Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Pancreatic Cancer

NCT04146298 | Recruiting Phase 1 DMC

• 1 other identifier: ChanghaiH-PP06
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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

Pancreatic Cancer; Pancreatic Neoplasms; Advanced Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

pancreatic cancer; TCR transduced T cells; adoptive cell therapy; KRAS

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of treatment-related adverse events

  Aggregate of all adverse events, as well as their frequency and severity

  18 months following cell infusion

• Objective response rate

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

  From the date of cell infusion to disease progression (up to 18 months after cell infusion).

Secondary Outcomes (2)

• The percentage of TCR transduced T cells in peripheral blood

  1, 3, 7, 14, 28, 42 and 84 days after cell infusion, then every 3 months, and up to 18 months after cell infusion.

• Overall survival

  From date of cell infusion until the date of death from any cause, whichever came first, assessed up to 18 months after cell infusion.

Study Arms (1)

TCR Transduced T cell therapy

EXPERIMENTAL

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.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Mutant KRAS G12V-specific TCR transduced autologous T cells; Drug: Anti-PD-1 monoclonal antibody

Interventions

Cyclophosphamide DRUG

Cyclophosphamide will be administered prior to cell infusion.

TCR Transduced T cell therapy

Fludarabine DRUG

Fludarabine will be administered prior to cell infusion.

TCR Transduced T cell therapy

Mutant KRAS G12V-specific TCR transduced autologous T cells BIOLOGICAL

After preconditioning regimen, T cells will be infused to the patient intravenously in the Patient Care Unit over approximately 30 to 50 minutes.

TCR Transduced T cell therapy

Anti-PD-1 monoclonal antibody DRUG

During the treatment, anti-PD-1 monoclonal antibody will be administered if needed.

Also known as: Anti-PD-1

TCR Transduced T cell therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Changhai Hospital: lead

Study Sites (1)

Changhai Hospital

Shanghai, 200433, China

RECRUITING

Related Publications (3)

• Xu 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 RESULT

• Cafri 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 RESULT

• Tran 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 RESULT

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cyclophosphamide; fludarabine; spartalizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Central Study Contacts

Shiwei Guo, Doctor

CONTACT

+8618621500666; gestwa@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Doctor

Study Record Dates

• First Submitted: October 26, 2019
• First Posted: October 31, 2019
• Study Start: October 21, 2021
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 24, 2025

Record last verified: 2025-08

Locations

CN (1)