Phase I/II Study of Autologous T Cells Engineered Using the Sleeping Beauty System to Express T-Cell Receptors (TCRs) Reactive Against Cancer-specific Mutations in Subjects With Solid Tumors
Phase: PHASE1
Conditions: Gynecologic Cancer, Colorectal Cancer, Pancreatic Cancer, Non-small Cell Lung Cancer, Cholangiocarcinoma, Ovarian Cancer, Endometrial Cancer, Ovarian Carcinoma, Ovary Neoplasm, Squamous Cell Lung Cancer, Adenocarcinoma of Lung, Adenosquamous Cell Lung Cancer
Sponsor: Alaunos Therapeutics



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Study Design 
This is a Phase I/II study of autologous T cells engineered using the Sleeping Beauty 
 system 
 
 
Subjects eligible for enrollment on this protocol are those for whom a TCR matching the subject’s 
somatic mutation(s) and HLA type restriction combination is available in Alaunos Therapeutics Inc.’s 
[Alaunos] Clinical TCR library and have progressive or recurrent disease following standard 
chemotherapy or standard systemic therapy or were intolerant to previous treatment will be eligible 
for enrollment on this Investigational Product Protocol. Subjects will be enrolled into subgroups 
according to the following tumor types: 
 
 

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Table 1: 
Tumor Type Subgroups 
Subgroup 
Tumor Type 
1a 
Ovarian 
1b 
Endometrial 
2 
Colorectal 
3 
Pancreatic 
4 
Non-small cell lung cancer 
5 
Cholangiocarcinoma 
 
Subjects will initially go through pre-screening to determine if there is a TCR matching the subject’s 
somatic mutation(s) and HLA type restriction combination in Alaunos’s Clinical TCR library. If 
subjects do not have a TCR identified, they will be discontinued and will not move forward with 
further screening. Upon confirming screening and apheresis eligibility, subjects will undergo an 
apheresis procedure to collect the cells needed to manufacture the TCR-T cell drug product. 
 
with Sleeping Beauty 
 
 Subjects will then 
be lymphodepleted starting 7 days prior to TCR-T cell drug product infusion.  NOTE: If subjects 
receive a bridging therapy, lymphodepletion may not be needed.   
Phase I: Dose Escalation 
The Phase I part of this study is a prospective, open-label, dose-escalation study of TCR-T cell drug 
product in patients with progressive or recurrent solid tumors who have failed standard therapy (refer 
to inclusion criteria #2). This study utilizes a Bayesian optimal interval design (BOIN) with an 
accelerated dose escalation to determine the MTD/RP2D of TCR-T cell drug product. Subjects who 
fulfill the eligibility criteria will receive a single infusion of TCR-T cell drug product at the assigned 
dose level on Day 0. Safety and pharmacokinetic (PK) profiles, and the preliminary efficacy will be 
examined for each dose level. 
The study starts with pre-screening to determine if there is a TCR match for the subject based on their 
somatic mutation(s) and HLA typing. If there is at least one TCR match for the subject, then they will 
begin screening assessments to determine initial eligibilityfor treatment with TCR-T cell drug product 
(Arm A) at Dose Level 1 (DL1) as shown in Figure 2. This dose level will follow an accelerated dose 
escalation and is planned to treat one subject at dose level 1 in the absence of a DLT. After the subject 
completes the DLT period (Day 0 to Day 28), the subject will be evaluated for toxicities. If the first 
subject experiences a DLT, 3 additional subjects will be enrolled and treated at DL1 before escalating 
to dose level 2 (DL2). If the first subject does not have a DLT(s), the next subject will be enrolled and 
treated at the next higher dose level (DL2). After DL1, the study will follow the pre-planned dose 
escalation decision rules detailed in Table 7 and defined in Appendix H. At least 2-3 subjects will be 
enrolled at DL2 to enable evaluation of TCR-T cell persistence data by the Safety Review Committee 
(SRC).   
The starting dose level will be DL1. If the manufacturing for the first patient meets the criteria for 
DL-1 (dose level minus 1) the current BOIN design (which accommodates 4 dose levels; refer to 
Appendix H) accelerated will be initiated at DL-1, subsequently patients will be enrolled, and dose 
levels will be escalated per the BOIN design. If there is the inability to manufacture at the current 

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metabolic complications, secondary macrophage-activation syndrome, prolonged cytopenia 
unresponsive to colony stimulating factors, grade 3 and 4 infections and subsequent malignancies) 
The detailed statistical methods for dose escalation and de-escalation and estimation of MTD/RP2D 
are described in Section 15.1.1 and Section 15.1.2. 
 
 
 
 
 

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Patients that do not have previous typing results must be willing to provide a blood sample for 
this testing. 
3. Patients who have previously received at least one line of standard systemic therapy for their 
advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the 
previous treatment for one of the following cancer types. 
• 
Gynecologic cancers (i.e., ovarian or endometrial) 
• 
Colorectal Cancer 
• 
Pancreatic Cancer 
• 
Non-small cell lung cancer (NSCLC;) NSCLC includes but is not limited to 
squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas 
• 
Cholangiocarcinoma 
4. Patients must be able to provide written informed consent. 
5. Patients must be age ≥ 18 years. 
6. Clinical Performance Status of Eastern Cooperative Group (ECOG) 0 or 1.  
7. Patients must not have any form of primary immunodeficiency (such as severe combined 
immunodeficiency disease) or uncontrolled autoimmune hemolytic anemia or idiopathic 
thrombocytopenic purpura, such as those patients with a declining hemoglobin level or 
platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of 
study drug, or the need for daily prednisone ≥10 mg daily (or corticosteroid equivalent) to 
control the autoimmune disease
 
 
8. Patients who have received any type of organ transplant in the past 12 months are excluded. 
9. Patients who have undergone xenotransplantation at any time are excluded. 
10. Patients must not have any history of severe immediate hypersensitivity reaction to 
cyclophosphamide, fludarabine, 
 
bendamustine (for subjects if required for lymphodepletion), or dimethyl sulfoxide (DMSO). 
11. Patients with a prior history or concurrent malignancy whose natural history or treatment does 
not have the potential to interfere with either the safety or efficacy assessment of the 
investigational regimen may be included after discussion with Sponsor, Alaunos Medical 
Monitor, or designee 
12. Patients must not have any active unstable or clinically significant medical condition that 
would, in the opinion of the Principal Investigator (PI) in consultation as warranted with 
medical monitor, result in risks to safety of a subject and/or their compliance with the 
protocol. Examples include, but are not limited to, a history of myocarditis or congestive heart 
failure (New York Heart Association functional Class III or IV), unstable angina, serious 
uncontrolled cardiac arrythmia, myocardial infarction within 6 months of screening, active 

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interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring chronic 
treatment with systemic steroids, uncontrolled asthma, or colitis. 
 
Screening Eligibility Criteria: 
Inclusion Criteria: 
1. Subjects with at least one TCR matching a combination of their somatic mutations and HLA 
type is available in Alaunos’s Clinical TCR library (refer to Appendix G) as evidenced by 
molecular testing results performed at a CLIA-certified or CLIA-accredited laboratory.  
 
2. Patients who have previously received at least one line of standard systemic therapy for their 
advanced/metastatic cancer and have either progressed, recurred, or were intolerant to the 
previous treatment. Specifically: 
• 
Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):  
a. Ovarian cancer: Subjects who are platinum-resistant, as defined by 
progression on a platinum-containing regimen or within 6 months of a 
previous platinum dose.  
b. Endometrial cancer: Subjects who have received at least 1 prior line of 
therapy for advanced/recurrent disease (including adjuvant chemotherapy 
and adjuvant chemo-radiation therapy) prior to apheresis. Prior hormonal 
therapy will not count towards prior lines of therapy. Note that 2 prior lines 
of treatment are required prior to lymphodepletion. 
• 
Subgroup 2. Colorectal cancer:  
• 
Patient has received systemic treatment for advanced unresectable or 
metastatic disease prior to apheresis 
• 
Must include an irinotecan or oxaliplatin-based therapy and if eligible, a 
targeted antibody therapy.  
• 
Subjects with deficient DNA mismatch repair (dMMR) or 
microsatellite instability-high (MSI-H) colorectal cancer 
should have received a checkpoint inhibitor such as 
pembrolizumab or nivolumab. Note that 2 prior lines of 
treatment are required prior to lymphodepletion. 
• 
Subgroup 3. Pancreatic cancer: Subjects who have progressive disease after 
receiving initial treatment with FOLFOX, (modified) FOLFIRINOX, and/or a 
gemcitabine-based therapy. 
• 
Subgroup 4. Non-small cell lung cancer (NSCLC): 
• 
Subjects with recurrent and/or metastatic disease who have disease 
progression or intolerance to treatment with a PD-1/PD-L1 inhibitor 
either as a single-agent or in combination with other checkpoint 
inhibitors (e.g., CTLA-4 inhibitors) and/or platinum-containing 
chemotherapy.  
• 
Subjects with targetable oncogene alterations (e.g., EGFR, ALK, ROS1, 
RET, MET, NTRK1-3, BRAF) must have had disease progression or 

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intolerance on at least one prior line of targeted therapy. 
• 
Subgroup 5. Cholangiocarcinoma: Subjects must have histologically confirmed 
diagnosis of cholangiocarcinoma Stage II, III, or IV (intra-hepatic, extra-hepatic 
and perihilar) that is not eligible for curative resection, transplantation, or 
ablative therapies. Subjects who have progressed after receiving at least one line 
of standard therapy.   
3. Patients must have measurable disease per RECIST 1.1 as assessed by the local site 
investigator/radiology. 
4.  Patient must agree to provide archival tissue (core or excisional biopsy) from a locally 
recurrent or inoperable or metastatic tumor lesion or new tissue must be obtained from a non-
target lesion for translational research assessments 
5. Patients must be able to provide written informed consent. 
6. Clinical Performance Status of Eastern Cooperative Group (ECOG) 0 or 1.  
7. Patient must provide written informed consent for the long-term follow-up protocol 
(TCR001-202) for up to 15 years post TCR-T Cell drug product infusion per FDA 
requirements. 
8. Adequate bone marrow reserves as assessed by the following hematology laboratory criteria: 
a. ANC ≥1,000/mm3 (filgrastim not within 7 days or pegfilgrastim not within 14 days) 
b. WBC ≥ 3,000/mm3 
c. Platelet count ≥ 50,000/mm3 
d. Hemoglobin > 8.0 g/dL. (Subjects may be administered red blood cell transfusions to 
achieve this cut-off value.) 
9. Adequate major organ system functions as determined by the following criteria: 
a. Cardiac 
i) Left ventricular ejection fraction ≥50% on multiple gated acquisition (MUGA) 
scan and/or by echocardiography at the discretion of the investigator. 
Note: No evidence of clinically significant pericardial effusion as determined by 
an ECHO. 
b. Pulmonary  
i) 
Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% on 
room air. 
c. Renal  
i) Serum creatinine within institutional limits; OR 
ii) 
Calculated creatinine clearance (ClCr) (e.g., Cockcroft-Gault equation) ≥ 45.0 
mL/min and not dialysis dependent  
d. Liver 
i) Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii) Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who must 
have a total bilirubin < 3.0 mg/dL 
10. Patients may have undergone minor surgical procedures or limited-field radiotherapy 
provided any major organ toxicities have recovered to ≤ Grade 1. 
11. Patients must not be pregnant or breastfeeding. 
12. Female patients of non-childbearing potential must meet at least 1 of the following criteria: 

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• 
Achieved postmenopausal status, defined as follows: cessation of regular menses for at 
least 12 consecutive months with no alternative pathological or physiological cause; if 
there is uncertainty as to whether the patient has a postmenopausal status, it will be 
confirmed with a serum follicle stimulating hormone (FSH) level confirming the 
postmenopausal state; 
• 
Have undergone a documented hysterectomy and/or bilateral oophorectomy;  
• 
Have medically confirmed ovarian failure.   
13. Patients of childbearing potential, including women with tubal ligations, must commit to 
using 2 highly effective forms of birth control (defined as the use of an intrauterine device, a 
barrier method with spermicide, condoms, or any form of hormonal contraceptives) for the 
duration of the study. 
14. Male patients must be sterile (biologically or surgically), or their partner(s) of childbearing 
potential must commit to the use of highly effective method of birth control for the duration 
of the study.   
15. Patients must be fully vaccinated against COVID-19 prior to lymphodepletion. This criterion 
includes a booster shot if at least 5 months have passed after receiving the second shot of a 2-
dose series or 2 months after a single-dose vaccine. Exceptions must be approved by the 
Alaunos Medical Monitor. 
 
Exclusion Criteria:  
1. Patients who have received any type of organ transplant in the past 12 months. 
2. Patients who have undergone xenotransplantation at any time. 
3. Patients with known active CNS metastases; Patients with prior CNS metastatic disease that 
has been effectively treated and have recovered from the acute effects of radiation therapy or 
surgery prior to study entry, have discontinued supra physiologic doses of corticosteroid 
treatment for these metastases (unless required for other than the treatment of brain 
metastases) for at least 2 weeks and are neurologically stable for 3 months (requires magnetic 
resonance imaging [MRI] confirmation) may be enrolled, stability for less than 3 months may 
be allowed after discussion with the Alaunos Medical Monitor. Any question pertaining to 
this criterion should be discussed with the Alaunos Medical Monitor. 
4. Positive beta-HCG in female of child-bearing potential defined as not post-menopausal for 12 
months or no previous surgical sterilization or lactating females. 
5. Concurrent systemic steroid therapy at a dose of >10 mg prednisone daily or equivalent is 
excluded. Physiologic dosing of steroids to treat adrenal insufficiency is permitted. Topical or 
inhaled steroids are permitted. 
6. Any form of primary immunodeficiency (such as severe combined immunodeficiency 
disease) or uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic 
purpura, such as those with a declining hemoglobin level or platelet count secondary to 
autoimmune destruction within the 4 weeks prior to first dose of study drug, or the need for 
daily prednisone ≥10 mg daily (or corticosteroid equivalent) to control the autoimmune 
disease (Note: the experimental treatment being evaluated in this protocol depends on an 

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limited to, active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis 
requiring chronic treatment with systemic steroids, uncontrolled asthma, or colitis. 
16. History of any one of the following cardiovascular conditions within the past 6 months: Class 
III or IV heart failure as defined by the NYHA (Refer to Appendix A), cardiac angioplasty 
or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac 
disease. 
Eligibility Criteria for Apheresis: 
These criteria should be confirmed prior to the subject undergoing apheresis (see SOA for collection 
windows).  
1.  Adequate bone marrow reserves as assessed by the following hematology laboratory criteria. 
This requirement may be satisfied by the initial screening in Section 6.1.1 if apheresis is 
scheduled within 7 days of the initial screening: 
a. ANC ≥ 1,000/mm3 (filgrastim not within 7 days or pegfilgrastim not within 14 days) 
b. WBC ≥ 3,000/mm3 
c. Platelet count ≥ 50,000/mm3 
d. Hemoglobin > 8.0 g/dL. (Subjects may be administered red blood cell transfusions to 
achieve this cut-off value.) 
2. Adequate major organ system functions as determined by the following criteria. This 
requirement may be satisfied by the initial screening in section 6.1.1 if apheresis is scheduled 
within 28 days of the initial screening: 
a. Cardiac 
i. 
Left ventricular ejection fraction ≥ 50% on multiple gated acquisition (MUGA) scan 
and/or by echocardiography at the discretion of the investigator.  
Note: No evidence of clinically significant pericardial effusion as determined by an 
ECHO. 
b. Pulmonary  
i. 
Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% on 
room air. 
c. Renal  
i. 
Serum creatinine within institutional limits; OR 
ii. 
Calculated creatinine clearance (ClCr) (e.g., Cockcroft-Gault equation) ≥ 45.0 
mL/min and not dialysis dependent  
d. Liver 
i. 
Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii. 
Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who must have 
a total bilirubin < 3.0 mg/dL 
3. A washout period must have elapsed since completion of any prior systemic therapy, with 
guidelines as follows (windows other than what is listed below should be allowed only after 
consultation with the Medical Monitor); subjects’ non-hematologic toxicities from any prior 

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systemic therapy must have recovered to ≤ Grade 1 (with the exception of neuropathy and 
alopecia) or baseline prior to starting apheresis. 
a. 
Nitrosoureas: 6 weeks 
b. 
Other cytotoxic agents: 4 weeks  
c. 
Anti-angiogenic agents: 4 weeks  
d. 
Targeted agents, including small molecule tyrosine kinase inhibitors: 5 half-lives or 2 
weeks, whichever is shorter 
e. 
Immune checkpoint inhibitor agents: 4 weeks and must have recovered to ≤ Grade 1 or 
baseline grade severity prior to checkpoint inhibitor administration from immune-related 
adverse events (IrAEs), other than endocrine side effects or those affecting nonessential 
organs or functions 
f. 
CAR-T, other T-cell product or investigational cancer vaccine: 6 weeks 
g. 
Systemic steroids of greater than 10 mg prednisone equivalence: 1 week 
4. Subjects must not be pregnant or breastfeeding. 
Eligibility Criteria for Lymphodepletion: 
The inclusion criteria below should be confirmed before entering the lymphodepletion phase of the 
study. 
1. Patients who have previously received at least one line of standard systemic therapy for their 
advanced/metastatic cancer and have either progressed, recurred, suboptimal response or 
were intolerant to the previous treatment. Specifically: 
 
• 
Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):  
a. Ovarian cancer: Subjects who are platinum-resistant, as defined by 
progression on a platinum-containing regimen or within 6 months of a 
previous platinum dose.  
b. Endometrial cancer: Subjects must have received at least 2 prior lines of 
therapy for advanced/recurrent disease (including adjuvant chemotherapy 
and adjuvant chemo-radiation therapy) prior to lymphodepletion. Prior 
hormonal therapy will not count towards prior lines of therapy. 
 
• 
Subgroup 2. Colorectal cancer:  
o Subjects must have received at least 2 prior lines of systemic treatment 
for advanced unresectable or metastatic disease prior to lymphodepletion, 
which must include an irinotecan or oxaliplatin-based therapy and if 
eligible, a targeted antibody therapy. Subjects with deficient DNA 
mismatch repair (dMMR) or microsatellite instability-high (MSI-H) 
colorectal cancer should have received a checkpoint inhibitor such as 
pembrolizumab or nivolumab. 
• 
Subgroup 3. Pancreatic cancer: Subjects who have progressive disease after 
receiving initial treatment with FOLFOX, (modified) FOLFIRINOX, and/or a 
gemcitabine-based therapy. 

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• 
Subgroup 4. Non-small cell lung cancer (NSCLC): 
o Subjects with recurrent and/or metastatic disease who have disease 
progression or intolerance to treatment with a PD-1/PD-L1 inhibitor 
either as a single-agent or in combination with other checkpoint 
inhibitors (e.g., CTLA-4 inhibitors) and/or platinum-containing 
chemotherapy.  
o Subjects with targetable oncogene alterations (e.g., EGFR, ALK, ROS1, 
RET, MET, NTRK1-3, BRAF) must have had disease progression or 
intolerance on at least one prior line of targeted therapy. 
• 
Subgroup 5. Cholangiocarcinoma: Subjects must have histologically confirmed 
diagnosis of cholangiocarcinoma Stage II, III, or IV (intra-hepatic, extra-hepatic 
and perihilar) that is not eligible for curative resection, transplantation, or 
ablative therapies. Subjects who have progressed after receiving at least one line 
of standard therapy.   
2. No active infection requiring systemic therapy or causing fever (temperature > 38.1˚C (100.6 
˚F)) or subjects with unexplained fever (temperature > 38.1˚C (100.6 ˚F)) within 7 days prior 
to the day of investigational product administration. Participants with known active, 
uncontrolled bacterial, fungal, or viral infection, are excluded.  In equivocal cases, subjects 
whose viral load is negative, may be eligible after discussion with the Alaunos Medical 
Monitor. 
3. Any contraindication to fludarabine or cyclophosphamide should be discussed with the 
Medical Monitor prior to lymphodepletion. 
4. Patients who have received any type of organ transplant in the past 12 months are excluded. 
5. Patients who have undergone xenotransplantation at any time are excluded. 
6. Absence of active autoimmune disease requiring ongoing systemic immunosuppressive 
therapy. Patients must not have any form of primary immunodeficiency (such as severe 
combined immunodeficiency disease) or uncontrolled autoimmune hemolytic anemia or 
idiopathic thrombocytopenic purpura, such as those patients with a declining hemoglobin 
level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first 
dose of study drug, or the need for daily prednisone ≥10 mg daily (or corticosteroid 
equivalent) to control the autoimmune disease (Note: the experimental treatment being 
evaluated in this protocol depends on an intact immune system. Patients who have decreased 
immune competence may be less responsive to the experimental treatment and more 
susceptible to its toxicities.) 
7. Negative serum pregnancy test within 7 days before lymphodepletion chemotherapy for 
women of childbearing potential, defined as those who have not been surgically sterilized or 
who have not been free of menses for at least 1 year. Patients also must not be breastfeeding. 
8. Clinical Performance Status of ECOG 0 or 1.  
9. Patients must have measurable disease per RECIST 1.1 as assessed by the local site 
investigator/radiology. 

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10. No treatment with any investigational agent on a different clinical trial between meeting the 
screening eligibility criteria and enrollment (date eligibility is confirmed for lymphodepleting 
chemotherapy). 
11.  Serum creatinine within institutional limits; OR Calculated creatinine clearance (ClCr) (e.g., 
Cockcroft-Gault equation) ≥ 45.0 mL/min and not dialysis dependent 
12. Liver 
i) Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii) Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who must 
have a total bilirubin < 3.0 mg/dL 
13. ANC ≥ 1,000/mm3 (≥1.0 × 109/L) within 1 week of lymphodepletion. 
14.  Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% on room air. 
15. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of ≥50% as 
assessed by echocardiogram or MUGA scan, or LVEF of 45-49% and clearance by a 
cardiologist; if patient receives cardiotoxic chemotherapy after enrollment, repeat 
echocardiogram or MUGA is required to reestablish eligible LVEF. 
16. Patients must be fully vaccinated against COVID-19 prior to lymphodepletion. This criterion 
includes a booster shot if at least 5 months have passed after receiving the second shot of a 2-
dose series or 2 months after a single-dose vaccine. Exceptions must be approved by the 
Alaunos Medical Monitor. 
17. Patients may have undergone minor surgical procedures or limited-field radiotherapy 
provided any major organ toxicities have recovered to ≤ Grade 1. 
18. Subjects must not require corticosteroid therapy or dose ≥ 10 mg per day of prednisone or the 
equivalent.  Pulsed corticosteroid dose for disease control is acceptable until the day before 
the start of lymphodepletion. 
19. Must not have received any live vaccines within 30 days prior to enrollment. 
20. Patients with known active CNS metastases are excluded; Patients with prior CNS metastatic 
disease that has been effectively treated and have recovered from the acute effects of 
radiation therapy or surgery prior to study entry, have discontinued supra physiologic doses 
of corticosteroid treatment for these metastases (unless required for other than the treatment 
of brain metastases) for at least 2 weeks and are neurologically stable for 3 months (requires 
magnetic resonance imaging [MRI] confirmation) may be enrolled, stability for less than 3 
months may be allowed after discussion with the Alaunos Medical Monitor. Any question 
pertaining to this criterion should be discussed with the Alaunos Medical Monitor. 
21. Patients must not have concurrent systemic steroid therapy at a dose of >10 mg prednisone 
daily or equivalent. Physiologic dosing of steroids to treat adrenal insufficiency is permitted. 
Topical or inhaled steroids are permitted. 
22. Patients must not have a history of severe immediate hypersensitivity reaction to 
cyclophosphamide, fludarabine, 
 
bendamustine (for subjects if required for lymphodepletion), or dimethyl sulfoxide (DMSO). 
23. Patients must not have a severe chronic respiratory condition as determined by the following:  
Symptoms of severe respiratory dysfunction or pleural effusion other than a malignant pleural 
effusion treatable by drainage with or without pleurodesis.  

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4. Neurotoxicity, if present following fludarabine administration, must be resolved to grade ≤ 1. 
If >grade 1, approval from medical monitor is required. 
5. Serum creatinine within institutional limits; OR Calculated creatinine clearance (ClCr) (e.g., 
Cockcroft-Gault equation) ≥ 45.0 mL/min and not dialysis dependent 
6. Adequate pulmonary function, defined as grade ≤2 dyspnea and SaO2 ≥ 90% on room air.  
7. ANC < 1,000/mm3 (< 1.0 × 109/L) within 72 hours prior to dosing of TCR-T cell 
administration. Subjects with ANC ≥1,000/mm3 (< 1.0 × 109/L) must be discussed with the 
medical monitor prior to TCR-T cell drug product administration. 
8. Must not have received any live vaccines within 30 days prior to enrollment. 
Duration of Study:  
The start of the study is defined as the date when the first subject is consented into the Investigational 
Product study and the study stop date is the date of the last subject’s last visit.  
The duration of this study from the time of initiating screening until the completion of survival 
follow-up is anticipated to be approximately 25 months. After subjects complete the follow-up period 
or discontinue from this study, they will be followed in the long-term follow-up protocol 
(TCR001-202) for up to 15 years post-TCR-T cell drug product infusion. 
Study Treatment, Dosage and Mode of Administration:  
Lymphodepletion Chemotherapy: 
The standard lymphodepleting regimen for most subjects is as follows: 
Cyclophosphamide: 60 mg/kg x 2 days IV in 250 mL D5W infused simultaneously with mesna 
according to institutional procedure.  
Fludarabine: 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Fludarabine will be started 
approximately 1-2 hours after the cyclophosphamide and mesna on days -7 and -6. Note: if ALC is 
<100, remaining doses of fludarabine may be stopped at the discretion of the investigator.  
At the discretion of the investigator, heavily pre-treated or irradiated subjects who are expected not to 
have as much bone marrow reserve may be treated with a lower dose lymphodepleting regimen:  
Cyclophosphamide: 30 mg/kg x 2 days IV in 250 mL D5W infused simultaneously with mesna 
according to institutional procedure.  
Fludarabine: 25 mg/m2/day IVPB daily over 30 minutes for 5 days. Fludarabine will be started 
approximately 1-2 hours after the cyclophosphamide and mesna on days -7 and -6. Note: if ALC is 
<100, remaining doses of fludarabine may be stopped at the discretion of the investigator. 
In the event the patient had previous intolerance to cyclophosphamide or due to supply issues, 
bendamustine 90 mg/m2/day for 2 days or bendamustine 70 mg/m2/day + fludarabine 30 mg/m2/day 
for 3 days may be substituted with approval from the medical monitor. 
Subjects who have sufficient lymphodepletion from bridging therapy do not need additional 
lymphodepletion as described in Section 8.2 prior to infusion of TCR-T cell drug product. 
 
 

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TCR-T cell drug product: 
Neoantigen-specific TCR-T cells: The Phase I study will examine up to 4 dose levels (Table 2). 
Dosing will begin at Dose Level 1. Dose-limiting toxicity (DLT) monitoring will occur through 28 
days after TCR-T cell infusion.  The proposed doses to be evaluated in the planned Phase I/II clinical 
study will be: 
Table 2. 
TCR-T Dose Levels (Intended Dose and Dose Range) 
Dose Level 
TCR+ Cells 
Minimum 
Maximum 
DL-1 
<1.0x109 
NA 
<1.0x109 
DL1 
5 x109 
1.0 x109 
<10x109 
DL2 
40 x109 
10x109 
<70x109 
DL3 
100x109 
70x109 
150x109 
Depending on cell concentration in the infusion bag(s) and the intended dose, subjects will receive an 
infusion of cells from one or more bags via non-filtered tubing. A maximum volume of 400 mL will 
be intravenously infused over a duration that may last up to 180 minutes or as clinically determined 
by an investigator for patient safety; bags will be gently agitated during infusion to prevent cell 
clumping. Dose splitting may be considered in certain situations (e.g. subject experiences cytokine 
release syndrome [CRS] or infusion-related reaction [IRR]) following consultation with the Alaunos 
Medical Monitor.  
Patients obtaining any response except progressive disease are potentially eligible for a repeat 
treatment consisting of lymphodepleting chemotherapy followed by an infusion of TCR-T cell drug 
product. Retreatment will be at least 2 months after the original treatment. The dose of TCR-T cells 
administered during repeat treatments will be at the dose level currently enrolling patients receiving 
initial TCR-T cell drug product infusions. The repeat treatments will include the same apheresis 
collection, if needed, lymphodepleting chemotherapy, and manufacturing schedule as the initial 
treatment, if residual TCR-T cell drug product is not available. If patients were initially matched to 
multiple TCRs a discussion between the investigator and Sponsor should occur to determine which 
TCR will be utilized for re-treatment. 
Patients must not have experienced a DLT with their first treatment and must meet the same 
eligibility requirements listed in Section 6.1. The patients must undergo screening evaluation as listed 
in Table 12 except infectious disease serology, and brain MRI are not required to be repeated unless 
clinically indicated. Follow-up testing for retreatment will be the same as for the first treatment. In the 
case where the planned infusion is with the same library TCR as the first infusion, patients must have 
molecular testing to confirm matching epitope (i.e., genomic testing and HLA typing of tumor tissue 
collected after initial TCR-T treatment). 
The patient maybe re-enrolled on the core/treatment study as a new patient to allow this re-treatment 
and these patients will be considered in the total sample size for this study. A maximum of 2 total 
treatments can be administered to any one patient, and at least 2 months must elapse between the first 
treatment and the second treatment.  
DLTs that occur in the cohort of patients receiving a repeat treatment will not affect the 
dose escalation of patients receiving an initial treatment. However, excessive DLTs among 
retreatment subjects will result in a discontinuation of this practice. Specifically, if 2 of the first 
3 patients re-treated, 3 or more of the first 6 re-treated patients, 4 or more of the first 9 retreated 

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• 
Occurrence of Grade 4 DLTs in 2 subjects at any time during the conduct of the study 
trial; 
• 
One treatment related death occurs after the administration of TCR-T cell drug product; 
• 
Death not related to disease progression; 
• 
Development of a secondary malignancy, Epstein-Barr virus (EBV) lymphoma or 
polyclonal lymphoproliferative disease (PLPD) in an EBV negative subject. Note: accrual 
of EBV positive subjects will be halted if this is observed. 
There are two dose escalation stopping rules in this BOIN study: 
• 
Stop the trial if the lowest dose is eliminated due to overt toxicities*;  
• 
Stop the dose escalation and estimate the MTD/RP2D if the number of new subjects 
treated at the current dose level reaches 9.  
* Overt Toxicities defined as: 
1. The occurrence of 2 or more dose limiting toxicities. 
2. Consideration will also be given to longer term toxicities (e.g. > 30 days post infusion: Immune 
Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cardiotoxicity, pulmonary toxicity, 
metabolic complications, secondary macrophage-activation syndrome, prolonged cytopenia 
unresponsive to colony stimulating factors, grade 3 and 4 infections and subsequent malignancies) 
If any of the above events occur, enrollment of new subjects will be paused, pending review by the 
SRC. The SRC will recommend if changes to the enrollment of additional subjects are required, 
including but not limited to amending the protocol prior to enrollment of additional subjects, or 
discontinuing enrollment in the study.  
In the event that any stopping rule is met, the FDA and Institutional Review Board will be informed 
in a timely manner. Alaunos will discuss the investigation and the data with the FDA to identify next 
steps, which may include stopping the study.  
 
