
procedures. 
• Providing oversight of the conduct of the study at the site and adherence to requirements 
of 21 Code of Federal Regulations (CFR), ICH guidelines, the IRB, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local regulations. 
10.4.2 Financial Disclosure 
Investigators and Sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
10.4.3 Informed Consent Process 
The Investigator or his/her representative will explain the nature of the study to the participant 
or his/her healthcare proxy and answer all questions regarding the study. 
Patients must be informed that their participation is voluntary. Patients or their healthcare proxy 
will be required to sign a statement of informed consent that meets the requirements of 21 CFR 
50, local regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
(HIPAA) requirements, where applicable, and the IRB or study center. 
The medical record must include a statement that written informed consent was obtained before 
the patient was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
Patients must be re-consented to the most current version of the ICF(s) during their participation 
in the study. 
A copy of the ICF(s) must be provided to the patient or the patient’s healthcare proxy. 

 
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10.4.4 Data Protection 
Patients will be assigned a unique identifier by the Sponsor. Any participant records or datasets 
that are transferred to the Sponsor will contain the identifier only; patient names or any 
information which would make the participant identifiable will not be transferred. 
The patient must be informed that his/her personal study-related data will be used by the Sponsor 
in accordance with local data protection law. The level of disclosure must also be explained to 
the patient. 
The patient must be informed that his/her medical records may be examined by Clinical Quality 
Assurance auditors or other authorized personnel appointed by the Sponsor, by appropriate IRB 
members, and by inspectors from regulatory authorities. 
10.4.5 Dissemination of Clinical Study Data 
A clinical study report (CSR) will be written after completion of the study.  
It is anticipated that the results of this study will be presented at scientific meetings and/or 
published in a peer reviewed scientific or medical journal. The basic principles regarding 
publication of study results are as follows: 
Both positive and negative study results will be disclosed. In general, the results of research will 
be submitted for publication to peer-reviewed scientific journals. These journals often do not 
consider negative results for publication. However, results will be otherwise disclosed on 
www.clinicaltrials.gov as per regulatory requirement. 
10.4.6 Data Quality Assurance 
All patient data relating to the study will be recorded on printed or eCRF unless transmitted to 
the Sponsor or designee electronically (e.g., laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
eCRF. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB review and regulatory agency 
inspections and provide direct access to source data documents. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality such 
as Risk Management and Mitigation Strategies and Analytical Risk-Based Monitoring), methods, 
responsibilities and requirements, including handling of noncompliance issues and monitoring 
techniques (central, remote, or on-site monitoring) are provided in the Monitoring Plan. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 

 
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The Sponsor assumes accountability for actions delegated to other individuals (e.g., contract 
research organization). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the study is 
being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the Investigator for at least 2 years after the last marketing application approval 
or 2 years after formal discontinuation of the clinical development of the investigational product 
or according to applicable regulatory requirement(s). If the Investigator withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person willing to 
accept the responsibility. The Sponsor must be notified immediately by telephone or e-mail and 
the notification confirmed in writing if a custodial change occurs. 
10.4.7 Source Documents 
Source documents provide evidence for the existence of the patient and substantiate the integrity 
of the data collected. Source documents are filed at the Investigator’s site. 
Data entered in the eCRF that are transcribed from source documents must be consistent with 
the source documents or the discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, current 
medical records must be available. 
Any electronic study data are to be entered into a secure, validated data processing system 
and a backup maintained. Any changes to electronic study data will be documented. 
10.4.8 Study and Site Closure 
The Sponsor designee reserves the right to close a study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB 
or local health authorities, the Sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the Investigator. 

