Tumor-Associated Antigen (TAA) Specific Cytotoxic T Lymphocytes Administered in Patients With Pancreatic Cancer
Phase: PHASE1
Conditions: Pancreatic Cancer
Sponsor: Baylor College of Medicine

Cover Page 
Official Study Title 
TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC CYTOTOXIC T LYMPHOCYTES 
ADMINISTERED IN PATIENTS WITH PANCREATIC CANCER (TACTOPS) 
 
NCT Number 
03192462 
 
Document/Version 
Date 
01/13/2022 
 
 

TACTOPS Version 1.0 2/20/2017 
Version 3.1 8/8/2017 
Version 5.0 10/2/2018 
Version 9.0 9/25/2020 
Version 2.0 3/29/20 
Version 3.2 10/04/2017 
Version 6.0 7/30/2019                    Version 9.1  1/13/2022 
Version 2.1 5/26/2017 
Version 4.0 1/12/2018 
Version 7.0 11/8/2019 
Version 3.0 6/27/2017 
Version 4.1 4/24/2018 
Version 8.0 2/7/2020 
 
 
 
TUMOR-ASSOCIATED ANTIGEN (TAA)-SPECIFIC CYTOTOXIC T LYMPHOCYTES 
ADMINISTERED IN PATIENTS WITH PANCREATIC CANCER (TACTOPS) 
 
 
 
 
PRINCIPAL INVESTIGATORS 
 
Ann M. Leen, PhD 
Benjamin Musher, MD 
 
 
CO-INVESTIGATORS 
Helen Heslop, MD 
Adrian Gee, PhD 
Bambi Grilley, RPh 
Carlos Ramos, MD 
Premal Lulla, MD 
George Carrum, MD  
Tannaz Armaghany, MD 
 
 
STATISTICAL CO-INVESTIGATOR 
Tao Wang, PhD 
 
Center for Cell and Gene Therapy 
Houston Methodist Hospital 
6565 Fannin St. 
Houston, TX 77030-2707 
 
Dan L. Duncan Comprehensive Cancer Center 
Baylor College of Medicine 
 
Conducted under Investigator-held IND: 17588 
 
 
 
 
 
 
 
 
 
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TACTOPS Version 9.1 1/13/2022 
 
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Table of Contents 
1.0 CHECKLIST FOR PATIENT ELIGIBILITY AND NECESSARY INFORMATION ................... 3 
2.0 OBJECTIVES .......................................................................................................................... 6 
3.0. BACKGROUND AND RATIONALE ....................................................................................... 6 
3.1 
TARGETING EBV-ASSOCIATED MALIGNANCIES USING ADOPTIVELY TRANSFERRED T CELLS ..................... 6 
3.2 
ADOPTIVE IMMUNOTHERAPY FOR NON-VIRAL TUMORS ....................................................................................... 6 
3.3 
CLINICAL EXPERIENCE TARGETING NON-VIRAL TAAS ........................................................................................ 7 
3.4 
TARGETING LYMPHOMA, MYELOMA AND SOLID TUMORS USING TUMOR-TARGETED T CELLS ............................ 8 
3.5 
EXTENDING OUR APPROACH TO TREAT PANCREAS CANCER .............................................................................. 8 
4.0 PATIENT ELIGIBILITY ........................................................................................................... 9 
4.1 
PROCUREMENT INCLUSION CRITERIA ..................................................................................................................... 9 
4.2 
PROCUREMENT EXCLUSION CRITERIA ................................................................................................................... 9 
4.3 
TREATMENT INCLUSION CRITERIA ........................................................................................................................... 9 
4.4 
TREATMENT EXCLUSION CRITERIA ...................................................................................................................... 11 
5.0 STUDY DESIGN ................................................................................................................... 11 
5.1 
BLOOD PROCUREMENT FOR MULTITAA T CELL AND APC GENERATION.............................................................. 12 
5.2 
ADMINISTRATION AND MONITORING ..................................................................................................................... 13 
6.0 TREATMENT PLAN.............................................................................................................. 14 
6.1 
DOSAGE ..................................................................................................................................................................... 14 
6.2 
DOSE SCHEDULE ...................................................................................................................................................... 14 
7.0   PATIENT EVALUATION ...................................................................................................... 14 
8.0 STUDY EVALUATIONS ........................................................................................................ 20 
9.0 STATISTICAL CONSIDERATIONS ...................................................................................... 20 
9.1 STUDY DESIGN SYNOPSIS .......................................................................................................................................... 20 
9.2 SAMPLE SIZE DETERMINATION AND TRIAL MONITORING ..................................................................................... 21 
9.3 STATISTICAL ANALYSIS ................................................................................................................................................ 21 
10.0 MODIFIED FOLLOW-UP AND OFF STUDY CRITERIA ...................................................... 23 
11.0   RECORDS TO BE KEPT ................................................................................................... 24 
12.0 REPORTING REQUIREMENTS ........................................................................................... 24 
13.0 INFORMED CONSENT ......................................................................................................... 25 
14.0 CLINICAL TRIAL OVERSIGHT AND MONITORING ........................................................... 25 
REFERENCE LIST ....................................................................................................................... 26 
APPENDIX I - GRADING OF CRS ............................................................................................... 31 

TACTOPS Version 9.1 1/13/2022 
 
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1.0 CHECKLIST FOR PATIENT ELIGIBILITY AND NECESSARY INFORMATION 
TUMOR CTL PROTOCOL (PROCUREMENT) 
PATIENT ID 
PATIENT NAME 
_ 
 
 
 
YES 
NO 
 
Any “NO” answers will make a patient ineligible for study participation. 
 
 
Any patient with biopsy proven pancreatic adenocarcinoma 
 
 
Life expectancy of  6 months 
 
 
Age > 18 
 
 
Hgb ≥ 7.0 g/dl (transfusion allowed) 
 
 
Informed Consent explained to, understood by and signed by patient. Patient given copy 
of informed consent. 
 
 
YES 
NO 
 
Any “YES” answers will make a patient ineligible for study participation. 
 
 
Severe intercurrent infection 
 
 
Active infection with HIV (can be pending at this time) 
 
 
 
Signature of MD 
Date 
_  
 
 
To check eligibility of a patient, telephone Dr. Musher at 713-798-3750. To register a patient, telephone 
Catherine Robertson (research coordinator) at the Center for Cell and Gene Therapy (832-824-4594). 

TACTOPS Version 9.1 1/13/2022 
 
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PATIENT ID 
PATIENT NAME 
_ 
 
 
TUMOR CTL PROTOCOL (TREATMENT) 
 
YES 
NO 
VALUE/DATE 
 
Any "NO" answers will make a patient ineligible for study participation: 
 
YES 
NO 
VALUE/DATE  
Any “NO” answers will make a patient ineligible for study participation. 
 
 
 
Any patient with biopsy proven pancreatic adenocarcinoma who has: 
 
Group A: Patients with locally advanced or metastatic pancreatic 
adenocarcinoma who experienced a documented best response of investigator 
assessed confirmed PR or SD per RECIST v1.1 
 
Group B: Patients with locally advanced or metastatic pancreatic 
adenocarcinoma who experienced progressive disease following first line 
chemotherapy or who are judged by the investigator as being ineligible to 
receive standard of care chemotherapy 
 
Group C: Patients with potentially resectable pancreatic cancer, who have 
completed planned preoperative neo-adjuvant chemotherapy, radiotherapy or 
combination chemoradiation 
 
 
 
Life expectancy of  12 weeks. 
 
