ClinicalTrials.gg
RecruitingNCT03190941Updated Nov 3, 2026

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

A Phase 1/2 interventional study of Cyclophosphamide and Fludarabine in Pancreatic Cancer, Gastric Cancer and Gastrointestinal Cancer, sponsored by National Cancer Institute (NCI). Recruiting at 1 site in United States. Open to participants aged 18 Years to 72 Years. Per ClinicalTrials.gov, last updated 2026-11-03.

Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Sep 2017; still recruiting 9 years 1 month later.
Updated Nov 3, 2026Primary completion movedStudy completion movedGo to Updates ↓
Phase
Phase 1/2
Study type
Interventional
Enrollment
110
Allocation
Non-randomized
Ages
18 Years to 72 Years
Sex
All
01

Study summary

Background:

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.

Objective:

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

Eligibility:

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

Design:

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.

Read the detailed description

Background:

  • We generated an HLA-A*11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12V-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL.
  • In co-cultures with HLA-A*11:01+ target cells expressing this mutated oncogene, mTCR transduced T cells lyse target cells and secrete IFN-gamma with high specificity.

Objectives:

Primary objectives:

  • Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12V mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin).
  • Phase II: Determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12V mutation.

Eligibility:

Patients must be/have:

  • Age greater than or equal to 18 years and less than or equal to 72 years
  • HLA-A*11:01 positive
  • Metastatic or unresectable RAS G12V-expressing cancer which has progressed after standard therapy (if available).

Patients may not have:

-Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide or fludarabine.

Design:

  • This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR in HLA-A*11:01 positive patients with advanced solid tumors expressing G12V mutated RAS.
  • PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
  • Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12V mTCR.
  • All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine.
  • On day 0, patients will receive their PBL transduced with the anti-KRAS G12V mTCR and will then begin high-dose aldesleukin.
  • A complete evaluation of lesions will be conducted approximately 6 weeks (+/- 2 weeks) after treatment.
  • The study will be conducted using a phase I/II Simon minimax design, with two separate

cohorts for the Phase II component: Cohort 2a, patients with RAS G12V pancreatic

cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer.

-A total of up to 110 patients may be required; approximately 24 patients in the phase I portion of the study and 86 (41, plus an allowance of up to 2 non-evaluable per phase II cohort) patients in the phase II portion of the study.

02

Conditions studied

  • Pancreatic Cancer
  • Gastric Cancer
  • Gastrointestinal Cancer
  • Colon Cancer
  • Rectal Cancer

Keywords

  • KRAS
  • HRAS
  • NRAS
  • Cell Therapy
  • Immunotherapy
03

In context

Pancreatic Neoplasms

3,896 studies on the registry are indexed under Pancreatic Neoplasms; 1,007 are open to participants now.

This study's planned enrollment of 110 is above the median of 47 across 2,932 interventional studies indexed under Pancreatic Neoplasms.

Browse Pancreatic Neoplasms studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 72 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Measurable (per V1.1 criteria, , or unresectable 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 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 chemotherapy.

OR

  • declined standard treatment
  • Patients with 3 or fewer 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 0 or 1
  • Patients must be willing to practice 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 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.

  • Serology

    • Seronegative for 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 antigen, and seronegative for 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.
  • Hematology

    • ANC greater than 1000/mm\^3 without the support of filgrastim
    • WBC greater than or equal to 2500/mm\^3
    • count greater than or equal to 80,000/mm\^3
    • > 8.0 g/dL. Subjects may be transfused to reach this cut-off.
  • Chemistry

    • Serum /AST less than or equal to 5.0 times
    • Total 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 > 60 mL/m (based on serum creatinine and lab nomogram) or a formal 6-24h > 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 document.
  • Willing to sign a durable power of attorney.
  • Subjects must be co-enrolled on protocol 03C0277.

Exclusion criteria

EXCLUSION CRITERIA:

  • Large volume pulmonary irradiation.
  • Women of who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  • Concurrent systemic 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 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 less than or equal to 45%.
  • For select patients with a clinical history prompting pulmonary evaluation: known less than or equal to 50% or DLCO less than 60%.
  • Patients who are receiving any other agents.
Terms in these criteria, in plain language(25)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

FEV1

From a breathing test (spirometry): how much air you can blow out in the first second. Often given as a percentage of what is expected for your age, height and sex.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
110 participants (estimated)

Study arms

  • Experimental
    1/Phase I

    Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

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

  • Experimental
    2/Phase II

    Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

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

Interventions

  • Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

  • Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

  • BiologicalAnti-KRAS G12V mTCR PBL

    Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

  • Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).

06

What researchers measure

Primary outcomes

  1. Response rate

    Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)

    Time frame: 6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per PI discretion

  2. Frequency and severity of treatment-related adverse events

    Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT

    Time frame: From time of cell infusion to two weeks after cell infusion

07

Study locations

1 of 1 sites recruiting
  • National Institutes of Health Clinical Center
    Bethesda, Maryland 20892, United States
    Recruiting
    • For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center · Contactirc@nih.gov · 866-820-4505
08

References and documents

Publications

  • 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. PubMed 21138872 ↗
  • 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. PubMed 26701267 ↗
  • 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. doi: 10.1006/cimm.1997.1224. PubMed 9514698 ↗

Individual participant data

Plan to share: Yes — All IPD recorded in the medical record will be shared with intramural investigators upon request.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form

Time frame: Clinical data will be available during the study and indefinitely.

Access criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.

09

Updates

2 registry updates since Sep 25, 2026
Primary completion
Jun 29, 2027→Jun 29, 2029
Nov 3, 2026
Study completion
Jun 29, 2028→Jun 29, 2030
Nov 3, 2026
Show all 2 updates
  1. Nov 3, 2026
    Primary completion Jun 29, 2027→Jun 29, 2029
    Study completion Jun 29, 2028→Jun 29, 2030
    + 1 other change: verification date
  2. Nov 2, 2026
    Minor edits only
    + 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT03190941
Responsible party
Sponsor
First posted
Jun 19, 2017
Start date
Sep 21, 2017
Primary completion
Jun 29, 2029 (estimated)
Completion
Jun 29, 2030 (estimated)
Last update
Nov 3, 2026

Study contacts

NCI SB Immunotherapy Recruitment Center
Contact
IRC@nih.gov
(866) 820-4505
James C Yang, M.D.
principal investigator · National Cancer Institute (NCI)

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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