Study of Anti-KRAS G12V mTCR PBL for Pancreatic, Gastric, and Other Cancers
This study is testing a new approach for certain cancers like pancreatic, gastric, and colon cancer that have a specific change in their cells called KRAS G12V. Researchers will take your white blood cells, modify them in the lab to recognize and fight the KRAS G12V cancer cells, and then give them back to you. Before receiving these modified cells (Anti-KRAS G12V mTCR PBL), you will receive two chemotherapy medicines, Cyclophosphamide and Fludarabine, followed by Aldesleukin. The main goals are to see if this treatment is safe and if it can shrink tumors. You may be eligible if you are between 18 and 72 years old and have a cancer with the KRAS G12V mutation.
- Study design
- This is an interventional study with a planned enrollment of 110 participants. It is designed to evaluate the safety and effectiveness of the Anti-KRAS G12V mTCR PBL treatment.
- What's involved
- You will be admitted to the hospital and receive two chemotherapy medicines for 5 days. Then, you will receive the Anti-KRAS G12V mTCR PBL cells intravenously, followed by Aldesleukin for up to 3 days.
- Compensation
- Not stated in the trial record.
- Follow-up
- Your response to treatment will be measured at 6 and 12 weeks, then every 3 months for a year, and then every 6 months for two years, with further follow-up at the doctor's discretion. Treatment-related side effects will be monitored for two weeks after cell infusion.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT03190941
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients
Recruiting
PHASE1Ages 18–72InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~110 participants
Updated 2026-08-24 on ClinicalTrials.gov
What's tested:CyclophosphamideFludarabineAnti-KRAS G12V mTCR PBLAldesleukin
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Response rate
Measured over 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
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- James C Yang, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Measurable (per RECIST V1.1 criteria, 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
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 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.
Serology
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.
Hematology
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.
Chemistry
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.
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.
Exclusion
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.
What this trial measures
- Response rate6 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
Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)
- Frequency and severity of treatment-related adverse eventsFrom time of cell infusion to two weeks after cell infusion
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