 
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• Discontinuation of further study drug development. 
10.4.9 Publication Policy 
All information regarding study drug supplied by the Sponsor to the Investigator or generated as 
a result of any clinical studies is privileged and confidential information belonging to the 
Sponsor. The Investigator agrees to use Sponsor’s confidential information solely to accomplish 
the study and will not use such information for any other purposes without the prior written 
consent of I-Mab. It is understood that there is an obligation to provide the Sponsor with 
complete and accurate data obtained during the study. The information obtained from the clinical 
study will be used towards the development of study drug and may be disclosed by I-Mab to 
regulatory authority(ies), other Investigators, corporate partners, or consultants as required.  
It is anticipated that the results of this study may be presented at scientific meetings and/or 
published in a peer reviewed scientific or medical journal. A Publications Committee, comprised 
of Investigators participating in the study and representatives from I-Mab as appropriate, will be 
formed to oversee any publication or presentation of the study results, which will reflect the 
experience of all participating study centers. All publications and presentations must be approved 
in advance by I-Mab, in its sole discretion. Subsequently, individual Investigators may publish 
results from the study in compliance with their agreement with the Sponsor. 
A pre-publication manuscript is to be provided to I-Mab at least 30 days prior to the submission 
of the manuscript to a publisher. Similarly, the Sponsor will provide any company-prepared 
manuscript to the Investigators for review at least 30 days prior to submission to a publisher. 
All publications and presentations must be approved in writing by I-Mab before public 
disclosure. 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 

 
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10.5 Clinical Laboratory Tests 
The tests detailed in Table 11 will be performed by the local/central laboratory. Investigators 
must document their review of each laboratory safety report. 
Protocol-specific laboratory requirements for inclusion or exclusion of participants are detailed 
in Section 5 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary by the 
Investigator or required by local regulations.  
 
Table 11:  Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
WBC count with differential 
Platelet count 
Mean corpuscular hemoglobin 
Mean corpuscular volume 
Red blood cell count and reticulocytes 
Hemoglobin 
Hematocrit 
Absolute neutrophil count 
HBV, HCB, HIV 
(Screening Only) 
Anti-hepatitis B surface antibody 
HBsAg 
Anti-HCV 
HIV-1 
HIV-2 
Coagulation 
Studies  
International normalized ratio (INR) 
Prothrombin time 
Activated partial thromboplastin time or 
Partial thromboplastin time 
 
Serum Chemistry 
Alanine aminotransferase (ALT) 
Aspartate aminotransferase (AST) 
Amylase 
Albumin 
Alkaline phosphatase  
Blood urea nitrogen 
Calcium 
Cholesterol 
Creatinine 
Gamma-glutamyl transferase 
Lactate dehydrogenase 
Sodium 
Bicarbonate 
Glucose 
Lipase 
Phosphorus 
Total bilirubin 
Total protein 
Magnesium  
Potassium 
Chloride 
CA125 (ovarian cohorts only) 
Uric Acid 
Urinalysis 
A dipstick urinalysis is to be performed for: 
Color 
pH 
Specific gravity 
Blood 
Protein 
Glucose 
Ketones 
 

 
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Laboratory 
Assessments 
Parameters 
If dipstick findings are abnormal, a microscopic examination is to be performed 
Pregnancy 
Testing 
Serum pregnancy test at Screening, Cycle 1 Day 1 (within 72 hours prior), Cycle 4 Day 1 
and Day 1 of every subsequent 4 cycles (i.e., Cycle 8 Day 1, Cycle 12 Day 1, etc.). The 
screening serum pregnancy test can be used as the test prior to Day 1 study treatment if it is 
performed within the prior 72 hours. Additional tests may be ordered at the Investigator’s 
discretion.  Positive urine test should be confirmed with a serum pregnancy test.  Follicle 
stimulating hormone (FSH) test is required for postmenopausal women only. 
 