 

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TABLE OF CONTENTS 
1. 
CLINICAL PROTOCOL SYNOPSIS ....................................................................... 2 
2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ........................... 33 
3. 
INTRODUCTION .................................................................................................. 36 
3.1. 
Background and Rationale ...................................................................................... 36 
3.2. 
Benefit/Risk Assessment ........................................................................................ 37 
3.2.1. 
Toxicity of Adoptive Cell Therapies ....................................................................... 37 
3.2.2. 
Risk Assessment ..................................................................................................... 38 
3.2.3. 
Benefit Assessment................................................................................................. 42 
3.2.4. 
Overall Benefit: Risk Conclusion ............................................................................ 42 
4. 
STUDY OBJECTIVES........................................................................................... 43 
4.1. 
Phase I Objectives .................................................................................................. 43 
4.1.1. 
Primary Objectives ................................................................................................. 43 
4.1.2. 
Secondary Objectives ............................................................................................. 43 
 
 
 
 
 
 
 
 
 
 
5. 
STUDY DESIGN ................................................................................................... 45 
5.1. 
Overall Study Design .............................................................................................. 45 
5.1.1. 
Description of Dose Escalation Phase I ................................................................... 46 
 
 
5.2. 
Study Endpoints ..................................................................................................... 51 
5.2.1. 
Phase I Endpoints ................................................................................................... 51 
5.2.1.1. 
Primary Endpoints .................................................................................................. 51 
5.2.1.2. 
Secondary Endpoints .............................................................................................. 51 
 
 
 
 
 
 
 
 
 
 

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5.3. 
Dose Limiting Toxicity Definition .......................................................................... 53 
5.4. 
Study Oversight for Safety Evaluation .................................................................... 54 
6. 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................ 55 
6.1. 
Subject Inclusion Criteria ....................................................................................... 55 
6.1.1. 
Inclusion Criteria: ................................................................................................... 55 
6.1.2. 
Exclusion Criteria: .................................................................................................. 59 
6.1.3. 
Eligibility Criteria for Lymphodepletion: ................................................................ 61 
6.1.4. 
Eligibility Criteria for TCR-T Cell Drug Product Infusion: ..................................... 66 
6.2. 
Withdrawal of Subjects from Study Treatment and/or Study ................................... 66 
6.2.1. 
Withdrawal of Consent: .......................................................................................... 67 
6.2.1.1. 
Reasons for Removal prior to Treatment with TCR-T Cell Drug Product ................ 67 
6.2.1.2. 
Lost to Follow-up ................................................................................................... 68 
6.3. 
Replacement of Subjects ......................................................................................... 69 
6.4. 
Premature Termination of Study or Study Site ........................................................ 69 
7. 
INVESTIGATIONAL PRODUCTS ....................................................................... 70 
7.1. 
Description of T-Cell Drug Product ........................................................................ 70 
 
 
7.3. 
Handling and Storage ............................................................................................. 71 
7.4. 
Accountability and Dispensation ............................................................................. 71 
7.5. 
Retreatment with TCR-T Cell Drug Product ........................................................... 72 
8. 
TREATMENT PLAN ............................................................................................. 73 
8.1. 
Bridging Therapy (while awaiting manufacture and delivery of TCR-T cell 
product to site) ........................................................................................................ 73 
8.1.1. 
Bridging Therapy.................................................................................................... 73 
8.2. 
Lymphodepleting Chemotherapy ............................................................................ 74 
8.2.1. 
Cyclophosphamide ................................................................................................. 75 
8.2.2. 
Fludarabine ............................................................................................................. 75 
8.2.3. 
Bendamustine ......................................................................................................... 75 
8.2.4. 
Mesna ..................................................................................................................... 75 
8.2.5. 
Tocilizumab............................................................................................................ 75 
 
 
8.4. 
Supportive Medications .......................................................................................... 76 

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8.5. 
TCR-T Cell Drug Product ....................................................................................... 76 
8.5.1. 
TCR-T Cell Drug Product Pre-medication .............................................................. 76 
8.5.2. 
TCR-T Cell Drug Product Dosing ........................................................................... 76 
8.5.3. 
TCR-T Cell Infusion (Day 0) .................................................................................. 77 
8.5.4. 
Days 0-4 (Day 0 = Day of TCR-T Cell Drug Product Infusion) .............................. 78 
8.6. 
Study Stopping and Pausing Rules .......................................................................... 78 
9. 
SAFETY MONITORING AND TOXICITY MANAGEMENT .............................. 79 
9.1. 
Known Adverse Events Related to the Lymphodepleting Chemotherapy ................ 79 
9.2. 
Known Adverse Events Related to Tocilizumab ..................................................... 79 
9.3. 
Known Adverse Events Related to Aldesleukin ...................................................... 79 
9.4. 
Known Adverse Events Related to the T-Cell Therapy ........................................... 79 
9.4.1. 
Insertional Mutagenesis .......................................................................................... 79 
9.4.2. 
Cytokine Release Syndrome (CRS) ........................................................................ 79 
9.4.3. 
Neurotoxicity .......................................................................................................... 80 
9.4.4. 
Tumor Lysis Syndrome (TLS) ................................................................................ 80 
9.4.5. 
Hemophagocytic Lymphohistiocytosis (HLH)/ Macrophage Activation 
Syndrome (MAS) ................................................................................................... 80 
9.4.6. 
Graft-versus-Host Disease (GVHD) ........................................................................ 80 
9.4.7. 
Localized Site Reactions ......................................................................................... 80 
9.5. 
Safety Monitoring and Adverse Effect Management ............................................... 80 
9.5.1. 
Severity Grading ..................................................................................................... 81 
10. 
CONCOMITANT THERAPY ................................................................................ 82 
10.1. 
Permitted Medications ............................................................................................ 82 
10.1.1. 
Infection Prophylaxis .............................................................................................. 82 
10.1.2. 
Empiric Antibiotics................................................................................................. 85 
10.1.3. 
Blood Product Support............................................................................................ 85 
10.1.4. 
Medication for Infusion-related Reactions (IRRs) ................................................... 85 
10.1.5. 
Medication for Injection Site Reactions (ISRs) ....................................................... 86 
10.1.6. 
Medication for Hypersensitivity Type 1 and Type 3 ................................................ 86 
10.1.7. 
Medication for Cytokine Release Syndrome (CRS)................................................. 86 
10.1.8. 
Fever (≥ 38.3°C; ≥ 101°F) Antipyretic Therapy ...................................................... 87 

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10.1.9. 
Medication for Immune Effector Cell-associated Neurologic Syndrome 
(ICANS) ................................................................................................................. 87 
10.1.10. 
Medication for Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage 
Activation Syndrome (MAS) .................................................................................. 87 
10.1.11. 
Medication for B cell depletion and Hypogammaglobulinemia ............................... 88 
10.1.12. 
Anti-Nausea and Anti-Diarrheal Medication ........................................................... 88 
10.1.13. 
Pain Medication ...................................................................................................... 88 
10.1.14. 
Hematopoietic Growth Factors ............................................................................... 88 
10.1.15. 
Transfusion Support ............................................................................................... 88 
10.1.16. 
Surgery ................................................................................................................... 89 
10.1.17. 
Anti-coagulation Therapy ....................................................................................... 89 
10.1.18. 
Other Concomitant Medications to Control Side Effects ......................................... 89 
10.2. 
Prohibited Medications/Therapies ........................................................................... 89 
11. 
STUDY PROCEDURES ........................................................................................ 90 
11.1. 
Written Informed Consent ...................................................................................... 90 
11.2. 
Subject Registration ................................................................................................ 90 
11.3. 
Schedule of Assessments and Observations ............................................................ 90 
11.3.1. 
Study Tests, Exams, and Procedures ....................................................................... 90 
11.3.1.1. 
Demographics, Medical and Cancer History ........................................................... 90 
11.3.1.2. 
Eastern Cooperative Oncology Group (ECOG) Performance Status ........................ 90 
11.3.1.3. 
Vital Signs .............................................................................................................. 91 
11.3.1.4. 
Oxygen Saturation .................................................................................................. 91 
11.3.1.5. 
Weight and Height .................................................................................................. 91 
11.3.1.6. 
Physical Examination ............................................................................................. 91 
11.3.1.7. 
Cardiac Evaluation ................................................................................................. 92 
11.3.2. 
Clinical Laboratory Assessments ............................................................................ 92 
11.3.2.1. 
Hemophagocytic Lymphohystiocytosis (HLH) and Macrophage Activation 
Syndrome (MAS) Assessment ................................................................................ 96 
11.3.3. 
Tumor Neoantigen .................................................... Error! Bookmark not defined. 
11.3.4. 
Imaging .................................................................................................................. 96 
11.3.5. 
Assessment of Cytokine Release Syndrome (CRS) ................................................. 96 
11.3.6. 
Cerebrospinal Fluid (CSF) ...................................................................................... 97 

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11.3.7. 
Assessment of Immune Effector Cell Associated Neurotoxicity Syndrome 
(ICANS) and Immune-effector Cell Encephalopathy (ICE) Score ........................... 97 
11.3.8. 
Immunosuppression Utilization .............................................................................. 97 
11.3.9. 
Handwriting Sample and Temperature Log ............................................................. 97 
11.3.10. 
Tumor Markers ....................................................................................................... 97 
11.3.11. 
Collection of Biospecimens for Translational Research Assessments ...................... 98 
11.3.12. 
Adverse Events Assessment and Grading................................................................ 98 
11.3.13. 
Concomitant Medications ....................................................................................... 99 
11.3.14. 
Schedule of Assessments ........................................................................................ 99 
11.3.14.1. Contraception ....................................................................................................... 113 
11.3.15. 
Retention of Unused Subject Material ................................................................... 113 
11.3.16. 
Long-Term Follow-Up ......................................................................................... 113 
12. 
TUMOR RESPONSE ASSESSMENTS ............................................................... 114 
12.1. 
Tumor Response ................................................................................................... 114 
12.2. 
Tumor Response Evaluation ................................................................................. 114 
12.2.1. 
Imaging Acquisition Parameters ........................................................................... 115 
12.2.2. 
Evaluation of Target Lesions – RECIST 1.1 ......................................................... 115 
12.2.3. 
Evaluation of Non-Target Lesions – RECIST 1.1 ................................................. 115 
13. 
SAFETY ASSESSMENTS ................................................................................... 116 
13.1. 
Adverse Events and Definitions ............................................................................ 117 
13.1.1. 
Adverse Event ...................................................................................................... 117 
13.1.2. 
Suspected Adverse Reaction ................................................................................. 118 
13.1.3. 
Adverse Reaction.................................................................................................. 118 
13.1.4. 
Unexpected Adverse Reaction .............................................................................. 118 
13.2. 
Evaluation of Adverse Events ............................................................................... 118 
13.3. 
Determination of Seriousness................................................................................ 119 
13.3.1. 
Serious Adverse Event .......................................................................................... 119 
13.3.2. 
Non-Serious Adverse Event .................................................................................. 120 
13.4. 
Determination of Severity ..................................................................................... 120 
13.5. 
Determination of Causality ................................................................................... 120 
13.6. 
Documenting Adverse Events ............................................................................... 121 
13.7. 
Dose-limiting Toxicity Assessment....................................................................... 121 

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15.3.9. 
Safety Analyses .................................................................................................... 132 
16. 
STUDY MANAGEMENT ................................................................................... 133 
16.1. 
Electronic Case Report Forms and Source Documentation .................................... 133 
16.2. 
Good Clinical Practice .......................................................................................... 133 
16.3. 
Sponsor Monitoring .............................................................................................. 133 
16.4. 
Duration of the Study............................................................................................ 134 
16.5. 
Audits and Inspections .......................................................................................... 134 
16.6. 
Retention of Records ............................................................................................ 134 
16.7. 
Communication with Supporting Companies and Laboratories ............................. 135 
16.8. 
Institutional Review Board/ Independent Ethics Committee .................................. 135 
16.9. 
Confidentiality and Health Insurance Portability and Accountability Act 
Information ........................................................................................................... 135 
16.10. 
Informed Consent ................................................................................................. 135 
16.10.1. 
Informed Consent Requirements ........................................................................... 135 
17. 
LIST OF REFERENCES ...................................................................................... 137 
18. 
APPENDICES ...................................................................................................... 140 
APPENDIX A. NEW YORK HEART ASSOCIATION (NYHA) CLASSIFICATION 
OF CARDIAC DISEASE ..................................................................................... 141 
APPENDIX B. ASTCT GRADING FOR CYTOKINE RELEASE SYNDROME1 ............... 142 
APPENDIX C. IMMUNE EFFECTOR CELL-ASSOCIATED ENCEPHALOPATHY 
(ICE) SCORE ....................................................................................................... 143 
APPENDIX D. DIAGNOSTIC CRITERIA FOR IEC-ASSOCIATED FULMINANT 
HEMOPHAGOCYTIC LYMPHOHISTIOCYTES (HLH)/MACROPHAGE 
ACTIVATION SYNDROME (MAS) ................................................................... 144 
APPENDIX E. ASTCT GRADING OF ICANS1 .................................................................. 145 
 
APPENDIX G. HLA ALLELES IN ALAUNOS’S CLINICAL TCR LIBRARY .................. 152 
APPENDIX H. SUPPLEMENTARY STATISTICAL METHODS FOR PHASE I 
DOSE ESCALATION 
 153 
APPENDIX I. PROTOCOL CRITERIA FOR RECIST (RESPONSE EVALUATION 
CRITERIA IN SOLID TUMORS) VERSION 1.1 AND IRECIST 
(IMMUNE RECIST) GUIDELINES .................................................................... 159 

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LIST OF TABLES 
Table 1: 
Tumor Type Subgroups ............................................................................................ 4 
Table 2. 
TCR-T Dose Levels (Intended Dose and Dose Range) ............................................ 19 
Table 3. 
Abbreviations and Specialist Terms ........................................................................ 33 
Table 4. 
Risk Assessment for TCR-T Cell Drug Product ...................................................... 39 
 
 
Table 6. 
Tumor Type Subgroups .......................................................................................... 45 
Table 7. 
TCR-T Dose Levels (Intended Dose and Dose Range) ............................................ 47 
Table 8 
Treatment Schedule ................................................................................................ 73 
Table 9: 
Management of COVID-19 .................................................................................... 84 
Table 10. 
Laboratory Assessments Performed Locally ........................................................... 93 
Table 11. 
Subgroup Specific Tumor Markers ......................................................................... 98 
Table 12. 
Schedule of Assessments – Pre- TCR-T Cell Drug Product Infusion ..................... 100 
Table 13. 
Schedule of Assessment – Post-TCR-T Cell Drug Product Infusion ...................... 106 
Table 14. 
Schedule of Sample Collection for Translational Research Assessments ............... 111 
Table 15. 
Dose escalation/de-escalation rule for the BOIN design ........................................ 154 
Table 16. 
Operating characteristics of the BOIN design ....................................................... 156 
Table 17. 
Trial and Design Specifications ............................................................................ 156 
Table 18. 
Simon’s Two-Stage Optimal design for each of the Tumor Type Subgroups ......... 158 
Table 19:  Integration of target, non-target and new lesions into response 
assessment ........................................................................................................... 161 
Table 20: Time-point (TP) iResponse ................................................................................... 163 
Table 21: iRECIST Best Overall Response (iBOR) .............................................................. 164 
Table 22: Management of CRS............................................................................................. 166 
Table 23: Management of ICANS ............................................ Error! Bookmark not defined. 
Table 24: Recommendations for Use of IL-6 Antagonists and Alternative Agents for 
Management of CRS and ICANS .............................. Error! Bookmark not defined. 
Table 25: Management of Diffuse Cerebral Edema and/or Raised Intracranial Pressure ......... 176 
 
 

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LIST OF FIGURES 
Figure 1. 
Treatment Arms for TCR-T Cell Drug Product ....................................................... 22 
Figure 2. 
Phase I Dose Escalation Study Schema ................................................................... 49 
Figure 3. 
BOIN Escalation and De-escalation Rules .............................................................. 50 
 
 
Figure 5. 
Flowchart for trial conduct using the BOIN design ............................................... 155 

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2. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 3. 
Abbreviations and Specialist Terms  
Abbreviation or 
Specialist Term 
Explanation 
AE 
Adverse event 
APC 
Antigen-presenting cells 
AESI 
Adverse event of special interest 
AUCD0-D28 
Area under the concentration over time curve from Day 0 to Day 28 
CBC 
Complete Blood Count 
Cmax 
Maximum concentration observed 
CoA 
Certificate of Analysis 
CR 
Complete Response 
CRC 
Colorectal Cancer 
CRS 
Cytokine Release Syndrome 
CTCAE 
Common Terminology Criteria for Adverse Events 
DL 
Dose Level 
DLT 
Dose-Limiting Toxicity 
dMMR 
Deficient in DNA mismatch repair 
DP 
Drug Product 
DSMB 
Data Safety Monitoring Board 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GM-CSF 
Granulocyte macrophage colony stimulating factor 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HLA 
Human Leukocyte Antigen 
HLH 
Hemophagocytic Lymphohistiocytosis 
ICANS 
Immune Effector Cell-Associate Neurotoxicity Syndrome 

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Abbreviation or 
Specialist Term 
Explanation 
ICE 
Immune Effector Cell-Associated Encephalopathy 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IFN-γ 
Interferon gamma 
 
 
IL-6 
Interleukin-6 
IrAE 
Immune-related Adverse Event 
IRB 
Institutional Review Board 
IRF 
Independent Review Facility 
IRR 
Infusion Related Reaction 
ISR 
Injection Site Reaction 
LMWH 
Low molecular weight heparin 
LOQ 
Limit of Quantification 
LVEF 
Left Ventricular Ejection Fraction 
KM 
Kaplan-Meier 
MAS 
Macrophage Activation Syndrome 
MSI-H 
Microsatellite-instability high 
MTD 
Maximum Tolerated Dose 
MUGA 
Multiple-gated Acquisition Scan 
NCI 
National Cancer Institute 
NSCLC 
Non-small Cell Lung Cancer 
OAE 
Other Significant Adverse Event 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PBL 
Peripheral Blood Lymphocyte 
 
 
PCR 
Polymerase Chain Reaction 
PD 
Progressive Disease 
PFS 
Progression-Free Survival 

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Abbreviation or 
Specialist Term 
Explanation 
PI 
Principal Investigator 
The investigator who leads the study conduct at an individual study center. 
Every study center has a principal investigator. 
PPP 
Per Protocol Population 
PR 
Partial Response 
REP 
Rapid Expansion Protocol 
RP2D 
Recommended Phase II Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Stable Disease 
SOP 
Standard Operating Procedure 
SRC 
Safety Review Committee 
TBV  
Total Blood Volume 
TCR 
T-Cell Receptor 
TCR-T 
T-cell receptor engineered T cell 
TIL 
Tumor Infiltrating Lymphocyte 
TLS 
Tumor Lysis Syndrome 
Tmax 
Time to Cmax 
 
 
WBC 
White Blood Cell 
 

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endogenous humoral responses were not limiting in the ability to achieve meaningful objective 
clinical response. Based on these findings, the impact of neutralizing humoral response to the 
murine constant chains of transposed TCRs poses a negligible risk to the patients. 
High frequencies of mTCR+ cells can be generated through enrichment by anti-mouse TCRβ 
constant chain antibody (clone H57) and expansion with pan-T cell (CD3-specific) activating 
antibody OKT3 in a rapid expansion protocol (D.C. Deniger et al., 2016). Sleeping Beauty DNA 
plasmids have been approved for use in clinical trials evaluating the ability of T-cells modified 
with chimeric antigen receptors to treat B-cell malignancies (ClinicalTrials.gov Identifier: 
NCT00968760, NCT01497184, NCT01362452, NCT01653717, NCT02194374, NCT02529813) 
(Field et al., 2013; Hackett, Largaespada, & Cooper, 2010; Jena, Dotti, & Cooper, 2010; 
Kebriaei et al., 2012; Peng et al., 2009; H. Singh, Huls, Kebriaei, & Cooper, 2014). Recently, the 
Sleeping Beauty system was adapted for expression of neoantigen-specific TCRs in patient 
peripheral, blood-derived T cells (D.C. Deniger et al., 2016). A Phase II clinical trial sponsored 
by National Cancer Institute (NCI) is underway, evaluating the adopted transfer of T-cells 
genetically modified with neoantigen-reactive, mTCRs using the Sleeping Beauty 
transposon/transposase system (ClinicalTrials.gov Identifier: NCT04102436). 
Development of this TCR-T cell therapy requires identification of the TCRs from the 
neoantigen-reactive T-cell culture and transfer of one or more of the TCRs into a younger 
repertoire of T cells from the peripheral circulation such that a high expression of 
the neoantigen-reactive TCRs occurs at clinically meaningful cell doses. Thus, it is important 
to evaluate the ability of T cells to target neoantigens expressed by the autologous tumor. The 
process that led to the identification of these TCRs is extensively described in the literature 
(Cafri et al., 2019; D. C. Deniger et al., 2018; Malekzadeh et al., 2019; Tran, Robbins, & 
Rosenberg, 2017; Wang et al., 2019). Briefly, next-generation sequencing is performed; the 
mutations expressed by the tumor cells are identified using bioinformatics tools. Next, reagents 
that mimic the mutated amino-acid sequence (tandem minigenes) as well as the mutated protein 
(long peptides) can be synthesized and introduced into antigen-presenting cells (dendritic cells) 
for presentation in the context of the patient’s own HLA molecules. T cells derived from tumors 
(tumor infiltrating lymphocytes) or from the blood are co-cultured with the dendritic cells 
expressing the mutated neoantigens. T-cell reactivity is evaluated by cytokine release assays and 
expression of the T-cell activation molecules tested by flow cytometry. Once the reactive T cells 
are sorted, the TCR sequence is evaluated by PCR and reconstructed in silico. Then the mutated 
TCR sequence is synthesized and can be cloned into the Sleeping Beauty vector for the 
generation of T cells expressing the specific mutated TCR and can be expanded exponentially as 
modified from (D.C. Deniger et al., 2016). 
3.2. 
Benefit/Risk Assessment 
3.2.1. 
Toxicity of Adoptive Cell Therapies 
Cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome 
(ICANS) can be fatal if not recognized early. Therefore, patients who undergo adoptive cell 
therapy need to be managed by specialized teams including physicians with expertise in these 
toxicities, intensive care specialists and neurologists.  Management of patients becomes more 
complicated when the therapy is administered in the outpatient setting.  In those cases, patients 

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should be hospitalized as soon as they develop a symptom or sign of toxicity, and caregivers 
must be taught to recognize symptoms of ICANS. 
The first clinical manifestation of adoptive cell toxicity is CRS.  It usually starts with fever that 
can exceed 40°C, and includes other symptoms such as malaise, headache, myalgias, and 
tachycardia.  Possible manifestations include organ dysfunctions, cytopenias, and coagulopathy.  
In severe cases, patients can develop life-threatening capillary leakage with hypoxia and 
hypotension.  Rarely, hemophagocytic lymphohistiocytosis can arise.  CRS usually occurs in the 
first week after adoptive cell infusion, although delayed CRS is possible.  Time to resolution is 
generally 7 to 8 days, but some patients may need more than 30 days to recover. 
The standard of care for CRS is Actemra® (tocilizumab), an anti‑IL‑6 receptor antagonist.  If the 
patient does not respond to Actemra® (tocilizumab), corticosteroids can be effective in reversing 
CRS.  Some data suggest that the anti‑IL‑6 monoclonal antibody siltuximab or the IL‑1 receptor 
antagonist anakinra may have clinical efficacy.  In CRS, patients can require vasopressors to 
correct hypotension and oxygen supply or intubation for hypoxia. 
The severity of CRS has been correlated with the peak of in vivo adoptive cell proliferation and 
disease burden.  A faster T cell expansion can be promoted by higher cell dose, heavily 
pretreated bone marrow disease, and also by some kinds of pre-conditioning, such as 
fludarabine‑containing regimens.  The risk of severe CRS is also increased in patients with 
comorbidities and in those who develop the syndrome within 3 days of infusion (Lee et al., 
2019).   
ICANS may occur as an adoptive cell‑related encephalopathy syndrome.  The clinical 
manifestations of ICANS are very wide ranging, as toxicity does not affect a specific region of 
the central nervous system.  They include encephalopathy (confusion or delirium), expressive 
aphasia or language disturbance, motor weakness, myoclonus or tremor, headache, seizures, and 
a depressed level of consciousness.  In rare cases patients can rapidly develop diffuse cerebral 
oedema.  Expressive aphasia seems to be a typical symptom.  ICANS onset can range from a few 
hours to three to four weeks after adoptive cell infusion.  It can occur almost simultaneously with 
CRS or even after CRS has resolved.  ICANS is usually self-limiting, and most symptoms 
reverse in three to four weeks, with persistent abnormalities being uncommon.  For ICANS, the 
American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading is 
based on 5 elements: the 10-point immune effector cell-associated encephalopathy (ICE) score, 
depressed level of consciousness, seizure, motor findings, and elevated intracranial 
pressure/cerebral edema (Appendix E). Severity can range from grade 1 to grade 4, with the 
grade determined by the most severe event.  The ICE score is a tool that measures alterations in 
speech, orientation, handwriting, and concentration (Appendix C). Severe ICANS develops 
almost only in patients who have experienced CRS, with severity being influenced by disease 
type, disease burden, patient’s age, and treatment history. For grading and management, refer to 
Appendix B. 
3.2.2. 
Risk Assessment 
Potential risks associated with the study intervention and study procedures and measures to 
control the risks are summarized in Table 4 and Table 5. Detailed information about the potential 
risks and reasonably expected AEs of adoptive cell therapies in general, and potentially of 

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Table 4. 
Risk Assessment for TCR-T Cell Drug Product (Continued) 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Neurologic adverse events 
(AEs) and immune effector 
cell associated neurologic 
syndrome (ICANS) 
Neurologic AEs occur very commonly 
following infusion with CAR -T 
products and ICANS occurs frequently 
with adoptive cell therapy and like 
CRS, is associated with rapid TCR-T 
cell expansion and high tumor burden 
as well as other factors. 
Subjects will receive aggressive 
treatment including corticosteroids.  
Actemra® (tocilizumab) may be 
administered if neurotoxicity is 
accompanied by CRS (Section 10.1.9  
and Appendix C). 
Prolonged cytopenia 
Grade 3 or higher prolonged cytopenia 
following lymphodepletion and 
adoptive cell therapy infusion occur 
and included thrombocytopenia, 
neutropenia, and anemia, and should be 
carefully monitored. 
Blood counts should be monitored 
following TCR-T cell product infusion, 
as prolonged neutropenia is associated 
with increased risk of infection. 
Tumor lysis syndrome 
(TLS) 
TLS occurs when tumor cells release 
their contents into the blood stream, 
either spontaneously or due to 
treatment, leading to metabolic 
disturbances including hyperuricemia, 
hyperkalemia, hypophosphatemia, and 
hypocalcemia. 
Management of cardiac and 
neuromuscular abnormalities and 
preservation of kidney function are 
most important. Allopurinol can be 
used to reduce the hyperuricemia and 
rasburicase can be used to preserve or 
improve renal function Section 9.4.4.  
Viral reactivation 
Viral infections are very commonly 
associated with lymphodepletion and 
adoptive cell therapy infusion. 
Herpes or Epstein Barr virus: 
Subjects can receive valacyclovir orally 
or acyclovir intravenously if the patient 
cannot take oral antiviral medications 
after lymphodepletion Section 10.1.1. 
Hypersensitivity reaction 
(Type 1 and Type 3) 
Type 1 hypersensitivity or allergic 
reactions are theoretically possible in 
response to an injected protein and may 
be manifested by shortness of breath, 
rash, anaphylaxis, or angioedema.   
Immune complex‑mediated Type 3 
hypersensitivity reactions are similar to 
Type 1 reactions but are likely to be 
delayed and may include, in addition to 
the aforementioned symptoms, 
polyarthritis, myalgia, fever, or 
glomerulonephritis. 
Subjects will be treated 
symptomatically with supportive care, 
antihistamines, or corticosteroids, and 
continued monitoring (Section 10.1.6). 
Nausea and diarrhea 
A general risk with cell therapies. 
Prophylactics can be used at the 
Investigator’s discretion with Sponsor 
approval (Section 10.1.12). 
Pain 
A general risk with cell therapies. 
Anti-inflammatory and opioid drugs 
can be administered as needed during 
the study as long as there is no known 
or expected drug‑drug interaction 
(Section 10.1.13). 
 

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3.2.3. 
Benefit Assessment 
Since this is a first‑in‑human (FIH) study, the benefit of the treatment of TCR-T cell drug 
product has not yet been determined; however, there may be an opportunity, at one or more dose 
levels, to provide clinical benefit to individual participant(s) based on previous experience with 
adoptive cell therapy.   
3.2.4. 
Overall Benefit: Risk Conclusion 
The success of this investigational therapy cannot be predicted at this time, but because the 
subjects will have progressed or recurred following standard chemotherapy or standard systemic 
therapy or were intolerant to previous treatment and have a short life expectancy, the potential 
benefit may outweigh the risks. 

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For the initial two subjects of Arms A and B there will be a dose staggering interval of 28 days. 
Dose administration for the subsequent subjects will not occur until the initial two subjects have 
completed their safety evaluation for dose-limiting toxicities.   
Subjects may be screened during this 4-week period so that apheresis material can be collected 
for manufacturing.  
There are two dose escalation stopping rules in this BOIN study. 
• Stop the trial if the lowest dose is eliminated due to overt toxicities*;  
• Stop the dose escalation and estimate the MTD/RP2D if the number of new subjects 
treated at the current dose level reaches 9.  
* Overt Toxicities defined as: 
1. The occurrence of 2 or more dose limiting toxicities. 
2. Consideration will also be given to longer term toxicities (e.g. > 30 days post infusion: 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cardiotoxicity, 
pulmonary toxicity, metabolic complications, secondary macrophage-activation 
syndrome, prolonged cytopenia unresponsive to colony stimulating factors, grade 3 and 
4 infections and subsequent malignancies) 
The detailed statistical methods for dose escalation and de-escalation and estimation of 
MTD/RP2D are described in Section 15.1.1 and Section 15.1.2. 

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Figure 3. 
BOIN Escalation and De-escalation Rules 
 
 

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For the null response rate, p0 (H0) for each tumor type subgroup; refer to Table 18 for additional 
details. 
5.2. 
Study Endpoints 
5.2.1. 
Phase I Endpoints 
5.2.1.1. 
Primary Endpoints 
• Number of DLTs and AEs 
o Neurotoxicity and cytokine release syndrome events will be assessed 
according to the ASTCT criteria (Lee et al., 2019). Refer to Appendix B, 
Appendix C, and Appendix E. 
o All other AEs will be as assessed by the NCI CTCAE (Version 5.0). 
• Frequency, relatedness, severity, and duration of treatment emergent and treatment 
related AEs (NCI CTCAE Version 5.0). 
5.2.1.2. 
Secondary Endpoints 
• Final T cell count, including percent viability, for appropriate clinical dose. 
Additional details will be provided in the Statistical Analysis Plan (SAP). 
• Duration of TCR-T cell drug product persistence 
 
 
 
 
 
 
 

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5.3. 
Dose Limiting Toxicity Definition 
Severity of AEs will be graded according to NCI CTCAE Version 5.0. For the purpose of dose 
escalation, any of the AEs listed below that occur within 28 days after the TCR-T cell drug 
product infusion and are attributable to TCR-T cell drug product and unrelated to tumor, 
intercurrent illness, or concomitant medications will be classified as DLTs. Due to the 
requirement for lymphodepletion prior to investigational product administration, and the 
expected toxicities associated with lymphodepletion, hematological toxicities will not be 
considered DLTs unless specified below. 
Clinically important or persistent toxicities (e.g., toxicities responsible for significant dose delay) 
that are not included in the definitions below may also be considered a DLT following review by 
the SRC.  All DLTs need to represent a clinically significant shift from baseline. 
A DLT is a study intervention related AE occurring within the DLT window (Day 0 to Day 28 
days post TCR-T cell drug product infusion), defined based on NCI CTCAE Version 5.0 as the 
following: 
Hematologic 
• Grade 4 neutropenia lasting ≥ 14 days 
• Grade 4 thrombocytopenia 
• Grade 3 thrombocytopenia associated with clinically significant bleeding, 
• ≥ Grade 3 febrile neutropenia associated with hemodynamic compromise or objective 
evidence of infection. 
Non-hematologic 
• CRS grade 3 or 4 that does not improve to grade ≤ 2 within 72 hours despite 
appropriate treatment. 
• Grade 3 Immune-effector cell-associated neurotoxicity syndrome (ICANS) that does 
not return to grade ≤2 or lower within 7 days. 
• Any grade 5 adverse event (not due to disease progression or to a known cause other 
than TCR-T (e.g., automobile accident)). 
• Grade 3 hepatic toxicity that does not return to grade ≤ 2 or lower within 7 days. 
• Grade 3 toxicity involving vital organs that does not improve to grade ≤ 2 or lower 
within 7 days of onset. 
• Grade 4 toxicity not previously specified. 
In addition to the related AEs mentioned above, any related grade 3 toxicity and all grade 4 
toxicities will be considered DLTs except the following: 
• Grade 3 anemia that is not associated with other clinically significant complications 
• Expected chemotherapy toxicities due to lymphodepletion including cytopenias, 
fludarabine related adverse reactions, and cyclophosphamide related hemorrhagic 
cystitis. 

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6. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1. 
Subject Inclusion Criteria 
This study will enroll subjects based on histologically confirmed tumor types:  
Subgroup 1a Gynecologic cancer — Ovarian 
Subgroup 1b Gynecologic cancer — Endometrial  
Subgroup 2 
Colorectal 
Subgroup 3 
Pancreatic 
Subgroup 4 
Non-small cell lung cancer (NSCLC). NSCLC includes but is not limited to 
squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma. 
Subgroup 5 
Cholangiocarcinoma 
6.1.1. 
Pre-screening Eligibility Criteria 
1. Patients with previous tumor genomic testing performed at a CLIA-certified or CLIA-
accredited laboratory must be willing to disclose results. Patients that do not have 
previous tumor genomic testing must have a planned biopsy or resection (or archived 
tumor tissue available for genomic testing) or must provide a blood sample for circulating 
tumor DNA (liquid biopsy) testing. 
2. Patients with previous high resolution, human leukocyte antigen (HLA) class I and II 
typing from a CLIA-certified or CLIA-accredited laboratory must be willing to disclose 
results. Patients that do not have previous typing results must be willing to provide a 
blood sample for this testing. 
3. Patients who have previously received at least one line of standard systemic therapy for 
their advanced/metastatic cancer and have either progressed, recurred, or were intolerant 
to the previous treatment for one of the following cancer types. 
o Gynecologic cancers (i.e., ovarian or endometrial) 
o Colorectal Cancer 
o Pancreatic Cancer 
o Non-small cell lung cancer (NSCLC): NSCLC includes but is not limited to 
squamous cell carcinoma, adenosquamous carcinoma or adenocarcinomas 
o Cholangiocarcinoma 
4. Patients must be able to provide written informed consent. 
5. Patients must be age ≥ 18 years. 
6. Clinical Performance Status of Eastern Cooperative Group (ECOG) 0 or 1.  
7. Patients must not have any form of primary immunodeficiency (such as severe combined 
immunodeficiency disease) or uncontrolled autoimmune hemolytic anemia or idiopathic 
thrombocytopenic purpura, such as those patients with a declining hemoglobin level or 

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platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose 
of study drug, or the need for daily prednisone ≥10 mg daily (or corticosteroid equivalent) 
to control the autoimmune disease (Note: the experimental treatment being evaluated in 
this protocol depends on an intact immune system. Patients who have decreased immune 
competence may be less responsive to the experimental treatment and more susceptible to 
its toxicities.) 
8. Patients who have received any type of organ transplant in the past 12 months are 
excluded 
9. Patients who have undergone xenotransplantation at any time are excluded. 
10. Patients must not have any history of severe immediate hypersensitivity reaction to 
cyclophosphamide, fludarabine,
 
bendamustine (for subjects if required for lymphodepletion), or dimethyl sulfoxide 
(DMSO). 
11. Patients with a prior history or concurrent malignancy whose natural history or treatment 
does not have the potential to interfere with either the safety or efficacy assessment of the 
investigational regimen may be included after discussion with Sponsor, Alaunos Medical 
Monitor, or designee 
12. Patients must not have any active unstable or clinically significant medical condition that 
would, in the opinion of the Principal Investigator (PI) in consultation as warranted with 
medical monitor, result in risks to safety of a subject and/or their compliance with the 
protocol. Examples include, but are not limited to, a history of myocarditis or congestive 
heart failure (New York Heart Association functional Class III or IV), unstable angina, 
serious uncontrolled cardiac arrythmia, myocardial infarction within 6 months of 
screening, active interstitial lung disease (ILD)/pneumonitis or a history of 
ILD/pneumonitis requiring chronic treatment with systemic steroids, uncontrolled asthma, 
or colitis. 
 
6.1.2. 
Screening Eligibility Criteria: 
Inclusion Criteria: 
1. Subjects with at least one TCR matching a combination of their somatic mutations and 
HLA type is available in Alaunos’s Clinical TCR library (refer to Appendix G) as 
evidenced by molecular testing results performed at a CLIA-certified or CLIA-accredited 
laboratory.  
 
2. Patients who have previously received at least one line of standard systemic therapy for 
their advanced/metastatic cancer and have either progressed, recurred, or were intolerant 
to the previous treatment. Specifically: 
• Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):  
a.  Ovarian cancer: Subjects who are platinum-resistant, as defined by 
progression on a platinum-containing regimen or within 6 months of a 
previous platinum dose.  