 
 
Measurable or evaluable disease per RECIST 1.1 criteria 
 
 
 
Age > 18 
 
 
 
Pulse oximetry of >95% on room air in patients with previous radiation therapy 
 
 
 
ECOG score of ≤ 2 or Karnofsky score of  50. 
 
 
 
Bilirubin < 2 x upper limit of normal 
 
 
 
Creatinine < 2x upper limit of normal for age 
 
 
 
AST < 3x upper limit of normal 
 
 
 
Hgb ≥ 7.0 g/dl (transfusion allowed) 
 
 
 
Off investigational therapy for 1 month prior to receiving treatment on this study. 
 
 
 
For entry into Groups B or C patients must be off conventional therapy for at 
least 1 week prior to receiving treatment on this study. 
 
 
 
Informed Consent explained to, understood by and signed by patient. Patient 
given copy of informed consent. 
 
 
 
Due to unknown effects of this therapy on a fetus, pregnant women are 
excluded from this research. The male partner should use a condom. Females 
of child-bearing potential must be willing to utilize one of the more effective birth 
control methods during the study unless female has had a hysterectomy or tubal 
ligation. 

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PATIENT ID 
PATIENT NAME 
_ 
 
 
TUMOR CTL PROTOCOL (TREATMENT) 
 
 
 
YES 
NO 
 
Any “YES” answers will make a patient ineligible for study participation. 
 
 
Severe intercurrent infection 
 
 
Receiving systemic corticosteroids (patients off steroids for at least 48 hours are eligible) 
 
 
Pregnant 
 
 
HIV positive 
 
 
Signature of MD 
Date 
_  
 
 
To check eligibility of a patient, telephone Dr. Musher at 713-798-3750. To register a patient, 
telephone the Center for Cell and Gene Therapy research coordinator at 832-824-4594 

TACTOPS Version 9.1 1/13/2022 
 
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2.0 
OBJECTIVES 
 
Primary endpoint 
2.1 To determine the safety of up to 6 intravenous infusions of multiTAA-specific T cells in 
pancreatic cancer patients with metastatic, locally advanced unresectable, or 
resectable disease. 
 
2.2 To determine the feasibility of completing a total of 6 intravenous infusions of multiTAA- 
specific T cells to pancreatic cancer patients with metastatic, locally advanced 
unresectable, or resectable disease. 
 
Secondary endpoint 
2.3 
To evaluate the progression-free and overall survival of patients after multiTAA- 
specific T cell infusions 
 
Tertiary endpoints 
2.4 
To obtain information on the expansion, persistence and anti-tumor effects of the 
adoptively-transferred TAA-specific T cells 
 
2.5 
To determine whether multiTAA-specific T cell infusion enables recruitment of the 
patients’ endogenous immune system as measured by epitope/antigen spreading 
 
3.0.      BACKGROUND AND RATIONALE 
 
3.1 
Targeting EBV-associated malignancies using adoptively transferred T cells 
The adoptive transfer of antigen-specific T cells has proven safe and effective when used to prevent 
and treat a range of virus-associated malignancies including EBV-associated post- transplant 
lymphoproliferative disease (PTLD), nasopharyngeal cancer (NPC) and EBV- associated Hodgkin 
(HL) and non-Hodgkin lymphoma (NHL). 
 
3.2 
Adoptive immunotherapy for non-viral tumors 
More recently we have extended the scope of our immune-based therapies to include non-viral 
tumor associated antigens (TAAs). From an immunotherapeutic perspective the model tumor 
antigen is one that is exclusively and universally expressed on tumor cells and ideally should be 
essential for the maintenance of the oncogenic phenotype of the tumor. However, the majority of 
antigens do not meet these criteria since they are not neo-antigens uniquely present in malignant 
cells but rather antigens that are also expressed in normal cells and against which peripheral blood 
T cells are tolerized or deleted. Tumor-specific antigens have nonetheless been identified, and 
these can be classified into 4 groups; 
(i) Unique antigens (eg. MUM1) result from single mutations that are tumor- and patient-specific 
and therefore are only expressed in neoplastic cells1-3. They are often considered ideal for 
immunotherapy since tumors can be specifically targeted without destroying nearby normal tissue1-
4. However, because they are also usually patient-specific, the identification of the mutated gene 
and then the generation of an individualized T cell product targeting the identified antigen is highly 
labor and cost intensive. 
(ii) Shared lineage-restricted antigens are expressed on tumors as well as their normal tissue of 
origin and include the melanoma-associated antigens MART, gp100 and Melan-A. These antigens 
are strongly immunostimulatory enabling the efficient and relatively simple generation 

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and expansion of tumor-specific T cells from healthy donors and patients with minimal in vitro 
manipulation5. However, T cell-mediated destruction of normal melanocytes, for example, has 
resulted in vitiligo as well as ocular and systemic autoimmunity in patients treated with melanoma- 
specific T cells or tumor infiltrating lymphocytes (TILs)6. 
(iii) Shared tumor-specific TAA (e.g. the cancer testis antigens [CTA] - MAGE, BAGE, GAGE, NY- 
ESO-1, SSX, PRAME) are expressed in multiple tumors including pancreatic cancer but not in 
healthy organs7-15, with the exception of germ line tissues that are immune privileged and therefore 
not susceptible to T cell attack. Most CTAs have heterogeneous expression in cancer tissues and 
are frequently expressed in high-grade or late tumor stages, with expression often correlated with 
a worse prognosis. Furthermore, tumors expressing one often express multiple CTAs, and several 
have been found to be targets of spontaneous humoral or cell-mediated immune responses16-18. 
Thus, CTAs are particularly attractive as targets for tumor immunotherapy since reactive T cells can 
be produced on a large scale to provide broad-spectrum protection against a variety of tumors. 
CTAs have been targeted in both vaccine and T cell therapy protocols, with evidence of clinical 
efficacy19-25. 
(iv) The last group of antigens are over expressed in many different tumors but expressed at low 
levels in healthy tissue (eg. hTERT, CEA and Survivin). T cells targeted to these antigens carry 
the risk of inducing collateral damage to normal tissues co-expressing the antigen (e.g. CEA and 
normal biliary epithelium), and there are limited clinical data available regarding the safety of 
targeting these antigens in vivo. However, Survivin- and CEA-specific T cells have been isolated 
from the peripheral blood of patients who have cleared their tumors, and increases in Survivin- 
specific T cells in patients receiving oncolytic viruses have been reported, suggesting that they can 
have efficacy without toxicity in patients26-31. 
 
3.3 
Clinical experience targeting non-viral TAAs 
3.3.1 Melanoma-targeted therapies 
T cell immunotherapies for non-viral tumor antigens have been described, with promising clinical 
results in some studies. Rosenberg and colleagues have long used melanoma-specific TILs, which 
include specificities directed to both CTAs/shared lineage antigens and neoantigens, to treat 
metastatic melanoma 32-34. Indeed, in a review of 93 patients with metastatic melanoma refractory 
to standard therapies, the administration of highly selected, TIL-derived, tumor-reactive T cells and 
high-dose IL-2 (720,000 IU/kg q 8h to tolerance) in conjunction with immunodepleting 
chemotherapy -/+ total body irradiation produced objective clinical responses to treatment in 52 
patients (39 PR, 12 CR), including regression of large bulky tumors35,36. These results have been 
recapitulated by others using selectively activated and in vitro expanded T cells melanoma- targeted 
T cells37,38,39,40. 
 