 
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10.6 Contraceptive Guidance 
10.6.1 Definitions 
10.6.1.1 Females of Childbearing Potential 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile. Permanent sterilization methods include hysterectomy, bilateral 
salpingectomy, and bilateral oophorectomy. 
10.6.1.2 Postmenopausal Female 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception or hormonal 
replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation 
with more than one FSH measurement >40 IU/L is required.  
Females on HRT whose menopausal status is not confirmed will be required to use one of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue their 
HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of 
postmenopausal status before study enrollment. 
10.6.2 Fertile Males 
A man is considered fertile after puberty (Tanner Stage II) unless permanently sterile by bilateral 
orchidectomy or vasectomy with medical assessment of surgical success. 
10.6.3 Highly Effective Contraception 
Methods that can achieve a failure rate of less than 1% per year when used consistently and 
correctly are considered as highly effective birth control methods (Clinical Trials Facilitation 
Group 201412). Such methods include: 
• Combined (estrogen and progestin containing) hormonal contraception associated with 
inhibition of ovulation (oral, intravaginal, transdermal). 
• Progestin-only hormonal contraception associated with inhibition of ovulation (oral, 
injectable, implantable). 
• Intrauterine device. 
• Intrauterine hormone-releasing system. 
• Bilateral tubal occlusion. 
• Vasectomized partner, provided that partner is the sole sexual partner of the female study 
participant and that the vasectomized partner has received medical assessment of the 
surgical success. 

 
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• Sexual abstinence- only if defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study and the 
preferred and usual lifestyle of the patient. 
10.6.4 Acceptable Birth Control Methods that are not Highly Effective Contraception 
Acceptable birth control methods that result in a failure rate of more than 1% per year include: 
• Progestin-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action. 
• Male or female condom with or without spermicide. 
• Cap, diaphragm, or sponge with spermicide. 
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double 
barrier methods) are also acceptable, but not highly effective, birth control methods. 
10.6.5 Unacceptable Contraception Methods 
• Periodic abstinence (calendar, symptothermal, post-ovulation methods). 
• Withdrawal (coitus interruptus). 
• Spermicides only. 
• Lactational amenorrhea method. 
• Combination of male and female condoms. 
10.6.6 Female Contraception Guidance 
Females of childbearing potential (FOCBP) may only be enrolled after confirming a negative 
highly sensitive serum pregnancy test during Screening and a urine or serum pregnancy test 
within 72 hours prior to receiving the first study drug administration.  
It is required that FOCBP agree to use at least 2 effective contraceptive methods (1 highly 
effective method in combination with a barrier method; oral, injectable, or implantable hormonal 
contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or 
vasectomized partner), one of which must be barrier, from signing the ICF date of ICF signature, 
throughout the study, and for up to 5 months following the last dose of TJ004309. 
10.6.7 Male Contraception Guidance 
Males must agree to use a condom (a latex condom is recommended) during sexual contact with 
a pregnant female or a female of childbearing potential and will avoid donation of sperm or 
having a female partner conceive from the time of date of ICF signature, while participating in 
the study, during dose interruptions, and for at least 5 months after the last dose of study 

 
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treatment, even if he has undergone a successful vasectomy. Consider contraception for the 
FOCBP partner. 
10.6.8 Collection of Pregnancy Information 
Pregnancy testing should be performed at monthly intervals in female participants. Female 
partners of male patients are also recommended to have pregnancy testing performed at monthly 
intervals. 
10.6.8.1 Female Participants who Become Pregnant 
The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the Pregnancy 
Reporting form and submitted to the Sponsor within 24 hours of learning of a participant's 
pregnancy.  
Any female patient who becomes pregnant while participating in the study must immediately 
discontinue study drug.  
10.6.8.2 Male Patients with Female Partners who Become Pregnant 
The Investigator will attempt to collect pregnancy information on any male patient’s female 
partner who becomes pregnant while the male participant is in this study. This applies only to 
male patients who receive study drug. 
After obtaining the necessary signed informed consent from the pregnant female partner directly, 
the Investigator will record pregnancy information on the appropriate form and submit it to the 
Sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also 
be followed to determine the outcome of the pregnancy. Information on the status of the mother 
and child will be forwarded to the Sponsor.  