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b. Endometrial cancer: Subjects who have received at least 1 prior line of 
therapy for advanced/recurrent disease (including adjuvant chemotherapy 
and adjuvant chemo-radiation therapy) prior to apheresis. Prior hormonal 
therapy will not count towards prior lines of therapy. Note that 2 prior 
lines of treatment are required prior to lymphodepletion. 
• Subgroup 2. Colorectal cancer:  
• Patient has received systemic treatment for advanced unresectable or 
metastatic disease prior to apheresis. 
• Must include an irinotecan or oxaliplatin-based therapy and if eligible, 
a targeted antibody therapy.  
• Subjects with deficient DNA mismatch repair (dMMR) or 
microsatellite instability-high (MSI-H) colorectal cancer 
should have received a checkpoint inhibitor such as 
pembrolizumab or nivolumab. Note that 2 prior lines of 
treatment are required prior to lymphodepletion. 
• Subgroup 3. Pancreatic cancer: Subjects who have progressive disease after 
receiving initial treatment with FOLFOX, (modified) FOLFIRINOX, and/or a 
gemcitabine-based therapy. 
• Subgroup 4. Non-small cell lung cancer (NSCLC):  
• Subjects with recurrent and/or metastatic disease who have disease 
progression or intolerance to treatment with a PD-1/PD-L1 inhibitor 
either as a single-agent or in combination with other checkpoint 
inhibitors (e.g., CTLA-4 inhibitors) and/or platinum-containing 
chemotherapy. 
• Subjects with targetable oncogene alterations (e.g., EGFR, ALK, 
ROS1, RET, MET, NTRK1-3, BRAF) must have had disease 
progression or intolerance on at least one prior line of targeted therapy. 
• Subgroup 5. Cholangiocarcinoma: Subjects must have histologically 
confirmed diagnosis of cholangiocarcinoma Stage II, III, or IV (intra-hepatic, 
extra-hepatic and perihilar) that is not eligible for curative resection, 
transplantation, or ablative therapies. Subjects who have progressed after 
receiving at least one line of standard therapy.   
3. Patients must have measurable disease per RECIST 1.1 as assessed by the local site 
investigator/radiology. 
4.  Patient must agree to provide archival tissue (core or excisional biopsy) from a locally 
recurrent or inoperable or metastatic tumor lesion or new tissue must be obtained from a 
non-target lesion for translational research assessments 
 
 
 

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5. Clinical Performance Status of Eastern Cooperative Oncology Group (ECOG) 0 or 1. . 
 
6. Patient must provide written informed consent for the long-term follow-up protocol 
(TCR001-202) for up to 15 years post TCR-T Cell drug product infusion per FDA 
requirements. 
 
7. Adequate bone marrow reserves as assessed by the following hematology laboratory 
criteria: 
a. ANC ≥ 1,000/mm3 (filgrastim not within 7 days or pegfilgrastim not within 14 days) 
b. WBC ≥ 3,000/mm3 
c. Platelet count ≥ 50,000/mm3 
d. Hemoglobin > 8.0 g/dL. (Subjects may be administered red blood cell transfusions to 
achieve this cut-off value.) 
8.  Adequate major organ system functions as determined by the following criteria: 
a. Cardiac 
i) Left ventricular ejection fraction ≥50% on multiple gated acquisition (MUGA) 
scan and/or by echocardiography at the discretion of the investigator. 
Note: No evidence of clinically significant pericardial effusion as determined 
by an ECHO. 
b. Pulmonary  
i) Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 
90% on room air. 
c. Renal  
i) Serum creatinine within institutional limits; OR 
ii) Calculated creatinine clearance (ClCr) (e.g., Cockcroft-Gault equation) ≥ 45.0 
mL/min and not dialysis dependent  
d. Liver 
i) Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii) Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who 
must have a total bilirubin < 3.0 mg/dL 
9. Patients may have undergone minor surgical procedures or limited-field radiotherapy 
provided any major organ toxicities have recovered to ≤ Grade 1. 
 
10. Patients must not be pregnant or breastfeeding. 
11. Female patients of non-childbearing potential must meet at least 1 of the following 
criteria: 
• Achieved postmenopausal status, defined as follows: cessation of regular menses for 
at least 12 consecutive months with no alternative pathological or physiological 
cause; if there is uncertainty as to whether the patient has a postmenopausal status, it 
will be confirmed with a serum follicle stimulating hormone (FSH) level confirming 
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• Have undergone a documented hysterectomy and/or bilateral oophorectomy;  
• Have medically confirmed ovarian failure.   
12. Patients of childbearing potential, including women with tubal ligations, must commit to 
using 2 highly effective forms of birth control (defined as the use of an intrauterine 
device, a barrier method with spermicide, condoms, or any form of hormonal 
contraceptives) for the duration of the study. 
13. Male patients must be sterile (biologically or surgically), or their partner(s) of 
childbearing potential must commit to the use of highly effective method of birth control 
for the duration of the study.   
14. Patients must be fully vaccinated against COVID-19 prior to lymphodepletion. This 
criterion includes a booster shot if at least 5 months have passed after receiving the 
second shot of a 2-dose series or 2 months after a single-dose vaccine. Exceptions must 
be approved by the Alaunos Medical Monitor. 
6.1.3. 
 Exclusion Criteria:  
1. Patients who have received any type of organ transplant in the past 12 months. 
2. Patients who have undergone xenotransplantation at any time. 
3. Patients with known active CNS metastases; Patients with prior CNS metastatic disease 
that has been effectively treated and have recovered from the acute effects of radiation 
therapy or surgery prior to study entry, have discontinued supra physiologic doses of 
corticosteroid treatment for these metastases (unless required for other than the treatment 
of brain metastases) for at least 2 weeks and are neurologically stable for 3 months 
(requires magnetic resonance imaging [MRI] confirmation) may be enrolled, stability for 
less than 3 months may be allowed after discussion with the Alaunos Medical Monitor. 
Any question pertaining to this criterion should be discussed with the Alaunos Medical 
Monitor. 
4. Positive beta-HCG in female of child-bearing potential defined as not post-menopausal 
for 12 months or no previous surgical sterilization or lactating females. 
5. Concurrent systemic steroid therapy at a dose of >10 mg prednisone daily or equivalent is 
excluded. Physiologic dosing of steroids to treat adrenal insufficiency is permitted. 
Topical or inhaled steroids are permitted. 
6. Any form of primary immunodeficiency (such as severe combined immunodeficiency 
disease) or uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic 
purpura, such as those with a declining hemoglobin level or platelet count secondary to 
autoimmune destruction within the 4 weeks prior to first dose of study drug, or the need 
for daily prednisone ≥10 mg daily (or corticosteroid equivalent) to control the 
autoimmune disease. Note: the experimental treatment being evaluated in this protocol 
depends on an intact immune system. Patients who have decreased immune competence 

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investigational regimen may be included after discussion with Sponsor, Alaunos Medical 
Monitor or designee 
15. Active unstable or clinically significant medical condition that would, in the opinion of 
the Principal Investigator (PI) in consultation as warranted with medical monitor, result 
in risks to safety of a subject and/or their compliance with the protocol. Examples 
include, but are not limited to, , active interstitial lung disease (ILD)/pneumonitis or a 
history of ILD/pneumonitis requiring chronic treatment with systemic steroids, 
uncontrolled asthma, or colitis. 
16.  History of any one of the following cardiovascular conditions within the past 6 months: 
Class III or IV heart failure as defined by the NYHA (Refer to Appendix A), cardiac 
angioplasty or stenting, myocardial infarction, unstable angina, or other clinically 
significant cardiac disease. 
6.1.4. 
Eligibility Criteria for Apheresis: 
These criteria should be confirmed prior to the subject undergoing apheresis (see SOA for 
collection windows). 
1. Adequate bone marrow reserves as assessed by the following hematology laboratory 
criteria. This requirement may be satisfied by the initial screening in Section 6.1.1 if 
apheresis is scheduled within 7 days of the initial screening: 
a. ANC ≥ 1,000/mm3 (filgrastim not within 7 days or pegfilgrastim not within 14 days) 
b. WBC ≥ 3,000/mm3 
c. Platelet count ≥ 50,000/mm3 
d. Hemoglobin > 8.0 g/dL. (Subjects may be administered red blood cell transfusions to 
achieve this cut-off value.) 
2. Adequate major organ system functions as determined by the following criteria. This 
requirement may be satisfied by the initial screening in section 6.1.1 if apheresis is 
scheduled within 28 days of the initial screening: 
a. Cardiac 
i) Left ventricular ejection fraction ≥50% on multiple gated acquisition (MUGA) 
scan and/or by echocardiography at the discretion of the investigator. 
Note: No evidence of clinically significant pericardial effusion as determined 
by an ECHO. 
b. Pulmonary  
i) Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% 
on room air. 
c. Renal  
i) Serum creatinine within institutional limits; OR 
ii) Calculated creatinine clearance (ClCr) (e.g., Cockcroft-Gault equation) ≥ 45.0 
mL/min and not dialysis dependent  
d. Liver 
i) Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii) Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who 
must have a total bilirubin < 3.0 mg/dL 

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3. A washout period must have elapsed since completion of any prior systemic therapy with 
guidelines as follows (windows other than what is listed below should be allowed only 
after consultation with the Medical Monitor); subjects’ non-hematologic toxicities from 
any prior systemic therapy must have recovered to ≤ Grade 1 (with the exception of 
neuropathy and alopecia) or baseline prior to starting apheresis. 
a. Nitrosoureas: 6 weeks 
b. Other cytotoxic agents: 4 weeks  
c. Anti-angiogenic agents: 4 weeks  
d. Targeted agents, including small molecule tyrosine kinase inhibitors: 5 half-lives or 2 
weeks, whichever is shorter 
e. Immune checkpoint inhibitor agents: 4 weeks and must have recovered to ≤ Grade 1 
or baseline grade severity prior to checkpoint inhibitor administration from immune-
related adverse events (IrAEs), other than endocrine side effects or those affecting 
nonessential organs or functions 
f. CAR-T, other T-cell product or investigational cancer vaccine: 6 weeks 
g. Systemic steroids of greater than 10 mg prednisone equivalence: 1 week 
4. Subjects must not be pregnant or breastfeeding. 
6.1.5. 
Eligibility Criteria for Lymphodepletion: 
The criteria should be confirmed before entering the lymphodepletion phase of the study. 
1. Patients who have previously received at least one line of standard systemic therapy for 
their advanced/metastatic cancer and have either progressed, recurred, suboptimal 
response or were intolerant to the previous treatment. Specifically: 
• 
Subgroup 1. Gynecologic cancers (i.e., ovarian or endometrial):  
a. Ovarian cancer: Subjects who are platinum-resistant, as defined by progression 
on a platinum-containing regimen or within 6 months of a previous platinum 
dose.  
b. Endometrial cancer: Subjects must have received at least 2 prior lines of therapy 
for advanced/recurrent disease (including adjuvant chemotherapy and adjuvant 
chemo-radiation therapy) prior to lymphodepletion. Prior hormonal therapy will 
not count towards prior lines of therapy. 
• 
Subgroup 2. Colorectal cancer:  
• Subjects must have received at least 2 prior lines of systemic treatment for 
advanced unresectable or metastatic disease prior to lymphodepletion, which must 
include an irinotecan or oxaliplatin-based therapy and if eligible, a targeted 
antibody therapy. Subjects with deficient DNA mismatch repair (dMMR) or 
microsatellite instability-high (MSI-H) colorectal cancer should have received a 
checkpoint inhibitor such as pembrolizumab or nivolumab. 
• Subgroup 3. Pancreatic cancer: Subjects who have progressive disease after receiving 
initial treatment with FOLFOX, (modified) FOLFIRINOX, and/or a gemcitabine-
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• Subgroup 4. Non-small cell lung cancer (NSCLC): 
• Subjects with recurrent and/or metastatic disease who have disease progression or 
intolerance to treatment with a PD-1/PD-L1 inhibitor either as a single-agent or in 
combination with other checkpoint inhibitors (e.g., CTLA-4 inhibitors) and/or 
platinum-containing chemotherapy.  
• Subjects with targetable oncogene alterations (e.g., EGFR, ALK, ROS1, RET, 
MET, NTRK1-3, BRAF) must have had disease progression or intolerance on at 
least one prior line of targeted therapy. 
• Subgroup 5. Cholangiocarcinoma: Subjects must have histologically confirmed 
diagnosis of cholangiocarcinoma Stage II, III, or IV (intra-hepatic, extra-hepatic and 
perihilar) that is not eligible for curative resection, transplantation, or ablative 
therapies. Subjects who have progressed after receiving at least one line of standard 
therapy.   
2. No active infection requiring systemic therapy or causing fever (temperature > 38.1˚C 
(100.6 ˚F)) or subjects with unexplained fever (temperature > 38.1˚C (100.6 ˚F)) within 7 
days prior to the day of investigational product administration. Participants with known 
active, uncontrolled bacterial, fungal, or viral infection, are excluded.  In equivocal cases, 
subjects whose viral load is negative, may be eligible after discussion with the Alaunos 
Medical Monitor. 
3. Any contraindication to fludarabine or cyclophosphamide should be discussed with the 
Medical Monitor prior to lymphodepletion. 
4. Patients who have received any type of organ transplant in the past 12 months are 
excluded. 
5. Patients who have undergone xenotransplantation at any time are excluded. 
6. Absence of active autoimmune disease requiring ongoing systemic immunosuppressive 
therapy. Patients must not have any form of primary immunodeficiency (such as severe 
combined immunodeficiency disease) or uncontrolled autoimmune hemolytic anemia or 
idiopathic thrombocytopenic purpura, such as those patients with a declining hemoglobin 
level or platelet count secondary to autoimmune destruction within the 4 weeks prior to 
first dose of study drug, or the need for daily prednisone ≥10 mg daily (or corticosteroid 
equivalent) to control the autoimmune disease (Note: the experimental treatment being 
evaluated in this protocol depends on an intact immune system. Patients who have 
decreased immune competence may be less responsive to the experimental treatment and 
more susceptible to its toxicities.) 
7. Negative serum pregnancy test within 7 days before lymphodepletion chemotherapy for 
women of childbearing potential, defined as those who have not been surgically sterilized 
or who have not been free of menses for at least 1 year. Patients also must not be 
breastfeeding. 
8. Clinical Performance Status of ECOG 0 or 1.  

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9. Patients must have measurable disease per RECIST 1.1 as assessed by the local site 
investigator/radiology. 
10. No treatment with any investigational agent on a different clinical trial between meeting 
the screening eligibility criteria and enrollment (date eligibility is confirmed for 
lymphodepleting chemotherapy). 
11.  Serum creatinine within institutional limits; OR Calculated creatinine clearance (ClCr) 
(e.g., Cockcroft-Gault equation) ≥ 45.0 mL/min and not dialysis dependent 
12. Liver 
i) Serum ALT/AST ≤ 3 x ULN or ≤ 5 x ULN if documented liver metastases 
ii) Total bilirubin ≤ 2 mg/dL, except in patients with Gilbert’s Syndrome, who 
must have a total bilirubin < 3.0 mg/dL 
13. ANC ≥ 1,000/mm3 (≥1.0 × 109/L) within 1 week of lymphodepletion. 
14. Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% on room 
air. 
15. Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of ≥50% 
as assessed by echocardiogram or MUGA scan, or LVEF of 45-49% and clearance by a 
cardiologist; if patient receives cardiotoxic chemotherapy after enrollment, repeat 
echocardiogram or MUGA is required to reestablish eligible LVEF. 
16. Patients must be fully vaccinated against COVID-19 prior to lymphodepletion. This 
criterion includes a booster shot if at least 5 months have passed after receiving the 
second shot of a 2-dose series or 2 months after a single-dose vaccine. Exceptions must 
be approved by the Alaunos Medical Monitor. 
17. Patients may have undergone minor surgical procedures or limited-field radiotherapy 
provided any major organ toxicities have recovered to ≤ Grade 1. 
18. Subjects must not require corticosteroid therapy or dose ≥ 10 mg per day of prednisone or 
the equivalent.  Pulsed corticosteroid dose for disease control is acceptable until the day 
before the start of lymphodepletion. 
19. Must not have received any live vaccines within 30 days prior to enrollment. 
20. Patients with known active CNS metastases are excluded; Patients with prior CNS 
metastatic disease that has been effectively treated and have recovered from the acute 
effects of radiation therapy or surgery prior to study entry, have discontinued supra 
physiologic doses of corticosteroid treatment for these metastases (unless required for 
other than the treatment of brain metastases) for at least 2 weeks and are neurologically 
stable for 3 months (requires magnetic resonance imaging [MRI] confirmation) may be 
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Appendix A), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or 
other clinically significant cardiac disease. 
30. Patients must not have any active unstable or clinically significant medical condition that 
would, in the opinion of the Principal Investigator (PI) in consultation as warranted with 
medical monitor, result in risks to safety of a subject and/or their compliance with the 
protocol. Examples include, but are not limited to, active interstitial lung disease 
(ILD)/pneumonitis or a history of ILD/pneumonitis requiring chronic treatment with 
systemic steroids, uncontrolled asthma, or colitis. 
6.1.6. 
Eligibility Criteria for TCR-T Cell Drug Product Infusion: 
Prior to administration of TCR-T cell drug product, subjects will have to meet the following 
criteria (within approximately 24 hours):  
1. CRP and ferritin results within normal institutional limits. Abnormal results to be 
discussed with medical monitor prior to TCR-T cell administration.  
2. Clinical Performance Status of ECOG 0 or 1.  
3. No active infection requiring systemic therapy or causing fever (temperature > 38.1˚C 
(100.6 ˚F)) or subjects with unexplained fever (temperature > 38.1˚C (100.6 ˚F)) within 7 
days prior to the day of investigational product administration. 
4. Neurotoxicity, if present, e.g., following fludarabine administration, must be resolved to 
grade ≤ 1. If >grade 1, approval from the Alaunos Medical Monitor is required. 
5. Serum creatinine within institutional limits; OR Calculated creatinine clearance (ClCr) 
(e.g., Cockcroft-Gault equation) ≥ 45.0 mL/min and not dialysis dependent.  
6. Adequate pulmonary function, defined as grade ≤ 2 dyspnea and SaO2 ≥ 90% on room 
air. 
7. ANC < 1,000/mm3 (< 1.0 × 109/L) within 72 hours prior to dosing of TCR-T cell 
administration. Subjects with ANC ≥1,000/mm3 (< 1.0 × 109/L) must be discussed with 
the medical monitor prior to TCR-T cell drug product administration.  
8.  Must not have received any live vaccines within 30 days prior to enrollment. 
6.2. 
Withdrawal of Subjects from Study Treatment and/or Study 
A subject 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 discontinuing from the study (e.g., due to disease 
progression, initiation of new-anticancer therapy, withdraw consent, etc.), if possible, an early 
discontinuation visit should be conducted and enrollment in the LTFU should occur if the subject 
received TCR-T cell drug product infusion. Refer to the Schedule of Assessments (Table 12 and 
Table 13) for assessments to be collected at the time of study discontinuation and follow-up and 
for any further evaluations that need to be completed. 
The early discontinuation visit applies only to participants who are enrolled and then are 
prematurely withdrawn from the study. Subjects should be questioned regarding their reason for 
withdrawal. These reasons must be documented in the subject’s medical record and on the eCRF. 

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If a subject withdraws from the study, he/she may request destruction of any remaining samples, 
but data already generated from the samples will continue to be available and may be used to 
protect the integrity of existing analyses. The investigator must document any such requests in 
the site study records. 
If the participant withdraws from the study and withdraws consent (Section 6.2.1 ) for disclosure 
of future information, no further evaluations should be performed, and no additional data should 
be collected. The sponsor may retain and continue to use any data or materials collected before 
such withdrawal of consent. 
When a participant withdraws from the study because of an SAE, the SAE must be recorded on 
the eCRF and reported on the Clinical Trial (CT) SAE Report. Every effort should be made to 
follow discontinued subjects for ongoing treatment-related AE/SAEs until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up. 
Lack of completion of all or any of the withdrawal/early termination procedures will not be 
viewed as protocol deviations so long as the participant’s safety was preserved. 
6.2.1. 
Withdrawal of Consent: 
Subjects who request to discontinue after receiving TCR-T cell drug product will be followed for 
progression and survival. In addition, every effort should be made to follow discontinued 
subjects for ongoing treatment-related AE/SAEs until the event is resolved, stabilized, otherwise 
explained, or the participant is lost to follow-up. The only exception to this is when a participant 
specifically withdraws consent for any further contact with him or her or persons previously 
authorized by the participant to provide this information. Subjects should notify the investigator 
in writing of the decision to withdraw consent from future follow-up, whenever possible. The 
withdrawal of consent should be explained in detail in the medical records by the investigator, as 
to whether the withdrawal is only from further receipt of investigational product or also from 
study procedures and/or post-treatment study follow-up and entered on the appropriate CRF 
page. Subject information garnered from public databases (e.g., SSDI death index) may be 
included in the database. 
6.2.1.1. 
Reasons for Removal prior to Treatment with TCR-T Cell Drug Product 
Reasons for removal from protocol required investigational products or procedures include any 
of the following: 
• Objective disease progression; 
• Global deterioration of health status requiring discontinuation; 
• Unacceptable toxicity; 
• Pregnancy; 
• Significant protocol violation; 
• Lost to follow-up; 
• Participant refused further treatment; 
• Study terminated by sponsor; 

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• Death. 
6.2.1.2. 
Withdrawal of Informed Consent for Data and Biological Samples 
Alaunos ensures that biological samples are returned to the source or destroyed at the end of a 
specified period as described in the informed consent.  If a subject withdraws consent to the use 
of donated biological samples, the samples will be disposed of/destroyed, and the action 
documented. If samples are already analyzed, Alaunos is not obliged to destroy the results of this 
research. As collection of the biological samples (except for the optional sample for genetics at 
screening) is an integral part of the study, then the subject is withdrawn from further study 
participation. 
The Principal Investigator: 
• 
Ensures subjects’ withdrawal of informed consent to the use of donated samples is 
notified immediately to Alaunos. 
• 
Ensures that biological samples from that subject, if stored at the study site, are 
immediately identified, disposed of/destroyed, and the action documented. 
• 
Ensures the organization(s) holding the samples is/are informed about the withdrawn 
consent immediately and that samples are disposed of/destroyed, the action documented 
and the signed document returned to the study site. 
• 
Ensures that the subject and Alaunos are informed about the sample disposal. 
Alaunos ensures the organization(s) holding the samples is/are informed about the 
withdrawn consent immediately and that samples are disposed of/destroyed and the action 
documented and returned to the study site. 
6.2.1.3. 
End of Study  
 
An individual subject will be considered to have completed the study if the subject was 
followed through their last protocol-specified visit/assessment (including telephone contact). 
Subjects will be considered not to have completed the study if consent was withdrawn or the 
subject was lost to follow-up. 
  
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last subject in the study. This date will 
be approximately 25 months after the last subject begins treatment or when the sponsor stops the 
study, whichever occurs earlier.  
6.2.1.4. 
Lost to Follow-up 
A subject will be considered lost to follow-up if s/he 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 subject fails to return to the clinic for a required study 
visit: 
• The study center must attempt to contact the participant and reschedule the missed 
visit within 1 business day following the missed scheduled visit and counsel the 
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whether the subject wishes to and/or should continue in the study. Study patient 
should be asked if they want to continue to complete study assessments per protocol 
follow-up visits via telephone (only if in-person assessments are not required at a 
visit), allow site to check subject’s medical records or permanently stop study 
participation, including site not allowed to check study patient’s medical records. 
• Before a subject is deemed lost to follow-up, the Investigator or designee must make 
every effort to regain contact with the subject (the site should attempt to get in contact 
with the subject by telephone three times and if the subject is still unresponsive send a 
certified letter to the subject’s last known mailing address, search of state death index 
or local equivalent methods). Site is expected to use a variety of contact attempts to 
follow-up with the subject. Each contact attempts should be documented in the 
subject’s medical record. Telephone calls to the study patient and/or caregivers 
should be completed at different times on different days of the week.  If site does not 
speak with a person during one of the telephone calls and only leaves a voice 
message, the telephone call will not be considered 1 of the 3 contact attempts 
(maximum of 5 total telephone calls).   
• Should the subject continue to be unreachable (after 5 telephone calls and no response 
to certified letter), s/he will be considered to have withdrawn from the study. 
6.3. 
Replacement of Subjects 
Subjects who receive lymphodepletion, but do not receive TCR-T cell drug product (e.g., 
manufacturing failure, change in clinical status) will be replaced. Subjects who receive TCR-T 
cell drug product and discontinue by Day 28 may be replaced. All subjects who receive TCR-T 
cell drug product will be included in the overall safety assessment. 
6.4. 
Premature Termination of Study or Study Site 
The sponsor has the right to close the study at any time, although this should occur only after 
mutual consultation between the sponsor and the investigators. The Institutional Review Board 
(IRB) or Independent Ethics Committee (IEC) must be informed of such action. Should the study 
or center be closed prematurely, all study materials (completed, partially completed, and blank 
electronic case report forms (eCRF), study medication, etc.) must be stored or disposed of 
according to the sponsor’s instructions. Events that may trigger premature termination of the 
study or closure of a center include but are not limited to the following: new toxicity findings; 
interim analysis results; noncompliance with the protocol; changes in the development plans for 
the study drug; slow recruitment; and poor-quality data. 

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7.3. 
Handling and Storage 
Study drugs must be stored in a restricted access area under the storage conditions indicated in 
the Investigator’s Brochure and/or Pharmacy Manual. All necessary precautions while handling 
potentially toxic compounds must be strictly followed.  
All cell manipulation procedures will be performed in a Good Manufacturing Practice (GMP) 
manufacturing site in accordance with current GMPs following process-specific procedures and 
batch records as described in the Pharmacy Manual. Cryopreserved TCR-T cell drug product will 
be shipped to and stored at the clinical site prior to administration. Details related to the storage 
and thawing of material prior to infusion can be found in the Pharmacy Manual. The final 
transposed cell product will be delivered to the Patient Care Unit and administered to the subject 
within the established stability window provided in the Pharmacy Manual.  
7.4. 
Accountability and Dispensation 
The investigator must maintain accurate records accounting for the receipt and dispensation of 
study drugs and investigational product. The investigational materials are to be prescribed only 
by the investigator or the sub-investigators named on FDA Form 1572 and may only be 
dispensed by authorized personnel at the institution(s) listed therein. Under no circumstances 
will the PI allow the investigational drug(s) to be used for purposes or in subjects other than as 
directed by the protocol.  
Any unused apheresis product, unused blood specimens, and unused manufactured cells will be 
banked at Alaunos and/or a GMP licensed facility (Alaunos designee) and may be used for future 
research studies. Peripheral blood samples will also be collected from subjects who consent to 
provide additional samples for undefined future research at time points shown in Treatment Plan. 

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7.5. Retreatment with TCR-T Cell Drug Product 
Eligibility for repeat treatments will be considered on a case-by-case basis and must be discussed 
with the Alaunos Medical Monitor. Patients obtaining any response except progressive disease 
are potentially eligible for a repeat treatment. Retreatment will be at least 2 months after the 
original treatment. The dose of TCR-T cells administered during repeat treatments will be at the 
dose level currently enrolling patients receiving initial TCR-T cell drug product infusions. The 
repeat treatments will include the same apheresis collection, lymphodepleting chemotherapy and 
manufacturing process as the initial treatment. If patients were initially matched to multiple 
TCRs a discussion between the investigator and Sponsor should occur to determine which TCR 
will be utilized for re-treatment. 
Patients must not have experienced a DLT with their first treatment and must meet the same 
eligibility requirements listed in Section 6.1. The patients must undergo screening evaluation as 
listed in Table 12 except infectious disease serology, and brain MRI are not required to be 
repeated unless clinically indicated. Follow-up testing for retreatment will be the same as for the 
first treatment. In the case where the planned infusion is with the same library TCR as the first 
infusion, patients must have molecular testing to confirm matching epitope (i.e., genomic testing 
and HLA typing of tumor tissue collected after initial TCR-T treatment). 
The patient may be re-enrolled on this treatment study as a new patient to allow this re-treatment, 
and these patients will be considered in the total sample size for this study. A maximum of 2 
total treatments can be administered to any one patient, and at least 2 months must elapse 
between the first treatment and the second treatment. 
DLTs that occur in the cohort of patients receiving a repeat treatment will not affect the dose 
escalation of patients receiving an initial treatment. However, excessive DLTs among 
retreatment subjects will result in a discontinuation of this practice. Specifically, if 2 of the first 3 
patients re-treated, 3 or more of the first 6 re-treated patients, 4 or more of the first 9 retreated 
patients, or greater than 1/3 of the total patients receiving a repeat treatment experience a DLT 
during repeat treatment, then repeat treatments will be discontinued altogether. 

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After leukapheresis, treatment may include one or more of the following:  
• Radiation therapy for local or bulky disease  
• Appropriately tapered corticosteroids (Note: a 7-day washout period of 
supraphysiologic doses prior to switch dose administration)  
• Non-chemotherapy (targeted) agents  
• Chemotherapy 
8.2. 
Lymphodepleting Chemotherapy 
After eligibility criteria for lymphodepletion has been confirmed, lymphodepleting 
chemotherapy treatment with cyclophosphamide, mesna and fludarabine will be administered 
according to the schedule and dose described in Table 8.  
Additional information can be found in the respective approved labels. Chemotherapy infusions 
may be slowed or delayed as medically indicated per standard of care requirements. 
Administration of diuretics, electrolyte replacement, and hydration and monitoring of 
electrolytes should all be performed as clinically indicated. 
At the discretion of the investigator, heavily pre-treated or radiated patients who do not have as 
much bone marrow reserve may be treated with a lower dose lymphodepleting regimen per Table 
8 . In the event the patient had previous intolerance to cyclophosphamide or at the discretion of 
the investigator, bendamustine 90 mg/m2/day for 2 days or bendamustine 70 mg/m2/day + 
fludarabine 30 mg/m2/day for 3 days may be substituted with approval from the Alaunos Medical 
Monitor. 
During the course of the study alternative lymphodepletion regimens may be explored after 
discussion with the investigators and Sponsor, for example cyclophosphamide 1000mg/m2 
(Days -5 to -3) fludarabine 30mg/m2 over 4 days (Day -6 to Day -3). 
Alternatively, patients may be given a lymphodepleting regimen of cyclophosphamide 
500 mg/m2 and fludarabine 30 mg/m2 on 3 consecutive days, respectively, on an out-patient 
basis. Also, after discussion between the investigator and the Sponsor, fludarabine and 
cyclophosphamide may be given on the same day concurrently.   
Expected toxicities of the suggested lymphodepletion regimen include: 
• Cytopenias 
• Anemia 
• Infections 
• Cardiac arrhythmias 
• Infusion related reactions (fludarabine) 
• Neurotoxicity (fludarabine) 
• Hemorrhagic cystitis (cyclophosphamide) 

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As noted previously, subjects who have sufficient lymphodepletion from bridging therapy may 
not need additional lymphodepletion prior to infusion of TCR-T therapy. Other methods of 
lymphodepletion must be discussed with Sponsor, Alaunos Medical Monitor or designee before 
other methods of lymphodepletion are used by site. 
8.2.1. 
Cyclophosphamide 
Cyclophosphamide is a nitrogen mustard-derivative, polyfunctional alkylating agent used to 
induce lymphopenia prior to TCR-T cell infusion. Institutional guidelines for handling, 
reconstitution and administration should be followed. Additional information regarding 
formulation, storage, stability, and administration of cyclophosphamide can be found in the 
respective approved label. Cyclophosphamide can cause temporary hair loss, nausea, vomiting, 
diarrhea, and lowering of the blood cell counts. Antiemetics should be used to minimize nausea 
and vomiting. At the dose of cyclophosphamide used in this study, these symptoms are expected 
to be minor. 
8.2.2. 
Fludarabine 
Fludarabine is an antimetabolite used to induce lymphopenia prior to TCR-T cell infusion. 
Institutional guidelines for handling, reconstitution and administration should be followed. 
Additional information regarding formulation, storage, stability, and administration of 
fludarabine can be found in the approved label. Fludarabine can cause lowering of blood counts, 
suppression of the immune system, nausea and vomiting, fever, hypersensitivity reaction, tumor 
lysis, transient elevation in serum transaminases, hemolysis, and neurotoxicity at doses higher 
than administered in this study. 
8.2.3. 
Bendamustine 
Bendamustine is an alkylating agent used to induce lymphopenia prior to TCR-T cell infusion. 
The chemical name of bendamustine hydrochloride is 1H-benzimidazole-2-butanoic acid, 
5-[bis(2-chloroethyl)amino]-1 methyl-, monohydrochloride. Its empirical molecular formula is 
C16H21Cl2N3O2 · HCl. Additional information regarding formulation, storage, stability, and 
administration of bendamustine can be found in the respective approved label. 
8.2.4. 
Mesna 
Mesna is a detoxifying agent used to inhibit the hemorrhagic cystitis induced by chemotherapy. 
The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-
mercaptoethane sulfonate with a molecular formula of C2H5NaO3S2. Mesna should be 
administered per institutional guidelines. Additional information regarding formulation, storage, 
stability, and administration of mesna can be found in the approved label. 
8.2.5. 
Tocilizumab 
Tocilizumab is an interleukin-6 (IL-6) receptor antagonist indicated for the treatment of cytokine 
release syndrome. Institutional guidelines for handling, reconstitution, and administration should 
be followed. Additional information regarding formulation, storage, stability, and administration 
of tocilizumab can be found in the respective approved label. Tocilizumab can cause serious 
infections, gastrointestinal perforations, lab parameters (neutropenia, thrombocytopenia, elevated 

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8.5.3. 
TCR-T Cell Infusion (Day 0) 
As shown in the Schedule of Assessments (Table 12), the TCR-T cell drug product will be 
infused on Day 0. Refer to Pharmacy Manual for additional details regarding thawing of drug 
product, drug product handling, and administration guidelines.  
Prior to thawing the drug product and before infusion, the TCR-T cell drug product identity label 
must be double-checked by two authorized staff (MD or RN), and an identification of the 
product and documentation of administration are entered in the subject’s chart. The TCR-T cell 
drug product will be infused in the Patient Care Unit at the assigned dose level defined in Table 
7. Infusion durations may be up to 180 minutes or as clinically determined by an investigator for 
subject safety; bags will be gently agitated during infusion to prevent clumping. Dose splitting 
may be considered in certain situations (e.g. subject experiences CRS or IRR) following 
consultation with the Alaunos Medical Monitor. 
Mild infusion reactions should be managed expectantly with antipyretics, antihistamines, and 
antiemetics per institutional standard of care.  
The following procedures must be followed for infusion of TCR-T cell drug product: 
1. Vital signs, oxygen saturation by pulse oximeter, laboratory examinations and urinalysis 
will be obtained pre-infusion on the day of infusion.  
2. TCR-T cell drug product will be infused via central venous catheter or via a peripherally 
inserted IV.  
3. Vital signs (temperature, heart rate, blood pressure, and respiratory rate) and oxygen 
saturation will be obtained on all subjects as follows: 
• Start of infusion; 
• Every 15 mins (± 5 mins) during the first hour of infusion;  
• Then, every 30 mins (± 5 mins) until 1 hour after completion of infusion; 
• Then, every hour (± 10 mins) as indicated by subject’s condition. 
Should a subject fail to meet TCR-T cell drug product eligibility criteria as specified in 
Section 6.1.6, the TCR-T cell drug product infusion must be delayed until the subject meets the 
eligibility criteria. If the TCR-T cell drug product infusion is delayed > 2 weeks, 
lymphodepletion must be repeated, unless otherwise agreed between the Investigator and 
Alaunos’s Medical Monitor or designee.  In all cases of TCR-T cell drug product infusion 
delays, Alaunos’s Medical Monitor or designee should be contacted for guidance.  
CRP and ferritin levels in combination with EASIX score measured on the day of TCR-T cell 
drug product infusion or shortly thereafter may be associated with increased risk of severe CRS 
and ICANS (Greenbaum et al., 2021).  
In addition to the above criteria, if the subject’s temperature is ≥ 38.0°C within 48 hours prior to 
TCR-T cell drug product infusion, or clinically meaningful increased CRP or ferritin levels the 
Alaunos’s Medical Monitor or designee must provide approval before proceeding with the TCR-
T cell drug product infusion. 