3.3.2 T cell therapy to prevent leukemic relapse 
Adoptive immunotherapy has also proven to be an effective strategy in preventing leukemic relapse 
in the allogeneic hematopoietic stem cell transplant (HSCT) setting. The first clinical trials involved 
the administration of donor peripheral blood [donor lymphocyte infusions (DLI)], which contained T 
cells that were able to mediate antitumor activity in vivo41. However, the increased risk of graft 
versus host disease (GVHD) due to the presence of relatively high numbers of cells with alloreactive 
potential led subsequently to the study of selectively-expanded T cell populations as an alternate 
therapeutic option. To date, the antigens targeted can be divided into 2 categories: 
(i) minor histocompatibility antigens (mHAgs) expressed by leukemia progenitors, and (ii) TAAs 
overexpressed by the leukemic cells with limited expression on normal cells. 
(i) 
mHAgs are HLA-binding peptides derived from endogenous proteins in cells of the 
HSCT recipient that differ from those of the donor due to genetic polymorphisms. As 
such they represent a unique class of antigens that can only be targeted after allogeneic 
HSCT to promote both graft vs leukemia (GVL) and GVHD effects in vivo.42 Warren and 
colleagues evaluated the safety of adoptively transferring donor-derived CD8+ clones 
recognizing mHAgs preferentially expressed on hematopoietic cells to 

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patients with relapsed acute leukemia after myeloablative allogeneic HSCT43 at cell 
doses ranging from 2.25 - 6.6 x 109 cells. Pulmonary toxicity was seen in 3 of the 7 
treated patients, and was severe in one, and correlated with the level of expression of 
the mHAg-encoding genes in lung tissue. However, the administration of steroids 
coincided with a rapid reversal in pulmonary symptoms43. 
(ii) 
In both the autologous and donor-specific setting adoptive transfer approaches are 
being developed against a number of leukemia-associated antigens including Wilms 
Tumor Gene 1 (WT1), Proteinase 3 (Pr3), human neutrophil elastase (NE), melanoma 
associated antigen A3 (MAGE-A3) and preferentially expressed antigen in melanoma 
(PRAME)17,18. Of these WT1 is perhaps the most extensively characterized and its 
clinical relevance is evidenced by the fact that disease control or remission in several 
vaccine studies has been associated with the induction of WT1-specific T cells. O’Reilly 
and colleagues have initiated a clinical trial of donor-derived WT1 peptide- specific T 
cells, activated using DCs loaded with an overlapping peptide library (15mers 
overlapping by 11 amino acids) spanning the entire sequence of the antigen, and 
infused as treatment of persistent minimal residual disease or recurrence of WT1+ AML, 
ALL, or MDS following allogeneic HSCT. In preliminary reports T cell infusions at the 
lowest dose levels were reported to be safe, well tolerated, and associated with clinical 
benefit44,45. 
 
3.4 
Targeting lymphoma, myeloma and solid tumors using tumor-targeted T cells 
To use an adoptive immunotherapeutic approach to treat patients with hematologic malignancies 
(lymphoma and multiple myeloma) and solid tumors we developed a protocol for the in vitro 
generation of T cell lines targeting the TAAs Survivin, PRAME, MAGE-A4, NY-ESO-1 and SSX2, 
which are expressed in a range of tumors. The multi-antigen-targeted (multiTAA) T cells were 
generated using dendritic cells (DCs) loaded with pepmixes (overlapping peptide libraries) spanning 
the 5 target antigens. 
 
Lymphoma: To date, 20 patients with lymphoma have been infused with multiTAA T cells without 
adverse events. Nine patients were treated for active disease. Of these, 2 patients had transient 
disease stabilization (5mo), 2 patients have stable disease (3mo ongoing), and 5 patients (3 HL, 
1 DLBCL, 1 composite lymphoma) achieved durable complete remissions by PET, without 
additional therapies. These clinical responses correlated with a progressive increase in the 
frequency of tumor-specific T cells directed against both targeted and non-targeted TAAs, indicating 
that the infused T cells induced localized in vivo inflammation, resulting in endogenous T cell 
activation and antigen/epitope spreading. A further 11 patients were infused as adjuvant therapy. 
Of these, all but 2 remain in remission (median 17 months postinfusion, range 6-34 months) - a 
benefit likely due to the infused cells as the best prior response in these patients produced 
remissions lasting a median of only 4 months (range 1-6 months). These data support both the 
safety and clinical benefit of autologous multiTAA T cells as adjuvant therapy for lymphoma patients. 
 
Myeloma and solid tumors: We subsequently extended this approach to other malignancies and to 
date we have infused 7 patients with multiple myeloma and 5 patients with solid tumors (1 
squamous cell carcinoma, 1 lung cancer, and 3 osteosarcoma) with a similar safety. 
 
3.5 
Extending our approach to treat pancreas cancer 
Given our demonstration that (i) targeting NY-ESO-1, PRAME, MAGE-A4, SSX2 and Survivin 
simultaneously is feasible and safe, and (ii) these antigens are expressed in pancreatic cancer, 
we now propose a clinical trial of multiTAA-specific T cells in patients with pancreatic cancer13,15,46,47. 
The T cell generation protocol will be identical to that used in our lymphoma, myeloma and solid 
tumor studies. In the current pilot study, we propose testing the antitumor activity of multiTAA-
specific T cells administered at a fixed dose of 1x107 cells/m2. 

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3.6 
Potential adverse events 
Although no toxicity has been associated with multiTAA-specific T cells to date, we will actively look 
for evidence of potential side effects such as: 
 
Cytokine Release Syndrome: 
There have been several reported SAEs associated with cytokine release syndrome (CRS) in 
patients who received T cells48 or bispecfic T-cell engagers49. The majority of CRS have been 
reported after the infusion of CAR T cells50-52, but CRS can also occur after the infusion of 
conventional antigen-specific T cells53 or tumor infiltrating lymphocytes54. Patients will be monitored 
closely as per study calendar and assessed for evidence of incipient CRS (onset of fever, malaise 
and dyspnea) and treated promptly. Management of CRS will follow published guidelines48,55, and 
is described in more detail in SOP F 05.11.XX and includes treatment options based on the clinical 
severity of the symptoms, such as oxygen, inotropic agents, IL-6 receptor antibody (4-8 mg/kg), 
TNF-α antibody (5-10 mg/kg), and/or steroids (1-2 mg/kg/day of methylprednisolone or equivalent). 
 
Pancreatitis: 
There have been reports of pancreatitis in patients who received t-cells on this study. A relationship 
between pancreatitis and pancreatic cancer is established, and may represent a normal overlap of 
pathology between the two conditions. Pancreatitis that occurs in the setting of pancreatic cancer 
could be via obstructive etiology from the primary or regionally metastatic tumors. Pancreatitis can 
also commonly relate to infectious processes in patients treated with pancreatic cancer, particularly 
as the duct system can provide an ideal reservoir for bacteria to accumulate. Based on the 
relationship between pancreatitis and pancreatic cancer we consider it more likely that the 
development of pancreatitis in patients who received t-cells is related to the cancer as opposed to 
the t-cell treatment however we cannot rule out the possible role of the t- cells in this process. 
 