 
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11 SUMMARY OF CHANGES (SOC) 
List of Minor/Administrative Changes:  
• Table of Contents was updated to reflect changes in protocol. 
• List of Tables and Figures was updated to reflect changes in protocol.  
• Minor changes were made to correct inconsistencies, typographical and 
grammatical errors.  
• Updated References 
Detailed Summary of Changes Version 2: 
Changes made from Protocol 
v2.0 
Rationale 
Relevant Section(s) 
Updated safety follow-up period 
to 90 days. 
Per FDA request the safety 
follow up period has been 
extended to 90 days. 
- 
Changes made throughout 
- 
Table 3: Schedule of 
Assessments 
Added term IMP to list of 
abbreviations 
The abbreviation IMP is used in 
the body of the protocol and 
was not included in the past list 
of abbreviations 
- 
List of Abbreviations 
Updated IC #4a to include ‘any’ 
high-grade serous component 
This is to clarify that any high-
grade serous component is 
acceptable for IC #4a. 
- 
Synopsis – Inclusion 
Criteria 
- 
Section 5.1 – Inclusion 
Criteria 
Removed language “such 
patients must have recovered 
adequately from any side effects 
of such therapy” 
This is an exclusion criterion so 
the language is not necessary. 
- 
Synopsis – Exclusion 
Criteria 
- 
Section 5.2 – Exclusion 
Criteria 
Updated pleural ascites drainage 
language 
Removed (<1 drainage) 
language to be definitive 
- 
Synopsis – Exclusion 
Criteria 
- 
Section 5.2 – Exclusion 
Criteria 
Added TSH to SOC 
Atezo single agent does not 
seem to affect thyroid functions 
vs combo therapy with atezo, 
where hypo/hyperthyroidism is 
more prevalent.   
- 
Schedule of Assessments 
Removed language for no 
protocol waivers or exemptions 
Removed: “Protocol waivers or 
exemptions to the inclusion and 
exclusion criteria are not 
permitted.” as IC #6 allows 
discussion with Medical 
- 
Section 5: Study 
Population 

 
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Changes made from Protocol 
v2.0 
Rationale 
Relevant Section(s) 
Monitor. 
Added section 4.5 Safety 
Follow-up Period to body of 
protocol 
This is included in the Synopsis 
but was previously not included 
in the body of the protocol.  
- 
Section 4.5 
Added Section 4.6 
Response/Survival Follow-up 
Period 
This is included in the Synopsis 
but was previously not included 
in the body of the protocol 
- 
Section 4.6 
Clarified disease progression 
SAE requirement 
The previous language was not 
clear that progression of 
leading to death should be 
reported as an SAE. 
- 
8.3.2.2 
 
 

 
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12 REFERENCES 
1. Pennock, G.K. and L.Q. Chow, The evolving role of immune checkpoint inhibitors in 
cancer treatment. The oncologist, 2015: p. theoncologist. 2014-0422. 
2. Wilson, R.A., et al., Immune checkpoint inhibitors: new strategies to checkmate cancer. 
Clinical & Experimental Immunology, 2018. 191(2): p. 133-148. 
3. Leone, R.D. and L.A. Emens, Targeting adenosine for cancer immunotherapy. Journal 
for ImmunoTherapy of Cancer, 2018. 6(1): p. 57. 
4. Blay, J., T.D. White, and D.W. Hoskin, The extracellular fluid of solid carcinomas 
contains immunosuppressive concentrations of adenosine. Cancer research, 1997. 
57(13): p. 2602-2605. 
5. Allard, B., et al., The ectonucleotidases CD 39 and CD 73: Novel checkpoint inhibitor 
targets. Immunological reviews, 2017. 276(1): p. 121-144. 
6. Allard, D., M. Turcotte, and J. Stagg, Targeting A2 adenosine receptors in cancer. 
Immunology and cell biology, 2017. 95(4): p. 333-339. 
7. Wang, L., et al., CD73 has distinct roles in nonhematopoietic and hematopoietic cells to 
promote tumor growth in mice. The Journal of clinical investigation, 2011. 121(6): p. 
2371-2382. 
8. Zhang, B., CD73: A Novel Target for Cancer Immunotherapy. Cancer Research, 2010. 
70(16): p. 6407-6411. 
9. Stagg, J., et al., CD73-deficient mice have increased antitumor immunity and are 
resistant to experimental metastasis. Cancer Res, 2011. 71(8): p. 2892-900. 
10. Overman, M.J., et al., Safety, efficacy and pharmacodynamics (PD) of MEDI9447 
(oleclumab) alone or in combination with durvalumab in advanced colorectal cancer 
(CRC) or pancreatic cancer (panc). Journal of Clinical Oncology, 2018. 36(15_suppl): 
p. 4123-4123. 
11. Siu, L.L., et al., Abstract CT180: Preliminary phase 1 profile of BMS-986179, an anti-
CD73 antibody, in combination with nivolumab in patients with advanced solid tumors. 
Cancer Research, 2018. 78(13 Supplement): p. CT180-CT180. 
12. Clinical Trials Facilitation Group. Recommendations related to contraception and 
pregnancy testing in clinical trials. September 2014. 
 