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8.5.4. 
Days 0-4 (Day 0 = Day of TCR-T Cell Drug Product Infusion)  
8.6. 
Study Stopping and Pausing Rules  
The study will be paused and further investigation initiated if: 
• Occurrence of Grade 4 DLTs in 2 subjects at any time during the conduct of the study 
trial; 
• One treatment related death occurs after the administration of TCR-T cell drug 
product; 
• Death not related to disease progression; 
• Development of a secondary malignancy, Epstein-Barr virus (EBV) lymphoma or 
polyclonal lymphoproliferative disease (PLPD) in an EBV negative subject. Note: 
accrual of EBV positive subjects will be halted if this is observed. 
If any of the above events occur, enrollment of new subjects will be paused, pending review by 
the SRC. The SRC will recommend if changes to the enrollment of additional subjects are 
required, including but not limited to amending the protocol prior to enrollment of additional 
subjects, or discontinuing enrollment in the study.  
In the event that any stopping rule is met, the FDA and Institutional Review Board will be 
informed in a timely manner. Alaunos will discuss the investigation and the data with the FDA to 
identify next steps, which may include stopping the study.  

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9. 
SAFETY MONITORING AND TOXICITY MANAGEMENT 
9.1. 
Known Adverse Events Related to the Lymphodepleting 
Chemotherapy 
Known adverse events related to Cyclophosphamide, Fludarabine and Bendamustine can be 
found in the study approved labels, Pharmacy Manual and Investigator’s Brochure. 
9.2. 
Known Adverse Events Related to Tocilizumab 
Known adverse events related to tocilizumab can be found in the approved label and 
Investigator’s Brochure. 
9.3. 
Known Adverse Events Related to Aldesleukin 
Known adverse events related to aldesleukin (IL-2) and guidance on their management are listed 
in the approved labels and Appendix F.   
9.4. 
Known Adverse Events Related to the T-Cell Therapy 
The investigational product, TCR-T cell drug product engineered using the Sleeping Beauty 
system, has not been previously used in humans, thus there are no known risks associated with 
this therapy. The risks with T-cell therapies in general include but are not limited to the 
following as described below. For subjects with suspected autoimmune toxicities, institutional 
guidelines for evaluation and management of suspected immune-mediated toxicities should be 
utilized. Institutional guidelines are not intended to replace the medical judgement of the treating 
physicians and should supplement other guidance provided in this protocol and Investigator 
Brochure. 
9.4.1. 
Insertional Mutagenesis 
There is a potential long-term toxicity that is a general concern of genetically manipulating T 
cells and potential for genotoxicity using integrating vectors. This relates to the risk of 
insertional mutagenesis. To date, there has been no genotoxicity detected in T cells genetically 
modified by Sleeping Beauty non-viral gene transfer (Micklethwaite et al., 2021). This will be 
monitored in this protocol as described in Section 14.4 (Assessment of Insertional Mutagenesis 
in the Event of Emergent Malignancies) and continue to be monitored on the LTFU protocol 
(TCR001-202).  
9.4.2. 
Cytokine Release Syndrome (CRS) 
For the purpose of this study, the ASTCT Consensus guidelines should be used for grading of 
cytokine release syndrome (Lee et al., 2019). Refer to Appendix B for CRS grading. T-cell 
infusion may produce cytokine release (pro-inflammatory as well as anti-inflammatories) into 
the blood stream causing a systemic inflammatory reaction most commonly manifested by fever, 
nausea, vomiting, chills, hypotension, tachycardia, asthenia, headache, pruritus, rash, cough, 
scratchy throat, dyspnea, fluid overload, acute elevation of liver enzymes among other systemic 
symptoms.  

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9.4.3. 
Neurotoxicity 
Immune effector cell (IEC) therapy may result in neurotoxicity, termed IEC-associated 
neurotoxicity syndrome (ICANS).  ICANS may include symptoms such as confusion, aphasia, 
seizure, and/or cerebral edema. The ASTCT Consensus guidelines should be used for the grading 
and management of immune effector cell- associated neurotoxicity syndrome (Lee et al., 2019). 
Refer to Appendix C for Immune Effector Cell-associated Encephalopathy (ICE) scoring and 
Appendix E for grading of ICANS. A neurology consult is recommended for subjects who 
develop Grade 1 or higher ICANS. 
9.4.4. 
Tumor Lysis Syndrome (TLS) 
Rapid destruction of malignant cells may result in TLS, manifesting as laboratory abnormalities, 
and in untreated cases renal failure. Subjects will be monitored and treated as per standard 
guidelines including close monitoring of blood chemistries, IV hydration, allopurinol and/or 
rasburicase in clinically relevant cases. 
9.4.5. 
Hemophagocytic Lymphohistiocytosis (HLH)/ Macrophage Activation 
Syndrome (MAS) 
Clinical and laboratory features of MAS include fever, increased ferritin levels, pancytopenia, 
hemophagocytosis in bone marrow or lymph nodes, fibrinolytic coagulopathy, and liver 
dysfunction. Specific treatment includes administration of tocilizumab and corticosteroids given 
intravenously. Canakinumab may also be used for additional information. Refer to Appendix D. 
9.4.6. 
Graft-versus-Host Disease (GVHD) 
The risk of GVHD is expected to be low for an autologous product but is at present 
undetermined. 
9.4.7. 
Localized Site Reactions 
Injection of agents into tissues carries a potential risk of local reactions that may be characterized 
as intense immunologic reaction at or near the injection site. By definition, injection site 
reactions (ISRs) include signs and symptoms of erythema, pruritus, pain, inflammation, rash, 
induration, and edema at the site where TCR-T cell drug product or aldesleukin are administered. 
They may occur immediately or within 24-48 hours post injection. Post-infusion reactions will 
be treated per institutional standard of care. ISRs will not be considered a DLT, but they may be 
reason for discontinuation from treatment. 
9.5. 
Safety Monitoring and Adverse Effect Management 
Parameters used in the safety analysis of all populations will include all laboratory tests, physical 
examinations, imaging scans, and spontaneous reports of AEs reported by subjects. Each subject 
will be assessed according to the scheduled study procedures (Table 12 and Table 13) and any 
unscheduled visits as a result of AEs. Other adverse events will be assessed according to the NCI 
Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 criteria.  

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9.5.1. 
Severity Grading  
As with all signs and symptoms, events should be recorded and graded as AEs according to the 
NCI CTCAE Version 5.0 criteria. Study stopping rules will not apply to a specific event if it is 
clearly unrelated to the study treatment. 

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10. 
CONCOMITANT THERAPY 
Information on concomitant medications including blood products, vitamins, supplements, and 
cancer treatments (chemo- and immunotherapies, radiation therapy, surgeries, and any associated 
toxicities) received will be collected through informed consent through the subject’s last study 
visit. 
10.1. 
Permitted Medications 
10.1.1. 
Infection Prophylaxis 
As subjects are receiving lymphodepleting chemotherapy, subjects should receive preventive and 
anti-infection medications for fungal infections, pneumocystis pneumonia, herpes virus, and 
varicella-zoster virus according to institutional guidelines. In the absence of institutional 
guidelines, refer to the Infection Prophylaxis Considerations for IEC Therapies (Center, 2020) 
for recommendations on the following medications: 
• Filgrastim (Granulocyte Colony-Stimulating Factor, G-CSF, Filgrastim, Neupogen): 
Filgrastim is recommended to be administered subcutaneously at a dose of 300ug/day 
per institutional practice to reduce the duration of neutropenia and incidence of 
infection. Beginning 1 day after TCR-T cell drug product infusion filgrastim should 
be administered subcutaneously at a dose of 300 µg/day). Filgrastim should be 
continued daily until ANC >1,000/mm3 x 3 days or ANC >5,000/mm3. Dose and 
route of administration may be altered as clinically indicated. 
• Pentamidine and sulfamethoxazole/trimethoprim (SMZ/TMP): Pentamidine 
inhaled or IV within one week prior to TCR-T cell drug product infusion and then 
transition to sulfamethoxazole/trimethoprim (SMZ/TMP) (preferred post-infusion) by 
3-4 weeks if counts have recovered is recommended per institutional standard of care 
to prevent Pneumocystis Jirovecii Pneumonia. SMZ/TMP should continue for at least 
one year post TCR-T cell infusion and until CD4 > 200 cells/μL for two consecutive 
measurements Dapsone (in G6PD deficient patients), or atovaquone may be 
substituted for SMZ/TMP. 
• Valacyclovir: Subjects with positive HSV or VZV serology should be given 
valacyclovir orally per institutional standard of care starting on the day of TCR-T cell 
drug product infusion. Prophylaxis for pneumocystis, HSV, and VZV will continue 
for 1-year post-TCR-T cell drug product infusion and may stop after 1 year if the 
CD4 count is > 200 cells/ μL for two consecutive measures. Acyclovir may be 
substituted for Valacyclovir to prevent the occurrence of herpes virus infections in 
patients who cannot take oral medications. 
• Entecavir: Subjects who are positive for HbsAg or HbcAb should receive entecavir 
per institutional standard. Entecavir should begin 2 weeks before TCR-T cell drug 
product infusion and stop 12-24 months post-infusion. Tenofovir alafenamide or 
Tenofovir disopoxil fumarate may be substituted. Infectious Disease and/or 
Hepatology should be consulted if not already following. Subjects should be 
monitored for HBV DNA PCR once a month while on prophylaxis and for a year 
after stopping.  

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• Anti-fungal 
o Fluconazole: It is recommended that low-risk patients receive fluconazole for 
fungal prophylaxis in accordance with institutional guidelines beginning on the 
day of TCR-T cell drug product infusion and until infection is controlled and 
ANC > 0.5 K/μL for 3 consecutive days without growth factor support. The drug 
may be given via IV in patients unable to take it orally. 
o Posaconazole: It is recommended that high-risk patients with leukemia, recent 
allogenic transplant, prior history of mold infection, neutropenia lasting ≥ 14 
days, Grade 3 or 4 CRS/ICANS, those who receive ≥ 3 days of corticosteroids, or 
those who develop hemophagocytic lymphohistiocytosis (HLH). If corticosteroids 
are given, continue Posaconazole for at least 1 month after completion of 
corticosteroids. Posaconazole should begin on the day of TCR-T cell drug product 
infusion and continue until clinically indicated. Do not stop posaconazole 
prophylaxis if ANC < 1K/μL. Voriconazole or isavuconazole may be used if the 
patient had previously been taking them or if Posaconazole is not covered by 
insurance. In the event Posaconazole, voriconazaole, isavuconazole, or 
echinocandin are contraindicated or pose affordability/access issues, then use 
fluconazole for prophylaxis and consider aspergillus antigen testing at least once a 
week during corticosteroids and for at least a month after completion of 
corticosteroids. Patients not meeting high risk definitions will be considered to be 
at low risk for fungal infections and should receive prophylaxis as detailed above.  
NOTE: Other anti-infective agents may be substituted at the discretion of the treating physician. 
• COVID Prophylaxis 
o See Table 9 for recommended management of COVID-19.  

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Table 9: 
Management of COVID-19 
 
 
Patient Status 
Recommendations 
Does not require 
hospitalization or 
supplemental oxygen 
For All Patients:  
• 
Offer symptomatic management. 
• 
Recommend against the use of dexamethasone or other systemic 
corticosteroids in the absence of another indication. 
For All Patients:  
• 
Preferred therapies, which are listed in order of preference: 
• 
Ritonavir-boosted nirmatrelvir (Paxlovid) 
• 
Remdesivir 
• 
Alternative therapies for use ONLY when neither of the preferred 
therapies are available, feasible to use, or clinically appropriate. 
Alternative therapies are listed in alphabetical order: 
• 
Bebtelovimab 
• 
Molnupiravir 
Discharged from 
hospital inpatient 
setting, in stable 
condition, and does not 
require supplemental 
oxygen 
Discontinue the use of remdesivir, dexamethasone, or baricitinib after 
hospital discharge. 
Discharged from 
hospital inpatient 
setting and requires 
supplemental oxygen 
(for those who are 
stable enough for 
discharge but still 
require oxygen) 
There is insufficient evidence to recommend either for or against the 
continued use of remdesivir or dexamethasone. 
Discharged from 
emergency department 
despite new or 
increasing need for 
supplemental oxygen 
(when hospital 
resources are limited, 
inpatient admission is 
not possible, and close 
follow-up is ensured) 
Initiate dexamethasone 6 mg PO orally administered once daily for the 
duration of supplemental oxygen (dexamethasone use should not 
exceed 10 days) with careful monitoring for adverse events. 
Because remdesivir is recommended for patients with similar oxygen 
needs who are hospitalized, clinicians may consider using it in this 
setting. As remdesivir requires intravenous infusions for up to 
5 consecutive days, there may be logistical constraints to administering 
remdesivir in the outpatient setting. 

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10.1.2. 
Empiric Antibiotics 
Subjects should be started on broad-spectrum antibiotics on the day of TCR-T cell drug product 
infusion in accordance with current institutional guidelines or at a minimum, a fever of 38.3°C 
(100.9°F) once or two temperatures ≥ 38.0°C (100.4°F) at least one hour apart, and an ANC 
<500/mm3. Treatment with antibiotics should continue until ANC>500/mm3 for 3 consecutive 
days without growth factor support. Infectious disease consultation should be obtained for all 
subjects with unexplained fever or any infectious complications and if the patient is allergic to 
quinolones and cephalosporins. Antibiotic coverage for central venous catheters may be provided 
at the discretion of the investigator. 
10.1.3. 
Blood Product Support 
Using daily CBCs as a guide, the subject will receive platelets and packed red blood cells as 
needed. All blood products will be irradiated and transfused per institutional guidelines and/or 
standard of care.  
10.1.4. 
Medication for Infusion-related Reactions (IRRs) 
IRRs may occur with either TCR-T cell drug product 
. It may be difficult to 
distinguish this from mild CRS. IRR is typically characterized by fever, chills (rigor), and less 
commonly, hypotension. The Investigator should follow institutional practices for primary 
prophylaxis. 
It is recommended that patients be pre-treated with acetaminophen (650 to 1000 mg) and 
diphenhydramine 12.5 mg (IV) or 25 to 50 mg (oral) or equivalent approximately 30 minutes 
prior to TCR-T cell drug product administration. Two additional doses of acetaminophen may be 
given every 4 to 6 hours as needed.  However, the Investigator should follow institutional 
practices if the local standard of care is different. All pretreatment and other medications given 
must be recorded in the subject’s eCRF. 
IRR will not be considered a DLT, but it may be reason for discontinuation from treatment. 
Suggested management of severe IRR symptoms is as follows: 
• Allergic reaction/anaphylaxis: Stop product infusion and administer corticosteroids 
(as per institutional standard), antihistamines, famotidine, and aggressive life 
support, as needed. If corticosteroids are to be utilized, Sponsor must be notified 
within 24-48hrs. 
• Bradycardia: Monitor closely, slow or stop product infusion, and continue hydration. 
• Bronchospasm: Stop product infusion and administer oxygen and a bronchodilator. If 
severe, add corticosteroids, antihistamines, and famotidine. 
• Chest tightness: Administer oxygen and slow or stop product infusion. 
• Chills: Stop product infusion. If severe, administer meperidine ± hydrocortisone 
(after discussion with medical monitor). Consider blood cultures and product 
cultures. 

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• Dyspnea: Administer oxygen, slow or stop product infusion, review fluid balance, 
and consider diuretic. 
• Erythema, rash: If hives, treat as an allergic reaction. Monitor and slow product 
infusion if needed. 
• Fever: Consider blood cultures and product cultures. Administer acetaminophen and 
slow product infusion. 
• Flushing: Slow product infusion and monitor; if worsens, treat as an allergic reaction. 
• Headache: Slow product infusion and administer analgesia and oxygen. 
• Hematuria (can occur after the infusion): Continue post-infusion hydration and 
monitor urine output. 
• Hypertension: Slow or stop product infusion. Administer antihypertensive 
(hydralazine) ± diuretics. 
• Hypotension: Consider medications to support blood pressure. Slow or stop product 
infusion and administer fluid bolus. 
• Nausea/vomiting: Administer antiemetics (eg, lorazepam). 
• Seizures: Stop product infusion and administer anticonvulsants and normal saline. 
10.1.5. 
Medication for Injection Site Reactions (ISRs) 
By definition, ISR includes signs and symptoms of erythema, pruritus, pain, inflammation, rash, 
induration, and 
 (Refer to Appendix F). It may occur 
immediately or within 24 to 48 hours post injection. 
Institutional practices should be followed for management of ISRs. ISRs will not be considered a 
DLT, but it may be a reason for discontinuation from treatment. 
10.1.6. 
Medication for Hypersensitivity Type 1 and Type 3 
Type 1 hypersensitivity or allergic reactions are theoretically possible in response to an injected 
protein and may be manifested by shortness of breath, rash, anaphylaxis, or angioedema. 
Immune complex-mediated Type 3 hypersensitivity reactions are similar to Type 1 
hypersensitivity reactions but are likely to be delayed and may include, in addition to the 
aforementioned symptoms, polyarthritis, myalgia, fever, or glomerulonephritis. 
The patient should be treated symptomatically with supportive care, antihistamines, and 
continued monitoring. Use of corticosteroids should be discussed with the Sponsor given their 
potential interference with TCR-T cell drug product. Symptomatic treatment should be 
documented in the eCRF. 
10.1.7. 
Medication for Cytokine Release Syndrome (CRS) 
CRS is commonly observed following immune-based biotherapeutics such as CAR-T cells and 
CD3-engaging bispecific antibodies. Subjects can present with fever, rigor, malaise, headache, 
nausea/vomiting, or more severe, life-threatening symptoms of hypoxia, pulmonary edema, 

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tachycardia, hypotension, aphasia, confusion, or seizures.  Early recognition of CRS is important 
(e.g., monitoring of symptoms, cytokines, CRP, and ferritin); however, diagnosis is difficult due 
to the non-specific symptoms that are observed. Recommendations for treatment and the grading 
system (Appendix B) is based on (Lee et al., 2019) and is shown in Appendix J. 
Premedication (tocilizumab) for CRS prophylaxis in all patients will be administered on Day-5 
as part of the subject’s pre-conditioning regimen (Section 8.2.5).  
10.1.8. 
Fever (≥ 38.3°C; ≥ 101°F) Antipyretic Therapy 
If grade 1 fever dose not respond to antipyretics/analgesics as needed after 24 hours initiate 
Actemra® (tocilizumab) therapy 8 mg/kg to be repeated every 4 to 6 hours as needed if no 
improvement in fever after 3 days. Dexamethasone 10 mg therapy may be administered 
concurrently. 
Total acetaminophen (APAP) utilization is not to exceed 2 g/day. 
10.1.9. 
Medication for Immune Effector Cell-associated Neurologic Syndrome (ICANS) 
ICANS occurs frequently with CAR T cell therapy and like CRS, is associated with rapid CAR T 
expansion and high tumor burden as well as other factors. Severe ICANS is associated with 
increased CSF protein levels, encephalopathy, and other signs of neurotoxicity.  Aggressive 
treatment is suggested and includes administering corticosteroids.  Actemra® (tocilizumab) may 
be administered if neurotoxicity is accompanied by CRS (Appendix J). 
10.1.10. 
Medication for Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage 
Activation Syndrome (MAS) 
Clinical and laboratory features of MAS include fever, increased ferritin levels, pancytopenia, 
hemophagocytosis in bone marrow or lymph nodes, fibrinolytic coagulopathy and liver 
dysfunction. Specific treatment includes administration of Actemra® (tocilizumab) and 
corticosteroids given intravenously. Canakinumab may also be used. Refer to (Center, 2020) for 
medication for Tumor Lysis Syndrome (TLS). 
TLS occurs when tumor cells release their content in the blood stream, either spontaneously or 
due to treatment, leading to metabolic disturbances including hyperuricemia, hyperkalemia, 
hypophosphatemia, and hypocalcemia.  The incidence and severity of TLS depends on tumor 
volume, potential for the tumor to lyse and patient characteristics. Management of cardiac and 
neuromuscular abnormalities and preservation of kidney function are most important. 
Allopurinol can be used to reduce hyperuricemia and rasburicase can be used to preserve or 
improve renal function. 
Because hyperkalemia can cause sudden death due to cardiac arrhythmias, patients should limit 
potassium and phosphorus intake during the TLS risk period (0 to 3 months). 
Frequent measurements of serum electrolytes, continuous cardiac monitoring and the 
administration of oral sodium polystyrene are recommended. Symptomatic hypocalcemia should 
be treated with calcium supplementation; non-symptomatic hypocalcemia does not require 
treatment. 

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10.1.11. 
Medication for B cell depletion and Hypogammaglobulinemia 
It is possible that B cell depletion and/or hypogammaglobulinemia will occur due to the effects 
of TCR-T cell drug product on normal B cells. Gammaglobulins may be administered for 
hypogammaglobulinemia according to institutional guidelines. At a minimum, trough IgG levels 
should be kept above 400 mg/dL, especially in the setting of infection (Center for International 
Bone Marrow Transplant Research, American Society for Bone and Morrow Transplantation). 
10.1.12. 
Anti-Nausea and Anti-Diarrheal Medication 
The choice of the prophylactic drug is up to the Investigator (with Sponsor approval) as well as 
the duration of treatment.  
10.1.13. 
Pain Medication 
Anti-inflammatory and opioid drugs are permitted as needed during the study as long as there is 
no known or expected drug-drug interaction. 
10.1.14. 
Hematopoietic Growth Factors 
The use of growth factors such as granulocyte colony-stimulating factor (G-CSF) is permitted in 
this study. Primary prophylactic use of growth factors may be permitted during the first 28 days 
or may be used during this time to treat treatment emergent neutropenia. The use of G-CSF is as 
indicated by the current ASCO guidelines and National Comprehensive Cancer Network 
(NCCN) guidelines. 
Use of granulocyte/macrophage stimulating growth factor (GM-CSF) is not recommended. High 
dose pulsed therapy with corticosteroid is also not permitted. In general, use of systemic 
corticosteroids should occur after discussion with the Sponsor. 
Erythropoietin may be used at the Investigator’s discretion for the supportive treatment of 
anemia. 
10.1.15. 
Transfusion Support 
Primary transfusion support for anemia may be permitted during screening and for treatment 
emergent anemia as indicated by the current ASCO and AABB guidelines (Kaufman et al., 
2015). 
Transfusion support is permitted if completed 24 hours before TCR-T cell drug product dosing. 
Primary prophylactic use of transfusion support for thrombocytopenia may be permitted in the 
screening period if it is completed 24 hours before TCR-T cell drug product dosing. Treatment 
emergent thrombocytopenia can be treated as indicated in the ASCO guidelines (Bohlius et al., 
2019). 
Attempts should be made to keep hemoglobin >8.0 g/dL and platelets > 20,000/mm3. Leukocyte 
filters should be utilized for all blood and platelet transfusions to decrease sensitization to 
transfused white blood cell (WBC)’s and decrease the risk of cytomegalovirus (CMV) infection. 

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10.1.16. 
Surgery 
Caution is advised on theoretical grounds for any surgical procedures during the study. The 
appropriate interval of time between surgery and the dose of TCR-T cell drug product required to 
minimize the risk of impaired wound healing and bleeding has not been determined. 
10.1.17. 
Anti-coagulation Therapy 
Subjects that are receiving maintenance anti-coagulation therapy should be transitioned to a low 
molecular weight heparin (LMWHs) therapy (e.g., dalteparin, enoxaparin, etc.) prior to 
lymphodepletion, and they should remain on the LMWH through 30 days post-TCR-T infusion, 
at which time they can be transitioned back to their prior anti-coagulation therapy if clinically 
indicated. 
10.1.18. 
Other Concomitant Medications to Control Side Effects 
Concomitant medications to control side effects of therapy may be given per institutional 
standard of care.  
10.2. 
Prohibited Medications/Therapies 
Except for adrenal replacement doses, chronic systemic corticosteroid use is not permitted. 
Symptomatic tapering treatment and acute emergency administration, topical, inhaled, eye drops, 
or local injection of corticosteroids are permitted. 
Corticosteroid therapy at a pharmacologic dose (> 5 mg/day of prednisone or equivalent doses of 
other corticosteroids) and other immunosuppressive drugs must be avoided for 7 days prior to 
lymphodepletion. 
Supratherapeutic systemic corticosteroids are discouraged 7 days prior to TCR-T cell drug 
product dose. 
Immunosuppressive drugs should also be avoided for 3 months after TCR-T cell drug product 
administration, unless used to manage TCR-T cell product related toxicities. 
The use of GM-CSF is prohibited at least 7 days prior to TCR-T cell drug product 
administration. 
Treatment such as chemotherapy, immunotherapy, targeted agents, radiation, and high dose 
corticosteroid, other than defined/allowed in this protocol, and other investigational agents are 
prohibited, except as needed for treatment of disease progression after the TCR-T cell drug 
product infusion. 
In addition, live vaccine administration is prohibited during the study, including the treatment 
period, until recovery of B lymphocytes to normal ranges following the TCR-T cell drug product 
administration. 
If permissibility of a specific medication/treatment is in question, the Medical Monitor or 
designee should be contacted before the medication/treatment is administered. 
 

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11. 
STUDY PROCEDURES 
11.1. 
Written Informed Consent 
The provided written Informed Consent Form (ICF) must be discussed with and signed by the 
subject before any protocol specific procedures and assessments can be performed. Adequate 
time for review, discussion of and answering subject’s questions should be made available to the 
subject to allow them to make an informed decision whether they want to voluntarily participate 
in this clinical trial. The ICF should be discussed in a quiet setting free from distractions.  A copy 
of the signed ICF will be given to the subject and a copy should be filed in the medical record. 
The original ICF should be kept on file with the study reports. Refer to Section 16.10 for further 
information. Patients will first sign the pre-screening consent form to determine if they have at 
least on TCR matching a combination of their somatic mutation and HLA type available in the 
Alaunos Clinical TCR Library. If the patient has at least one TCR match, they will sign the main 
consent form before completing screening assessments/procedures. 
11.2. 
Subject Registration 
Centralized registration of subjects will be completed according to a process defined by the 
sponsor. Eligible subjects will be assigned a unique study identification number. Once assigned, 
a subject’s identification number will not be reused. 
11.3. 
Schedule of Assessments and Observations 
Screening assessments must be performed within the time frames outlined in Table 12. All study 
visits must be completed as described in the protocol. Follow-up assessment visit windows are 
shown in Table 13. Translational research samples should be collected at the visits outlined in 
Table 14. 
11.3.1. 
Study Tests, Exams, and Procedures 
11.3.1.1. Demographics, Medical and Cancer History  
Each subject’s complete medical history will be documented during screening, including 
demographic information, relevant medical history, current primary cancer diagnosis, and 
immunotherapy related biomarker diagnostics (e.g., MSI, MMR, PD-1/PD-L1), if available, 
prior cancer treatments (chemo- and immunotherapies, radiation therapy, surgeries, and any 
associated toxicities) including regimen, doses, start and stop dates, any associated residual 
toxicity, and best response for each regimen.  
11.3.1.2. Eastern Cooperative Oncology Group (ECOG) Performance Status 
The ECOG Performance Status measures the ability of cancer subjects to perform ordinary tasks. 
Scores range from 0 to 5 with a lower score meaning that the subject is better able to carry out 
daily activities. ECOG Performance Status is used to determine a subject’s prognosis, to measure 
changes in a subject’s ability to function, or to decide if a subject could be included in a clinical 
trial. For this trial, subjects must have an ECOG Performance Status score of 0 or 1 at the 
Screening Visit, apheresis eligibility check, lymphodepletion eligibility check, and TCR-T 
product infusion eligibility check to be included in the study.  

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11.3.1.3. Vital Signs 
Temperature (oral, tympanic, temporal, or axillary), pulse rate, and blood pressure (BP) will be 
assessed and recorded either in a supine or seated position. Vital signs should be taken in the 
same position, if possible, throughout the study. Site is requested to make a notation of the 
subject’s position at time of vital signs collected in site’s electronic medical record. 
For BP assessment, the same arm (preferably the dominant arm) should be used throughout the 
study. A BP cuff, which has been properly sized and calibrated, should be used to measure BP. 
The use of automated devices for measuring BP is acceptable.  
BP and pulse measurements should be preceded by at least 5 minutes of rest for the subject in a 
quiet setting without distractions (e.g., television, cell phones).  
Vital signs will consist of 1 pulse and 3 blood pressure measurements (3 consecutive blood 
pressure readings will be recorded at intervals of at least 1 minute). The average of the 3 blood 
pressure readings will be recorded on the eCRF. Single blood pressure readings can be 
performed after 14 days. 
On Day 0, vitals should be obtained as per Section 8.5.3.  For the remainder of the subject’s 
inpatient stay, starting on Day 1 monitoring of vital signs must be every 4 hours (±30 mins) 
while awake (starting at the first vital signs taken each day; inpatient encounter assessment). For 
outpatients, monitoring of vital signs after TCR-T infusion (for at least 14 days post-TCR-T 
infusion) will be collected at least once daily for the first 7 days and every other day up to 14 
days.  
Vital sign assessments simultaneously scheduled with electrocardiogram (ECG) assessments 
should be taken after the ECG assessment. The date/time of each vital sign and pulse oximetry 
assessment, as well as the position of the assessment, are to be recorded in the eCRF. 
11.3.1.4. Oxygen Saturation  
Oxygen saturation by pulse oximeter will be obtained according to the Schedule of Assessments. 
Assessment of oxygen saturation is required prior to, during, and up to an hour after infusion.  
11.3.1.5. Weight and Height 
Weight and Height (screening only) will be measured and recorded according to Schedule of 
Assessments.  
11.3.1.6. Physical Examination 
A full physical examination includes an examination of all major body systems (including 
general appearance, head, ears, eyes, nose, mouth, throat, neck, thyroid, lungs, heart, breasts, 
abdomen, neurological examination and musculoskeletal as clinically indicated), weight, which 
may be performed by a physician, nurse practitioner, or other qualified health care provider, will 
be required as per the schedule of assessments in Table 12 and Table 13. 
The use of individualized nutritional support during the course of this trial may improve 
important clinical outcomes. Therefore, systematically screening subjects prior to 
lymphodepletion, independent of their medical condition, followed by a nutritional assessment 
and introduction of individualized nutritional support in patients at risk or in deficit is required. 

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Findings should be recorded in the source documents, and any change from baseline considered 
by the investigation to be clinically significant should be recorded as an AE in the eCRF.  
Physical examinations will also include the following neurological examinations at each 
timepoint:  
1. Mentation  
2. Cranial nerves  
3. Motor  
4. Reflexes  
5. Sensory  
6. Coordination  
7. Additional tests may be performed as clinically indicated (e.g., Dix–Hallpike test, HINTS 
exam [Head-Impulse-Nystagmus-Test of Skew]) Neurologic findings should also be 
recorded in source documents, and any change from baseline considered by the 
Investigator to be clinically significant should be recorded as an AE in the eCRF. 
11.3.1.7. Cardiac Evaluation 
11.3.1.7.1. Electrocardiogram (ECG) 
A single 12-lead ECG will be obtained as outlined in Table 12 and Table 13 using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and ST. 
Additional triplicate recordings should be taken and evaluated by a qualified medical person to 
confirm a prolonged QTc. 
11.3.1.7.2. Echocardiogram or MUGA scan 
An echocardiogram or MUGA scan will be obtained at Screening. 
11.3.1.7.3. Pulmonary Function Testing (Unscheduled Only) 
For subjects with a prolonged history of cigarette smoking (> 20 pack-year smoking history, with 
cessation within the past two years), NSCLC, clinically significant respiratory dysfunction, or 
other clinical indications which may include thoracic surgeries, conventional pulmonary function 
testing may be performed as a screen for underlying respiratory abnormalities and to provide 
baseline lung function measurements. Parameters should include conventional forced expiratory 
volume in one second (FEV1), forced vital capacity (FVC), total lung capacity (TLC) by 
spirometry, and also diffusing capacity of carbon monoxide (simpler single breath method is 
acceptable) (DLCO SB). 
11.3.2. 
Clinical Laboratory Assessments 
Refer to the Schedule of Assessments in Table 12 and Table 13 for the timing and frequency of 
clinical laboratory assessments. Refer to  
 

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Table 10 for additional details on the analytes for each laboratory test. 
Hematology and blood chemistry will be drawn at the timepoints described in the SOA and 
analyzed at local laboratories.  
All laboratory tests at any time during the study, which have abnormal result values that are 
considered clinically significant (AESIs or SAEs) should be repeated, on a schedule as 
determined by the Investigator, until the values return to normal or baseline or are no longer 
considered clinically significant by the Investigator or medical monitor.  If such values do not 
return to normal/baseline within a period of time judged reasonable by the Investigator, an 
attempt at determining the etiology should be identified and the Sponsor notified.  
All protocol-required laboratory assessments, as defined below, must be conducted in 
accordance with the Laboratory Manual and as outlined in Table 12 and Table 13. 
Additional local laboratory assessments outside of the timepoints outlined in Table 12 and 
Table 13 may be obtained for patient safety evaluation at the discretion of the Investigator.  
The Investigator must review the laboratory report, 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 that are not associated with the subject’s disease unless judged by 
the Investigator to be more severe than expected for the subject’s condition. 
The below analyses will be performed at the clinical research site ( 
 
Table 10).   
 
 
Table 10. 
Laboratory Assessments Performed Locally 
Laboratory Assessments 
Parameters 
Hematology  
Platelet Count  
Red Blood Cell Count (RBC)  
Hemoglobin (Hb or Hgb)  
Hematocrit (HCT)  
  
Red Blood Cell Indices:  
Mean corpuscular volume (MCV)  
Mean corpuscular hemoglobin 
(MCH)  
  
Mean corpuscular hemoglobin 
concentration (MCHC)  
  
% Reticulocytes  
White Blood Cell Count (absolute) with 
Differential:  
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils  
 
Immature cells absolute count and 
percent (metamyelocytes, myelocytes, 
promyelocytes, blasts, etc.)  

