T cell therapy targeting KRAS G12V mutation 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

This study is testing a new T cell therapy that uses patients' own immune cells to target a specific mutation in advanced pancreatic cancer to see if it can help them fight the disease.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Changhai Hospital (Academic / other)
• Drugs / interventions: chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai)
• Trial ID: NCT04146298 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of T cell therapy specifically designed to target the KRAS G12V mutation in patients with advanced pancreatic cancer. The approach involves genetically engineering patients' own T cells to express a T cell receptor (TCR) that recognizes the KRAS G12V mutation, allowing these T cells to selectively attack cancer cells while sparing normal cells. Patients eligible for this trial must express the KRAS G12V mutation and the HLA-A*11:01 allele. The study will also assess the survival of these engineered T cells in the patient's body after infusion.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 75 with advanced pancreatic cancer that expresses the KRAS G12V mutation and the HLA-A*11:01 allele.

Not a fit: Patients without the KRAS G12V mutation or those who do not express the HLA-A*11:01 allele may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could provide a targeted treatment option for patients with advanced pancreatic cancer, potentially improving survival rates.

How similar studies have performed: Other studies targeting KRAS mutations have shown promise, indicating that this approach may be viable and effective.

Eligibility criteria

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.

Where this trial is running

Shanghai

• Changhai Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Shiwei Guo, Doctor

Conditions Pancreatic Cancer; Pancreatic Neoplasms; Pancreatic Ductal Adenocarcinoma; Advanced Cancer; pancreatic cancer; TCR transduced T cells; adoptive cell therapy; KRAS