 
 
 
 
 
 
 

 
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13 APPENDICES 
Appendix 1: Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and 
Immune-related RECIST 
Response and progression will be evaluated in this study using the international criteria proposed 
by the RECIST 1.1 and iRECIST. 
Tumor evaluation must include thoracic, abdominal, and pelvic imaging. This anatomic coverage 
is appropriate for both baseline imaging and on-treatment imaging. 
Contrast-enhanced computed tomography (CT) is the preferred method to measure lesions 
selected for response assessment. This protocol has defined measurability of lesions when CT 
slice thickness is 5 mm or less. Magnetic resonance imaging (MRI), typically with gadolinium-
based intravenous (IV) contrast, is also acceptable in certain situations, positron emission 
tomography (PET)-CT scans may be used providing that the measures are obtained from the CT 
scan and the CT scan is of the same diagnostic quality to a diagnostic CT (with IV and oral 
contrast). 
RECIST 
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are 
used in the RECIST 1.1. Rules described in the following for CT are equally valid for MRI. 
Measurable disease 
Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 10 mm by CT scan 
• 10 mm caliper measurement by clinical exam 
• 20 mm by chest x-ray 
Computed tomography is strongly recommended.  
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph 
node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will 
be measured and followed. See also notes below on ‘Baseline documentation of target and non-
target lesions’ for information on lymph node measurement. 
Non-measurable disease 
All other lesions, including small lesions (longest diameter <10 mm or pathological lymph nodes 
with ≥10 to <15 mm short axis) as well as truly non-measurable lesions. Lesions considered truly 
non-measurable include: leptomeningeal disease, ascites, pleural or pericardial effusion, 

 
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inflammatory breast disease, lymphangitic involvement of skin or lung. Bone lesions, cystic 
lesions, and lesions previously treated with local therapy require particular comment. 
Bone lesions: 
• Bone scan, PET scan, or plain films are not considered adequate imaging techniques to 
measure bone lesions. 
• Lytic bone lesions, or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as CT or 
MRI can be considered as measurable lesions if the soft tissue component meets the 
definition of measurability described above. 
• Blastic bone lesions are non-measurable. 
Cystic lesions: 
• Lesions that meet radiographic criteria for simple cysts should not be considered 
malignant lesions (neither measurable nor non-measurable). 
• “Cystic lesions” thought to be cystic metastases can be considered as measurable lesions, 
if they meet the definition of measurability. However, if non-cystic lesions are present in 
the same participants, these should be preferably selected for assessment. 
Lesions with prior local treatment: 
• Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-situated in a previously irradiated area, or in an area subjected to other loco-regional 
therapy, are usually not considered measurable unless there has been demonstrated 
progression in the lesion. 
Non-target lesions 
All other lesions (or sites of disease) including pathological lymph nodes (with short axis 
≥10 mm and <15 mm) should be identified as non-target lesions and should also be recorded at 
baseline. Measurements are not required and these lesions should be followed as ‘present,’ 
‘absent,’ or in rare cases ‘unequivocal progression’ (more details to follow). In addition, it is 
possible to record multiple non-target lesions involving the same organ as a single item on the 
Case Report Form (e.g., ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’). 
Response Criteria: The BOR is the best response recorded from the start of the study treatment 
until the end of treatment. The subject’s BOR assignment will depend on the findings of both 
target and non-target disease and will also take into consideration the appearance of new lesions.  
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have decreased in size to have a short axis of <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking 
as reference the baseline sum diameters. 