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Laboratory Assessments 
Parameters 
Clinical Chemistry  
BUN  
Creatinine  
Glucose non-fasting  
Magnesium (Total Mg)  
Chloride  
Potassium  
Sodium  
Calcium (Total)  
 Lipase 
Albumin  
Uric acid  
CRP  
Amylase 
AST / SGOT  
ALT / SGPT  
ALP  
Lactate dehydrogenase  
Total and direct bilirubin  
GGT  
Triglycerides  
Creatine Kinase as clinically indicated  
Total Protein  
Inorganic Phosphorus  
Potassium  
Total CO2  
Coagulation  
INR  
PT  
APTT or PTT 
Ferritin 
ESR 
Thrombin time (as clinically indicated)  
Fibrinogen  
Urinalysis  
Color  
Appearance  
Occult Blood  
Protein  
Bilirubin  
Urobilinogen  
Ketones  
Leukocyte esterase  
Microscopy* of urine sediment (if 
clinically indicated, i.e.., if urine 
dipstick is positive for occult blood, 
protein, nitrites or leukocyte 
esterase)  
pH  
Nitrite urine  
Specific gravity  
Glucose  
Viral serology as clinically 
indicated**  
HIV I and II  
Hepatitis C Virus (quantitative)  
  
HbsAg:  
HbsAg (hepatitis B surface antigen)  
HbcAb (hepatitis B core antibody)  
HbsAb (hepatitis B surface 
antibody)  
HbeAg (hepatitis B type e antigen)  
Optional Infectious Disease Screening 
as clinically indicated:  
Herpes virus 6 and 7  
EBV  
T spot to assess for exposure or history 
of tuberculosis  
anti-HTLV antibody HTLV I/II Ab  
RPR syphilis  
CMV IgG and IgM  
West Nile Virus nucleic acid test 
T Cruzi antibody 
Varicella Zoster Virus 

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Laboratory Assessments 
Parameters 
Thyroid  
free triiodothyronine (FT3) 
free thyroxine (FT4) 
thyroid stimulating hormone (TSH) 
Other Laboratory Tests  
Pregnancy Tests: 
FSH  
Serum pregnancy test or urine pregnancy test  
Cytokines: 
The following may be included in the local testing panel: pro-inflammatory and 
immune modulating cytokines: IL‐ 6, TNF-α, and IFN-γ; immune effector 
molecules: Granzyme A, Granzyme B, Perforin, and sFasL; and chemokines: 
MIP‐1α MCP-1 and haptoglobin   
Optional cytokines that may be tested include, but are not limited to: IL‐8, IL-1β, 
IL‐2, IL-7, IL-10, IP-10, GM‐CSF, and IL‐15  
TBNK: 
TBNK (T cell, B cell, and NK cell counts) 
Urine Microscopy*  
Crystalluria calcium oxalate and/or hippurate crystals  
Leukocyturia   
White and red cell casts  
Hyaline casts  
Granular cast  
Waxy casts  
Fatty casts  
Broad casts (Broad waxy casts)  
CSF (Refer to Section 11.3.7)  Cerebrospinal pressure  
Proteins  
WBC cells/cell subsets  
Cytokines  
Viruses (including HHV 6 and 7), bacteria, other organisms if suspected   
ALP = alkaline phosphatase; ALT = alanine aminotransferase; APTT = activated partial thromboplastin time; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CMV = cytomegalovirus; CO2 = carbon dioxide; 
CRP = C-reactive protein; EBV = Epstein-Barr virus; ESR= erythrocyte sedimentation rate; FSH = follicle-
stimulating hormone; GGT = gamma-glutamyl transpeptidase ; HBV = hepatitis B; HCV = hepatitis C; HHV = 
Human herpes virus; HIV = human immunodeficiency virus; HTLV = human T cell lymphotropic virus; INR = 
international normalized ratio; LDH = lactate dehydrogenase; MCH = mean cell hemoglobin; MCV = mean cell 
volume; PT = prothrombin time; PTT= partial prothrombin time; RBC = red blood cell; RPR = rapid plasma reagin; 
SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; WBC = white 
blood cell  
*NOTE: Subjects with urine dipstick results that are positive for occult blood, protein, nitrites or leukocyte esterase 
will have urine microscopy sample collected 
**NOTE: Subjects with hepatitis B (HbsAg+) who have controlled infection (serum hepatitis B virus DNA PCR that 
is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted. Subjects with 

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controlled infections must undergo periodic monitoring of HBV DNA. Subjects must remain on anti-viral therapy 
for at least 6 months beyond the last dose of investigational study drug.   
NOTE: Subjects who are hepatitis C virus antibody positive (HCV Ab+) who have controlled infection 
(undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV 
therapy) are permitted.   
11.3.2.1. Hemophagocytic Lymphohystiocytosis (HLH) and Macrophage Activation 
Syndrome (MAS) Assessment 
Subjects should be assessed for HLH and MAS at the timepoints specified in Table 12 and 
Table 13. HLH and MAS assessments will be performed at screening, prior to lymphodepletion 
(Day -8) and Day -1.  If HLH/MAS is suspected during the study, serum ferritin, triglycerides, 
haptoglobin will be measured as clinically indicated. Refer to Center, 2020 and Appendix D for 
diagnostic criteria of HLH and MAS.  
• Clinical and laboratory features of MAS include fever, increased ferritin levels, 
pancytopenia, hemophagocytosis in bone marrow or lymph nodes, fibrinolytic 
coagulopathy, and liver dysfunction.  Specific treatment includes administration of 
Actemra® (tocilizumab) and corticosteroids given intravenously.  Canakinumab may 
also be used. 
11.3.3. 
HLA Class I and Class II Allele Determination 
A blood sample will be collected and submitted to a CLIA-certified laboratory for testing using 
next generation sequencing for HLA class I and class II genes as part of the initial pre-screening 
if results are not already available to meet inclusion criteria.  
11.3.4. 
Tumor Neoantigen Determination 
To determine somatic mutations, tumor tissue sample (collected during biopsy or resection 
conducted as part of standard-of-care treatment) that in some instances may be paired with a 
blood sample, archived tumor tissue, or a liquid biopsy will be sent to a CLIA-certified (or 
accredited) laboratory for molecular genetic test (e.g., OncomineTM) as part of the initial pre-
screening if such diagnostic results are not already available. 
11.3.5. 
Imaging 
Tumor response will be obtained using imaging scans including CT or MRI and evaluated as 
defined by RECIST guidelines (v1.1) (Eisenhauer et al., 2009) for assessment of tumor burden 
and disease progression. Follow-up imaging studies will be performed using the same imaging 
technique utilized at screening. Refer to Section 12 for further details. Scans will be provided to 
the central imaging vendor in the event the sponsor wants to perform central reads.  
11.3.6. 
Assessment of Cytokine Release Syndrome (CRS) 
Assessment of CRS includes grading of the following CRS parameters: fever, hypotension, 
hypoxia according to the ASTCT Grading guidance (refer to Appendix B). CRS grade should be 
determined at least twice daily where indicated in Table 12 and Table 13 and any time there is a 
change in subject’s status. 

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11.3.7. 
Cerebrospinal Fluid (CSF) 
Subjects with symptoms of central nervous system malignancy such as new onset of severe 
headaches, neck stiffness, or any focal neurologic findings on physical exam will have lumbar 
puncture performed at the screening visit for examination of cerebral spinal fluid. Refer to  
 
Table 10 for CSF testing parameters. Lumbar puncture may be performed as applicable for 
patients with new onset of ≥ grade 2 neurotoxicities post-TCR-T cell drug product 
administration. 
11.3.8. 
Assessment of Immune Effector Cell Associated Neurotoxicity Syndrome 
(ICANS) and Immune-effector Cell Encephalopathy (ICE) Score 
A thorough neurologic exam, including imaging of the brain (preferably MRI with and without 
contrast but CT without contrast is acceptable if MRI cannot be performed) to rule out any 
central nervous system disease and also to serve as a baseline for comparison in case the subject 
develops ICANS; diagnostic lumbar puncture, and ICE Score (refer to Appendix C and 
Appendix E).  Assessment and grading for ICANS should be completed at least every 12 hours 
where indicated in Table 12 and Table 13 including the ICE scoring. Care giver can be trained to 
administer this test if subject is outpatient. This information may be requested from the care 
giver. 
11.3.9. 
Immunosuppression Utilization 
Use of IL-6 antagonists and alternative immunosuppressive agents (including but not limited to 
tocilizumab, siltuximab, anakinra) for the management of CRS and ICANS will be recorded and 
analyzed throughout the study. 
11.3.10. 
Handwriting Sample and Temperature Log 
Subjects should be instructed to complete daily temperature readings and handwriting samples in 
the Handwriting and Temperature log from time of discharge through Day 28. Subjects should 
be instructed to return the log when they return for their Week 4 visit. Additional samples may 
be collected as clinically indicated. Caregiver should be trained in this process and may be asked 
to return these logs to the study coordinator. Both the Handwriting Sample and the Temperature 
Log will be submitted centrally to allow for Medical Monitor review.  
11.3.11. 
Tumor Markers 
Tumor markers will include the following per tumor subgroup listed below in Table 11.  
Note: If a conventional tumor marker is found to be elevated at baseline, a repeat 
scheduled/unscheduled sample should be obtained to assess for decrease to baseline/ 
normalization if indicated to confirm a complete clinical response in conjunction with radiologic 
studies in accordance with the RECIST v1.1 guideline. 

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Table 11. 
Subgroup Specific Tumor Markers 
 
Subgroup 
Tumor Marker 
1: 
Ovarian 
2: 
Endometrial 
3: 
Colorectal 
4: 
Pancreatic 
5: 
NSCLC 
6: 
Cholangiocarcinoma 
alpha-fetoprotein 
(AFP) 
 
 
 
 
X 
X 
Calretinin 
X 
 
 
 
 
 
Cancer Antigen 125 
(CA-125) 
X 
X 
 
 
 
 
Carcinoembryonic 
Antigen (CEA) 
 
 
X 
X 
 
X 
C-Reactive Protein 
(CRP) 
 
 
X 
X 
 
 
Cancer Antigen 19-
9 (CA19-9) 
 
 
X 
X 
 
X 
CK19, K19 
 
 
 
 
X 
 
Microsatellite 
instability 
 
 
X 
 
 
 
11.3.12. 
Collection of Biospecimens for Translational Research Assessments 
Blood and tissue specimens for research will be collected throughout the study to evaluate the 
metrics as outlined in Section 14.1. Samples will be collected according to the schedule specified 
in Table 14. Procedures regarding the collection, processing, storage, and shipment of 
biospecimens are detailed in the Study Laboratory Manual. 
11.3.13. 
Adverse Events Assessment and Grading 
Adverse events will be assessed according to the NCI Common Terminology Criteria for 
Adverse Events (CTCAE) Version 5.0 criteria. Reporting from the time of informed consent 
until lymphodepletion will only include AEs and SAEs that have an attribution of at least 
possibly related to a study procedure (e.g., blood draw). AEs that have an attribution of at least 
possibly related to a study procedure (e.g., blood draw) will be recorded as adverse events in the 
CRF as outlined in Section 13.6. SAEs that have an attribution of at least possibly related to a 
study procedure (e.g., blood draw) will be recorded in the CRF as outlined in Section 13.6 and 
reported to Sponsor as defined in Section 13.8. AEs and SAEs considered not protocol-related 
should be considered medical history.  
The reporting period of all adverse events and serious adverse events will begin from the start of 
lymphodepletion through end of study regardless of relationship to study treatment. Refer to 
Section 13 for more details. 

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11.3.14. 
Concomitant Medications 
Information on concomitant medications, including all medications, blood products, vitamins, 
and other supplements, will be collected from informed consent through the subject’s last study 
visit.  
11.3.15. 
Schedule of Assessments 
The schedule of assessments is provided in Table 12 and Table 13. 

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 Table 12. 
Schedule of Assessments – Pre- TCR-T Cell Drug Product Infusion 
Study Period 
Pre-ScreeningA 
Screening1 
Pre-Treatment 
Treatment 
Pre-Apheresis 
Apheresis32 
 
Lymphodepletion 
 
Pre-
TCR T-
cell 
drug 
product 
infusion 
Assessment 
 
 
 
 
Day 
-8 
Day 
-7 
Day 
-6 
Day 
-5 
Day 
-4 
Day 
-3 
Day 
-2 
Day 
-1 
Day 0 
Visit Window 
 
≤ 2 weeks from 
signing the 
screening consent 
≤ 2 days prior 
to apheresis 
 
 
 
 
 
 
 
 
 
 
Informed Consent2 
XA 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical History3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam4 
 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
Nutrition Consultation 
 
 
 
 
X4 
 
 
 
 
 
 
 
 
ECOG PS 
X 
X 
 
 
X 
 
 
 
 
 
 
X 
X 
Weight (Height at screening only) 
 
X 
 
 
 
X 
 
 
 
 
 
 
X 
Vital Signs5 
 
X 
X 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
Oxygen Saturation6 
 
X 
X* 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
Pregnancy Test7 
 
X 
X 
 
X 
 
 
 
 
 
 
 
 
Urinalysis8 
 
X 
 
 
X 
 
 
 
 
 
 
X 
 
Telemetry (optional) 
 
 
 
 
 
 
 
 
 
 
 
 
X 
ECHO or MUGA9 
 
X 
X* 
 
X9 
 
 
 
 
 
 
 
 
ECG10 
 
X 
 
 
X 
 
 
 
 
 
 
 
X 
Adverse Events11 
CONTINOUS 
Concomitant Medications12 
CONTINOUS 

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Study Period 
Pre-ScreeningA 
Screening1 
Pre-Treatment 
Treatment 
Pre-Apheresis 
Apheresis32 
 
Lymphodepletion 
 
Pre-
TCR T-
cell 
drug 
product 
infusion 
Assessment 
 
 
 
 
Day 
-8 
Day 
-7 
Day 
-6 
Day 
-5 
Day 
-4 
Day 
-3 
Day 
-2 
Day 
-1 
Day 0 
Visit Window 
 
≤ 2 weeks from 
signing the 
screening consent 
≤ 2 days prior 
to apheresis 
 
 
 
 
 
 
 
 
 
 
Immunosuppression Utilization 
CONTINOUS 
Overall Survival 
CONTINOUS 
Infectious Disease Testing13 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematology14 
 
X 
X** 
 
X14 
X 
X 
X 
X 
X 
 
X 
X 
Blood Chemistry14 
 
X 
X* 
 
X14 
X 
X 
X 
X 
X 
 
X 
X 
Coagulation Panel14 
 
 
 
 
X14 
X 
X 
X 
X 
X 
 
 
 
TBNK 
 
 
 
 
X14 
 
 
 
 
 
 
 
 
Thyroid Panel14 
 
 
 
 
X14 
 
 
 
 
 
 
 
 
CT or MRI15 
 
X 
 
 
X16 
 
 
 
 
 
 
 
 
Neoantigen Determination17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HLA Allele Determination17 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility18 
X 
X 
X 
 
X 
 
 
 
 
 
 
X 
X 
Enrollment18 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Tumor Markers19 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Lumber Puncture20 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Local assessment of cytokines14 
 
 
 
 
X 
 
 
 
 
 
 
X 
 

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Study Period 
Pre-ScreeningA 
Screening1 
Pre-Treatment 
Treatment 
Pre-Apheresis 
Apheresis32 
 
Lymphodepletion 
 
Pre-
TCR T-
cell 
drug 
product 
infusion 
Assessment 
 
 
 
 
Day 
-8 
Day 
-7 
Day 
-6 
Day 
-5 
Day 
-4 
Day 
-3 
Day 
-2 
Day 
-1 
Day 0 
Visit Window 
 
≤ 2 weeks from 
signing the 
screening consent 
≤ 2 days prior 
to apheresis 
 
 
 
 
 
 
 
 
 
 
Hospitalization21 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
HLH/MAS Assessment22 
 
X 
 
 
 
X 
 
 
 
 
 
X 
 
Assessment of ICANS including ICE 
score23 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Handwriting Sample and 
Temperature Log164 
 
 
 
 
 
 
 
 
 
 
 
 
 
Bridging Therapy25 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
Infection Prophylaxis17 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Apheresis18 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Lymphodepletion 19 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
 
CRS Prophylaxis20 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Injection Site Reaction Assessment30 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCR-T Pre-medication21 
 
 
 
 
 
 
 
 
 
 
 
 
X 
A Patients will initially sign the pre-screening consent form to determine if the subject has at least one TCR matching a combination of their somatic mutation(s) and 
HLA type is available in Alaunos’s Clinical TCR library. If subjects don’t have at least one TCR match identified, they will be discontinued and will not move 
forward with further screening for the study. 
* Assessments completed for the screening eligibility review will satisfy this criterion if apheresis is scheduled within 28 days of the initial screening 
** Assessments completed for the screening eligibility review will satisfy this criterion if apheresis is scheduled within 7 days of the initial screening 

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1 Screening assessments must be performed within 2 weeks after the subject signs the main consent form. 
2 Informed consent must be obtained prior to undergoing any study specific procedures. The main consents for the protocol TCR001-201 and the consent for 
protocol TCR001-202 (LTFU Protocol) must be obtained at the same time. 
3 Medical history includes demographic information, relevant medical history, current primary cancer diagnosis, and immunotherapy related biomarker diagnostics 
(e.g., MSI, MMR, PD-1/PD-L1), if available, prior cancer treatments (chemo- and immunotherapies, radiation therapy, surgeries, and any associated toxicities) 
including regimen, doses, start and stop dates, any associated residual toxicity, and best response for each regimen. 
4 A complete physical examination including, but not limited to cardiovascular, dermatological, gastrointestinal, musculoskeletal, neurological, pulmonary systems. 
Refer to Section 11.3.1.6 for full guidance on physical examinations. Patients with symptoms of central nervous system malignancy such as new onset severe 
headaches, neck stiffness, or any focal neurologic findings on PE will have lumbar puncture performed at the screening visit for examination of cerebral spinal 
fluid. Symptom directed PEs should be performed as appropriate at each time point and on an as needed basis for assessment of AEs.  Symptom directed PE can be 
performed only if clinically indicated. Toxicity assessment will be ongoing and any toxicities or infections will be evaluated. The use of individualized nutritional 
support during the course of this trial may improve important clinical outcomes. Therefore, systematically screening subjects prior to lymphodepletion, 
independent of their medical condition, followed by a nutritional assessment and introduction of individualized nutritional support in patients at risk or in deficit is 
required. 
5 Vital signs should be collected before blood collection on days where laboratory tests are collected. Vital signs include body temperature (oral, tympanic, temporal 
or axillary), blood pressure, and pulse rate to be recorded in the sitting position after 5 minutes of rest. Vital signs will consist of 1 pulse and 3 blood pressure 
measurements (3 consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the 3 blood pressure readings will be 
recorded on the eCRF. Single blood pressure readings can be performed after 7 days. On Day 0, vitals should be obtained as per Section 8.5.3 . For the remainder 
of the subject’s inpatient stay, starting on Day 1 monitoring of vital signs must be every 4 hours (±30 mins) while awake (starting at the first vital signs taken each 
day; inpatient encounter assessment). For outpatients, monitoring of vital signs after TCR-T infusion (for at least 14 days post-TCR-T infusion) will be collected at 
least once daily for the first 7 days and every other day up to 14 days. Vital sign assessments simultaneously scheduled with electrocardiogram (ECG) assessments 
should be taken after the ECG assessment. The date/time of each vital sign and pulse oximetry assessment, as well as the position of the assessment, are to be 
recorded in the eCRF. 
6 Oxygen saturation by pulse oximeter will be obtained. Assessment of oxygen saturation is required prior to, during and up to an hour after infusion. 
7 Females of childbearing potential will have a serum or urine pregnancy test at the Screening Visit and a serum pregnancy test within 7 days prior to 
lymphodepletion, with a negative pregnancy outcome prior to treatment.  Females of non-childbearing potential is defined as: Achieved postmenopausal status, 
defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed 
with a serum follicle stimulating hormone (FSH) level confirming the postmenopausal state, have undergone a documented hysterectomy and/or bilateral 
oophorectomy, or have medically confirmed ovarian failure.    
8 The urinalysis panel (dipstick) is required and includes color, appearance, pH, specific gravity, glucose, protein/albumin, and presence of blood, ketones, bilirubin, 
urobilirubin, nitrates, and leukocyte esterase. In addition, a microscopic exam for casts, crystals, and cells will be done if clinically indicated (i.e., if urine dipstick 
is positive for occult blood, protein, nitrites or leukocyte esterase). 
9 A baseline ECHO or MUGA must be performed to measure left ventricular ejection fraction (LVEF).  The same modality will be used throughout the study. The 
ECHO or MUGA collected to confirm eligibility prior to lymphodepletion can be collected within 28 days prior to Day -8. 
10 At each time point, 12 lead ECG will be performed to determine heart rate, PR, QRS, QT, ST and mean QTcF intervals. On Day 0, triplicate ECG will be 
performed prior to TCR-T cell drug product administration and at the end of infusion.  At other time points, a single ECG can be performed.  If the mean QTcF is 
prolonged (>500 msec), or > than 60 msec change from baseline of QTc, the ECG should be re-evaluated by a qualified person at the institution for confirmation, 
and triplicate ECGs may be performed as clinically indicated. 
11 Adverse events will be assessed according to the NCI CTCAE v5.0 criteria. Reporting from the time of informed consent until lymphodepletion will only 
include AEs and SAEs that have an attribution of at least possibly related to a study procedure (e.g., blood draw). AEs that have an attribution of at least possibly 

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related to a study procedure (e.g., blood draw) will be recorded as adverse events in the CRF as outlined in Section 13.6. SAEs that have an attribution of at least 
possibly related to a study procedure (e.g., blood draw) will be recorded in the CRF as outlined in Section 13.6 and reported to Sponsor as defined in Section 13.8. 
AEs and SAEs considered not protocol-related should be considered medical history. The reporting period of all adverse events and serious adverse events will 
begin from the start of lymphodepletion through end of study regardless of relationship to study treatment. Refer to Section 13 for more details. SAEs must be 
reported within 24-hours of awareness. After the initial AE/SAE report, the investigator is required to proactively follow each subject at subsequent visits/contacts. 
All SAEs will be followed until the event is resolved, stabilized, otherwise explained, or the participant is lost to follow-up.  Refer to Section 13 Safety 
Assessments for more information on AE/SAE reporting including what is not considered an AE/SAE. 
12 Concomitant medications will be monitored and recorded throughout the study.  Medications received in the period preceding consent (~28 days), in addition to 
those ongoing at screening, will be captured in the eCRF.  Concomitant medications include all medications, blood products, vitamins and other supplements and 
will be collected from informed consent through the subject’s last visit. 
13 Serology testing for HIV, Hepatitis B, Hepatitis C, Cytomegalovirus, Herpes Simplex Virus, Epstein-Barr Virus, Varicella Zoster Virus, and other viruses 
according to institutional practice. 
14 Refer to Table 10  for analytes. Blood samples collected to confirm eligibility prior to lymphodepletion may be collected within the 3 days prior to Day -8 
15 Appropriate cancer staging procedures should be performed during screening per RECIST v1.1. For the purpose of this clinical trial, the following imaging is 
expected at screening: a. CT of the chest, and CT (or MRI) of the abdomen b. MRI (or CT) of the brain, if brain metastases are known or suspected c. CT or MRI 
of other anatomical regions as clinically indicated.  All imaging should be of diagnostic quality and include IV contrast. Disease sites are to be imaged throughout 
the study using the same method(s) used at screening. Chest and abdomen imaging are required for all follow-up imaging time points; images of the brain and 
other anatomical regions should be acquired on follow-up if positive at screening and as clinically indicated. 
16Subjects that are treated with bridging therapy will have an additional CT or MRI to serve as a baseline assessment. The CT or MRI collected to confirm eligibility 
prior to lymphodepletion can be collected within 7 days prior to Day -8 (preferred) or at Day -2. 
17For somatic mutation determination, prior genetic testing results, archival tissue, or a new tumor biopsy and a blood sample (if being performed as standard-of-
care) is required. If no prior mutation results are available, and a re-biopsy is not feasible, a liquid biopsy must be performed for somatic mutation determination. 
Results of a high resolution, HLA class I and II typing from a CLIA laboratory will be collected if previously performed. In the absence of such a result, a blood 
sample will be collected and submitted to a CLIA-certified or -accredited laboratory for testing. 
18All patients will need to meet the screening eligibility criteria requirements.  Once deemed eligible, the subject’s dose level will be assigned by the Sponsor. 
Subjects will be considered enrolled into the study once eligibility for lymphodepletion has been approved by the Alaunos Medical Monitor or designee.  Subject 
eligibility criteria should be re-assessed prior to treatment with TCR-T cell drug product to ensure the safety of the subject. Refer to Section 6.1. 
19Tumor markers will be assessed as listed in Table 10 . If markers are not elevated at baseline, additional sample collection is not required. 
20 Subjects with symptoms of central nervous system malignancy such as new onset severe headaches, neck stiffness, or any focal neurologic findings on physical 
exam will have lumbar puncture performed at the screening visit for examination of cerebral spinal fluid.  Refer to Section 11.3.7 for additional requirements. 
Lumbar puncture may be performed as applicable for patients with new onset of ≥ grade 2 neurotoxicities post TCR-T cell drug product administration. 
21 Lymphodepletion will occur on an out-patient basis unless hospitalization is clinically determined to be in the best interest of the patient. Subjects may be 
hospitalized from Day -1 through Day 7 or longer if medically indicated.  Duration of hospitalization may be decreased once safety profile has been determined.  
Subjects must stay within close proximity of the treating hospital for 28 days after TCR-T cell drug product administration. 
22 HLH and MAS assessments will be performed at screening, Day -7 prior to lymphodepletion and Day -1. If HLH/MAS is suspected, serum ferritin, triglycerides, 
haptoglobin will be measured. 
23Neurological assessment: ASTCT Grading of ICANS: Q12 hours while in hospital. ICE score does not have to be collected in the hospital and only upon 
discharge.  When not collected in the log, ICE will be captured in the hospital source documents.  If this is not within institutional practice, continue the recording 
on the log. 

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24 Subjects should be instructed to complete daily temperature readings and handwriting samples in Handwriting and Temperature log from time of discharge 
through Day 28. Subjects should be instructed to return the log when they return for their Week 4 visit. 
25 Subjects will be allowed to receive bridging therapy following apheresis after consultation with the Alaunos Medical Monitor. The consultation with the Alaunos 
Medical Monitor will determine the type and duration of bridging therapy based on the subject’s tumor type. Subjects who have sufficient lymphodepletion from 
bridging therapy do not need additional lymphodepletion as described in Section 8.2 prior to infusion of TCR-T cell drug product. 
26 Infection prophylaxis should be given according to institutional guidelines. In the absence of institutional guidelines, refer to Section 10.1.1 for recommendations 
on prophylaxis medications. 
27 Apheresis must be approved by Alaunos to accommodate receipt and processing of apheresis at the manufacturing facility. 
28 Lymphodepleting chemotherapy will follow the schedule outlined in Table 7 in Section 8.2. Lymphodepletion may commence following notification from 
Alaunos that the subject’s TCR-T cell drug product has been manufactured and Certification of Analysis is available. 
29 Subjects will receive a single, intravenous dose (600mg) of tocilizumab as part of their preconditioning regimen. NOTE: Substitutions may be considered due to 
supply issues after discussion between the investigator and Alaunos Medical Monitor. 
30 Subjects should be monitored for injection site reactions at 1 and 3hrs post- infusion of TCR-T cell drug product 
 
at 1 and 3hrs post. Refer to Section 9.4.7 and Section 10.1.5 for further details. 
31 All subjects should receive TCR-T cell drug product pre-medication as outlined in Section 8.5.1. 
32 The apheresis collection will occur at any time during the subject’s clinical course after the subject meets the eligibility criteria for apheresis collection. 
Manufacturing will begin once receipt, inspection, and release of the leukapheresis product is completed and a manufacturing slot is available. 

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Table 13. 
Schedule of Assessment – Post-TCR-T Cell Drug Product Infusion 
Study Period 
Treatment 
Follow-Up 
Un-
scheduled 
Visit 
TCR-T Cell 
Drug Product 
Infusion  
Post TCR-T Cell Drug Product Infusion   
Assessment 
Day 0  
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Week 2 & 
4 
(±3 days) 
Week 6 
(±1 
week) 
Week 12 
(±2 
weeks) 
Every 3 
months1 
(±2 weeks) 
Early 
Discontinuation 
Visit24 
Physical Exam2 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG PS 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
X 
Weight (Height at 
screening only) 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Vital Signs3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Oxygen Saturation 4 X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
Pregnancy Test5 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urinalysis6 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
Telemetry (optional)  
X 
X 
X 
 
 
 
 
 
 
 
 
 
X 
ECHO or MUGA7 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
ECG 8 
 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
X 
Adverse Events9 
CONTINUOUS 
Concomitant 
Medications10 
CONTINUOUS 
Immunosuppression 
Utilization 
CONTINUOUS 
 
 
 
 
 

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Study Period 
Treatment 
Follow-Up 
Un-
scheduled 
Visit 
TCR-T Cell 
Drug Product 
Infusion  
Post TCR-T Cell Drug Product Infusion   
Assessment 
Day 0  
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Week 2 & 
4 
(±3 days) 
Week 6 
(±1 
week) 
Week 12 
(±2 
weeks) 
Every 3 
months1 
(±2 weeks) 
Early 
Discontinuation 
Visit24 
Overall Survival  
CONTINUOUS 
Infectious Disease 
Testing 11 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Hematology12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood Chemistry12 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panel12  
X 
 
 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
TBNK 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Thyroid Panel12 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
 
X 
CT or MRI13 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
X 
Tumor Markers14 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
X 
Assessment of 
CRS15 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
X 
Lumbar Puncture16 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Local assessment of 
cytokines12 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
X 
Hospitalization17 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
HLH/MAS 
Assessment18 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 

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Study Period 
Treatment 
Follow-Up 
Un-
scheduled 
Visit 
TCR-T Cell 
Drug Product 
Infusion  
Post TCR-T Cell Drug Product Infusion   
Assessment 
Day 0  
Day 
1 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
6 
Day 
7 
Week 2 & 
4 
(±3 days) 
Week 6 
(±1 
week) 
Week 12 
(±2 
weeks) 
Every 3 
months1 
(±2 weeks) 
Early 
Discontinuation 
Visit24 
Assessment of 
ICANS including 
ICE score19 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
Handwriting Sample 
and Temperature 
Log20  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
Infection 
Prophylaxis21 
 
 
 
 
 
 
 
 
 
Injection Site 
Reaction Assessment 
23 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
X 
TCR-T cell drug 
product infusion 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Visits occur every 3 months from Week 12 until subjects complete the 2-year follow-up or discontinue due to disease progression. 
2 A complete physical examination including, but not limited to cardiovascular, dermatological, gastrointestinal, musculoskeletal, neurological, pulmonary systems. 
Refer to Section 11.3.1.6 for full guidance on physical examinations. Patients with symptoms of central nervous system malignancy such as new onset severe 
headaches, neck stiffness, or any focal neurologic findings on PE will have lumbar puncture performed at the screening visit for examination of cerebral spinal 
fluid. Symptom directed Pes should be performed as appropriate at each time point and on an as needed basis for assessment of AEs. Symptom directed PE can be 
performed only if clinically indicated. Toxicity assessment will be ongoing and any toxicities or infections will be evaluated.  
3 Vital signs should be collected before blood collection on days where laboratory tests are collected. Vital signs include body temperature (oral, tympanic, temporal 
or axillary), blood pressure, and pulse rate to be recorded in the sitting position after 5 minutes of rest. Vital signs will consist of 1 pulse and 3 blood pressure 
measurements (3 consecutive blood pressure readings will be recorded at intervals of at least 1 minute). The average of the 3 blood pressure readings will be 
recorded on the eCRF. Single blood pressure readings can be performed after 7 days. On Day 0, vitals should be obtained as per Section 8.5.3 . For the remainder 
of the subject’s inpatient stay, starting on Day 1 monitoring of vital signs must be every 4 hours (±30 mins) while awake (starting at the first vital signs taken each 
day; inpatient encounter assessment). For outpatients, monitoring of vital signs after TCR-T infusion (for at least 14 days post-TCR-T infusion) will be collected at 
least once daily for the first 7 days and every other day up to 14 days. Vital sign assessments simultaneously scheduled with electrocardiogram (ECG) assessments 

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should be taken after the ECG assessment. The date/time of each vital sign and pulse oximetry assessment, as well as the position of the assessment, are to be 
recorded in the eCRF. 
4 Oxygen saturation by pulse oximeter will be obtained. Assessment of oxygen saturation is required prior to, during and up to an hour after infusion. 
5 Females of childbearing potential will have a serum or urine pregnancy test at the Screening Visit and a serum pregnancy test within 7 days prior to 
lymphodepletion, with a negative pregnancy outcome prior to TCR-T cell drug product infusion. 
6 The urinalysis panel (dipstick) is required and includes color, appearance, pH, specific gravity, glucose, protein/albumin, and presence of blood, ketones, bilirubin, 
urobilirubin, nitrates, and leukocyte esterase. In addition, a microscopic exam for casts, crystals, and cells will be done if clinically indicated (i.e.., if urine dipstick 
is positive for occult blood, protein, nitrites or leukocyte esterase). 
7 A baseline ECHO or MUGA must be performed to measure left ventricular ejection fraction (LVEF).  The same modality will be used throughout the study. 
8 At each time point, 12 lead ECG will be performed to determine mean QTcF interval.  On Day 0, triplicate ECG will be performed prior to TCR-T administration 
and at the end of infusion.  At other time points, a single ECG can be performed.  If the mean QTcF is prolonged (>500 msec), or > than 60 msec change from 
baseline of QTc, the ECG should be re-evaluated by a qualified person at the institution for confirmation, and triplicate ECGs may be performed as clinically 
indicated. 
9 Adverse events will be assessed according to the NCI CTCAE v5.0 criteria. Reporting from the time of informed consent until lymphodepletion will only include 
AEs and SAEs that have an attribution of at least possibly related to a study procedure (e.g., blood draw). AEs that have an attribution of at least possibly related to 
a study procedure (e.g., blood draw) will be recorded as adverse events in the CRF as outlined in Section 13.6. SAEs that have an attribution of at least possibly 
related to a study procedure (e.g., blood draw) will be recorded in the CRF as outlined in Section 13.6 and reported to Sponsor as defined in Section 13.8. AEs and 
SAEs considered not protocol-related should be considered medical history. The reporting period of all adverse events and serious adverse events will begin from 
the start of lymphodepletion through end of study regardless of relationship to study treatment. Refer to Section 13 for more details. SAEs must be reported within 
24-hours of awareness. After the initial AE/SAE report, the investigator is required to proactively follow each subject at subsequent visits/contacts. All SAEs will 
be followed until the event is resolved, stabilized, otherwise explained, or the participant is lost to follow-up.  Refer to Section 13 Safety Assessments for more 
information on AE/SAE reporting including what is not considered an AE/SAE. 
10 Concomitant medications will be monitored and recorded throughout the study.  Medications received in the period preceding consent (~28 days), in addition to 
those ongoing at screening, will be captured in the eCRF. Concomitant medications include all medications, blood products, vitamins and other supplements and 
will be collected from informed consent through the subject’s last visit 
11 Serology testing for HIV, Hepatitis B, Hepatitis C, Cytomegalovirus, Herpes Simplex Virus, Epstein-Barr Virus, Varicella Zoster Virus, and other viruses 
according to institutional practice 
12 Refer to Table 10  for analytes. 
13 Appropriate cancer staging procedures should be performed during screening per RECIST v1.1. For the purpose of this clinical trial, the following imaging is 
expected at screening: a. CT of the chest, and CT (or MRI) of the abdomen b. MRI (or CT) of the brain, if brain metastases are known or suspected c. CT or MRI 
of other anatomical regions as clinically indicated.  All imaging should be of diagnostic quality and include IV contrast. Disease sites are to be imaged throughout 
the study using the same method(s) used at screening. Chest and abdomen imaging are required for all follow-up imaging time points; images of the brain and 
other anatomical regions should be acquired on follow-up if positive at screening and as clinically indicated. 
14 Tumor markers will be assessed as listed in Table 11. If markers are not elevated at baseline, additional sample collection is not required. 
15 Cytokine release syndrome grading should be assessed per ASTCT Consensus Guidelines. Refer to Appendix B. Assessment and grading of CRS should occur 
Q12 hours while in hospital.  Toxicity assessment will also include HLH and MAS which may occur in the setting of CRS. 
16 Subjects with symptoms of central nervous system malignancy such as new onset severe headaches, neck stiffness, or any focal neurologic findings on physical 
exam will have lumbar puncture performed at the screening visit for examination of cerebral spinal fluid. Refer to Section 11.3.7 for additional requirements. 
Lumbar puncture may be performed as applicable for patients with new onset of ≥ grade 2 neurotoxicities post TCR-T cell drug product administration. 