4.0 
PATIENT ELIGIBILITY 
 
4.1 
Procurement Inclusion Criteria 
 
4.1.1 Any patient with biopsy proven pancreatic adenocarcinoma. 
 
4.1.2 Patients with life expectancy > 6 months. 
 
4.1.3 Age >18 years 
 
4.1.4 Hgb ≥7.0 g/dl (transfusions allowed), 
 
 
4.1.5 
Informed Consent explained to, understood by and signed by patient. 
Patient given copy of informed consent. 
 
4.2 
Procurement Exclusion Criteria 
 
4.2.1 Patients with severe intercurrent infection. 
 
4.2.2 Patients with active HIV infection (can be pending at this time) 
 
4.3 
Treatment Inclusion Criteria 

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4.3.1 Any patient with biopsy-proven pancreatic adenocarcinoma: 
Group A: Patients with locally advanced or metastatic pancreatic 
adenocarcinoma who experienced a documented best response of 
investigator-assessed confirmed PR or SD per RECIST v1.1 
Group B: Patients with locally advanced or metastatic pancreatic 
adenocarcinoma who experienced progressive disease following first line 
chemotherapy or who are judged by the investigator as being ineligible to 
receive standard of care chemotherapy 
Group C: Patients with potentially resectable pancreatic cancer who have 
completed planned preoperative neo-adjuvant chemotherapy, 
radiotherapy or combination chemoradiation 
 
4.3.2 Patients must have measurable or evaluable disease per RECIST 1.1 
criteria. 
 
4.3.3 Patients with life expectancy >12 weeks 
 
4.3.4 Age >18 
 
4.3.5 Pulse oximetry of >95% on room air in patients who previously received 
radiation therapy 
 
4.3.6 Patients with an ECOG score of ≤ 2 or Karnofsky score of > 50 as described 
below: 
ECOG Performance Status 
 
Grade 
ECOG 
0 
Full active, able to carry on all pre- 
disease performance without restriction 
1 
Restricted in physically strenuous 
activity but ambulatory and able to 
carry out work of a light or sedentary 
nature, e.g., light house work, office 
work 
2 
Ambulatory and capable of all selfcare 
but unable to carry out any work 
activities. Up and more than 50% of 
waking hours 
3 
Capable of only limited selfcare, 
confined to bed or chair more than 50% 
of waking hours 
4 
Completely disabled. Cannot carry on 
any selfcare. Totally confined to bed or 
chair 
5 
Dead 
 
Performance Status Criteria 
Karnofsky performance scores are intended to be multiples of 10 
Karnofsky 
Score 
Description 
100 
Normal, no complaints, no evidence of 
disease 

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90 
Able to carry on normal activity, minor signs 
or symptoms of disease 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
70 
Cares for self, unable to carry on normal 
activity or do active work. 
60 
Required occasional assistance, but is able 
to care for most of his/her needs. 
50 
Requires considerable assistance and 
frequent medical care. 
40 
Disabled, requires special care and 
assistance. 
30 
Severely disabled, hospitalization indicated. 
Death not imminent. 
20 
Very sick, hospitalization indicated. Death 
not imminent. 
10 
Moribund, fatal processes progressing 
rapidly. 
 
 
 
4.3.7 Patients with bilirubin <2x upper limit of normal, AST <3x upper limit of 
normal, Hgb ≥7.0 g/dl (transfusion allowed). 
 
4.3.8 Patients with a creatinine <2x upper limit of normal for age 
 
4.3.9 Patients should have been off other investigational therapy for one month 
prior to receiving treatment on this study. 
 
4.3.10 For Groups B or C patients must be off conventional therapy for at least 1 
week prior to receiving treatment on this study. 
 
4.3.11 Informed Consent explained to, understood by and signed by patient. Patient 
given copy of informed consent. 
 
4.3.12 Due to unknown effects of this therapy on a fetus, pregnant women are 
excluded from this research. The male partner should use a condom. 
Females of child-bearing potential must be willing to utilize one of the more 
effective birth control methods during the study unless female has had a 
hysterectomy or tubal ligation. 
 
4.4 
Treatment Exclusion Criteria 
 
4.4.1 Patients with severe intercurrent infection. 
 
4.4.2 Patients receiving systemic corticosteroids (Patients off steroids for at least 
48 hours are eligible) 
 
4.4.3 Pregnant 
 
4.4.4 HIV positive 
 
 
5.0 
STUDY DESIGN 

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This protocol will be discussed with eligible patients and informed consent for participation 
in the study will be obtained for the generation of the cell lines. The protocol will be discussed 
with patients undergoing treatment at other medical Institutions at the time they are referred 
to Houston Methodist Hospital (HMH). 
 
All cell culture manipulations will be carried out in the Center for Cell and Gene Therapy 
GMP facility using current standard operating procedures (SOPs). After quality assurance 
testing of the manufactured cell product is complete, a certificate of analysis will be issued. 
 
5.1 
Blood procurement for multiTAA T cell and APC generation 
Generation of multiTAA T cells requires the generation of several different 
components from peripheral blood mononuclear cells (PBMC). The line will be 
derived from patient PBMCs, by stimulation with antigen presenting cells (APCs) 
pulsed with pepmixes spanning the TAAs SSX2, MAGEA4, Survivin, PRAME, and 
NY-ESO-1. The initial stimulation will be performed in the presence of the Th1/pro- 
proliferative cytokines interleukin (IL) 7, IL12, IL15, and IL6 and cells will be 
expanded in the presence of IL2 or IL15. The APCs used to stimulate and expand 
the tumor-specific T cells will be DCs derived from patient mononuclear cells. 
 
For T cell generation, we will collect either: 
* a unit of blood (~450ml) (for patients with ALC of >500) or 
* a maximum blood draw of 450 ml peripheral blood obtained in 1-3 draws over a 
two month period for CTL generation, testing for infectious viruses and HLA typing. 
PBMCs will be separated from whole blood using ficoll gradients. T cells and 
monocyte-derived dendritic cells (DCs) can be prepared from fresh or cryopreserved 
PBMC. 
 
To initiate multiTAA T cells we will make DCs by culture of PBMC-derived 
monocytes with cytokines (GM-CSF, IL-4) followed by maturation with a standard 
DC maturation cocktail (IL-1, IL6, TNF and PGE1). These mature DCs will be 
pulsed for 30-60 mins with a mastermix of pepmixes spanning the target antigens 
PRAME, SSX2, MAGEA4, NY-ESO-1 and Survivin. For dilution 1ul of each pepmix 
(200ng/peptide) will be added to 200ul Cell Genix/RPMI media and 50-100ul will 
be used to pulse the DCs (≤5x10e6 DCs - 50ul; >5x10e6 DCs - 100ul). Subsequently 
the DCs will be washed once and used to stimulate PBMC-derived T cells in the 
presence of a T cell activating cocktail, IL7, IL15, IL12 and IL6 at a 
responder:stimulator ratio of at least 10:1. For initiation, DCs will be prepared from 
peripheral blood and the T cells will be derived from the monocyte-depleted PBMC 
fraction. 
 
To expand the tumor-specific T cells we will use pepmix-pulsed DCs for the second 
and subsequent stimulations and cells will be cultured in the presence of IL2 or IL15. 
 
At the end of the culture period, multiTAA T cells will be cryopreserved and aliquots 
tested for phenotype, function, specificity, identity and sterility. The frequency of 
tumor-specific T cells will be determined using intracellular cytokine staining, 
ELIspot assay, and/or HLA multimers, if available. Effector memory phenotype and 
T cell subsets will be analyzed by flow cytometry. 
 
Products that meet study specific release criteria, as detailed on the COA, will be 
infused as per Section 5.2. 

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If a positive sterility testing result is reported after the product is infused, the FDA 
and other relevant parties will be notified as per manufacturing SOP B01.03.XX 
(Product Quality Assurance Program and Release and Return of Clinical GMP/GTP 
Products) and clinical research SOP J02.06.XX (Serious Adverse Experience and 
Unanticipated Problem Reporting). Our management of such a situation is further 
described in our SOP F05.09.XX (Management of Culture Positive Cell Therapy 
Products). 
 