 
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Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for progressive disease (PD), taking as reference the smallest sum diameters while on 
study. 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. For non-target lesions, unequivocal progression (see 
comments below) of existing lesions represents PD. Note: the appearance of one or more new 
lesions is also considered progression. 
Lymph nodes identified as target lesions should always have the actual short axis measurement 
recorded (measured in the same anatomical plane as the baseline examination), even if the nodes 
regress to below 10 mm on study. This means that when lymph nodes are included as target 
lesions, the ‘sum’ of lesions may not be zero even if CR criteria are met, since a normal lymph 
node is defined as having a short axis of <10 mm. 
To achieve unequivocal progression in participants with measurable disease on the basis of the 
non-target disease, there must be an overall level of substantial worsening in non-target disease 
such that, even in presence of SD or PR in target disease, the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy. A modest ‘increase’ in the size of one or more 
non-target lesions is usually not sufficient to qualify for unequivocal. 
In the absence of measurable disease, the same general concepts apply here as noted above. 
Target and Non-target Lesion Response 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all 
evaluated 
No 
PR 
SD 
Non-PD or not all 
evaluated 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations: CR = complete response; NE = not evaluable; PD = progressive disease; PR = partial response; SD = stable 
disease.   
Participants 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. 

 
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Response duration 
The duration of OS is measured from the time measurement criteria are initially met for CR/PR 
(whichever is initially recorded) until the initially date that recurrent or PD is objectively 
documented (taking as reference for PD the smallest measurements recorded on study). 
The duration of overall CR is measured from the time measurement criteria are initially met for 
CR until the initially date that recurrent disease is objectively documented. 
Stable disease (SD) duration 
Stable disease is measured from the start of the treatment until the criteria for progression are 
met, taking as reference the smallest sum on study (if the baseline sum is the smallest, this is the 
reference for calculation of PD). 
Methods 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 follow-up. When lesions can be evaluated 
by both clinical exam and imaging, imaging evaluation should be undertaken since it is more 
objective. 
CT/MRI - CT and MRI are the best currently available and reproducible methods to measure 
target lesions selected for response assessment. As a general rule, the minimum size of a 
measurable lesion at baseline should be no less than double the slice thickness and also have a 
minimum size of 10 mm which requires a slice thickness. An MRI is also acceptable in certain 
situations. 
Ultrasound - Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for 
independent review at a later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken from one assessment to the 
next. If new lesions are identified by ultrasound in the course of the study, confirmation by CT or 
MRI is advised. If there is concern about the radiation exposure at CT, MRI may be used instead 
of CT in selected instances. 
Tumor markers: tumor markers alone cannot be used to assess objective tumor response. If 
markers are initially above the upper normal limit, however, they must normalize for a 
participant to be considered in CR. 
When effusions are known to be a potential adverse effect of treatment (e.g., angiogenesis 
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears or 
worsens during treatment can be considered if the measurable tumor has met criteria for response 
or SD in order to differentiate between response (or SD) and PD. 
 