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17 Lymphodepletion will occur on an out-patient basis unless hospitalization is clinically determined to be in the best interest of the patient. Subjects may be 
hospitalized from Day -1 through Day 7 or longer if medically indicated.  Duration of hospitalization may be decreased once safety profile has been determined.  
Subjects must stay within close proximity of the treating hospital for 28 days after TCR-T cell administration. 
18 HLH and MAS assessments will be performed at screening, Day -7 prior to lymphodepletion and Day -1. If HLH/MAS is suspected, serum ferritin, triglycerides, 
haptoglobin will be measured. 
19 Neurological assessment: ASTCT Grading of ICANS: Q12 hours while in hospital. ICE score does not have to be collected in the hospital and only upon 
discharge. When not collected in the log, ICE will be captured in the hospital source documents. If this is not within institutional practice, continue the recoding on 
the log. 
20 Subjects should be instructed to complete daily temperature readings and handwriting samples in Handwriting and Temperature log from time of discharge 
through Day 28. Subjects should be instructed to return the log when they return for their Week 4 visit. 
21 Infection prophylaxis should be given according to institutional guidelines. In the absence of guidelines, refer to Section 10.1.1 for recommendations on 
prophylaxis medications. 
 
23 Subjects should be monitored for injection site reactions at 1 and 3hrs post- infusion of TCR-T cell drug product 
 
. Refer to Section 9.4.7, Section 10.1.4, and Section 10.1.5 for further details. 
24Early discontinuation is at the time the subject discontinues from the study (e.g., due to disease progression, initiation of new-anticancer therapy, withdraw 
consent, etc.). Subjects should be questioned regarding their reason for withdrawal. These reasons must be documented in the subject’s medical record and on the 
eCRF. 
 
 

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11.3.15.1. Contraception 
All participants of child-bearing potential must practice effective birth control while on study. 
Acceptable forms of birth control for female subjects include hormonal birth control, intrauterine 
device, diaphragm with spermicide, condom with spermicide, or abstinence, for 30 days from the 
time of the TCR-T cell infusion. If the participant is a female and becomes pregnant or suspects 
pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during 
this study, she will be taken off this study. Men who are of child-bearing potential must use 
effective birth control while on the study. The acceptable form of birth control for male subjects 
is condom with spermicide, for 30 days from the time of the TCR-T cell infusion. If the male 
participant fathers a child or suspects that he has fathered a child while on the study, he must 
immediately notify his doctor. If a subject should become pregnant while on-study, guidance for 
submitting a Pregnancy Form can be found in Section 13.11  
11.3.16. 
Retention of Unused Subject Material 
The unused apheresis product, biorepository blood specimens, and unused manufactured cells 
will be stored at Alaunos and/or its affiliates and may be used for future retreatment or research 
studies which may include one or more of the following: cryopreservation, phenotyping, 
genotyping, genetic modification, propagation of cells and derivatives for the purposes of 
improving understanding of immunotherapy of cancer. If the subject refuses consent, the cells 
will be destroyed. 
11.3.17. 
Long-Term Follow-Up 
Enrolled research participants who receive TCR-T cell drug product will be required to 
participate in the long-term follow-up (LTFU) protocol (TCR001-202) per the guidelines set 
forth by the FDA’s Biologic Response Modifiers Advisory Committee (BRMAC) that apply to 
gene transfer studies. Current recommendations from the FDA require a minimum of 15 years of 
follow-up after infusion of genetically modified cells. Since the long-term effects of gene and 
cell therapy are unknown, after receiving an infusion of genetically modified T cells, the subject 
will be required to participate in a study for LTFU of gene and cell therapy subjects and sign the 
associated consent/assent form. This participation is mandatory. If the research participant dies, 
then an autopsy will be requested, but is not mandatory. Subjects will begin the LTFU protocol 
once they complete the follow-up period or discontinue from this study (e.g., due to disease 
progression, initiation of new-anticancer therapy, withdraw consent, etc.).  

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12. 
TUMOR RESPONSE ASSESSMENTS 
12.1. 
Tumor Response 
Response and progression will be evaluated in this study using the international criteria proposed 
by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (v1.1) 
(Eisenhauer et al., 2009). Target and non-target lesions should be selected and measured as per 
the RECIST guideline.  
12.2. 
Tumor Response Evaluation 
Tumor response will be assessed locally using RECIST (v1.1) criteria (refer to Appendix I). 
Subjects should be imaged throughout the study using the same method(s) and techniques as 
were used for the screening images. Post-treatment tumor biopsies may occur as available and at 
the discretion of the investigator. A repeat scan to confirm response should be completed at least 
4 weeks (per RECIST) after first documentation of response.  
Final progression determinations will be made by the investigator. Every effort should be made 
to follow subjects radiographically until disease progression is confirmed per RECIST criteria.  
Subjects without confirmed disease progression should continue to have tumor assessments 
approximately every 12 weeks until disease progression has been identified and confirmed. If 
subjects have yet to progress when this treatment protocol is complete, i.e., 2 years post TCR-T 
cell drug product infusion, they will continue to be scanned until progression on the LTFU 
protocol TCR001-202.  
All radiological studies acquired at all scheduled time points and any additional (unscheduled) 
radiological images acquired to evaluate for potential metastatic disease will be sent to an 
Independent Review Facility (IRF) for storage and may be analyzed at a later date. All scans sent 
to the IRF must be in original Digital Imaging and Communications in Medicine (DICOM) 
format. Electronic transfer of scan files (via file transfer protocol [FTP], hypertext transfer 
protocol [HTTP], or similar means) is preferred, although transfer on physical media (such as 
digital versatile disc [DVD] or compact disc [CDs] is acceptable. For digital media, each disk 
should contain one timepoint for one patient. The site is expected to maintain a copy of digital 
data for the retention period applicable to the protocol, Good Clinical Practice (GCP), and 
federal, international and/or state legal and medical requirements. Sponsor and or designee will 
retain the media for the life of the study. 
If desired by the Sponsor, the IRF may evaluate imaging studies and supportive clinical data in a 
central and independent fashion. The IRF will be comprised of board-certified radiologists and 
nuclear medicine physicians who will identify baseline lesions and assign post-baseline 
timepoint responses. Details regarding IRF member qualification, training, methods, procedures, 
and other issues relevant to IRF will be described in the IRF Charter, if needed. 
The interpretation of scans in subjects treated with TCR-T cell drug product has an inherent 
uncertainty that stems from the pseudo-progression phenomena. Pseudo-progression is a term 
used to describe the appearance of radiographic disease progression due to increase contrast 
enhancement without true tumor progression. The increase in contrast enhancement can be 
influenced by several parameters including differences in radiologic technique, the amount of 
contrast agent used, the timing of the contrast agent administration relative to the imaging, 

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infarction, treatment related inflammation, seizure activity, sub-acute radiation effects, radiation 
necrosis, and corticosteroid use. Consideration of these factors by experts and clinical experience 
is likely to identify these subjects.   
12.2.1. 
Imaging Acquisition Parameters 
The following image acquisition parameters may be recorded as applicable: tomographic slice 
thickness and reconstruction interval, pulse sequence, contrast agent (including brand name), 
contrast agent dose and route of administration, contrast agent injection start and stop times, and 
contrast agent injector type (e.g., manual or power/auto injector). 
12.2.2. 
Evaluation of Target Lesions – RECIST 1.1 
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum of diameters. 
Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also 
considered progression). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum of diameters while on study. 
12.2.3. 
Evaluation of Non-Target Lesions – RECIST 1.1 
Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor 
marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).  
NOTE: If tumor markers are initially above the upper normal limit, they must normalize for a 
subject to be considered in complete clinical response. 
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions. Unequivocal progression should not normally trump 
target lesion status. It must be representative of overall disease status change, not a single lesion 
increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances. 

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13. 
SAFETY ASSESSMENTS 
Safety will be evaluated based on frequency and severity of AEs, SAEs, and findings from 
laboratory tests, electrocardiograms, vital signs, and physical/neurologic examinations. The 
severity of AEs will be graded using NCI CTCAE v5.0.  
Reporting from the time of informed consent until lymphodepletion will only include AEs and 
SAEs that have an attribution of at least possibly related to a study procedure (e.g., blood draw). 
AEs that have an attribution of at least possibly related to a study procedure (e.g., blood draw) 
will be recorded as adverse events in the CRF as outlined in Section 13.6 . SAEs that have an 
attribution of at least possibly related to a study procedure (e.g., blood draw) will be recorded in 
the CRF as outlined in Section 13.6 and reported to Sponsor as defined in Section 13.8. AEs and 
SAEs considered not protocol-related should be considered medical history.  
The reporting period of all adverse events and serious adverse events will begin from the start of 
lymphodepletion through end of study regardless of relationship to study treatment.  
• Protocol-related: The event occurred due to a procedure or intervention that was 
described in the protocol for which there is no alternative etiology present in the 
subject’s medical record. 
• Not protocol-related: The event is related to an etiology other than the study 
procedure (the alternative etiology must be documented in the study subject’s medical 
record). 
Worsening of signs and symptoms of the malignancy under study should be recorded as AEs in 
the appropriate section of the CRF.  Disease progression assessed by measurement of malignant 
lesions on radiographs or other methods should not be reported as an AE. 
Events not considered to be reportable SAEs: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 
• Abnormal safety assessments which are 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 expected progression, signs, or symptoms of the 
disease/disorder being studied, 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 preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

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After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up. 
All SAEs must be reported to Alaunos Safety within 24 hours of awareness. Email the SAE 
Report Form (and any supporting documentation) to TCRSAE@alaunos.com 
Documents can also be sent via fax to: +1-888-922-5939 
For medical questions call the Alaunos Safety Hotline: + 1-866-990-2291 
Questions or assistance with completing forms can be directed to Alaunos Therapeutics, Drug 
Safety and Pharmacovigilance: TCRSAE@alaunos.com  
Additional data concerning the SAE (e.g., diagnostic test reports, hospital summaries, etc.) must 
be promptly reported (within 24 hours of receipt) to the sponsor or sponsor’s designee, until 
resolution of the SAE. Should the FDA or National Regulatory Authorities require that the 
sponsor submit additional data on the event, the investigator will be asked to provide those data 
to the sponsor in a timely fashion. 
13.1. 
Adverse Events and Definitions  
13.1.1. 
Adverse Event  
Any untoward medical occurrence associated with the use of a study drug in humans, whether 
considered drug related. An AE can be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporarily associated with the use of a 
medical treatment or procedure, and any worsening of a pre-existing condition regardless of 
causality to study drug. An AE is also known as an adverse experience. Abnormal laboratory 
assessments that are an unexpected outcome of lymphodepleting chemotherapy administered 
before TCR-T cell drug product infusion will be recorded. Since a decreased lymphocyte count 
is not only expected but is also the desired therapeutic outcome of LD, decreased lymphocyte 
count and dependent decreased white blood cell count will be recorded, but will not be 
considered adverse events. 
For non-serious events that occur prior to the administration of any study drug (i.e., after 
informed consent and before administration), an assessment of protocol relatedness must be 
made. Only those considered protocol-related should be entered as AEs. Events considered not 
protocol-related should be considered medical history. 
• Protocol-related: The event occurred due to a procedure or intervention that was 
described in the protocol for which there is no alternative etiology present in the 
subject’s medical record. 
• Not protocol-related: The event is related to an etiology other than the study 
procedure (the alternative etiology must be documented in the study subject’s medical 
record). 
Worsening of signs and symptoms of the malignancy under study should be recorded as AEs in 
the appropriate section of the CRF.  Disease progression assessed by measurement of malignant 
lesions on radiographs or other methods should not be reported as an AE. 

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13.1.2. 
Suspected Adverse Reaction  
A suspected adverse reaction is any AE for which there is evidence to suggest a causal 
relationship (reasonable possibility) between the drug and the AE. A suspected adverse reaction 
implies less certainty about causality than an adverse reaction.  
13.1.3. 
Adverse Reaction  
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all suspected 
adverse reactions which provide a reason to conclude that the study drug caused the event.  
13.1.4. 
Unexpected Adverse Reaction  
Any AE that is (a) not listed in the Reference Safety Information (RSI) of Investigator’s 
Brochures, (b) not listed with the specificity and severity that is being observed, (c) not 
consistent with the risk information described in the general investigational plan or elsewhere in 
the current application (in the absence of an investigator brochure), and (d) listed as occurring 
with a class of drugs, but not specifically mentioned as occurring with the particular drug under 
investigation.   
13.2. 
Evaluation of Adverse Events  
Adverse events include:  
• Suspected adverse drug reactions  
• Reactions from study drug overdose, abuse, withdrawal, sensitivity, or toxicity  
• Significant changes or abnormalities in signs, symptoms, clinical laboratory results, 
or physiological testing when compared to baseline. This includes any worsening of a 
pre-existing condition temporally associated with the use of a study drug.  
• Other untoward medical events, regardless of their relationship to the study drug, 
such as injury, events that require surgery, accidents, extensions of symptoms, or 
apparently unrelated illnesses  
• Worsening of signs and symptoms of the malignancy under study should be recorded 
as AEs in the appropriate section of the CRF. 
The following considerations apply when identifying an AE:  
• Anticipated day-to-day fluctuations of pre-existing conditions, including the disease 
under study, that do not represent a clinically significant exacerbation or worsening 
need not be considered AEs.  
• If a constellation of symptoms results in a confirmed diagnosis, the diagnosis (not the 
symptoms) should be recorded as the AE.  
• If a diagnosis cannot be established, the symptoms should be recorded as the AEs.  
• If an ongoing symptom has been included in the medical history, an associated 
severity grade and frequency should also be documented so that a worsening in 
severity or frequency of a symptom can be readily identified as an AE.  

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• Disease progression assessed by measurement of malignant lesions on radiographs or 
other methods should not be reported as an AE. Disease progression assessed by 
measurement of malignant lesions on radiographs or other methods should not be 
reported as an AE.  
After the initial AE/SAE report, the investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up. 
13.3. 
Determination of Seriousness  
13.3.1. 
Serious Adverse Event  
An AE is considered an SAE if at least one of the following conditions applies:  
• Death occurring during the study. In addition, this includes a reported death at any 
time post-study that is thought to be related to study drug administration.  
• Life-threatening: An AE that places the subject, in the view of the investigator, at 
immediate risk of death from the event as it occurred (i.e., this does not include a 
reaction that, had it occurred in a more severe form, might have caused death). 
• Permanent, persistent, or significant disability: A disability is defined as any 
substantial disruption of a person’s ability to conduct normal life functions. 
• Inpatient hospitalization or prolongation of existing hospitalization (in general, for at 
least a 24-hour stay). Hospitalizations for routine blood transfusions, for an elective 
or diagnostic procedure, or for surgery for a pre-existing condition that has not 
worsened are not considered SAEs. Emergency room visits that do not result in a 
hospital admission are not considered as SAEs.  
• A congenital anomaly/birth defect, that is, a fixed, permanent impairment established 
at or before birth.  
• An important medical event that may not result in death, be life-threatening, or 
require hospitalization may be considered SAEs when, based upon appropriate 
medical judgment, they jeopardize the subject and require medical or surgical 
intervention to prevent a life-threatening situation, hospitalization or death.  
Events not considered to be reportable SAEs: 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 
• Abnormal safety assessments which are 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 expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 

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• 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 preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
13.3.2. 
Non-Serious Adverse Event  
An AE that does not fulfill the criteria for a SAE is classified as a non-serious AE.  
13.4. 
Determination of Severity  
The severity of AEs will be assessed according to the NCI CTCAE Version 5.0. If an AE is not 
specifically defined in the NCI CTCAE, Version 5.0, the investigator will determine the severity 
of an AE based on the following recommended general definitions (NCI 2017):  
• Mild (Grade 1): The AE is noticeable to the subject but does not interfere with routine 
activity. The AE does not require intervention.  
• Moderate (Grade 2): The AE interferes with routine activity but responds to 
symptomatic therapy or rest. The AE may require minimal, local, or noninvasive 
intervention.  
• Severe (Grade 3): The AE significantly limits the subject’s ability to perform routine 
activities despite symptomatic therapy. In addition, the AE may necessitate the 
subject’s hospitalization or prolongation of hospitalization.   
• Life-threatening (Grade 4): The AE requires urgent intervention to resolve. The 
subject is at immediate risk of death.  
• Death (Grade 5): The subject dies as a direct result of the AE complication or 
condition.  
13.5. 
Determination of Causality  
The investigator will use medical consideration, based on his/her clinical judgment, to determine 
the potential relationship of the AE to the study drugs. Assessment of causality will be based 
upon the following:  
• Alternative possible causes of the AE, including other drugs, other host, 
environmental factors, and the subject’s underlying disease or comorbid conditions  
• The temporal sequence between the exposure to study drug and the AE 
• Whether the clinical or laboratory manifestations of the AE are consistent with known 
actions or previously reported toxicity of the study drug or similar drugs 
These relationship assessments indicate a “Not Related” study drug:  

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• None: The event is related to an etiology other than the investigational product (the 
alternative etiology must be documented in the study subject’s medical record and/or 
SAE form).  
• Unlikely or Remote: The event is unlikely to be related to the study drug and likely to 
be related to factors other than the study drug.  
These relationship assessments indicate a “Related” study drug:  
• Possible: There is an association between the event and the study drug and there is a 
plausible mechanism for the event to be related to the study drug; but there may also 
be an alternative etiology, such as characteristics of the subject’s clinical status or 
underlying disease.  
• Probable: There is an association between the event and the study drug and a 
plausible mechanism for the event to be related to the study drug. The event could not 
be reasonably explained by known characteristics of the subject’s clinical status or an 
alternative etiology is not apparent.  
• Definite: There is an association between the event and the study drug. A plausible 
mechanism exists for the event to be related to the study drug and causes other than 
the study drug have been ruled out.  
For non-serious events that occur prior to the administration of any study drug (i.e., after 
informed consent and before administration), an assessment of protocol relatedness must be 
made. Only those considered protocol-related should be entered as AEs. Events considered not 
protocol-related should be considered medical history. Only those that are assessed by the 
investigator as protocol-related should be reported to the sponsor.  
• Protocol-related: The event occurred due to a procedure or intervention that was 
described in the protocol for which there is no alternative etiology present in the 
subject’s medical record. 
• Not protocol-related: The event is related to an etiology other than the study 
procedure (the alternative etiology must be documented in the study subject’s medical 
record). 
13.6. 
Documenting Adverse Events  
All AEs, including SAEs, are to be accurately recorded on the Adverse Event CRF. Each event 
will be assessed for serious criteria, severity, and causality (Section 13.3, Section 13.4, and 
Section 13.5). The date of onset, as well as the duration of the event will be recorded. In 
addition, treatments provided to the subject, actions taken with the study drugs, and the outcome 
of the AE will also be noted.  
13.7. 
Dose-limiting Toxicity Assessment 
Severity of AEs will be graded according to NCI CTCAE Version 5.0.  For the purpose of dose 
escalation, any of the AEs listed below that occur within 28 days after the infusion which are 
attributable to study treatment and unrelated to tumor, intercurrent illness, or concomitant 
medications will be classified as DLTs.  Due to the requirement for lymphodepletion prior to 

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investigational product administration, and the expected toxicities associated with 
lymphodepletion, hematological toxicities will not be considered DLTs unless specified below. 
Clinically important or persistent toxicities that are not included in the definitions below may 
also be considered a DLT following review by the CRC.  All DLTs need to represent a clinically 
significant shift from baseline. 
13.7.1. 
Dose-limiting Toxicity (DLT) Definitions 
A DLT is a study intervention-related AE occurring within the DLT window (Day 0 to Day 28), 
defined based on NCI CTCAE Version 5.0 as the following: 
Hematologic 
• Grade 4 neutropenia lasting ≥ 14 days 
• Grade 4 thrombocytopenia 
• Grade 3 thrombocytopenia associated with clinically significant bleeding, 
• ≥ Grade 3 febrile neutropenia associated with hemodynamic compromise or objective 
evidence of infection. 
Non-hematologic 
• CRS grade 3 or 4 that does not improve to grade ≤ 2 within 72 hours despite 
appropriate treatment. 
• Grade 3 Immune-effector cell-associated neurotoxicity syndrome (ICANS) that does 
not return to grade ≤2 or lower with 7 days. 
• Any grade 5 adverse event (not due to disease progression or to a known cause other 
than TCR-T (e.g., automobile accident)). 
• Grade 3 hepatic toxicity that does not return to grade ≤ 2 or lower within 7 days. 
• Grade 3 toxicity involving vital organs that does not improve to grade ≤ 2 or lower 
within 7 days of onset. 
• Grade 4 toxicity not previously specified. 
In addition to the related AEs mentioned above, any related grade 3 toxicity and all grade 4 
toxicities will be considered DLTs except the following: 
• Grade 3 anemia that is not associated with other clinically significant complications 
• Expected chemotherapy toxicities due to lymphodepletion including cytopenias, 
fludarabine related adverse reactions, and cyclophosphamide related hemorrhagic 
cystitis. 

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13.8. 
Reporting Serious Adverse Events  
13.8.1. 
Time Frame for Reporting  
All SAEs must be reported to Alaunos Safety within 24 hours of awareness. Email the SAE 
Report Form (and any supporting documentation) to TCRSAE@alaunos.com.  
Documents can also be sent via fax to: +1-888-922-5939 
For medical questions call the Alaunos Safety Hotline: + 1 866-990-2291 
Questions or assistance with completing forms can be directed to Alaunos Therapeutics, Drug 
Safety and Pharmacovigilance: TCRSAE@alaunos.com. 
Additional data concerning the SAE (e.g., diagnostic test reports, hospital summaries, etc.) must 
be promptly reported (within 24 hours of receipt) to the sponsor or sponsor’s designee, until 
resolution of the SAE. Should the FDA or National Regulatory Authorities require that the 
sponsor submit additional data on the event, the investigator will be asked to provide those data 
to the sponsor in a timely fashion. 
The Investigator must sign and date the SAE Report Form.  If the person completing the report 
form is different from the investigator, he/she must sign and date the report as well. 
If the investigator is not immediately available to sign the report, it can be submitted with the 
reporter’s signature. The Investigator signoff is expected within 48 hours. Once signed, 
submit the updated SAE Report form. Information to be Provided by the Investigator  
Within 24 hours of becoming aware of the SAE, the investigator must notify the sponsor, 
Alaunos Medical Monitor or designee and transmit information to the sponsor, Alaunos Medical 
Monitor or designee as follows:  
1. Information (initial and follow-up) should be provided on an electronic and/or paper SAE 
Report form signed and dated by the investigator.  
2. The SAE Report form and copies of source documents with subject identifiers redacted 
will be transmitted by email or fax.  
3. A hospital discharge summary should be provided if the subject was hospitalized. 
An SAE report will be considered final once all relevant information has been received and 
reviewed by the sponsor.  
The SAE report form is provided in the investigator study files. Refer to the investigator study 
files for instructions on how to complete these forms. The investigator will provide all the 
following information related to the event:  
• Investigator identification  
• Subject identification (e.g., subject number, initials, sex, age, or year of birth)  
• Information regarding study procedure (e.g. start/stop time)  
• Day of SAE occurrence  
• Description of event  

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• Action taken with the study procedures/treatments in relation to the SAE  
• Outcome of the SAE  
In addition to the above information, the investigator must provide, for each event term, an 
assessment of:  
• Severity/intensity  
• Relationship to the study drug (causality assessment)  
13.9. 
Sponsor and Investigator Responsibility for Reporting Adverse 
Events  
All AEs and SAEs will be reported to Regulatory Authorities (RAs), IRBs/IECs, and 
investigators in accordance with all applicable global laws and regulations, including but not 
limited to 21 CFR 312.32. The investigator must submit all Safety Letters received from the 
sponsor to his/her IRB/IEC per agreements and local requirements. The investigator must keep 
copies of all safety reports/letters, including correspondence with Alaunos and the IRB/IEC, in 
the study file.  
13.10. 
Follow-up Information for Adverse Events  
Appropriate diagnostic tests should be performed and therapeutic measures, as medically 
indicated, should be instituted. After the initial AE/SAE report, the investigator is required to 
proactively follow each subject at subsequent visits/contacts. All SAEs will be followed until the 
event is resolved, stabilized, otherwise explained, or the participant is lost to follow-up. 
13.11. 
Pregnancies 
The sponsor should be immediately notified if subjects become pregnant during the study.  
An initial Pregnancy Report form and updates as additional information becomes available are to 
be completed by the investigator or designee. The Pregnancy Report form and the completion 
instructions will be provided in the investigator study files. Refer to the investigator study files 
for details on how to complete these forms. 
13.12. 
Overdose  
Investigational product overdose of study subject, with or without associated AEs/SAEs, should 
be reported within 24 hours of awareness to sponsor (Alaunos Therapeutics, Drug Safety and 
Pharmacovigilance, TCRSAE@alaunos.com or +1-866-990-2291). All AEs or SAEs as a result 
of overdose should be reported as described previously in Section 13.6 and Section 13.8.  

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14. 
TRANSLATIONAL RESEARCH ASSESSMENTS 
To enable investigation of correlative biomarkers, molecular signatures, mechanism of action, or 
other such translational hypotheses as specified in the study objectives or otherwise, samples will 
be collected prior to, during, and following TCR-T-cell infusion as outlined in Table 14. The 
assessments of these samples are outlined in Section 14 subsections below. If clinical 
circumstance limits the collection of samples from a subject at a given time point(s), samples 
should be prioritized in the following order: Samples that inform Secondary Objectives, samples 
that inform Exploratory Objectives, then samples that inform additional translational analyses. If 
a subject progresses, TCR-T-cell persistence and insertion-site clonality of TCR-T cell drug 
product assessments will be assessed per the schedule of assessments in the Long-Term Follow-
up protocol, as well as Insertional Mutagenesis assessments (Section 14.4) to monitor for 
delayed adverse events (Food and Drug Administration, 2020). While collection volumes are 
designed to limit the amount of sample to only that which is required to complete the specified 
assessment, any unused subject material (e.g., cells, RNA, or DNA) will be retained by the 
Sponsor for future translational research if the subject consents. 
14.1. 
Assessments from Peripheral Blood and Serum 
Blood and serum will be collected and assessed from all subjects with evaluable samples 
according to the schedule of sample collection shown in Table 14. Refer to the laboratory manual 
for collection, processing, and shipment of samples. Samples will be analyzed for of the 
following (including but not limited to): 
14.1.1. 
Translational Assessments in Blood and Serum Related to Secondary 
Objectives: 
• TCR-T-cell persistence, as defined by the duration that TCR-T cell drug product is 
measurable by VCN in peripheral blood samples. 
14.1.2. 
Translational Assessments in Blood and Serum Related to Exploratory 
Objectives: 
• TCR-T cellular persistence in peripheral blood (e.g., Cmax, Tmax, AUCD0-D28, etc.) 
over time determined by VCN. 
• Insertion-site clonality of TCR-T cell drug product will be measured by tracking the 
transposon insertion-site(s) of gene-modified cells in peripheral blood samples. 
• Serum cytokine concentrations including, but not limited to IFN-γ, IL-6, TNF-α, GM-
CSF, IL-2, IL-7, and IL-15 will be determined by multiplex immunoassay. 
• Immunogenicity elicited against the transgenic components of the TCR therapy (i.e., 
anti-drug antibody and T-cell responses) will be assessed by immunoassay of 
peripheral blood and serum samples. 
Data collected from these samples will be analyzed, in part, as they relate to fulfillment of the 
study objectives as outlined above.  

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14.1.3. 
Additional Translational Assessments Planned in Blood 
In addition to the assessments above that are related to study objectives, planned study analyses 
of blood samples include the following: 
• Immunophenotyping of immune cell population markers in the peripheral blood will 
be assessed by flow cytometry. Cell subsets/characteristics assessed may include     
T-cell subsets (e.g., naïve, central memory, etc.), activated T cells, T-cell exhaustion, 
classic immune cell subsets (e.g., B cells, NK cells, etc.). Markers assessed may 
include but are not limited to cluster of differentiation (CD) antigens CD3, CD4, 
CD8, CD45RA/RO, CD25, CD137 (4-1BB) and CD279 (PD-1). 
• Genomic analysis of peripheral blood samples of TCRvβ diversity using NGS or 
other appropriate methodologies. 
• Gene expression analysis (e.g., RNA-Seq) of peripheral blood samples. 
• Exploratory biorepository samples will be collected and retained by the Sponsor for 
future translation research. 
14.2. 
Assessments of Tumor Tissues 
Tumor tissue samples will be collected from all subjects at baseline, and on-treatment prior to the 
12-week imaging scan. Additionally, an optional biopsy will be requested at the time of 
confirmed or suspected progression. These timepoints are described in greater detail below (refer 
to laboratory manual(s) for details related to collection, processing and shipment). Fine needle 
aspirates (FNA) are not acceptable. 
• Baseline tumor tissue is required for all subjects. Tissue may be provided from an 
archival tumor resection or biopsy sample (most recent tumor sample collected prior 
to lymphodepletion available and not to have been collected more than 6 months prior 
to subject enrollment on this study). If archival tissue (refer to Lab Manual for 
minimum tissue requirement) is not available, then a new biopsy from a non-target 
lesion must be obtained. See Table 14 for more details.  
• On-treatment tumor biopsy collected at Week 12 (±2 weeks) prior to the 12-week 
imaging scan is required for all subjects. The tissue should be collected from the same 
lesion as the Baseline sample if possible. 
• Progression tumor biopsy collected at time of progression or suspected progression 
(optional for all subjects; within 1 month of confirmed progressive or suspected 
disease) as defined in Section 12.2.2 or from unscheduled visits. The tissue should be 
collected from the same lesion as the On-treatment and/or Baseline biopsy sample if 
possible. 
14.2.1. 
 Translational Assessment of Tumor Tissues Related to Exploratory Objectives 
The collection of tumor tissue samples is to enable the investigation of all T cells in the tumor. 
The following parameters will be evaluated by DNA sequencing, RNA-Seq, IHC, or other 
suitable methodology in biopsy samples collected at baseline, on-treatment (i.e., Week 12) and 
progression or suspected progression: 

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• T-cell infiltration (e.g., total CD3, CD4, and CD8) 
• TCR-T cell infiltration 
• Changes in the tumor associated with progression such as: 
o 
Presence of HLA alleles in tumor samples 
o 
Presence of tumor-specific neoantigens in tumor samples 
Additional confirmatory analyses of these samples (e.g., IHC or ISH to verify target expression) 
may be performed based on emergent data and sufficient sample availability. Data collected from 
these samples will be analyzed, in part, as they relate to fulfillment of the study objectives as 
outlined above. Tumor specimens may be evaluated for other cell types or molecular markers 
driven by emergent data. 
14.3. 
Assessment of Circulating Tumor DNA (ctDNA) 
14.3.1. 
Translational Assessment of ctDNA Related to Exploratory Objectives: 
To evaluate the levels of blood-based tumor neoantigen biomarkers, peripheral blood samples 
collected from all subjects according to the schedule shown in   may be analyzed. Refer to the 
laboratory manual for collection, processing, and shipment of samples for ctDNA analysis. 
Analysis of ctDNA samples by NGS may include the determination of: 
• Presence of neoantigen alleles 
• Quantification of variant allele frequency of tumor neoantigen specific gene(s)  
These data may be used to assess the appropriateness of ctDNA as a surrogate pharmacodynamic 
marker.  
14.4. 
Assessment of Insertional Mutagenesis in the Event of Emergent 
Malignancies 
In the event of a new malignancy, unrelated to any current or prior diagnosis, an appropriate 
sample will be obtained of the tumor (i.e., needle biopsy for solid tumors, bone marrow biopsy or 
blood sample for hematological malignancies) to assess for potential relatedness to TCR-T cell 
therapy. Methods for collection, processing, and shipment of such sample(s) will be provided by 
the Sponsor after consultation with the investigator, should such an event occur. Assessment of 
this sample will include evaluation of:  
• Presence of TCR-T cell drug product by VCN  
• Clonality (transposon insertion-sites) of any TCR-T cell drug product present in the 
sample  
Other laboratory assessments may be conducted on the sample as appropriate, based on the 
nature of the malignancy and the sample obtained. The objective of these analyses is to evaluate 
the likelihood that the new malignancy is the result of insertional mutagenesis caused by the 
transposon.  

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15.2. 
Analysis Sets 
For the purposes of analysis, the following analysis sets are defined: 
Enrolled  
The enrolled analysis set (ENR) will consist of all 
participants who have received lymphodepletion. 
 
Full Analysis Set  
The full analysis set (FAS) will consist of ENR participants 
who received a TCR-T cell drug product infusion and have at 
least one valid post-baseline assessment (PK, PD, Efficacy). 
 
Safety Analysis Set  
The safety analysis set (SAF) will consist of ENR 
participants who received a TCR-T cell drug product 
infusion. 
 
Per Protocol Analysis Set  
The per protocol analysis set (PPS) consists of SAF 
participants who do not have major treatment protocol 
violation during the DLT observation period. Participants 
with major treatment deviations during DLT observation 
period unrelated to safety or tolerability events are not 
evaluable for the dose-escalation assessment and will be 
replaced as needed. 
 
Dose Determining Analysis 
Set  
The dose-determining analysis set (DDS) will consist of PPS 
participants who have completed the planned TCR-T cell 
drug product infusion and experienced a DLT or completed 
the DLT observation period. 
 
15.3. 
Statistical Analyses 
The following sections detail key analysis definitions, methods and approaches. 
15.3.1. 
General Considerations 
This section summarizes the key, planned reporting and statistical analytic methods of the study 
data.  A forthcoming Statistical Analysis Plan (SAP) will develop these concepts in detail. 
In general, continuous variables, including baseline characteristics, will be summarized by 
reporting the number of observations, mean, standard deviation (SD), median, minimum and 
maximum and categorical/discrete variables will be summarized using frequency tables showing 
the number and percentage of patients within a category. 
Time-to-event data will be summarized using Kaplan-Meier or Nelson-Aalen statistical 
techniques, as appropriate, with parameter estimates displayed at pre-defined time points along 
with the number of censored observations.  A 2-sided 95% confidence interval for median time 
to event estimates will be produced in addition to the event 25th and 75th percentile summary 
statistic. 