We will use pepmixes produced by JPT Technologies as an antigen source. These 
pepmixes are overlapping peptide libraries (15 mers overlapping by 11 amino acids) 
spanning the entire sequence of each of the antigens of interest as per our 
lymphoma (TACTAL), myeloma (TACTAM), and solid tumor (TACTASOM) studies. 
 
5.2 
Administration and Monitoring 
 
Three disease groups will be studied. 
Group A: Patients with locally advanced or metastatic adenocarcinoma who are 
responding (defined as stable disease or tumor volume reduction) following 3 cycles 
of first line chemotherapy will be evaluated in the clinic and receive 6 infusions with 
a fixed dose of multiTAA T cells starting on chemotherapy cycle 4 and occurring on 
the 4th week of the cycle, which is a chemotherapy “off” week. 
 
Group B: Patients with locally advanced or metastatic adenocarcinoma who have 
failed first line chemotherapy or are intolerant or ineligible to receive standard of care 
chemotherapy will be evaluated in the clinic and receive 6 infusions (administered 
at monthly intervals) with a fixed dose of multiTAA T cells. 
 
Group C: Patients with resectable pancreatic adenocarcinoma following completion 
of neoadjuvant chemotherapy, radiotherapy or combination. These patients will 
receive 6 infusions with a fixed dose of multiTAA T cells. One infusion will occur 4 
weeks prior to surgical resection (with an option to infuse up to one week earlier) 
and after the completion of all pre-operative chemotherapy and/or radiation. The 
subsequent 5 infusions will occur at monthly intervals beginning 8 weeks post-
surgery. 
 
Monitoring: Patients will be monitored for clinical toxicity by the CTEP NCI Common 
Toxicity Criteria Scale (Version 4.X, See Section 12.3) with the exception of CRS 
toxicities that are related to T cell infusions. CRS toxicities will be graded according 
to Appendix I. We will also analyze immunological parameters including T cell 
frequencies by ELIspot and multimer studies in patients who have HLA types for 
which multimers are available. Functional analyses (antigen-specific cytotoxicity 
and cytokine release) will be performed by chromium release assays and 
ELIspot/intracellular cytokine staining, respectively. The levels of serum cytokines 
before and following infusion will be compared. A time period of 4 weeks post the 1st 
infusion will constitute the time for clinical efficacy and safety monitoring. Thereafter 
patients will receive 5 additional infusions of cells at the same cell dose (or below 
the patient’s original dose can be administered) at monthly intervals. Patients that 
undergo surgical resections (Group C) will receive 1 infusion prior to surgery and 5 
additional infusions of cells at the same cell dose (or below the patient’s original 
dose can be administered) at monthly intervals after surgery. 

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6.0 
TREATMENT PLAN 
This study will evaluate the clinical safety and look for evidence of benefit associated with 
the administration of tumor-targeted T cells in a fixed dose study. 
 
6.1 
Dosage 
 
Patients will receive 6 infusions of multiTAA T cells at a fixed dose of 1x107 cells/m2. 
 
6.2 
Dose Schedule 
 
This protocol is designed as a pilot fixed-dose study. 
 
Each patient will receive 6 infusions of multiTAA T cells at a fixed cell dose (1 x 
107 cells/m2) within the same week at the times specified in the study calendar. The 
expected volume of infusion will be 1 to 10 cc. 
 
 
6.3 
Patients may be premedicated with diphenhydramine (Benadryl) up to 1mg/kg IV 
(max 50mg) and acetaminophen (Tylenol) 10mg/kg po (max 650mg), though this 
is not mandatory. 
 
6.4 
Cell Administration: Tumor-specific T cells will be given by intravenous injection over 
1-10 minutes through either a peripheral or a central line. 
 
6.5 
Monitoring will be undertaken according to institutional standards for administration 
of blood products with the exception that the injection will be given by a physician. 
 
6.6 
Patients will receive supportive care for acute or chronic toxicity, including blood 
components or antibiotics, and other intervention as appropriate. 
 
6.7 
All treatments will be administered at the Center for Cell and Gene Therapy in 
Houston Methodist Hospital. Patient follow up and regular care will be at the Dan 
L. Duncan Cancer Center at Baylor Clinic or Smith Clinic. 
 
 
7.0 
PATIENT EVALUATION 
 
7.1 
Follow-up Interval 
Patients shall be seen in clinic prior to each T cell infusion and evaluated (seen in 
clinic or contacted by research coordinator) at 1 and 2 weeks after each infusion, 
week 4, 6, and 8 after the last infusion and then at 3, 6, 9 and 12 months after the 
last infusion. Study-related blood draws will cease 12 months after the last T cell 
infusion but we will then continue to follow patients clinically for up to 4 additional 
years (total of 5 years follow-up) to evaluate long-term disease responses. If 
persistence of cells is noted at the 12 month visit, additional follow up will be added. 
Additional visits will be obtained as clinically indicated. 
 
7.2 
A complete history and physical examination is necessary prior to administration of 
multiTAA T cells. Medical history will be obtained at every follow-up visit and will be 
reviewed annually for 5 years. 

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7.3 
Other Studies 
 
7.3.1 The following investigations will be obtained at the time points specified in 
the study calendar: 
CBC and differential, BUN, creatinine, bilirubin, SGOT, SGPT, alkaline 
phosphatase, Na, K, Cl, CO2, albumin and total protein, and CA19-9. 
7.3.2 Pregnancy testing (blood) is required on female patients of childbearing 
potential prior to multiTAA T cell infusion #1. 
7.3.3 Diagnostic imaging (CT scans, MRI, nuclear imaging) and/or blood tests 
(serum cytokines) to document measurable disease and response to therapy 
prior to the first infusion and every 2-3 months thereafter for up to 1 year 
after the last infusion, as per standard clinical care monitoring for patients 
with pancreatic cancer. The time may vary by 1-2 weeks due to scheduling 
issues and may be done earlier if clinically indicated. If diagnostic imaging 
studies are performed at other times either during or after treatment on this 
study, that data will be collected and information gained will be used for this 
study. 
7.3.4 The following investigations will be obtained at the time points specified in 
the study calendar. 20-40ml of peripheral blood will be collected in 
preservative-free heparin.. This blood will be used for analysis of specificity 
of multiTAA T cell response using HLA multimer analysis and immune 
function assays including ELIspot, intracellular cytokine staining and 
cytotoxicity assays. Serum will be batched for analysis of blood cytokine 
levels. These studies will be done on patients on whom the appropriate 
reagents are available. 
7.3.5 Study specific blood tests will cease 12 months after the last T cell infusion 
but we will continue to follow patients clinically once a year for up to 4 
additional years (total of 5 years follow-up) to evaluate long term disease 
responses. 
7.3.6 Other Tissues: Should the patient undergo a tumor biopsy/surgical resection 
at any time while they are on study, a sample of this will be used to assess 
the tumor antigen expression profile and to look for evidence of T cell 
infiltration. 
 
7.3.7  If a patients’ hemoglobin is <7.0g/dl at any of the evaluation times, the 
amount of blood drawn for the evaluation will be reduced and may be 
obtained over more than one venipuncture, if necessary. 

