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Protocol Details

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced with a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts




Sponsoring Institute

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18 Years
Max Age: 72 Years

Referral Letter Required


Population Exclusion(s)

Pregnant Women;


Cell Therapy;

Recruitment Keyword(s)



Pancreatic Cancer;
Gastric Cancer;
Gastrointestinal Cancer;
Colon Cancer;
Rectal Cancer

Investigational Drug(s)

Anti-KRAS G12V murine TCR transduced PBL

Investigational Device(s)



Drug: Cyclophosphamide
Drug: Fludarabine
Biological/Vaccine: Anti-KRAS G12V mTCR PBL
Drug: Aldesleukin

Supporting Site

National Cancer Institute


A new cancer therapy involves taking white blood cells from a person, growing them in the lab, genetically modifying them, then giving them back to the person. This therapy is called gene transfer using anti-KRAS G12V mTCR cells.


To see if anti-KRAS G12 V mTCR cells are safe and can shrink tumors.


Adults at least 18 years old with cancer that has the KRAS G12V molecule on the surface of tumors.


In another protocol, participants will:

Be screened

Have cells harvested and grown

Have leukapheresis

In this protocol, participants will have the procedures below.

Participants will be admitted to the hospital.

Over 5 days, participants will get 2 chemotherapy medicines as an infusion via catheter in the upper chest.

A few days later, participants will get the anti-KRAS G12V mTCR cells via catheter.

For up to 3 days, participants will get a drug to make the cells active.

A day after getting the cells, participants will get a drug to increase their white blood cell count. This will be a shot or injection under the skin.

Participants will recover in the hospital for 1-2 weeks. They will have lab and blood tests.

Participants will take an antibiotic for at least 6 months.

Participants will have visits every few months for 2 years, and then as determined by their doctor.

Visits will be 1-2 days. They will include lab tests, imaging studies, and physical exam. Some visits may include leukapheresis or blood drawn.

Participants will have blood collected over several years.

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-Measurable, metastatic, or unresectable malignancy expressing G12V mutated KRAS as assessed by one of the following methods: RT-PCR on tumor tissue, tumor DNA sequencing, or any other CLIA-certified laboratory test on resected tissue. Patients shown to have tumors expressing G12V mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12V mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope.

-Patients must be HLA-A*11:01 positive as confirmed by the NIH Department of Transfusion Medicine.

-Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology.

-Patients must have:

--previously received standard systemic therapy for their advanced cancer and have been either non-responders or have recurred, specifically:

---Patients with metastatic colorectal cancer must have had at least two systemic chemotherapy regimens that include 5FU, leucovorin, bevacizumab, oxaliplatin, and irinotecan (or similar agents), or have contraindications to receiving those medications.

---Patients with pancreatic cancer must have received gemcitabine, 5FU, and oxaliplatin (or similar agents), or have contraindications to receiving those medications.

---Patients with non-small cell lung cancer (NSCLC) must have had appropriate targeted therapy as indicated by abnormalities in ALK, EGFR, or expression of PDL- 1. Other patients must have had platinum-based chemotherapy.

---Patients with ovarian cancer or prostate cancer must have had approved first-line chemotherapy.


-declined standard treatment

-Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients

with surgically resected brain metastases are eligible.

-Age greater than or equal to 18 years and less than or equal to 72 years.

-Clinical performance status of ECOG 0 or 1

-Patients of both genders must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for women and for 4 months after treatment for men.

-Women of child-bearing potential must be willing to undergo pregnancy testing prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.

NOTE: Certain malignancies may secrete hormones that produce false positive pregnancy tests. Serial blood testing (e.g. HCG measurements) and/ or ultrasound may be performed for clarification.


--Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be 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 patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.


--ANC greater than 1000/mm^3 without the support of filgrastim

--WBC greater than or equal to 2500/mm^3

--Platelet count greater than or equal to 80,000/mm^3

--Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.


--Serum ALT/AST less than or equal to 5.0 times ULN

--Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin less than 3.0 mg/dL.

-Patients must have either an eGFR > 60 mL/m (based on serum creatinine and lab nomogram) or a formal 6-24h CrCl > 60 mL/m.

-Patients must have completed any prior systemic therapy at the time of enrollment.

Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to less than or equal to grade 1.

-Ability of subject to understand and the willingness to sign a written informed consent document.

-Willing to sign a durable power of attorney.

-Subjects must be co-enrolled on protocol 03C0277.


-Large volume pulmonary irradiation.

-Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

-Concurrent systemic steroid therapy.

-Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

-Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

-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.)

-History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

-History of coronary revascularization or ischemic symptoms

-For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

-For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50% or DLCO less than 60%.

-Patients who are receiving any other investigational agents.

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Davis JL, Theoret MR, Zheng Z, Lamers CH, Rosenberg SA, Morgan RA. Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin Cancer Res. 2010 Dec 1;16(23):5852-61. doi: 10.1158/1078-0432.CCR-10-1280.

Wang QJ, Yu Z, Griffith K, Hanada K, Restifo NP, Yang JC. Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors. Cancer Immunol Res. 2016 Mar;4(3):204-14. doi: 10.1158/2326-6066.CIR-15-0188. Epub 2015 Dec 23.

Abrams SI, Khleif SN, Bergmann-Leitner ES, Kantor JA, Chung Y, Hamilton JM, Schlom J. Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. Cell Immunol. 1997 Dec 15;182(2):137-51.

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Principal Investigator

Referral Contact

For more information:

James C. Yang, M.D.
National Cancer Institute (NCI)

NCI SB Immunotherapy Recruitment Center
National Cancer Institute (NCI)

(866) 820-4505

Recruitment Center - SB
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Building 10, Room 2-1730, Bethesda, Maryland 20892, United States
(866) 820-4505

Clinical Trials Number:


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