 
 

 
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iRECIST 
iRECIST is based on RECIST 1.1 but adapted to account for the unique tumor response seen 
with immunotherapeutic drugs. iRECIST will be used by the Investigator to assess tumor 
response and progression and make treatment decisions. When clinically stable, participants 
should not be discontinued until progression is confirmed by the Investigator, working with local 
radiology. This allowance to continue treatment despite initial radiologic PD takes into account 
the observation that some participants can have a transient tumor flare in the first few months 
after the start of immunotherapy, and then experience subsequent disease response. This data 
will be captured in the clinical database. 
Assessment at Screening and Prior to RECIST 1.1 Progression 
Until radiographic disease progression based on RECIST 1.1, there is no distinct iRECIST 
assessment. 
Assessment and Decision at RECIST 1.1 Progression 
For participants who show evidence of radiological PD by RECIST 1.1 as determined by the 
Investigator, the Investigator will decide whether to continue a participant on study treatment 
until repeat imaging is obtained using iRECIST for participant management. This decision by the 
Investigator should be based on the participant’s overall clinical condition. 
Clinical stability is defined as the following:  
• Absence of symptoms and signs indicating clinically significant progression of disease 
• No decline in ECOG performance status  
• No requirements for intensified management, including increased analgesia, radiation, or 
other palliative care 
Any participant deemed clinically unstable should be discontinued from study treatment at site-
assessed first radiologic evidence of PD and is not required to have repeat tumor imaging for 
confirmation of PD by iRECIST. 
If the Investigator decides to continue treatment, the participant may continue to receive study 
treatment and the tumor assessment should be repeated 4 to 8 weeks later to confirm PD by 
iRECIST, per Investigator assessment.   
Tumor flare may manifest as any factor causing radiographic progression per RECIST 1.1, 
including: 
• Increase in the sum of diameters of target lesion(s) identified at baseline to ≥20% and 
≥5 mm from nadir 
o Note: the iRECIST publication uses the terminology “sum of measurements”, but 
“sum of diameters” will be used in this protocol, consistent with the original 
RECIST 1.1 terminology. 

 
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• Unequivocal progression of non-target lesion(s) identified at baseline 
• Development of new lesion(s) 
iRECIST defines new response categories, including iUPD (unconfirmed progressive disease) 
and iCPD (confirmed progressive disease). For purposes of iRECIST assessment, the first visit 
showing progression according to RECIST 1.1 will be assigned a visit (overall) response of 
iUPD, regardless of which factors caused the progression. 
At this visit, target and non-target lesions identified at baseline by RECIST 1.1 will be assessed 
as usual. 
New lesions will be classified as measurable or non-measurable, using the same size thresholds 
and rules as for baseline lesion assessment in RECIST 1.1. From measurable new lesions, up to 5 
lesions total (up to 2 per organ), may be selected as New Lesions – Target.  The sum of 
diameters of these lesions will be calculated and kept distinct from the sum of diameters for 
target lesions at baseline.  All other new lesions will be followed qualitatively as New Lesions – 
Non-target. 
Assessment at the Confirmatory Imaging 
On the confirmatory imaging, the participant will be classified as progression confirmed (with an 
overall response of iCPD), or as showing persistent unconfirmed progression (with an overall 
response of iUPD), or as showing disease stability or response (iSD/iPR/iCR). 
Confirmation of Progression 
Progression is considered confirmed, and the overall response will be iCPD, if ANY of the 
following occurs: 
• Any of the factors that were the basis for the initial iUPD show worsening 
o For target lesions, worsening is a further increase in the sum of diameters of 
≥5 mm, compared to any prior iUPD time point 
o For non-target lesions, worsening is any significant growth in lesions overall, 
compared to a prior iUPD time point; this does not have to meet the 
“unequivocal” standard of RECIST 1.1 
o For new lesions, worsening is any of these: 
 An increase in the new lesion sum of diameters by ≥5 mm from a prior 
iUPD time point  
 Visible growth of new non-target lesions  
 The appearance of additional new lesions 
• Any new factor appears that would have triggered PD by RECIST 1.1 
Persistent iUPD 
Progression is considered not confirmed, and the overall response remains iUPD, if: 

