Clinical trial · Interventional
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
Clinical Trial Evaluating the Safety and Activity of Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This clinical trial will evaluate the safety and activity of mutant KRAS G12V-specific TCR transduced T cell therapy for advanced pancreatic cancer patients who express the KRAS G12V mutation and HLA-A\*11:01 allele. The theoretical basis of this study is that mutant KRAS antigen-specific TCR transduced autologous Tcells will target and kill HLA-matched mutant KRAS cancer cells but not normal cells.
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Advanced Cancer | Malignant Neoplasm | CURATED_BROADER | 0.78 |
| Pancreatic Cancer | Malignant Pancreatic Neoplasm | CURATED_EXACT | 0.92 |
| Pancreatic Ductal Adenocarcinoma | Pancreatic Ductal Adenocarcinoma | ONTOLOGY_EXACT | 0.98 |
| Pancreatic Neoplasms | Pancreatic Neoplasm | ONTOLOGY_EXACT | 0.98 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Anti-PD-1 monoclonal antibody | Drug | Anti-PD1 Monoclonal Antibody | ALIAS |
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Fludarabine | Drug | Fludarabine | ALIAS |
| Mutant KRAS G12V-specific TCR transduced autologous T cells | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- TCR Transduced T cell therapy
- description
- Pre-conditioning: Non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine TCR transduced T cell infusion: mutant KRAS G12V-specific TCR transduced autologous T cells (1e9\~1e11). If the participant responds to the first infusion, the second or more infusions will be considered when the disease is progressing. Anti-PD-1 therapy: anti-PD-1 will be administered if needed.
- interventionNames
- Drug: Cyclophosphamide
- Drug: Fludarabine
- Biological: Mutant KRAS G12V-specific TCR transduced autologous T cells
- Drug: Anti-PD-1 monoclonal antibody
Primary outcomes (2)
- measure
- Frequency and severity of treatment-related adverse events
- timeFrame
- 18 months following cell infusion
- description
- Aggregate of all adverse events, as well as their frequency and severity
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
Inclusion Criteria: * Patients with measurable and pathologically confirmed advanced pancreatic cancer, including metastatic pancreatic cancer (who have received standard chemotherapy) and recurrent pancreatic cancer (who have received surgery and adjuvant chemotherapy previously). * Patient's tumor must express the KRAS G12V mutation, or a G12V mutation in HRAS or NRAS, as determined by DNA or RNA sequencing methods. * Patients must be HLA-A\*11:01. * Patients with brain metastasis may be eligible if they are asymptomatic and there are fewer than 3 brain lesions that are each less than 1 cm in diameter. * Patients between 18 to 75 years old are eligible. * Patients should have good clinical performance status (ECOG 0 or 1). * Patients must practice birth control once enrolled into the study and for up to four months after therapy. * Patients must be seronegative for HIV antibody. * Patients must be seronegative for hepatitis B surface antigen and core antibody (or HBV non-detectable by QPCR). * Patients must be seronegative for hepatitis C antibody (or HCV non-detectable by QPCR). * Baseline hematology criteria: * Absolute neutrophil count of at least 1000/mm\^3. * White blood cell count of at least 3000/mm\^3. * Platelet count of at least 100,000/mm\^3. * Hemoglobin \> 8.0 g/dL. * Baseline chemistry criteria: * Serum ALT/AST less than or equal to 3.0 x ULN. * Total bilirubin less than or equal to 1.5 mg/dL, unless the patient has Gilbert's Syndrome in which case total bilirubin must be less than or equal to 3.0 mg/dL. * Serum creatinine less than or equal to 1.6 mg/dL. * Anticipated lifespan greater than 12 weeks. * Patients must be willing and able to comply with all study-related procedures and follow-up requirements. * Patients must be able to understand and sign a written Informed Consent Document as well as a durable power of attorney. Exclusion Criteria: * Women who are pregnant or breastfeeding. * Patients with any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or HIV). * Patients with active systemic infections, coagulation disorders, or any other major medical illnesses. * Patients with concurrent opportunistic infections. * Patients on concurrent systemic steroid therapy. * Patients with a history of severe immediate hypersensitivity reaction to any of the medicines used in this study (e.g., cyclophosphamide, fludarabine). * Patients with active coronary ischemic symptoms. * Patients who are receiving any other investigational agents.
References
Publications (3)
- RESULTXu X, Guo S, Gu H, Cha Z, Shi X, Yin X, Wang H, Gao S, Li B, Zhu L, Jing W, Zheng K, Shao Z, Cheng P, Zheng C, Shih YP, Li Y, Qian B, Gao D, Tran E, Jin G. Identification and validation of a T cell receptor targeting KRAS G12V in HLA-A*11:01 pancreatic cancer patients. JCI Insight. 2025 Jan 23;10(2):e181873. doi: 10.1172/jci.insight.181873. PMID 39846249
- RESULTCafri G, Yossef R, Pasetto A, Deniger DC, Lu YC, Parkhurst M, Gartner JJ, Jia L, Ray S, Ngo LT, Jafferji M, Sachs A, Prickett T, Robbins PF, Rosenberg SA. Memory T cells targeting oncogenic mutations detected in peripheral blood of epithelial cancer patients. Nat Commun. 2019 Jan 25;10(1):449. doi: 10.1038/s41467-019-08304-z. PMID 30683863
- RESULTTran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016 Dec 8;375(23):2255-2262. doi: 10.1056/NEJMoa1609279. PMID 27959684