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Baseline is defined as the last available observation prior to the first administration of study 
treatment. 
In addition, analyses may be performed separately for each individual TCR. 
Any deviations from the SAP will be reported in the clinical study report. 
15.3.2. 
Baseline Characteristics 
Subject disposition, demographics and other baseline characteristics, medical history, prior 
therapy, concomitant medications will be summarized by treatment, disease subgroup and 
overall, as applicable. 
15.3.3. 
Analysis of Phase I Primary Endpoint  
Dose Limiting Toxicities (DLTs): 
The primary analyses will characterize the incidence of DLTs as defined in Section 5.3. The 
DLT incidence will be used as a component of the MTD/RP2D selection criteria. 
Adverse Events: 
Treatment-emergent AEs through 28 days after last protocol therapy will be summarized by 
Medical Dictionary for Regulatory Activities (MedDRA) Version 13.1 (or higher) System Organ 
Class and preferred term. The incidences and percentages of participants experiencing each AE 
preferred term will be summarized with descriptive statistics. AEs will also be summarized by 
NCI CTCAE, Version 5.0, by grade and by causality (attribution to study treatment). 
Laboratory abnormalities: 
Laboratory results will be classified according to NCI CTCAE, Version 5.0. Laboratory results 
not corresponding to an NCI CTCAE term will not be graded. Incidences of laboratory 
abnormalities will be summarized with descriptive statistics. 
15.3.4. 
Analysis of Phase I Secondary Endpoints 
The Phase I secondary endpoint for evaluating the duration of persistence of TCR-T cell drug 
product by VCN is defined as the length of time from the date of infusion of TCR-T cell product 
to the date of the last measurable (i.e., ≥ LOQ) TCR-T cell level by VCN. 
Final T cell count, including percent viability, for appropriate clinical dose will be evaluated and 
details will be provided in the SAP. 
15.3.5. 
Analysis of Phase I Exploratory Endpoint 
Exploratory endpoints for analysis will be performed in the FAS. 
Analysis of exploratory endpoints may be performed separately by dose level and tumor type, or 
where appropriate combined. Details of the analyses will be described in the SAP. 
Objective Response Rate (ORR): 
Objective Response Rate (ORR) is defined as the proportion of FAS subjects achieving a 
confirmed PR or CR according to RECIST 1.1 and iRECIST during study. All objective 
responses (CR or PR) require confirmation by a repeat tumor assessment at least 4 weeks (28 

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16. 
STUDY MANAGEMENT 
16.1. 
Electronic Case Report Forms and Source Documentation 
For each subject, eCRFs and corresponding source records will be maintained at each clinical 
site. The sponsor or designee will provide the study sites with secure access to and sufficient 
training on the electronic data capture (EDC) application, to permit site personnel to enter or 
correct information in the eCRFs for the subjects for whom they are responsible.  
The eCRFs should be completed in a timely manner, and every effort should be made to have 
forms completed and up to date in anticipation of a visit by the sponsor’s monitor. Specific 
instructions will be provided to the site. All requested information must be entered on the eCRF 
in the spaces provided. If an item is not available or is not applicable, it should be documented as 
such; do not leave a space blank.  
It is the investigator’s responsibility to ensure the accuracy, completeness, clarity, and timeliness 
of the data reported in the subject’s eCRF. Through the EDC application, the investigator must 
provide formal approval of all subject information in the eCRFs and changes to the eCRFs to 
endorse the final submitted data for the subjects for whom he/she is responsible. The audit trail 
entry will show the user’s identification information and the date and time of any corrections.  
eCRF completion may be delegated to other study personnel included on study site’s Delegation 
of Authority/Responsibility Log; however, such delegation must be documented in writing and 
approved by site’s Principal Investigator on site’s Delegation of Authority/Responsibility Log 
before the delegated study personnel completes any actions for this study. If, for any reason, 
certain data are lacking to complete an individual report form, the investigator will provide a 
written statement explaining the reasons for the lack of data.  
Sponsor or designee will retain the eCRF data and corresponding audit trails. A copy of the final 
archival eCRF in the form of a compact disk or other electronic media will be placed in the 
investigator’s study file.  
16.2. 
Good Clinical Practice  
The study will be conducted in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Conference on Harmonization 
(ICH) Good Clinical Practice (GCP) guidelines, applicable regulatory requirements, and Alaunos 
policies.  
16.3. 
Sponsor Monitoring 
After satisfactory receipt of all necessary regulatory paperwork, the sponsor’s monitor will 
arrange that all study material be delivered to the study site at a mutually convenient time. A site 
initiation visit (SIV) by Alaunos and its monitoring personnel will be made. At this meeting, all 
personnel expected to be involved in the conduct of the study will undergo an orientation to 
include review of study protocol, instruction for eCRF completion and overall responsibilities, 
including those for drug accountability and study file maintenance. 
Throughout the course of the study, the sponsor’s monitor will make frequent contact with the 
investigator, and this will include telephone and/or onsite visits. During these visits, eCRFs will 

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be reviewed for completeness and adherence to protocol. As part of the data audit, it is expected 
that source documents (e.g., hospital records, office records) will be made available for review 
by the Medical Monitor. The monitor also will perform drug accountability checks and may 
periodically request review of the investigator’s study file to assure completeness of 
documentation in all respects of study conduct. 
Upon study completion, the monitor will arrange for a final review of the study files, after which 
the file should be secured by storage for the appropriate period as specified in Section 16.6. The 
investigator or appointed delegate will receive the sponsor’s representative during these onsite 
visits and will cooperate in providing the documents for inspection and responding to inquiries 
that may arise as part of this review. The investigator will also permit inspection of the study 
files by authorized representatives of the FDA. 
16.4. 
Duration of the Study 
The duration of accrual from the time of initiating subject enrollment until the completion of 
survival follow-up is anticipated to be approximately 7 years.   
The overall duration is expected to be up to 2 years and 1 month for an individual subject, 
including the following: 
• Screening period of up to 2 weeks 
• Study treatment period of approximately 5 weeks (Days -7 through Day 28) 
• The Follow-up Period includes assessment of tumor response at 6 weeks (± 1 week), 
and then every 3 months (± 2 weeks) for up to two-years post-TCR-T cell drug 
product infusion.  
In addition, subjects who receive investigational product without objective evidence of disease 
progression during the 2-year follow-up period will continue to be followed until progression has 
been documented via the Long-Term Follow-Up protocol (TCR001-202).   
16.5. 
Audits and Inspections 
Authorized representatives of Alaunos, a regulatory authority, and/or an Independent Ethics 
Committee or an Institutional Review Board may visit the site to perform audits or inspections, 
including source data verification. The purpose of a Alaunos audit or inspection is to 
systematically and independently examine all study-related activities and documents to 
determine whether these activities were conducted, and data were recorded, analyzed, and 
accurately reported according to the protocol, Good Clinical Practice guidelines of the 
International Conference on Harmonization, and any applicable regulatory requirements. The 
investigator should contact Alaunos immediately if contacted by a regulatory agency about an 
inspection. 
16.6. 
Retention of Records 
Records of drug disposition, eCRFs, and reports of the clinical trial must be maintained by the 
investigator for a period of at least 2 years following the date on which the investigational 
product is approved by FDA for marketing for the purposes that were investigated in the study. If 

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no application is to be filed or if the application is not approved for such indication, the records 
must be stored for two additional years and then returned to Alaunos.  
16.7. 
Communication with Supporting Companies and Laboratories 
Anonymized data and/or specimens may be generated, shared and/or stored with the sponsor, 
Alaunos, and its contracted vendors. Data may also be shared with the investigators/programs at 
the clinical site/institution who are involved with patient care and manufacturing of TCR-T cell 
drug product and/or testing of samples collected during the study.  
16.8. 
Institutional Review Board/ Independent Ethics Committee 
This protocol and the study ICF must be reviewed and approved by the IRB/IEC prior to the start 
of the study, and a copy of the approval letter supplied to Alaunos. During the study, the 
investigator shall make timely and accurate reports to the IRB/IEC on study progress at intervals 
not exceeding 1 year, as well as satisfying any other local IRB/IEC reporting regulations. Copies 
of all reports to, and correspondence with, the IRB/IEC must be provided to Alaunos. 
Furthermore, within 3 months of the completion or early termination of the study, a final report 
should be made to the IRB/IEC and Alaunos by the investigator. 
All protocol revisions must originate with and be documented by Alaunos. If the requested 
revision is an amendment, the investigator must sign it. The investigator must submit the 
amendment to his/her IRB/IEC for review and approval prior to implementation. Documentation 
of approval signed by the chairperson or designee of the IRB/IEC must be sent to Alaunos. 
It is the investigator’s obligation to maintain an IRB/IEC correspondence file and to make this 
available for review to Alaunos representatives as part of the routine study-monitoring process. 
16.9. 
Confidentiality and Health Insurance Portability and Accountability 
Act Information 
The written ICF will explain that study data will be stored in a database, maintaining 
confidentiality in accordance with national data legislation. All data processed by Alaunos, or its 
representatives, will be identified by subject number and study code. 
The written ICF will also explain that, for data verification purposes, authorized representatives 
of Alaunos, a regulatory authority (FDA), and/or the IRB/IEC may require direct access to parts 
of the hospital or clinic records relevant to the study that include the subject’s medical history. 
The written ICF will be accompanied by or include a separate document incorporating United 
States Health Insurance Portability and Accountability Act (HIPAA)-compliant wording by 
which the subjects authorize the use and disclosure of their Protected Health Information. 
16.10. 
Informed Consent 
16.10.1. 
Informed Consent Requirements 
The investigator or his/her staff will explain the nature of the study, its purpose and associated 
procedures, the expected duration, and the potential risks involved to the prospective subject 
prior to enrollment. The ICF should also indicate that, by signature, the prospective subject (or 

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where appropriate, a legal guardian) permits access to relevant medical records by the sponsor 
and by representatives of the FDA. If a prospective subject does not understand English, an 
appropriate translation of the ICF into the subject’s primary language must be made available. 
The investigator or designee will obtain written, informed, and witnessed consent. The 
prospective subject will have ample time and opportunity to ask questions. The prospective 
subject will be informed about the right to withdraw from the study at any time without any 
disadvantage and without having to provide a reason for this decision. Following the discussion 
regarding the study, the prospective subject will be asked if he/she is willing to personally sign 
and date a statement of informed consent. Only if the prospective subject voluntarily agrees to 
sign the informed consent statement and has done so, is he/she enrolled into the study. A copy of 
the signed and dated ICF will be provided to each prospective subject. The signed ICF is to 
remain in the investigator’s file. 
The ICF and any other written information provided to the subjects will be revised whenever 
important new information becomes available that may be relevant to the subject’s consent, or if 
there is an amendment to the protocol that necessitates a change to the content of the study’s 
ICF. The investigator will inform the subject of changes in a timely manner and will ask the 
subject to confirm continuation of his/her participation in the study by his/her signature on the 
revised ICF, if applicable. Any written ICF and written information must receive IRB/IEC 
approval/favorable opinion in advance of use. 
Alaunos will provide a sample subject ICF for modification by the investigator as appropriate. 

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17. 
LIST OF REFERENCES 
Bohlius, J., Bohlke, K., Castelli, R., Djulbegovic, B., Lustberg, M. B., Martino, M., . . . Lazo-
Langner, A. (2019). Management of Cancer-Associated Anemia With Erythropoiesis-
Stimulating Agents: ASCO/ASH Clinical Practice Guideline Update. Journal of Clinical 
Oncology, 37(15), 1336-1351. doi:10.1200/jco.18.02142 
Cafri, G., Yossef, R., Pasetto, A., Deniger, D. C., Lu, Y. C., Parkhurst, M., . . . Rosenberg, S. A. 
(2019). Memory T cells targeting oncogenic mutations detected in peripheral blood of 
epithelial cancer patients. Nat Commun, 10(1), 449. doi:10.1038/s41467-019-08304-z 
Center, U. o. T. M. A. C. (2020). IEC Therapy Toxicity Assessment and Management (also 
known as CARTOX)-Adult. Retrieved from https://www.mdanderson.org/documents/for-
physicians/algorithms/clinical-management/clin-management-cytokine-release-web-
algorithm.pdf 
Davis, J. L., Theoret, M. R., Zheng, Z., Lamers, C., Rosenberg, S. A., & Morgan, R. A. (2010). 
Development of Human Anti-Murine T-cell Receptor Antibodies in Both Responding 
and Non-responding Patients Enrolled in TCR Gene Therapy Trials. Clin Cancer Res, 
16(23), 5852-5861. doi:10.1158/1078-0432.CCR-10-1280 
Deniger, D. C., Pasetto, A., Robbins, P. F., Gartner, J. J., Prickett, T. D., Paria, B. C., . . . 
Rosenberg, S. A. (2018). T-cell Responses to TP53 "Hotspot" Mutations and Unique 
Neoantigens Expressed by Human Ovarian Cancers. Clin Cancer Res, 24(22), 5562-
5573. doi:10.1158/1078-0432.CCR-18-0573 
Deniger, D. C., Pasetto, A., Tran, E., Parkhurst, M. R., Cohen, C. J., Robbins, P. F., . . . 
Rosenberg, S. A. (2016). Stable, Nonviral Expression of Mutated Tumor Neoantigen-
specific T-cell Receptors Using the Sleeping Beauty Transposon/Transposase System. 
Mole Ther, 1-12.  
Dutcher, J. P., Schwartzentruber, D. J., Kaufman, H. L., Agarwala, S. S., Tarhini, A. A., Lowder, 
J. N., & Atkins, M. B. (2014). High dose interleukin-2 (Aldesleukin) - expert consensus 
on best management practices-2014. J Immunother Cancer, 2(1), 26. 
doi:10.1186/s40425-014-0026-0 
Eisenhauer, E. A., Therasse, P., J, B., Schwartz, L. H., Sargent, D., Ford, R., . . . Verweij, J. 
(2009). New response evaluation criteria in solid tumours:  Revised RECIST guideline 
(version 1.1). European Journal of Cancer, 45, 228-247.  
Field, A. C., Vink, C., Gabriel, R., Al-Subki, R., Schmidt, M., Goulden, N., . . . Qasim, W. 
(2013). Comparison of lentiviral and sleeping beauty mediated alphabeta T cell receptor 
gene transfer. PLoS One, 8(6), e68201. doi:10.1371/journal.pone.0068201 
Food and Drug Administration, C. f. B. E. a. R. (2020). Guidance for Industry: Long Term 
Follow-Up After Administration of Human Gene Therapy Products. Retrieved from 
https://www.fda.gov/media/113768/download 
Gattinoni, L., Powell, D. J., Jr., Rosenberg, S. A., & Restifo, N. P. (2006). Adoptive 
immunotherapy for cancer: building on success. Nature reviews. Immunology, 6(5), 383-
393. doi:10.1038/nri1842 
Greenbaum, U., Strati, P., Saliba, R. M., Torres, J., Rondon, G., Nieto, Y., . . . Ahmed, S. (2021). 
CRP and ferritin in addition to the EASIX score predict CAR-T-related toxicity. Blood 
Adv, 5(14), 2799-2806. doi:10.1182/bloodadvances.2021004575 
Hackett, P. B., Largaespada, D. A., & Cooper, L. J. N. (2010). A Transposon and Transposase 
System for Human Application. Mol Ther, 18(4), 674-683. doi:doi:10.1038/mt.2010.2 

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Schwartz, R. N., Stover, L., & Dutcher, J. P. (2002). Managing toxicities of high-dose 
interleukin-2. Oncology (Williston Park), 16(11 Suppl 13), 11-20. Retrieved from 
https://www.ncbi.nlm.nih.gov/pubmed/12469935 
Simon, R. (1989). Optimal two-stage designs for phase II clinical trials. Control Clin Trials, 
10(1), 1-10. doi:10.1016/0197-2456(89)90015-9 
Singh, H., Huls, H., Kebriaei, P., & Cooper, L. J. N. (2014). A new approach to gene therapy 
using Sleeping Beauty to genetically modify clinical-grade T cells to target CDE19. 
Immunological Reviews, 257, 181-190.  
Singh, H., Serrano, L. M., Pfeiffer, T., Olivares, S., McNamara, G., Smith, D. D., . . . Cooper, L. 
J. N. (2007). Combining Adoptive Cellular and Immunocytokine Therapies to Improve 
Treatment of B-Lineage Malignancy. Cancer Research, 67(6), 2872. doi:10.1158/0008-
5472.CAN-06-2283 
Tran, E., Robbins, P. F., & Rosenberg, S. A. (2017). 'Final common pathway' of human cancer 
immunotherapy: targeting random somatic mutations. Nat Immunol, 18(3), 255-262. 
doi:10.1038/ni.3682 
Wang, S., O'Rourke, D. M., Chawla, S., Verma, G., Nasrallah, M. P., Morrissette, J. J. D., . . . 
Mohan, S. (2019). Multiparametric magnetic resonance imaging in the assessment of 
anti-EGFRvIII chimeric antigen receptor T cell therapy in patients with recurretn 
glioblastoma. British J Cancer, 120, 54-56.  
Yuan, Y., Hess, K. R., Hilsenbeck, S. G., & Gilbert, M. R. (2016). Bayesian Optimal Interval 
Design: A Simple and Well-Performing Design for Phase I Oncology Trials. Clin Cancer 
Res, 22(17), 4291-4301. doi:10.1158/1078-0432.CCR-16-0592 
 
 

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18. 
APPENDICES 

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APPENDIX A. NEW YORK HEART ASSOCIATION (NYHA) 
CLASSIFICATION OF CARDIAC DISEASE 
 
The following table presents the NYHA classification of cardiac disease.  
Class 
Functional Capacity 
Objective 
Assessment 
I 
Patients with cardiac disease but without resulting limitations of 
physical activity.  Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain. 
No objective evidence 
of cardiovascular 
disease. 
II 
Patients with cardiac disease resulting in slight limitation of physical 
activity.  They are comfortable at rest.  Ordinary physical activity 
results in fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
minimal 
cardiovascular disease. 
III 
Patients with cardiac disease resulting in marked limitation of 
physical activity.  They are comfortable at rest.  Less than ordinary 
activity causes fatigue, palpitation, dyspnea, or anginal pain. 
Objective evidence of 
moderately severe 
cardiovascular disease. 
IV 
Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort.  Symptoms of heart failure or 
the anginal syndrome may be present even at rest.  If any physical 
activity is undertaken, discomfort is increased. 
Objective evidence of 
severe cardiovascular 
disease. 
 
 
 

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APPENDIX B. ASTCT GRADING FOR CYTOKINE RELEASE 
SYNDROME1 
(Note: CRS grade should be determined at least twice daily and any time there is a change in 
patient’s status) 
CRS parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever2 
Yes 
Yes 
Yes 
Yes 
 
 
With 
Hypotension3 
None 
Requiring IV fluids 
but not requiring 
vasopressors 
Requiring a 
vasopressor with or 
without vasopressin 
Requiring 
multiple 
vasopressors 
(excluding 
vasopressin) 
 
 
And/Or 
Hypoxia3 
None 
Requiring low-flow O2 
via nasal cannula4 or 
blow-by 
Requiring O2 via 
high-flow nasal 
cannula4, facemask, 
nonrebreather 
mask, or Venturi 
mask 
Requiring O2 via 
positive pressure 
(e.g., CPAP, 
BiPAP, and 
mechanical 
ventilation) 
Adapted from (Lee et al., 2019) 
 
CPAP=continuous positive airway pressure 
BiPAP=bilevel positive airway pressure 
 
1Organ toxicities associated with CRS may be graded according to CTCAE v5.0 but they do not influence CRS 
grading. 
2 Fever is defined as temperature ≥ 38 °C not attributable to any other cause. In patients who have CRS then receive 
antipyretics or anti-cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent 
CRS severity. In this case, CRS grading is driven by hypotension and/or hypoxia. 
3 CRS grade is determined by more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a patient with temperature of 39.5 °C, hypotension requiring 1 vasopressor, and hypoxia requiring low-
flow nasal cannula is classified as grade 3 CRS. 
4 Low-flow nasal cannula is defined as oxygen delivered at ≤ 6 L/min. Low flow also includes blow-by oxygen 
delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at > 6 L/min. 
 
 

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APPENDIX C. IMMUNE EFFECTOR CELL-ASSOCIATED 
ENCEPHALOPATHY (ICE) SCORE 
ICE Assessment 
Orientation: orientation to year, month, city, hospital: 4 points (1 point each) 
Naming: ability to name 3 objects (e.g., clock, pen, button): 3 points (1 point each) 
Following commands: ability to follow simple commands (e.g., “Show me 2 fingers” or “Close your 
eyes and stick out your tongue”): 1 point 
Writing: ability to write a standard sentence (e.g., “Our national bird is the bald eagle”): 1 point 
Attention: ability to count backwards from 100 by 10: 1 point 
 
Score 10: No Impairment 
Score 7-9: Grade 1 ICANS 
Score 3-6: Grade 2 ICANS 
Score 0-2: Grade 31 ICANS  
Score 0 due to patient unarousable or unable to perform ICE assessment: Grade 4 ICANS 
 
1A patient with an ICE score of 0 may be classified as having Grade 3 ICANS if the patient is awake with global 
aphasia or may be classified as having Grade 4 ICANS if the patient is unarousable 
 
 
 
 

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APPENDIX D. DIAGNOSTIC CRITERIA FOR IEC-ASSOCIATED 
FULMINANT HEMOPHAGOCYTIC 
LYMPHOHISTIOCYTES (HLH)/MACROPHAGE 
ACTIVATION SYNDROME (MAS) 
• Consider HLH/MAS if a subject has a peak ferritin > 10,000ng/mL during the CRS 
phase and develops any two of the following organ toxicities after IEC therapy 
− ≥ Grade 3 increase in bilirubin, aspartate transaminase, or alanine transaminase1 
− ≥ Grade 3 oliguria or increase in creatinine1 
− ≥ Grade 3 pulmonary edema1 
− Presence of hemophagocytosis by morphology and/or CD68 immunohistochemistry 
in bone marrow or organs 
• If HLH/MAS is suspected, obtain baseline fasting triglyceride level and serum 
soluble IL-2 receptor 
1 Grading per Common Terminology Criteria for Adverse Events, NCI CTCAE Version 5.0 
 
 
 
 
 

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APPENDIX E. ASTCT GRADING OF ICANS1 
 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE score2 
7-9 
3-6 
03-2 
03 (patient is 
unarousable and unable 
to perform ICE) 
Depressed levels 
of consciousness4 
Awakens 
spontaneously 
Awakens to voice 
Awakens only to 
tactile stimulus 
Patient is unarousable 
or requires vigorous or 
repetitive tactile stimuli 
to arouse. Stupor or 
coma 
Seizure 
N/A 
N/A 
Any clinical seizure 
focal or generalized 
that resolves rapidly or 
nonconvulsive 
seizures on EEG that 
resolve with 
intervention 
Life-threatening 
prolonged seizure (> 5 
min); or repetitive 
clinical or electrical 
seizures without return 
to baseline in between 
Motor findings5 
N/A 
N/A 
N/A 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 
Elevated 
intracranial 
pressure 
(ICP)6/cerebral 
edema 
N/A 
N/A 
Focal/local edema on 
neuroimaging7 
Diffuse cerebral edema 
on neuroimaging; 
Decerebrate or 
decorticate posturing; 
or cranial nerve VI 
palsy; or papilledema; 
or Cushing’s triad 
Adapted from (Lee et al., 2019) 
 
1.ICANS grading is determined by the most severe event (ICE score, level of consciousness, seizure, motor findings, 
raised ICP/cerebral edema) not attributable to any other cause; for example, a patient with an ICE score of 3 who has 
a generalized seizure is classified as grade 3 ICANS.  
N/A indicates not applicable. 
2.Refer to Appendix D for ICE Score.  
3.A patient with an ICE score of 0 may be classified as having Grade 3 ICANS if the patient is awake with global 
aphasia or Grade 4 ICANS if the patient is unarousable  
4.Depressed level of consciousness should not be attributable to any other cause (e.g., sedating medication) 
5 Tremors and myoclonus associated with immune effector cell therapies may be graded according to CTCAE v5.0, 
but they do not influence ICANS grading. 
6.Opthamology may be consulted to assess for papilledema if concern for elevated ICP, but otherwise not needed for 
all patients 
7 Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is excluded 
from ICANS grading. It may be graded according to CTCAE v5.0. 
 

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APPENDIX H. SUPPLEMENTARY STATISTICAL METHODS 
FOR PHASE I DOSE ESCALATION 
 
STAGED FUTILITY 
Phase I: 
The Bayesian optimal interval (BOIN) design (Liu & Yuan, 2015; Yuan et al., 2016) will be 
used to find the MTD. 
The target toxicity rate for the MTD is 𝜙𝜙= 0.3 and the maximum sample size is 12. We will 
enroll and treat patients in dose cohorts of size 3. DLTs are defined in Section 5.3, and only 
those DLTs that occur within the first cycle will be used for dose finding. As shown in Figure 5, 
the BOIN design uses the following rule, optimized to minimize the probability of incorrect dose 
assignment, to guide dose escalation/de-escalation: 
• if the observed DLT rate at the current dose is ≤ 0.253, escalate the dose to the next 
higher dose level; 
• if the observed DLT rate at the current dose is > 0.359, de-escalate the dose to the 
next lower dose level; 
• otherwise, stay at the current dose. 
For the purpose of overdose control, doses 𝑗𝑗 and higher levels will be eliminated from further 
examination if Pr(𝑝𝑝𝑗𝑗> 0.3 | data) > 0.95 and at least 3 evaluable patients have been treated at 
dose level 𝑗𝑗, where 𝑝𝑝𝑗𝑗 is the true DLT rate of dose level 𝑗𝑗, 𝑗𝑗= 1,⋯, 4. This posterior probability 
is evaluated based on the beta-binomial model 𝑦𝑦𝑗𝑗∣𝑝𝑝𝑗𝑗∼binomial(𝑝𝑝𝑗𝑗) with 𝑝𝑝𝑗𝑗∼uniform(0,1), 
where 𝑦𝑦𝑗𝑗 is the number of patients experienced DLT at dose level 𝑗𝑗. When the lowest dose is 
eliminated, stop the trial for safety. The probability cutoff 0.95 is chosen to be consistent with 
the common practice that when the target DLT rate <=1/6, a dose with 2/3 patients experienced 
DLT is eliminated. The above dose escalation/de-escalation and elimination rule can be 
equivalently presented in Table 15, which will be used to conduct the trial. 
The steps to implement the BOIN design are described as follows: 
1. 
Perform accelerated titration as follows. Treat the first patient at dose level 2 and escalate 
the dose in the one-patient-per-dose-level fashion until any of the following events is 
observed: (i) the first instance of DLT, (ii) the second instance of moderate (grade 2) 
toxicity, or (iii) the highest dose level is reached. Then, treat 2 additional subjects at the 
current dose level. Hereafter, subjects are treated in dose cohorts of size 3 as described in 
steps 2 and 3. 
2. 
To assign a dose to the next dose cohort of patients, conduct dose escalation/de-escalation 
according to the rule displayed in Table 15. When using Table 15, please note the 
following: 
a. 
“Eliminate” means eliminate the current and higher doses from the trial to prevent 
treating any future patients at these doses because they are overly toxic. 

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b. 
When we eliminate a dose, automatically de-escalate the dose to the next lower 
level. When the lowest dose is eliminated, stop the trial for safety. In this case, no 
dose should be selected as the MTD. 
c. 
If none of the actions (i.e., escalation, de-escalation or elimination) is triggered, treat 
the new patients at the current dose. 
d. 
If the current dose is the lowest dose and the rule indicates dose de-escalation, treat 
the new patients at the lowest dose unless the number of DLTs reaches the 
elimination boundary, at which point terminate the trial for safety. 
e. 
If the current dose is the highest dose and the rule indicates dose escalation, treat the 
new patients at the highest dose. 
3. 
Repeat step 2 until the maximum sample size of 12 is reached, or stop the trial if the number 
of evaluable patients treated at the current dose reaches 9 and the decision according to 
Table 15 is to stay at the current dose. 
Table 15. 
Dose escalation/de-escalation rule for the BOIN design 
 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Number of evaluable patients treated at 
current dose 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Escalate if # of DLT <= 
0 
0 
0 
1 
1 
1 
1 
2 
2 
Deescalate if # of DLT >= 
1 
1 
2 
2 
2 
3 
3 
3 
4 
Eliminate if # of DLT >= 
NA NA 
3 
3 
4 
4 
5 
5 
5 
Note. “# of DLT” is the number of patients with at least 1 DLT. When none of the actions (i.e., 
escalate, de-escalate or eliminate) is triggered, stay at the current dose for treating the next dose 
cohort of patients. “NA” means that a dose cannot be eliminated before treating 3 evaluable 
patients. 

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Figure 5. 
Flowchart for trial conduct using the BOIN design 
 
 
After the trial is completed, select the MTD based on isotonic regression as specified in (Liu & 
Yuan, 2015). This computation is implemented by the shiny app available at 
http://www.trialdesign.org. Specifically, select as the MTD the dose for which the isotonic 
estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, select the higher 
dose level when the isotonic estimate is lower than the target toxicity rate and select the lower 
dose level when the isotonic estimate is greater than or equal to the target toxicity rate. 
 
  
 
Operation Characteristics 
Table 16 shows the operating characteristics of the trial design based on 1000 simulations of the 
trial using shiny app “BOIN” (BOIN V2.6.5.0) available at http://www.trialdesign.org. The 
operating characteristics show that the design selects the true MTD, if any, with high probability 
and allocates more patients to the dose levels with the DLT rate closest to the target of 0.3. 
 
 

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Table 16. 
Operating characteristics of the BOIN design 
 
1 
2 
3 
4 
Number of 
Patients 
% Early 
Stopping 
Scenario 1 
 
 
 
 
 
 
True DLT Rate 
0.3 
0.47 
0.55 
0.64 
 
 
Selection % 
44.3 
34.5 
13.5 
2.6 
 
5.1 
% Pts Treated 
29.2 
38.4 
21.8 
10.6 
11.8 
 
Scenario 2 
 
 
 
 
 
 
True DLT Rate 
0.11 
0.3 
0.45 
0.67 
 
 
Selection % 
13.4 
47.4 
35.8 
3.2 
 
0.2 
% Pts Treated 
11.1 
36.7 
34.6 
17.6 
11.9 
 
Scenario 3 
 
 
 
 
 
 
True DLT Rate 
0.02 
0.13 
0.3 
0.47 
 
 
Selection % 
0.1 
20.9 
47.8 
31.2 
 
0 
% Pts Treated 
1.1 
23.5 
37.1 
38.3 
11.8 
 
Scenario 4 
 
 
 
 
 
 
True DLT Rate 
0.05 
0.1 
0.15 
0.3 
 
 
Selection % 
0.3 
4.6 
23.9 
71.2 
 
0 
% Pts Treated 
0.8 
15.4 
26 
57.8 
11.5 
 
Note: “% Early Stopping”" refers to early stopping due to excessive DLT. 
Table 17. 
Trial and Design Specifications 
Parameter 
Value 
Number of doses 
4 
Starting dose 
2 
Max sample size 
12 
Dose cohort size 
3 
Stop trial if # patients assigned to single dose reaches 
9 
Use accelerated titration 
TRUE 
Target toxicity probability 
0.3 
Use the default alternatives to minimize decision errors 
FALSE 
Alternative (unacceptable high toxicity) for optimization 
0.42 
Alternative (unacceptable low toxicity) for optimization 
0.21 
Eliminate dose threshold 
0.95 
Impose a more stringent safety stopping rule 
FALSE 
Require the isotonic estimate of the DLT probability for the dose selected as the MTD 
less than the de-escalation boundary 
FALSE 
Number of repetitions per scenario 
1000 
Random number generator seed 
6 

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APPENDIX I. PROTOCOL CRITERIA FOR RECIST (RESPONSE 
EVALUATION CRITERIA IN SOLID TUMORS) 
VERSION 1.1 AND IRECIST (IMMUNE RECIST) 
GUIDELINES 
Response and progression will be evaluated in this study using the revised international criteria 
(1.1) proposed by the RECIST (Response Evaluation Criteria in Solid Tumors) committee as 
well as the modified iRECIST guidelines. Investigators should note the different requirements 
for confirmatory scans as well as follow up for the two criteria. 
1 
RECIST 1.1 Response and Evaluation Endpoints 
 
1.1 
Measurable Disease. Measurable tumor lesions (nodal, subcutaneous, lung 
parenchyma, solid organ metastases) are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) as ≥10 
mm with CT scan or clinical examination. Bone lesions are considered 
measurable only if assessed by CT scan and have an identifiable soft tissue 
component that meets these requirements (soft tissue component ≥10 mm by 
CT scan). Malignant lymph nodes must be ≥15 mm in the short axis to be 
considered measurable; only the short axis will be measured and followed. All 
tumor measurements must be recorded in millimeters (or decimal fractions of 
centimeters). Previously irradiated lesions are not considered measurable unless 
progression has been documented in the lesion. 
 
1.2 
Non-measurable Disease. All other lesions (or sites of disease), including small 
lesions are considered non- measurable disease. Bone lesions without a 
measurable soft tissue component, leptomeningeal disease, ascites, 
pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast 
disease, lymphangitic involvement of lung or skin and abdominal masses 
followed by clinical examination are all non-measurable. Lesions in previously 
irradiated areas are non-measurable, unless progression has been demonstrated. 
 
1.3 
Target Lesions. When more than one measurable tumor lesion is present at 
baseline all lesions up to a maximum of 5 lesions total (and a maximum of 2 
lesions per organ) representative of all involved organs should be identified as 
target lesions and will be recorded and measured at baseline. Target lesions 
should be selected on the basis of their size (lesions with the longest diameter), 
be representative of all involved organs, but in addition should be those that lend 
themselves to reproducible repeated measurements. Note that pathological nodes 
must meet the criterion of a short axis of ≥15 mm by CT scan and only the short 
axis of these nodes will contribute to the baseline sum. All other pathological 
nodes (those with short axis≥10 mm but <15 mm) should be considered non-
target lesions. Nodes that have a short axis <10 mm are considered non-
pathological and should not be recorded or followed. At baseline, the sum of the 
target lesions (longest diameter of tumor lesions plus short axis of lymph nodes: 

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overall maximum of 5) is to be recorded. After baseline, a value should be 
provided on the CRF for all identified target lesions for each assessment, even if 
very small. If extremely small and faint lesions cannot be accurately measured 
but are deemed to be present, a default value of 5 mm may be used. If lesions 
are too small to measure and indeed are believed to be absent, a default value of 
0 mm may be used. 
 
1.4 
Non-target Lesions. All non-measurable lesions (or sites of disease) plus any 
measurable lesions over and above those listed as target lesions are considered 
non-target lesions. Measurements are not required but these lesions should be 
noted at baseline and should be followed as “present” or “absent”. 
 