 
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• None of the progression-confirming factors identified above occurs AND 
• The target lesion sum of diameters (initial target lesions) remains above the initial PD 
threshold (by RECIST 1.1) 
Additional imaging for confirmation should be scheduled 4 to 8 weeks from the imaging on 
which iUPD is seen. This may correspond to the next visit in the original visit schedule.  The 
assessment of the subsequent confirmation imaging proceeds in an identical manner, with 
possible outcomes of iCPD, iUPD, and iSD/iPR/iCR. 
Resolution of iUPD 
Progression is considered not confirmed, and the overall response becomes iSD/iPR/iCR, if: 
• None of the progression-confirming factors identified above occurs, AND 
• The target lesion sum of diameters (initial target lesions) is not above the initial PD 
threshold.  
The response is classified as iSD or iPR (depending on the sum of diameters of the target 
lesions), or iCR if all lesions resolve. 
In this case, the initial iUPD is considered to be pseudo-progression, and the level of suspicion 
for progression is “reset”. This means that the next visit that shows radiographic progression, 
whenever it occurs, is again classified as iUPD by iRECIST, and the confirmation process is 
repeated before a response of iCPD can be assigned. 
Management Following the Confirmatory Imaging 
If repeat imaging does not confirm PD per iRECIST, as assessed by the Investigator, and the 
participant continues to be clinically stable, study treatment may continue and follow the regular 
imaging schedule. If PD is confirmed, participants will be discontinued from study treatment. 
NOTE: If a participant has confirmed radiographic progression (iCPD) as defined above, but the 
participant is achieving a clinically meaningful benefit an exception to continue study treatment 
may be considered following consultation with the Sponsor. In this case, if study treatment is 
continued, tumor imaging should continue to be performed following the intervals as outlined in 
Section 13 and may be submitted to a central imaging vendor during the study per Sponsor’s 
request. 
Detection of Progression at Visits After Pseudo-progression Resolves 
After resolution of pseudo-progression (i.e., achievement of iSD/iPR/iCR), iUPD is indicated by 
any of the following events: 
• Target lesions 
o Sum of diameters reaches the PD threshold (≥20% and ≥5 mm increase from 
nadir) either for the first time, or after resolution of previous pseudo-progression. 
The nadir is always the smallest sum of diameters seen during the entire trial, 
either before or after an instance of pseudo-progression. 

 
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• Non-target lesions 
o If non-target lesions have never shown unequivocal progression, their doing so for 
the first time results in iUPD. 
o If non-target lesions have shown previous unequivocal progression, and this 
progression has not resolved, iUPD results from any significant further growth of 
non-target lesions, taken as a whole. 
• New lesions 
o New lesions appear for the first time 
o Additional new lesions appear 
o Previously identified new target lesions show an increase of ≥ 5 mm in the new 
lesion sum of diameters, from the nadir value of that sum 
o Previously identified non-target lesions show any significant growth 
If any of the events above occur, the overall response for that visit is iUPD, and the iUPD 
evaluation process (see Assessment at the Confirmatory Imaging above) is repeated. Progression 
must be confirmed before iCPD can occur. 
The decision process is identical to the iUPD confirmation process for the initial PD, with one 
exception:  if new lesions occurred at a prior instance of iUPD, and at the confirmatory imaging 
the burden of new lesions has increased from its smallest value (for new target lesions, the sum 
of diameters is ≥5 mm increased from its nadir), then iUPD cannot resolve to iSD or iPR. It will 
remain iUPD until either a decrease in the new lesion burden allows resolution to iSD or iPR, or 
until a confirmatory factor causes iCPD. 
 
 

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

 
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Imaging and Treatment for Clinically Stable Participants Treated with TJ004309 after 
First Radiologic Evidence of PD Assessed by the Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Comparison of RECIST 1.1 and iRECIST Criteria 
 
Sources:  
Eisenhauer EA, Therassse P, Boggaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST 
guideline (version 1.1). Eur J Cancer. 2009;45(2):228-247. doi: 10.1016/j.ejca.2008.10.026. 
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.