NCT02858310 · REGISTRY CONDITION SEARCH

E7 TCR T Cells for Human Papillomavirus-Associated Cancers

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2026-03-09

Background: Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an HPV protein called E7 inside of their cells. In this new therapy, researchers take a person's blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 T cell receptor (TCR) cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people. Objective: To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients. Eligibility: Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal. Design: Participants will list all their medicines. Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein. Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm. The cells will be changed in the lab. Participants will stay in the hospital. Over several days, they will get: Chemotherapy drugs E7 TCR cells Shots or injections to stimulate the cells Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests. Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays. Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis. Participants will be followed for 15 years.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Phase II: Overall Response Rate Partial Response + Complete Response (PR +CR)

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outcome · POSTED

Phase I: Number of Dose Limiting Toxicities (DLT)

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outcome · POSTED

Progression-free Survival

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outcome · POSTED

Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: * INCLUSION CRITERIA: 1. Measurable metastatic or refractory/recurrent human papillomavirus (HPV-16+ cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test). 2. Patients must be human leukocyte antigen (HLA-A\*02 by low resolution typing, and HLA-A\*02:01 by one of the high-resolution type results. 3. All patients must have received prior first line standard therapy or declined standard therapy. 4. Patients with three or fewer brain metastases that have been treated with surgery or stereotactic radiosurgery are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. Patients with surgically resected brain metastases are eligible. 5. Greater than or equal to 18 years of age. 6. Able to understand and sign the Informed Consent Document. 7. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1. 8. Individuals must be willing to practice birth control from the time of enrollment on this study up to twelve (12) months after treatment. Individuals must be willing to undergo testing for HPV-16 prior to becoming pregnant after this period. 9. Individuals of childbearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus. Individuals of childbearing potential are defined as all individuals except individuals who are postmenopausal or who have had a hysterectomy. Postmenopausal will be defined as individuals over the age of 55 who have not had a menstrual period in at least one year. Because there is a potential risk for adverse events in nursing infant's secondary to treatment of the mother with E7 T cell receptor (TCR) transduced peripheral blood lymphocytes (PBLs), breastfeeding should be discontinued if the individual is treated with E7 TCR transduced PBL. These potential risks may also apply to other agents used in this study. 10. Serology: * Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then the patient must be tested for the presence of antigen by reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative. a. Hematology: * Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim. * White blood count (WBC) greater than or equal to 3000/mm\^3 * Platelet count greater than or equal to 100,000/mm\^3 * Hemoglobin \> 8.0 g/dL b. Chemistry: * Serum Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal * Calculated creatinine clearance (CCr) greater than or equal to 50 mL/min/1.73\^2 using the Cockcroft-Gault equation * Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL c. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the E7 TCR cells. Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to Grade 1 or less. EXCLUSION CRITERIA: 1. Active systemic infections (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, severe obstructive or restrictive pulmonary disease. Patients with abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. Concurrent opportunistic infections (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). 4. Patients with autoimmune diseases such as Crohn's disease, ulcerative colitis, rheumatoid arthritis, autoimmune hepatitis or pancreatitis, and systemic lupus erythematosus. Hypothyroidism, vitiligo and other minor autoimmune disorders are not exclusionary. 5. Patients on immunosuppressive drugs including corticosteroids. With the exception of: intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) -Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent; or, -Steroids as premedication for hypersensitivity reactions (e.g., computed tomography (CT) scan premedication) 6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine or aldesleukin. 7. Patients with a history of coronary revascularization or ischemic symptoms unless patient has a normal cardiac stress test. 8. Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested. The following patients will undergo cardiac evaluations 1. Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or 2. Age greater than or equal to 50 years old 9. Any other condition, which would, in the opinion of the Principal Investigator, indicate that the subject is a poor candidate for the clinical trial or would jeopardize the subject or the integrity of the data obtained. 10. Subjects with baseline screening pulse oxygen level of \< 95% on room air will not be eligible. If the underlying cause of hypoxia improves, then they may be reevaluated
healthy Volunteers: false
maximum Age: 120 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Non-myeloablative, lymphocyte depleting preparative regimen, followed by E7 T cell receptor (TCR) Cells at escalating doses, followed by aldesleukin.
intervention Names
Biological: E7 TCR cells
Drug: Aldesleukin
Drug: Fludarabine
Drug: Cyclophosphamide
Diagnostic Test: EKG
Procedure: Biopsy
Diagnostic Test: Chest CT and MRI or PET
Diagnostic Test: PFT
Drug: Granisetron
Drug: Ondansetron
Drug: Droperidol
Drug: Prochlorperazine
label
Arm 1: Phase I
type
EXPERIMENTAL
description
1 x 10\^e11 E7 Cells that was determined in Phase I + aldesleukin.
intervention Names
Biological: E7 TCR cells
Drug: Aldesleukin
Drug: Fludarabine
Drug: Cyclophosphamide
Diagnostic Test: EKG
Procedure: Biopsy
Diagnostic Test: Chest CT and MRI or PET
Diagnostic Test: PFT
Drug: Granisetron
Drug: Ondansetron
Drug: Droperidol
Drug: Prochlorperazine
label
Arm 2: Phase II
type
EXPERIMENTAL