TACTOPS Version 9.1 1/13/2022 
 
16 
 
 
 
7.4 Summary of Monitoring 
 
 
Group A 
Study week 
Pre- 
Infusion 
Treatment 
Wk1 
Wk2 
Wk3 
Wk4 
Wk5 
Wk6 
Wk7 
Wk8 
Wk9 
Wk10 
Wk11 
Events 
 
 
SOC 
SOC 
SOC  
SOC 
SOC 
SOC  
SOC 
SOC 
SOC 
T cells 
 
x 
 
 
 
x 
 
 
 
x 
 
 
 
History 
X 
 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
 
Physical 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
CBC/diff 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, 
SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, 
CO2, albumin, 
total protein, 
CA 19-9$ 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
Imaging^ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
X 
 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
 
Pregnancy 
test# 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group A 
Study week 
Wk12 
Wk13 
Wk14 
Wk15 
Wk16 
Wk17 
Wk18 
Wk19 
Wk20 
Wk21 
Wk22* 
Events 
 
SOC 
SOC 
SOC 
 
SOC 
SOC 
SOC 
 
SOC 
SOC 
T cells 
x 
 
 
 
x 
 
 
 
x 
 
 
History 
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Physical 
x 
 
 
 
x 
 
 
 
x 
 
 
CBC/diff 
x 
 
 
 
x 
 
 
 
x 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, 
SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, 
CO2, 
albumin, total 
protein, CA 
19-9$ 
x 
 
 
 
x 
 
 
 
x 
 
 
Imaging^ 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Pregnancy 
test# 
 
 
 
 
 
 
 
 
 
 
 

TACTOPS Version 9.1 1/13/2022 
 
17 
 
 
 
 
 
Group B 
Study week 
Pre- 
Infusio 
n 
Treatment 
Wk 
1 
Wk2 
Wk3 
Wk4 
Wk5 
Wk6 
Wk7 
Wk8 
Wk9 
Wk10 
Wk11 
T cells 
 
x 
 
 
 
x 
 
 
 
x 
 
 
 
History 
X 
 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
 
Physical 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
CBC/diff 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, 
CO2, albumin, 
total protein, 
CA 19-9$ 
X 
 
 
 
 
x 
 
 
 
x 
 
 
 
Imaging^ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
X 
 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
 
Pregnancy 
test# 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group B 
Study week 
Wk12 
Wk13 
Wk14 
Wk15 
Wk16 
Wk17 
Wk18 
Wk19 
Wk20 
Wk21 
Wk22* 
T cells 
x 
 
 
 
x 
 
 
 
x 
 
 
History 
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Physical 
x 
 
 
 
x 
 
 
 
x 
 
 
CBC/diff 
x 
 
 
 
x 
 
 
 
x 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, 
SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, 
CO2, 
albumin, total 
protein, CA 
19-9$ 
x 
 
 
 
x 
 
 
 
x 
 
 
Imaging^ 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Pregnancy 
test# 
 
 
 
 
 
 
 
 
 
 
 

TACTOPS Version 9.1 1/13/2022 
 
18 
 
 
 
 
 
 
 
 
Group C 
Study 
week 
Pre- 
Infusio 
n 
Treatm 
ent& 
Wk1 
Wk 
2 
Wk 
3 
Wk4 
Infusi 
on 
#2% 
Wk1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
5 
Wk 
6 
Wk 
7 
Events 
 
 
 
 
 
Surgery  
SO 
C 
SO 
C 
SO 
C 
 
SO 
C 
SO 
C 
SO 
C 
T cells 
 
x 
 
 
 
 
x 
 
 
 
x 
 
 
 
History 
X 
 
x 
x 
 
 
x 
x 
x 
 
x 
x 
x 
 
Physical 
X 
 
 
 
 
 
x 
 
 
 
x 
 
 
 
CBC/diff 
X 
 
 
 
 
 
x 
 
 
 
x 
 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, 
SGPT, 
alkaline 
phosphatas 
e, Na, K, Cl, 
CO2, 
albumin, 
total 
protein, CA 
19-9$ 
X 
 
 
 
 
 
x 
 
 
 
x 
 
 
 
Imaging^ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
X 
 
x 
x 
 
 
x 
x 
x 
 
x 
x 
x 
 
Pregnancy 
test# 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group C 
Study week 
Wk8 
Wk9 
Wk10 
Wk11 
Wk12 
Wk13 
Wk14 
Wk15 
Wk16 
Wk17 
Wk18* 
Events 
 
SOC 
SOC 
SOC 
 
 
 
 
 
 
 
T cells 
x 
 
 
 
x 
 
 
 
x 
 
 
History 
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Physical 
x 
 
 
 
x 
 
 
 
x 
 
 
CBC/diff 
x 
 
 
 
x 
 
 
 
x 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, 
SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, 
CO2, 
albumin, total 
protein, CA 
19-9$ 
x 
 
 
 
x 
 
 
 
x 
 
 
Imaging^ 
 
 
 
 
 
 
 
 
 
 
 
Immune 
Function
x 
x 
x 
 
x 
x 
x 
 
x 
x 
x 
Pregnancy 
test# 
 
 
 
 
 
 
 
 
 
 
 

TACTOPS Version 9.1 1/13/2022 
 
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Generic Long term follow-up Table 
 
Study 
timepoint 
(after last 
infusion) 
Wk4 
Wk6 
Wk8 
Mth 
3, 6, 
9, 12 
Yr 2, 
3, 4, 
5 
T cells 
 
 
 
 
 
History 
x 
x 
x 
x 
x 
Physical 
 
 
 
 
 
CBC/diff 
 
 
 
 
 
BUN, 
creatinine, 
bilirubin, 
SGOT, SGPT, 
alkaline 
phosphatase, 
Na, K, Cl, CO2, 
albumin, total 
protein, CA 19- 
9$ 
 
 
 
 
 
Imaging^ 
 
 
 
 
 
Immune 
Function
x 
x 
x 
x 
 
Pregnancy 
test# 
 
 
 
 
 
 
 
SOC = Standard of care 
* Following this study time point monitoring will be performed per long term follow-up Table 
& For Group C the 1st infusion occurs at 4 weeks prior to surgery with a provision to infuse up to 
1 week earlier to allow for variations in surgery scheduling. 
% For Group C the 2nd infusion will occur 8 weeks post-surgery 
^See Section 7.3.3. Imaging studies can be performed within 8 weeks of T cell administration 
and post-infusion monitoring will be per standard of care 
 See Section 7.3.4 
# See Section 7.3.2 
$ Or any other serum tumor marker that is elevated because of the pancreatic tumor (such as 
CEA or CA-125) 

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8.0 
RESPONSE CRITERIA 
 
A 4-week period after the first infusion will constitute a course, which will be evaluated for critical 
toxicity. 
 
 
Patients with measurable disease will be assessed by standard criteria to determine clinical 
response. Evaluations of tumor size will be performed pre-infusion and approx. every 2-3 months 
thereafter as per standard clinical care patient monitoring. All patients who receive multiTAA T cells 
and continue to be enrolled on the study will be evaluable for response. Patient long term overall 
and progression free survival will also be evaluated at 1 year and then annually for up to an 
additional 4 years (total of 5 years follow-up). 
 
8.1 Definitions 
This study will use the RECIST 1.1 criteria 
 
Definitions 
Response and progression will be evaluated in this study using the international criteria 
proposed by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) Committee. 
Changes in only the largest diameter (unidimensional measurement) of the tumor lesions 
are used in the RECIST criteria. Measurable lesions 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, MRI, or clinically using calipers. The investigator will identify up to 5 
measurable lesions to be followed for response. Serial measurements are to be done with 
CT or MRI. The same method of assessment is to be used to characterize each identified 
and reported lesion at baseline and during follow-up. 
 