1.5 
Response. 
 
All patients will have their BEST RESPONSE from the start of study treatment 
until the end of study classified as outlined below: 
 
Complete Response (CR): disappearance of target and non-target lesions and 
normalization of tumor markers. Pathological lymph nodes must have short axis 
measures <10 mm (Note: continue to record the measurement even if <10 mm 
and considered CR). Residual lesions (other than nodes <10 mm) thought to be 
non-malignant should be further investigated (by cytology specialized imaging 
or other techniques as appropriate for individual cases before CR can be 
accepted. Confirmation of response is only required in non-randomized studies. 
 
Partial Response (PR): at least a 30% decrease in the sum of measures (longest 
diameter for tumor lesions and short axis measure for nodes) of target lesions, 
taking as reference the baseline sum of diameters. Non target lesions must be 
non-PD. Confirmation of response is only required in non-randomized studies. 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor 
sufficient increase to qualify for PD taking as reference the smallest sum of 
diameters on study. 
 
Progressive Disease (PD): at least a 20% increase in the sum of diameters of 
measured lesions taking as references the smallest sum of diameters recorded 
on study (including baseline) AND an absolute increase of ≥5 mm. Appearance 
of new lesions will also constitute progressive disease (including lesions in 
previously unassessed areas). In exceptional circumstances, unequivocal 
progression of non-target disease may be accepted as evidence of disease 
progression, where the overall tumor burden has increased sufficiently to merit 
discontinuation of assessment or where the tumor burden appears to have 
increased by at least 73% in volume. Modest increases in the size of one or 
more non-target lesions are NOT considered unequivocal progression. If the 
evidence of PD is equivocal (target or non-target), assessment may continue 
until the next assessment, but if confirmed, the earlier date must be used. 
 

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2.1 
Confirming Progression 
 
Unlike RECIST 1.1, iRECIST requires the confirmation of progression and uses 
the terms iUPD (unconfirmed progression) and iCPD (confirmed progression). 
Confirmatory scans should be performed at least 4 weeks, but no longer than 8 
weeks after iUPD. 
iCPD is confirmed if further increase in tumor burden, compared to the last 
assessment, is seen as evidenced by one or more of the following: 
• 
Continued increase in tumor burden (from iUPD) where RECIST 1.1 
definitions of progression had been met (from nadir) in target, non-
target disease or new lesions 
o Progression in target disease worsens with an increase of at least 
5 mm in the absolute value of the sum 
o Continued unequivocal progression in non-target disease with 
an increase in tumor burden 
o Increase in size of previously identified new lesion (s) (an 
increase of at least 5 mm in the absolute value of the sum of 
those considered to be target new lesions) or additional new 
lesions. 
• 
RECIST 1.1 criteria are met in lesion types (target or non-target or new 
lesions) where progression was not previously identified, including the 
appearance of additional new lesions. 
If iUPD is not confirmed at the next assessment, then the appropriate response 
will be assigned (iUPD if the criteria are still met, but no worsening, or iSD, iPR 
or iCR if those criteria are met compared to baseline). As can be seen in table 
2, the prior documentation of iUPD does not preclude assigning iCR, iPR, or 
iSD in subsequent time-point assessments or as best overall response (BOR) 
providing that iCPD is not documented at the next assessment after iUPD. 
2.2 
New lesions 
New lesions should be assessed and measured as they appear using RECIST 1.1 
criteria (maximum of 5 lesions, no more than 2 per site, at least 10 mm in long 
axis (or 15 mm in short axis for nodal lesions) and recorded as New Lesions-
Target (NLT) and New Lesion-Non-Target (NLNT) to allow clear differentiation 
from baseline target and non-target lesions. 
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or 
iCPD). However, the measurements of target lesions should NOT be included in 
the sum of measures of original target lesions identified at baseline. Rather, these 
measurements will be collected on a separate table in the case record form. 
PD is confirmed in the New Lesion category if the next imaging assessment, 
conducted at least 4 weeks (but not more than 8 weeks) after iUPD confirms 
further progression from iUPD with either an increase of at least 5 mm in the 
absolute value of the sum of NLT OR an increase (but not necessarily 

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unequivocal increase) in the size of NLNT lesions OR the appearance of 
additional new lesions 
Table 20: 
Time-point (TP) iResponse 
Target 
Lesions* 
Non-Target Lesions* 
New 
Lesions* 
Time Point Response 
No prior 
iUPD** 
Prior iUPD**; *** 
iCR 
iCR 
No 
iCR 
iCR 
iCR 
Non-iCR/Non- iUPD No 
iPR 
iPR 
iPR 
Non-iCR/Non- iUPD No 
iPR 
iPR 
iSD 
Non-iCR/Non- iUPD No 
iSD 
iSD 
iUPD with 
no change 
OR 
decrease 
from last 
TP 
iUPD with no change 
OR decrease from last 
TP 
Yes 
NA 
NLs confirms iCPD if NLs were previously identified and 
increase in size (≥5 mm in SOM for NLT or any increase 
for NLNT) or number. If no change in NLs (size or 
number) from last TP, remains iUPD 
iSD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based in further 
increase in size of NT disease (need not meet RECIST 1.1 
criteria for unequivocal PD) 
iUPD 
Non-iCR/Non- iUPD No 
iUPD 
Remains iUPD unless iCPD confirmed based on: 
o further increase in SOM of at least 5 mm, otherwise 
remains iUPD 
iUPD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based on further 
increase in: 
o previously identified T lesion iUPD SOM ≥5 mm and / 
or 
o NT lesion iUPD (prior assessment - need not be 
unequivocal PD) 
iUPD 
iUPD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed based on further 
increase in: 
o previously identified T lesion iUPD ≥5 mm and / or 
o previously identified NT lesion iUPD (need not be 
unequivocal) and /or 
o size or number of new lesions previously identified 
Non- 
iUPD/PD 
Non-iUPD/PD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed based on 
o increase in size or number of new lesions previously 
identified 
* Using RECIST 1.1 principles. If no PSPD occurs, RECIST 1.1 and iRECIST categories for CR, PR and SD 
would be the same. ** in any lesion category. *** previously identified in assessment immediately prior to this TP. 

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All patients will have their iBOR from the start of study treatment until the end of study 
classified as outlined below. 
Table 21: 
iRECIST Best Overall Response (iBOR) 
TPR1 
TPR2 
TPR3 
TPR4 
TPR5 
iBOR 
iCR 
iCR,
iP
R, iUPD, NE 
iCR, iPR, iUPD, NE iUPD 
iCPD 
iCR 
iUPD 
iPR, iSD, NE iCR 
iCR, iPR, iSD, iUPD, NE iCR, iPR, iSD, iUPD, iCPD, NE iCR 
iUPD 
iPR 
iPR, iSD, iUPD, NE iPR, iSD, iUPD, NE, iCPD iPR, iSD, iUPD, NE, iCPD 
iPR 
iUPD 
iSD, NE 
PR 
iPR, iSD, iUPD, NE 
iPR, iSD, iUPD, iCPD, NE 
iPR 
iUPD 
iSD 
iSD, iUPD, NE 
iSD, iUPD, iCPD, NE 
iSD, iUPD, ICPD, NE 
iSD 
iUPD 
iCPD 
Anything 
Anything 
Anything 
iCPD 
iUPD 
iUPD 
iCPD 
Anything 
Anything 
iCPD 
iUPD 
NE 
NE 
NE 
NE 
iUPD 
• 
Table assumes a randomised study where confirmation of CR or PR is not required. 
• 
NE = not evaluable that cycle. 
• 
Designation “I” for BOR can be used to indicate prior iUPD to aid in data interpretation. 
• 
For patients with non-target disease only at baseline, only CR or non-CR/non-PD can be assigned at each 
TPR but is not shown in the table for ease of presentation. 
5 
Response and Stable Disease Duration (RECIST 1.1 and iRECIST) 
Response duration will be measured from the time measurement criteria for CR/PR or 
iCR/iPR (whichever is first recorded) are first met until the first date that recurrent or 
progressive disease is objectively documented, taking as reference the smallest 
measurements recorded on study (including baseline). 
Stable disease duration will be measured from the time of start of treatment until the criteria 
for progression are met, taking as reference the smallest sum on study (including baseline). 
6 
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. Assessments should be 
identified on a calendar schedule and should not be affected by delays in therapy. While on 
study, all lesions recorded at baseline should have their actual measurements recorded at 
each subsequent evaluation, even when very small (e.g., 2 mm). If it is the opinion of the 
radiologist that the lesion has likely disappeared, the measurement should be recorded as 0 
mm. If the lesion is believed to be present and is faintly seen but too small to measure, a 
default value of 5 mm should be assigned. For lesions which fragment/split add together the 
longest diameters of the fragmented portions; for lesions which coalesce, measure the 
maximal longest diameter for the “merged lesion”. 
6.1 
Clinical Lesions. Clinical lesions are not useful in assessment of lesion size 
and should not be used as a method of measurement and will not be an 
allowed modality for lesion determinations in this study. For qualitative use of 
skin lesions, documentation by color photography including a ruler to estimate 

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the size of the lesion is recommended. If feasible, imaging is preferred.Chest 
X-ray. Chest CT is preferred over chest X-ray, particularly when progression 
is an important endpoint, since CT is more sensitive than X-ray, particularly in 
identifying new lesions. Chest X-ray is not useful in assessment of lesion size 
and should not be used as a method of measurement and will not be an 
allowed modality for lesion determinations in this study. 
6.2 
CT, MRI. CT is the best currently available and reproducible method to measure 
lesions selected for response assessment. This guideline has defined 
measurability of lesions on CT scan based on the assumption that CT slice 
thickness is 5 mm or less. When CT scans have slice thickness greater than 5 
mm, the minimum size for a measurable lesion should be twice the slice 
thickness. MRI is also acceptable in certain situations (e.g. for body scans, liver 
lesions). While PET scans are not considered adequate to measure lesions, PET-
CT scans may be used providing that the measures are obtained from the CT 
scan and the CT scan is of identical diagnostic quality to a diagnostic CT (with 
IV and oral contrast). 
6.3 
Ultrasound. Ultrasound is not useful in assessment of lesion size and should not 
be used as a method of measurement. If new lesions are identified by ultrasound 
during the study, confirmation by CT is advised. 
6.4 
Endoscopy, Laparoscopy. The utilization of these techniques for objective 
tumor evaluation is not advised. However, they can be useful to confirm 
complete pathological response when biopsies are obtained or to determine 
relapse in trials where recurrence following complete response or surgical 
resection is an endpoint. 
6.5 
Tumor Markers. Tumor markers alone cannot be used to assess objective tumor 
response. Note: If markers are initially above the upper normal limit, they may 
need to normalize for a patient to be considered in complete response. Note: this 
should be discussed with the Alaunos Medical Monitor. 
6.6 
Cytology, Histology. When effusions are known to be a potential adverse effect 
of treatment (e.g., with certain taxane compounds or angiogenesis inhibitors), 
the cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment when the measurable tumor has met 
criteria for response or stable disease is advised to differentiate between 
response or stable disease and progressive disease 
 
 
 

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APPENDIX J. IMMUNE-EFFECTOR CELL TOXICITY ASSESSMENT AND MANAGEMENT 
Immune-effector cell toxicity assessment and management should be performed per the CARTOX criteria (https://www.mdanderson.org/documents/for-
physicians/algorithms/clinical-management/clin-management-cytokine-release-web-algorithm.pdf). 
Table 22: 
Management of CRS 
CRS Grade 
CRS Parameter 
Management 
Diagnostic Work-Up 
Supportive Care 
Anti-IEC Therapies 
Grade 1 
Fever 
● Assess for infection with 
blood and urine cultures, 
and chest radiography 
● Cardiac telemetry and 
pulse oximetry 
● Acetaminophen and hypothermia blanket as needed for 
the treatment of fever 
● Ibuprofen if fever is not controlled with above; use with 
caution or avoid with thrombocytopenia or renal 
dysfunction 
● Empiric broad-spectrum antibiotics and consider 
filgrastim products if neutropenic 
● Maintenance IV fluids for hydration 
● Symptomatic management of constitutional symptoms 
and organ toxicities as per standard guidelines 
● If not on seizure prophylaxis, initiate levetiracetam 500 
mg PO twice daily 
● Administer tocilizumab1 for 1 dose for 
persistent fever lasting greater than 3 days 
1 See Table 24  for Dosing of IL-6 Antagonists and Alternative Agents 

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Management of CRS - continued 
 
CRS Grade 
CRS Parameter 
Management 
Diagnostic Work-up 
Supportive Care 
Anti-IEC Therapies 
Grade 2 
Hypotension 
● Cardiac telemetry 
● Fever work-up if not 
previously performed 
○ Assess for infection with 
blood and urine cultures, 
and chest radiography 
● IV fluid bolus of 500 – 1,000 mL normal saline; repeat once 
as needed to maintain normal BP 
● If hypotension persists after IV fluids, tocilizumab, and 
dexamethasone, start vasopressors, 
transfer patient to ICU, obtain ECHO, and refer to further 
management as in Grade 3 or 4 CRS 
● Symptomatic management of fever as in Grade 1 CRS 
● Symptomatic management of constitutional symptoms and 
organ toxicities as per standard guidelines 
● Administer tocilizumab1 for 1 dose and 
consider dexamethasone 4 - 10 mg IV for 
1 dose (or methylprednisolone equivalent) 
and reassess in 6 hours or earlier if 
clinically indicated 
○ Tocilizumab may be repeated every 8 
hours for up to 3 doses in a 24-hour 
period 
Hypoxia 
● Pulse oximetry 
● Fever work-up if not 
previously performed 
○ Assess for infection with 
blood and urine cultures, 
and chest radiography 
● Use supplemental oxygen as needed 
● If hypoxia persists after above interventions, but oxygen 
requirement is stable with low-flow nasal cannula, continue 
close monitoring. If oxygen requirement increases to high-
flow nasal cannula, face mask, or positive pressure 
ventilation, refer to further management as in Grade 3 or 4 
CRS 
● Symptomatic management of fever as in Grade 1 CRS 
● Symptomatic management of constitutional symptoms and 
organ toxicities as per standard guidelines 
● Administer tocilizumab1 for 1 dose and 
consider dexamethasone 4 - 10 mg IV for 
1 dose (or methylprednisolone equivalent) 
and reassess in 6 hours or earlier if 
clinically indicated 
○ Tocilizumab may be repeated every 8 
hours for up to 3 doses in a 24-hour 
period 
1 See Table 24  for Dosing of IL-6 Antagonists and Alternative Agents 

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Management of CRS - continued 
 
CRS Grade 
CRS Parameter 
Management 
Diagnostic Work-up 
Supportive Care 
Anti-IEC Therapies 
Grade 3 
Hypotension 
● Obtain ECHO if not 
performed already 
● Cardiac telemetry 
● Fever work-up if not 
previously performed 
○ Assess for infection with 
blood and urine cultures, 
and chest radiography 
● Transfer patient to ICU 
● IV fluid boluses as needed as in Grade 
2 CRS 
● Use vasopressors as needed 
● Symptomatic management of fever as 
in Grade 1 CRS 
● Symptomatic management of 
constitutional symptoms and organ 
toxicities as per standard guidelines 
● Tocilizumab1 as in Grade 2 CRS if not administered previously; 
tocilizumab may be repeated every 8 hours for up to 3 doses in a 24-
hour period 
● If on one vasopressor: tocilizumab as in Grade 2 CRS and 
dexamethasone 10 mg IV every 6 hours (or methylprednisolone 
equivalent) 
● If on two vasopressors: tocilizumab as in Grade 2 CRS and 
dexamethasone 20 mg IV every 6 hours (or methylprednisolone 
equivalent) 
● If vasopressin and norepinephrine equivalent2 is ≥ 15 mcg/minute, 
follow as in Grade 4 CRS 
● Once CRS improves to Grade 1 or less, taper and/or stop 
corticosteroids depending on clinical situation 
Hypoxia 
● Pulse oximetry 
● Fever work-up if not 
previously performed 
○ Assess for infection with 
blood and urine cultures, 
and chest radiography 
● Supplemental oxygen including high- 
flow nasal cannula, face mask, non- 
rebreather mask, or Venturi mask as 
needed 
● Symptomatic management of fever as 
in Grade 1 CRS 
● Symptomatic management of 
constitutional symptoms and organ 
toxicities as per standard guidelines 
● Tocilizumab1 and dexamethasone 10 mg IV every 6 hours (or 
methylprednisolone equivalent) if not administered previously; 
tocilizumab may be repeated every 8 hours for up to 3 doses in a 24-
hour period 
● If there is no improvement in hypoxia within 24 hours or there is 
rapid progression of pulmonary infiltrates or sharp increase in FiO2 
requirements, increase dexamethasone to 20 mg IV every 6 hours (or 
methylprednisolone equivalent) 
● Once CRS improves to Grade 1 or less, taper and/or stop 
corticosteroids depending on clinical situation 
1 See Table 24 for Dosing of IL-6 Antagonists and Alternative Agents 
2 VASST Trial vasopressor equivalent equation: norepinephrine equivalent dose = [norepinephrine (mcg/minute)] + [dopamine (mcg/kg/minute) / 2] + [epinephrine (mcg/minute)] 
+ [phenylephrine (mcg/minute) / 10] 

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Management of CRS - continued 
 
CRS Grade 
CRS Parameter 
Management 
Diagnostic Work-up 
Supportive Care 
Anti-IEC Therapies 
Grade 4 
Hypotension 
● Obtain ECHO if not 
performed already 
● Cardiac telemetry 
● Fever work-up if not 
previously performed 
○ Assess for infection 
with blood and urine 
cultures, and chest 
radiography 
● Transfer patient to ICU 
● IV fluid boluses as needed as in 
Grade 2 CRS 
● Vasopressors as in Grade 3 CRS 
● Use vasopressors as needed 
● Symptomatic management of fever as 
in Grade 1 CRS 
● Symptomatic management of 
constitutional symptoms and organ 
toxicities as per standard guidelines 
● Tocilizumab1 as in Grade 2 CRS if not administered previously; 
tocilizumab may be repeated every 8 hours for up to 3 doses in a 24-
hour period 
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days 
followed by rapid taper as per clinical situation 
● If hypotension is refractory for ˃ 24 hours or if patient is deteriorating 
rapidly, consider additional therapies (see Table 24 including 
activation of safety switches if applicable 
Hypoxia 
● Monitor oxygen 
saturation while on 
mechanical ventilation 
● Fever work-up if not 
previously performed 
○ Assess for infection 
with blood and urine 
cultures, and chest 
radiography 
● Transfer patient to ICU 
● Positive pressure ventilation 
including CPAP, BiPAP, mechanical 
ventilation 
● Symptomatic management of fever as 
in Grade 1 CRS 
● Symptomatic management of 
constitutional symptoms and organ 
toxicities as per standard guidelines 
● Tocilizumab1 as in Grade 2 CRS if not administered previously; 
tocilizumab may be repeated every 8 hours for up to 3 doses in a 24-
hour period 
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days 
followed by rapid taper as per clinical situation 
● If hypoxia is refractory for > 24 hours or if patient is deteriorating 
rapidly, consider additional therapies (see Table 24) including activation 
of safety switches if applicable 
1 See Table 24 for Dosing of IL-6 Antagonists and Alternative Agents 
 
 
 
 
 
 

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Table 23: 
Management of ICANS 
ICANS 
Grade 
Sign or 
symptom 
Management 
Diagnostic Work-up 
Supportive Care 
Anti-IEC Therapies 
Grade 1 
Encephalopathy 
and/or 
depressed level 
of 
consciousness 
● MRI imaging of the brain with and without 
contrast; CT of brain without contrast may be 
performed if MRI is not feasible; MRI spine 
if focal deficits are noted 
● Neurology consultation 
● ICE Score assessment every 6 hours or more 
frequently if clinically indicated 
● EEG 
● Consider diagnostic lumbar puncture if other 
causes of encephalopathy are suspected (e.g., 
infections, autoimmune, leptomeningeal 
disease) 
○ Add a meningitis-encephalitis panel from CSF 
in patients with neurologic symptoms that 
persist or worsen after ICANS therapy and/or 
if symptoms start after corticosteroids 
● Vigilant supportive care; aspiration precautions; IV 
hydration 
● Withhold oral intake of food/medications/fluids and 
assess swallowing; convert all oral medications 
and/or nutrition to IV if swallowing is impaired 
● Avoid medications that cause central nervous system 
depression 
● Low doses of lorazepam after EEG is performed 
(0.25-0.5 mg IV every 8 hours) or 
haloperidol (0.5 mg IV every 6 hours) may be used 
with careful monitoring for agitated patients 
● If no seizures on EEG, continue prophylactic 
levetiracetam 
● If EEG shows focal or generalized convulsive or non- 
convulsive seizure or convulsive status epilepticus, 
refer to further management as in Grade 3 or 4 
ICANS 
● Dexamethasone 10 mg IV for 1 dose (or 
methylprednisolone equivalent) and reassess 
in 6 hours or earlier if clinically indicated 
○ If associated with concurrent CRS, add 
tocilizumab1 
Grade 2 
Encephalopathy 
and/or 
depressed level 
of 
consciousness 
● Neurological work-up as in Grade 1 ICANS 
● Supportive care as in Grade 1 ICANS 
● Dexamethasone 10 mg IV every 12 hours (or 
methylprednisolone equivalent) 
○ If associated with concurrent CRS, add 
tocilizumab1 
● Once ICANS improves to Grade 1 or less, 
taper and/or stop corticosteroids depending 
on clinical situation 
 

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ICANS 
Grade 
Sign or 
symptom 
Management 
Diagnostic Work-up 
Supportive Care 
Anti-IEC Therapies 
 
Grade 3 
Encephalopathy 
and/or 
depressed level 
of 
consciousness 
● Neurological work-up as in Grade 1 ICANS 
● Consider repeat neuro-imaging (CT or MRI) 
every 2-3 days for persistent ≥ Grade 3 
encephalopathy 
● Consider diagnostic lumbar puncture if 
Grade 3 encephalopathy persists ≥ 2 days or 
earlier if other causes are suspected 
(e.g., infections, autoimmune, leptomeningeal 
disease) 
○ Add a meningitis-encephalitis panel from 
CSF in patients with neurologic symptoms 
that persist or worsen after ICANS therapy 
and/or if symptoms start after corticosteroids 
● Supportive care as in Grade 1 ICANS 
● Consider ICU transfer 
● If there are new abnormal findings on brain 
imaging1 not related to primary malignancy, 
control hypertension with the goal of 
maintaining mean arterial pressure (MAP) within 
20-25 mmHg of baseline MAP; correct any 
uremia (dialysis if needed) and/or coagulopathy 
(transfuse to keep platelets > 20-50 K/microliter, 
fibrinogen > 200 mg/dL and INR < 1.5) 
● Dexamethasone 10 mg IV every 6 hours (or 
methylprednisolone equivalent) 
○ If associated with concurrent CRS, add tocilizumab2 
● If Grade 3 encephalopathy is persistent for > 24 hours, 
increase dexamethasone to 20 mg IV every 6 hours (or 
methylprednisolone equivalent) 
● Once ICANS improves to Grade 1 or less, taper and/or 
stop corticosteroids depending on clinical situation 
Seizure 
● Neurological work-up as in Grade 1 ICANS 
● EEG if clinically indicated (e.g., ongoing 
seizures, depressed level of consciousness) 
● Rule out other potential causes of 
seizure (i.e., beta-lactams, etc.) 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● For focal or generalized convulsive seizures, or 
non- 
convulsive seizures, treat as per Appendix K  
● Dexamethasone 20 mg IV every 6 hours (or 
methylprednisolone equivalent) 
○ If associated with concurrent CRS, add tocilizumab2 
● Once ICANS improves to Grade 1 or less, taper and/or 
stop corticosteroids depending on clinical situation 
Focal cerebral 
edema 
● Neurological work-up as in Grade 1 ICANS 
● Consider repeat neuro-imaging (CT or MRI) 
every 24 hours until edema resolves or more 
frequently if clinically indicated 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● If focal edema is in brain stem or thalamus, 
methylprednisolone 1,000 mg/day in divided doses IV for 
3 days followed by taper depending on clinical situation 
○ If associated with concurrent CRS, add tocilizumab2 
● If focal edema is in other areas of brain, 
methylprednisolone 1,000 mg/day in divided doses IV for 
1 day; assess daily and continue or taper depending on 
clinical situation 
○ If associated with concurrent CRS, add tocilizumab2 
1Abnormal findings on imaging where correction of hypertension, uremia, and/or coagulopathy should be performed include changes suggestive of typical or atypical posterior reversible encephalopathy 
syndrome (PRES), temporal lobe and limbic system encephalitis (autoimmune or infection), acute disseminated encephalomyelitis, emboli, vasculitis, strokes, and/or seizure-related changes  
2See Table 24 for Dosing of IL-6 Antagonists and Alternative Agents 
 
 
 

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ICANS 
Grade 
Sign or 
symptom 
Management 
Diagnostic Work-Up 
Supportive Care 
Anti-IEC Therapies 
Grade 4 
Encephalopathy 
and/or depressed 
level of 
consciousness 
● Neurological work-up 
as in Grade 1 ICANS 
● Repeat neuro-imaging 
and lumbar puncture 
as in Grade 3 ICANS 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● Consider mechanical ventilation for airway 
protection 
● If there are new abnormal findings on brain 
imaging1 not related to primary malignancy, 
control hypertension with the goal of maintaining 
MAP within 20-25 mmHg of baseline MAP; 
correct any uremia (dialysis if needed) and/or 
coagulopathy (transfuse to keep platelets > 20 - 
50 K/microliter, fibrinogen > 200 mg/dL and INR < 
1.5) 
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days followed 
by taper as clinically indicated; if associated with concurrent CRS, add 
tocilizumab2 
● Continue corticosteroids until improvement to less than or equal to Grade 1 
ICANS and then taper and stop corticosteroids depending on clinical situation 
● If Grade 4 ICANS is refractory for ˃ 24 hours or if patient is deteriorating 
rapidly, consider additional therapies  (see Table 24 )including activation 
of safety switches if applicable 
Seizure 
● Neurological work-up 
as in Grade 1 ICANS 
● Rule out other potential 
causes of seizure (i.e., 
beta-lactams, etc.) 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● For focal or generalized convulsive or non-
convulsive seizure or convulsive status 
epilepticus, treat as in Appendix K  
● For convulsive status epilepticus, treat as in 
Appendix L  
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days followed by 
taper as clinically indicated; if associated with concurrent CRS, add tocilizumab2 
● If Grade 4 ICANS is refractory for ˃ 24 hours or if patient is deteriorating 
rapidly, consider additional therapies (see Table 24 ) including activation 
of safety switches if applicable 
Motor Weakness 
● Neurological work-up 
as in Grade 1 ICANS 
● MRI with and without 
contrast of the spine 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days followed by 
taper as clinically indicated; if associated with concurrent CRS, add 
tocilizumab2 
● If Grade 4 ICANS is refractory for ˃ 24 hours or if patient is deteriorating 
rapidly, consider additional therapies (see Table 24 ) including activation 
of safety switches if applicable 
Diffuse cerebral 
edema or raised 
intracranial 
pressure 
● Neurological work-up 
as in Grade 1 ICANS 
● Consider repeat neuro- 
imaging as in focal 
cerebral edema from 
Grade 3 ICANS 
● Transfer to ICU 
● Supportive care as in Grade 1 ICANS 
● For diffuse cerebral edema or signs of raised 
intracranial 
pressure, treat as in Table 25   
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days followed 
by taper as clinically indicated; if associated with concurrent CRS, add 
tocilizumab2 
● If Grade 4 ICANS is refractory for ˃ 24 hours or if patient is deteriorating 
rapidly, consider additional therapies (see Table 24 ) including activation 
of safety switches if applicable 

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1Abnormal findings on imaging where correction of hypertension, uremia, and/or coagulopathy should be performed include changes suggestive of typical or atypical posterior reversible encephalopathy syndrome 
(PRES), temporal lobe and limbic system encephalitis (autoimmune or infection), acute disseminated encephalomyelitis, emboli, vasculitis, strokes, and/or seizure-related changes. 2 See Table 24 for dosing of IL-6 
 
Table 24: 
Recommendations for Use of IL-6 Antagonists and Alternative Agents for Management of CRS and ICANS 
Drug 
Recommended Dose for CRS and/or ICANS 
Maximum Dose 
Mechanism of Action 
Comments 
Tocilizumab 
8 mg/kg IV 
Maximum 800 mg 
per dose 
IL-6 receptor antagonist 
● Maximum of 4 doses total over the entire course of CRS 
andICANS 
● Dose may be repeated every 8 hours for up to three doses in a 
24-hour period 
Siltuximab 
11 mg/kg IV once 
- 
IL-6 antibody 
● Recommended primarily for patients who are intolerant to 
tocilizumab 
● No more than 1 dose in a 3-week period 
Anakinra 
100 mg subcutaneously daily for 7 days 
- 
IL-1 receptor antagonist 
● Renal dose adjustment may be needed for creatinine 
clearance < 30 mL/minute 
Cyclophosphamide 1,500 mg/m2 IV for one dose 
- 
Alkylating agent 
● Give with mesna 1500 mg/m2 IV over 24 hours for one dose 
Anti-thymocyte 
globulin (rabbit) 
1-2 mg/kg IV daily for 3 days 
- 
Immunosuppressant 
● Hypersensitivity reactions can occur; premedicate with 
diphenhydramine and scheduled dose of corticosteroid 
● Infuse over a minimum of 6 hours 
Safety switches 
- 
- 
- 
● If the IEC product contains a safety switch (e.g., iCapsase-9 or 
EGFRt-positive), the corresponding drug to eliminate those 
cells can be considered in doses according to manufacturer 
Examples include rimiducid to eliminate iCaspase-9 or 
cetuximab to eliminate EGFRt-positive cells 
 
 
 
 

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APPENDIX K.  MANAGEMENT OF FOCAL OR GENERALIZED CONVULSIVE OR NON-CONVULSIVE SEIZURES 
• Consult Neurology 
• For focal and generalized convulsive seizures, lorazepam 1-2 mg IV and repeat as needed (to a maximum cumulative dose of 4 mg) 
• For electrographical seizures, including non-convulsive status epilepticus, lorazepam 0.5 mg IV and repeat every 5 minutes as needed (to a maximum cumulative dose of 
2 mg) 
• Levetiracetam 500-1,500 mg IV bolus (in addition to maintenance dose) 
• Replete with magnesium as needed to maintain magnesium level > 2 mg/dL 
• Thiamine 100 mg IV every 8 hours for 5 days 
• If non-convulsive seizures persist, transfer to ICU and add phenobarbital loading dose of 60 mg IV (monitor for respiratory depression, bradycardia and hypotension) 
• Maintenance doses after resolution of non-convulsive status epilepticus 
o Lorazepam 0.5 mg IV every 8 hours for 3 doses 
o Levetiracetam 1,000-1,500 mg IV every 12 hours 
o Phenobarbital 30 mg IV every 12 hours (~0.5 mg/kg every 12 hours) 
 Monitor for respiratory depression, bradycardia and hypotension 
 Assess for drug-drug interactions (i.e., may induce metabolism of azole antifungals or other CYP3A4 substrates) and consider alternative therapy if drug 
interactions are significant 
 Target serum trough levels 15-40 mcg/mL 
 
 

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APPENDIX L.  MANAGEMENT OF CONVULSIVE STATUS EPILEPTICUS 
• Assess circulation, airway, breathing (CAB) / consider airway protection / check blood glucose 
• Transfer to ICU 
• Consult Neurology 
• Lorazepam 0.1 mg/kg (maximum 4 mg/dose) given at a maximum rate of 2 mg/minute; may repeat in 5 to 10 minutes 
• Levetiracetam 500-1,500 mg IV bolus (in addition to maintenance dose) 
• Replete with magnesium as needed to maintain magnesium > 2 mg/dL 
• Thiamine 100 mg IV every 8 hours for 5 days 
• If seizures persist, add phenobarbital loading dose of 15 mg/kg IV (monitor for respiratory depression, bradycardia and hypotension) 
• If refractory, consider additional therapies (see Appendix K) including activation of safety switches if applicable 
• Maintenance doses after resolution of convulsive status epilepticus 
o Levetiracetam 1,000-1,500 mg IV every 12 hours 
o Phenobarbital 0.5 mg/kg IV every 12 hours 
 Monitor for respiratory depression, bradycardia and hypotension 
 Assess for drug-drug interactions (i.e., may induce metabolism of azole antifungals or other CYP3A4 substrates) and consider alternative therapy if drug 
interactions are significant 
 Target serum trough levels 15-40 mcg/mL 
• Continuous EEG monitoring if seizures are refractory to treatment 
 

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Table 25: 
Management of Diffuse Cerebral Edema and/or Raised Intracranial Pressure 
For papilledema without diffuse 
cerebral edema or other signs of raised 
intracranial pressure 
● Acetazolamide 1,000 mg IV followed by 250-1,000 mg IV every 12 hours (monitor renal function and acid/base balance once or 
twice daily and adjust dose accordingly) 
● Dexamethasone 20 mg IV every 6 hours (or methylprednisolone equivalent) and start taper after resolution of papilledema 
For diffuse cerebral edema on 
neuroimaging or signs of raised 
intracranial pressure such as 
decerebrate or decorticate posturing, 
cranial nerve VI palsy, or Cushing’s 
triad 
● Methylprednisolone 1,000 mg/day in divided doses IV for 3 days followed by taper as clinically indicated 
● Elevate head end of patient’s bed to an angle of 30 degrees 
● Hyperventilation to achieve target PaCO2 of 28-30 mmHg, but maintained for no longer than 24 hours 
● Hyperosmolar therapy with either mannitol (20 g/dL solution) or hypertonic saline (3% or 23.4% as detailed below) 
○ Mannitol: initial dose 0.5-1 g/kg IV; maintenance dose 0.25-1 g/kg IV every 6 hours while monitoring metabolic profile and 
serum osmolality every 6 hours; and withhold mannitol if serum osmolality is ≥ 320 mOsm/kg or osmolality gap is ≥ 40) 
○ Hypertonic 3% saline: initial dose 250 mL IV over 15 minutes, maintenance dose of 50-75 mL/hour IV while monitoring 
electrolytes every 4 hours; withhold infusion if serum sodium levels reach ≥ 155 mEq/L) 
○ Hypertonic 23.4% saline (for patients with imminent herniation): dose to be administered by physician; initial dose of 30 mL IV; 
repeat after 15 minutes, if needed 
● If patient has ommaya reservoir, drain CSF to target OP < 20 mmHg 
● Control hypertension with the goal of maintaining mean arterial pressure (MAP) within 20-25 mmHg of baseline MAP; correct any 
uremia (dialysis if needed) and/or coagulopathy (transfuse to keep platelets ˃ 20-50 K/microliter, fibrinogen ˃ 200 mg/dL and INR 
< 1.5) 
● Consider neurosurgery consultation and IV anesthetics for burst-suppression pattern on EEG; transfuse to keep platelets ≥ 100 
K/microliter if possible and correct coagulopathy in case of surgical intervention 
● Consider additional therapies (see Table 24 ) including activation of safety switches if applicable 
● Metabolic profile every 6 hours and daily CT scans of head without contrast, with adjustments in usage of aforementioned 
medications to prevent rebound cerebral edema, renal failure, electrolyte abnormalities, hypovolemia and hypotension 

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