interventions

arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
T cells genetically engineered with a T cell receptor (TCR) targeting human papillomavirus (HPV -16 E7 (E7 TCR) that display specific reactivity against human leukocyte antigen (HLA-A2+, HPV-16+ target cells.
name
E7 TCR cells
other Names
E7 T Cell Receptor (TCR) cells
type
BIOLOGICAL
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Following cell infusion, the patient receives high-dose bolus aldesleukin, which is dosed to individual patient tolerance. Aldesleukin improves the survival of E7 T cell receptor (TCR) cells after infusion.
name
Aldesleukin
other Names
Interleukin-2
IL-2
Proleukin
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
name
Fludarabine
other Names
Fludara
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Part of the non-myeloablative lymphocyte-depleting preparative regimen.
name
Cyclophosphamide
other Names
Cytoxan
Neosar
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Screening/Baseline. Follow-up (end of treatment).
name
EKG
other Names
Electrocardiogram
type
DIAGNOSTIC_TEST
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Screening/Baseline. Following treatment (6 weeks post treatment preferred) and at disease progression only.
name
Biopsy
other Names
Bx
type
PROCEDURE
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Screening/Baseline. Follow-up (end of treatment). 40 days (+/- 2 weeks) after cell infusion; additional visits as indicated.
name
Chest CT and MRI or PET
other Names
Chest computed tomography and magnetic resonance imaging and positron emission tomography
type
DIAGNOSTIC_TEST
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Screening/Baseline.
name
PFT
other Names
Pulmonary function test
type
DIAGNOSTIC_TEST
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Supportive medication for nausea/vomiting/anorexia. 0.01 mg/kg intravenous (IV) every(q) day as needed (prn).
name
Granisetron
other Names
Kytril
Sancuso
Sustol
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Supportive medication for nausea/vomiting/anorexia. Ondansetron 10mg intravenous (IV) every(q) 8 hours(hr) as needed (prn).
name
Ondansetron
other Names
Zofran
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Supportive medication for nausea/vomiting/anorexia. 1mg intravenous (IV) at 4-6 hours(h) as needed (prn).
name
Droperidol
other Names
Inapsine
Droleptan
Dridol
Xomolix
Innovar
type
DRUG
arm Group Labels
Arm 1: Phase I
Arm 2: Phase II
description
Supportive medication for nausea/vomiting/anorexia. 25mg per rectum (PR) as needed (prn) or 10mg intravenous (IV) every(q) 6hours(h) prn.
name
Prochlorperazine
other Names
Compazine
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 224
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
measure
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
time Frame
Adverse Events were monitored/assessed from the first study intervention, Study Day 0, through 40 days after the study therapy was last administered up to a maximum of 12 months

primary Outcomes

description
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Compete Response is 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 is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
measure
Phase II: Overall Response Rate Partial Response + Complete Response (PR +CR)
time Frame
At 12 weeks, every 3 months x 3, and every 6 months for approximately 5 years
description
Adverse events were assessed by the Common Terminology Criteria for Adverse Events v4.0. Grade 3 is serious. Grade 4 is life-threatening. Grade 5 is death related to adverse event. A DLT is defined as all Grade 3 and greater toxicities occurring within 30 days of the cell infusion with the exception of: Cytokine Release Syndrome (CRS) that resolves ≤ grade 2 within 14 days of the last dose of aldesleukin. Autoimmune toxicity that resolves to ≤ grade 2 within 14 days for starting symptom treatment (e.g. steroids). Cardiac, gastrointestinal, dermatological, hepatic, pulmonary, renal, hematologic, neurologic toxicity, or toxicity in Appendix C of the protocol attributable to aldesleukin that resolves to ≤ grade 2 within 14 days of the last dose of aldesleukin. Transient grade 3 hypoxia associated with cell infusion that corrects to ≤ grade 2 with supplemental oxygen and/or that resolves to ≤ grade 2 within 24 hours or before starting aldesleukin.
measure
Phase I: Number of Dose Limiting Toxicities (DLT)
time Frame
From the day of cell infusion (Day 0) to Day +30

secondary Outcomes

description
Progression-free survival is the time from start of treatment to disease progression or death from any cause. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progressions.
measure
Progression-free Survival
time Frame
From the time of cell infusion (Day 0) until documented progressive disease; a maximum of 12 months