Complete Response: Disappearance of all target lesions 
 
Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) 
of target lesions, taking as reference the baseline sum LD 
 
Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, 
taking as reference the smallest sum LD recorded since the treatment started or the 
appearance of one or more new lesions 
 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum LD since the treatment started 
 
9.0 
STATISTICAL CONSIDERATIONS 
 
9.1 Study Design Synopsis 
 
This study is designed as a fixed-dose pilot study to evaluate the safety and feasibility (primary 
endpoints), and efficacy (tertiary endpoint) of up to 6 intravenous infusion of multiTAA-specific T 
cells in pancreas cancer patients with metastatic, locally advanced unresectable, or resectable 
disease. 
 
In each disease group, the sample size is a maximum of 15 patients who receive at least one 
infusion of multiTAA-specific T cells. The total sample size of the study will be a maximum of 45. 

TACTOPS Version 9.1 1/13/2022 
 
21 
 
 
We expect to enroll 15-20 patients per year and therefore expect the study to conclude accrual 
within the estimated period of 36 months. 
 
Treatment-related serious adverse events (tSAE) are defined as grade III-IV CTCAE toxicity or 
grade 3-4 CRS toxicities that are determined to be related to T cells. 
 
9.2 Sample Size Determination and Trial Monitoring 
 
In each of the disease groups, the primary goals are to study the safety of multiTAA-specific T cells 
and determine the feasibility of administering 6 infusions of cells. 
 
To assess the safety of multiTAA-specific T cells: The sample size is 15 patients in each disease 
group, calculated based on the considerations as follows. To study whether there are excessive 
treatment-related serious adverse events (tSAE), a tSAE rate of 20% is considered excessive 
(corresponding to the alternative hypothesis), while a rate below 20% is considered acceptable. 
Based our previous experience with T cell therapy, we anticipate at most 1.5% rate (corresponding 
to the null hypothesis). The monitoring rule is that if more than one tSAE is observed, then the 
treatment is considered unsafe and the accrual to the trial will be halted for that disease group. 
 
Under the alternative hypothesis that the true tSAE rate is 20%, then the probability of observing 
more than one tSAE event out of 15 patients is 83.3% (statistical power for rejecting the null 
hypothesis, based on the exact binomial distribution). Under the null hypothesis that the true tSAE 
rate is 1.5%, the probability of observing more than one tSAE event out of 15 patients is only 2.08% 
(type I error for rejecting the null hypothesis, based on the binomial distribution). 
 
There will be no formal interim analysis of safety but we will employ an ad hoc monitoring rule. The 
cumulative number of treatment-related serious adverse events will be counted for every 3 patients 
within each group. If there is more than 1 tSAE within a group, then the accrual to that group will be 
halted for excessive treatment-related serious adverse events. We will be looking at the data for at 
most 5 times for each group. Under the null hypothesis that the true tSAE rate is 1.5%, the 
probability of observing more than one tSAE event out of every 3, 6, 9, 12 and15 patients is 
0.07%,0.32%,0.76%, 1.34% and 2.08%, respectively. The overall type I error is thus controlled at 
4.57% level. 
 
The total sample size is 45. If there is any death deemed possibly or probably related to multiTAA 
T cell infusion, the study will halt patient accrual for the respective disease group, and the data will 
undergo a thorough internal review and the outcome discussed with the FDA. 
 
We employ a deterministic rule to assess the feasibility of giving 6 intravenous infusions of 
multiTAA-specific T cells: In each disease group the feasibility of completing all 6 infusions 
(henceforth called a series) will be monitored separately using a method similar to the 3+3 
procedure. The cumulative number of successful completions of an infusion series will be 
accounted for every 3 patients. If at most one patient cannot finish the infusion series, then the trial 
will be allowed to accrue 3 additional patients. If after 6 patients, there are 2 or more patients who 
are unable to finish the infusion series, then the treatment strategy will be determined to be 
unfeasible but additional enrollments on that arm will continue. 
 
9.3 Statistical Analysis 
 
9.3.1 Safety Analysis of Toxicity and Adverse Event Data 
All patients who receive at least one infusion of multiTAA-specific T cells will be included in the 
safety analysis. Patients will be monitored for clinical toxicity by the CTEP NCI Common Toxicity 

TACTOPS Version 9.1 1/13/2022 
 
22 
 
 
Criteria Scale (Version 4.X, See Section 12.3) with the exception of CRS toxicities that are related 
to T cell infusions. CRS toxicities will be graded according to Appendix I. 
 
Adverse event data and corresponding toxicity grades after T cell infusions and during long-term 
follow-up will be summarized in the form of tables. Incidence tables will be generated to summarize 
incidence of patients reporting at least one episode of each specific adverse event, incidence of 
adverse events causing withdrawal and incidence of serious adverse events. The total number of 
episodes for each event reported (Frequency Table), the severity and attribution to study therapy 
of each episode reported (Severity Table and Attribution Table) will also be calculated. 
 
Listings of adverse events by patients will include the time to onset, the duration of each event, 
the severity of each event, and the relationship of the event to study therapy, whether it was a 
serious event, and whether it caused withdrawal. Safety data will be summarized for each patient 
group and for all treated patients. 
 
9.3.2. Analysis of anti-tumor activity, progression-free and overall survival data 
Although tumor response and survival are not the primary endpoint of this trial, we will summarize 
tumor response by calculating overall response rates along with exact 95% binomial confidence 
intervals. Response will be evaluated as described in section 8.4. The progression-free and overall 
survival of patients will be summarized using the Kaplan-Meier method. The analysis will be done 
for each patient group and for all treated patients. We will also explore the relationship between the 
patient baseline characteristics and response as well as PFS/OS based on eth logistic model and 
the Cox regression methods, respectively. 
 
9.3.3. Analysis of expansion and persistence of the adoptively-transferred TAA-specific T cells 
 
Summary statistics such as mean ± SD, medians and ranges will be calculated at pre- and post- 
infusion time points to evaluate the T cell expansion and persistence based on the immunological 
parameters including phenotype and T cell frequencies by ELIspot and multimer studies, functional 
analyses (antigen-specific cytotoxicity and cytokine release) by chromium release assays and 
ELIspot/intracellular cytokine staining, and the levels of serum cytokines. 
 
Changes in each of the immunological parameters from pre-infusion to each time point of post- 
infusion will be assessed and compared using paired t-tests, or when appropriate, the Wilcoxon 
signed ranks test. Paired comparisons of these T cells within a patient at each time point will also 
be performed. These analyses will be performed in each disease group and in the overall patient 
group. 
 
Plots of growth curves will be generated to graphically illustrate patterns of T-cell expansion and 
persistence. Longitudinal modeling techniques such as the random coefficient mixed model will 
be employed to model each of the repeatedly-measured T cells. These models account for variation 
in individual-level intercepts and slopes over the follow-up time. Thus, we will be able to model 
proliferation of T cells over time and estimate the magnitude of expansion or decline of T cells. 
Correlations between frequencies of these immunological parameters at each time point of follow-
up will be assessed using measures of correlation coefficients. 
 
Alternative strategies to analyze these immunological parameters include calculation of area under 
the curve over time or piecewise longitudinal models based on apparent trends from plots of growth 
curves. Despite the small patient numbers, a data-dense study will be generated due to the repeat 
measurements on proliferation, immune function, and other parameters on each patient. The 
modeling strategies proposed here are amenable to these types of data but will however be 
considered exploratory and interpreted with caution due to limited study power. The 

TACTOPS Version 9.1 1/13/2022 
 
23 
 
 
validity of the normality assumption on these data will be tested and appropriate transformations 
will be considered whenever indicated. 
 
9.3.4. Analysis of Laboratory Data 
Laboratory data, which includes CBC, BUN, creatinine, and liver function tests, will be examined 
in different ways. Descriptive statistics (means, standard deviations, medians and ranges) at pre- 
infusion, at weeks 1, 2, 4, 6, 8 and at months 3, 6, 9, and 12 post- T cell infusion will be calculated 
and summarized. A scatter diagram depicting laboratory values at each time point for each patient 
will also be generated. To analyze changes in laboratory values, a shift table with Stuart-Maxwell 
chi-square analysis of the change in the normal range from pre-infusion to post infusion time points 
(using high, normal, low) will be performed. When appropriate, these tables will be collapsed and 
the McNemar’s test applied in place of the Stuart-Maxwell test. Diagnostic imaging (CT scans, MRI, 
nuclear imaging) and/or blood tests (serum cytokines) will be also summarized and plotted. These 
statistical analyses will be performed for each disease group and the overall patient group. 
 
9.4. Stopping Guidelines 
 
Statistical monitoring of grade III-IV CTCAE toxicity or grade 3-4 CRS toxicities related to T cells 
is employed. Safety guideline and the rule for halting the accrual will be implemented separately for 
each cohort. The guidelines serve as a trigger for consultation with the FDA for additional review, 
and are not formal “stopping rules” that would mandate automatic closure. Additionally, after 
consultation with the FDA, the PI can stop the study early. 
 
In Group C, it is extremely unlikely that patients who receive their first T cell infusions will not 
undergo surgical resection since all imaging studies and a clinical plan will be determined prior to 
infusion and it is unlikely that the T cells will cause inflammation precluding/delaying subsequent 
surgical resection. The accrual to Cohort C will be halted if any patient experiences a delay in 
subsequent surgical resection due to toxicity related to the T-cell infusion and this issue will be 
discussed with the FDA to develop a plan. The plan would be submitted to the DRC and IRB prior 
to resuming accrual to Cohort C. 
 
10.0 
MODIFIED FOLLOW-UP AND OFF STUDY CRITERIA 
 
 
10.1 Criteria for Modified Follow-Up 
The following criteria will result in the patient being ineligible for further treatment on 
the protocol, although response data will continue to be collected as applicable. 
 
10.1.1 
Any patient who develops grade III-IV toxicity related to multiTAA T cells . 
In such patient the toxicities will be followed until resolution or until their 
off study date. Although no toxicity has been associated with the infusion 
of this product in patients with Hodgkin and non-Hodgkin lymphoma or 
multiple myeloma, we will actively look for evidence of any adverse 
events, such as cytokine release syndrome. 
 
10.1.2 Any patient who receives any other hematopoietic cell product excluding 
blood or platelets. In such patients, adverse event data collection will cease. 

TACTOPS Version 9.1 1/13/2022 
 
24 
 
 
10.1.3 Any patient who experiences Grade 3 or 4 cytokine release syndrome that 
persists beyond 72 hours. In such patients, the toxicity will be followed until 
resolution or until their off study date. 
 
10.1.4 Any patient whose disease progresses (based on RECIST criteria) and who 
receives another therapy. In such patients, adverse event data collection will 
cease. 
 
10.1.5 If the patient desires to discontinue treatment or if the physician feels that it 
is in the best interest of the patient. 
 
Patients who meet modified follow-up criteria remain on long-term follow-up as per the 
Summary of Monitoring (see table in Section 7.3.1) 
 
10.2 OFF STUDY 
10.2.1 Completion of study-specified procedures. 
10.2.2 Refusal of study follow up by patient/Patient withdrawal of consent 
10.2.3 Lost to follow up 
10.2.4 Death 
 
Any questions regarding patients on this study should be addressed to Dr. Musher at 
713-798-3750. 
 
11.0 
RECORDS TO BE KEPT 
 
The CAGT research nurse/coordinator will maintain a database documenting on study 
information, adverse events, off study notification and death information. The dates and 
doses of therapy as well as clinical chemistries, hematologic parameters, the clinical status 
and occurrence of any adverse events and subsequent interventions are to be kept on all 
patients. 
 
Imaging reports 
Surgical summaries 
Autopsy summaries, where appropriate 
Informed consent documents 
 
All required clinical evaluation records will be the responsibility of Principal Investigator who 
will also be responsible for analysis of the clinical outcome and toxicity. 
 
The laboratory evaluation of immunological efficacy will be the responsibility of Drs. Leen 
and Tzannou. 
 
12.0 
REPORTING REQUIREMENTS 
 
12.1 
Register all patients with Cell and Gene Therapy Research Coordinator. 
12.2 
Enter all patients by phoning Dr. Musher. The following data will be captured: 
Eligibility 
Pre-study 
Concomitant Medication 
Adverse event 

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25 
 
 
CRS Adverse Event (if applicable) 
Off study 
Death 
 
12.3 
Drug Toxicity and/or Adverse Reactions 
 
12.3.1 Toxicity Grading: The criteria listed in the CTEP (Version 4.X) of the NCI 
Common Toxicity Criteria Scale will be used in grading toxicity with the 
exception of CRS toxicities that are related to T-cell infusions. CRS 
toxicities will be graded according to Appendix I. 
12.3.2 The CTEP CTCAE (Version 4.X) is identified and located on the CTEP 
website at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
12.3.3 Adverse events will be collected as per SOP J 02.05.XX and J 02.75.XX. 
Data on adverse experiences/toxicities regardless of seriousness, must 
be collected for documentation purposes only for 8 weeks after the last 
dosing of study drug/biologic. 
12.3.4 Serious adverse events will be collected as per SOP J 02.06.XX. 
 
13.0 
INFORMED CONSENT 
All patients must sign a document of informed consent consistent with local institutional and 
Federal guidelines stating that they are aware of the investigational nature of this protocol 
and of the possible side effects of treatment. Further, patients must be informed that no 
efficacy of this therapy is guaranteed, and that unforeseen toxicities may occur. Patients 
have the right to withdraw from this protocol at any time. No patient will be accepted for 
treatment without such a document signed by his or her legal guardian. Full confidentiality 
of patients and patient records will be provided according to institutional guidelines 
 
 
14.0 CLINICAL TRIAL OVERSIGHT AND MONITORING 
 
This protocol will be conducted in accordance with the Cell and Gene Therapy Monitoring 
Plan on file with the FDA. 
 
This protocol will be monitored in accordance with the current Data Safety Monitoring Plan 
for investigator-initiated Phase I and II studies in the Dan L Duncan Comprehensive Cancer 
Center at Baylor College of Medicine. 
 
The conduct of this clinical trial will be evaluated in accordance with Center for Cell and 
Gene Therapy Quality Assurance Policy and Procedure Plan. 

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Appendix I - Grading of CRS 
 
CRS Grading Scale 
 
Grade 
Symptoms 
 
1 
 
 Symptoms are not life threatening and require symptomatic treatment only 
(e.g. fever, nausea, fatigue, headache, myalgia, malaise) 
 
2 
 Symptoms require and respond to moderate intervention 
 Oxygen requirement <40% or hypotension responsive to fluids or 
 low dose of one vasopressor or Grade 2 organ toxicity 
 
3 
 Symptoms require and respond to aggressive intervention 
 Oxygen requirement ≥ 40% or 
hypotension requiring high dose or multiple vasopressors or 
 Grade 3 organ toxicity or Grade 4 transaminitis 
 
4 
 Life-threatening symptoms 
 Requirements for ventilator support or 
Grade 4 organ toxicity (excluding transaminitis) 
 
5 
 
 Death