Full study description

brief Summary: Background: Human papillomavirus (HPV) can cause cervical, throat, anal, and genital cancers. Cancers caused by HPV have an HPV protein called E7 inside of their cells. In this new therapy, researchers take a person's blood, remove certain white blood cells, and insert genes that make them to target cancer cells that have the E7 protein. The genetically changed cells, called E7 T cell receptor (TCR) cells, are then given back to the person to fight the cancer. Researchers want to see if this can help people. Objective: To determine a safe dose and efficacy of E7 TCR cells and whether these cells can help patients. Eligibility: Adults ages 18 and older with an HPV-16-associated cancer, including cervical, vulvar, vaginal, penile, anal, or oropharyngeal. Design: Participants will list all their medicines. Participants will have many screening tests, including imaging procedures, heart and lung tests, and lab tests. They will have a large catheter inserted into a vein. Participants will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm. The cells will be changed in the lab. Participants will stay in the hospital. Over several days, they will get: Chemotherapy drugs E7 TCR cells Shots or injections to stimulate the cells Participants will be monitored in the hospital up to 12 days. They will get support medicine and have blood and lab tests. Participants will have a clinic visit about 40 days after cell infusion. They will have a physical exam, blood work, scans, and maybe x-rays. Participants will have many follow-up visits with the same procedures. At some visits, they may undergo leukapheresis. Participants will be followed for 15 years.
detailed Description: Background: * Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies. * HPV-16+ cancers constitutively express the HPV-16 E7 oncoprotein, which is absent from healthy human tissues. * Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies including HPV-16+ cancers. * T cells genetically engineered with a TCR targeting HPV-16 E7 (E7 TCR) display specific reactivity against human leukocyte antigen (HLA)-A2+, HPV-16+ target cells. Objectives: Phase I Primary Objective \- To determine a safe dose for E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers. Phase II Primary Objective -To determine safety and efficacy of E7 TCR cells plus aldesleukin for the treatment of metastatic HPV-16+ cancers. Eligibility: * Patients greater than or equal to 18 years old with metastatic or refractory/recurrent HPV-16+ cancer. * Prior first line systemic therapy is required unless the patient declines standard treatment. * Patients must be HLA-A\*02:01-positive. Design: * This is a phase I/II clinical trial that will test the safety and efficacy of E7 TCR cells. * All patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine followed by a single infusion of E7 TCR cells. Cell infusion will be followed by high dose aldesleukin. * Re-enrollment will be allowed for a small number of subjects.

Source references

references

citation
Draper LM, Kwong ML, Gros A, Stevanovic S, Tran E, Kerkar S, Raffeld M, Rosenberg SA, Hinrichs CS. Targeting of HPV-16+ Epithelial Cancer Cells by TCR Gene Engineered T Cells Directed against E6. Clin Cancer Res. 2015 Oct 1;21(19):4431-9. doi: 10.1158/1078-0432.CCR-14-3341.
pmid
26429982
type
BACKGROUND
citation
Stevanovic S, Draper LM, Langhan MM, Campbell TE, Kwong ML, Wunderlich JR, Dudley ME, Yang JC, Sherry RM, Kammula US, Restifo NP, Rosenberg SA, Hinrichs CS. Complete regression of metastatic cervical cancer after treatment with human papillomavirus-targeted tumor-infiltrating T cells. J Clin Oncol. 2015 May 10;33(14):1543-50. doi: 10.1200/JCO.2014.58.9093. Epub 2015 Mar 30.
pmid
25823737
type
BACKGROUND
citation
Hinrichs CS, Restifo NP. Reassessing target antigens for adoptive T-cell therapy. Nat Biotechnol. 2013 Nov;31(11):999-1008. doi: 10.1038/nbt.2725. Epub 2013 Oct 20.
pmid
24142051
type
BACKGROUND
citation
Jin BY, Campbell TE, Draper LM, Stevanovic S, Weissbrich B, Yu Z, Restifo NP, Rosenberg SA, Trimble CL, Hinrichs CS. Engineered T cells targeting E7 mediate regression of human papillomavirus cancers in a murine model. JCI Insight. 2018 Apr 19;3(8):e99488. doi: 10.1172/jci.insight.99488. eCollection 2018 Apr 19.
pmid
29669936
type
BACKGROUND
citation
Nagarsheth NB, Norberg SM, Sinkoe AL, Adhikary S, Meyer TJ, Lack JB, Warner AC, Schweitzer C, Doran SL, Korrapati S, Stevanovic S, Trimble CL, Kanakry JA, Bagheri MH, Ferraro E, Astrow SH, Bot A, Faquin WC, Stroncek D, Gkitsas N, Highfill S, Hinrichs CS. TCR-engineered T cells targeting E7 for patients with metastatic HPV-associated epithelial cancers. Nat Med. 2021 Mar;27(3):419-425. doi: 10.1038/s41591-020-01225-1. Epub 2021 Feb 8.
pmid
33558725
type
RESULT