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

Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorChanghai Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Cyclophosphamide

    Drug

    Cyclophosphamide will be administered prior to cell infusion.

  • Fludarabine

    Drug

    Fludarabine will be administered prior to cell infusion.

  • Mutant KRAS G12V-specific TCR transduced autologous T cells

    Biological/Vaccine

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

  • Anti-PD-1 monoclonal antibody

    Drug

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

Treatment groups

30 Participants
are divided into 1 treatment group
Group A: TCR Transduced T cell therapyExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Frequency and severity of treatment-related adverse events

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

Time frame
18 months following cell infusion
2

Objective response rate

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

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

Secondary outcomes

1

The percentage of TCR transduced T cells in peripheral blood

The percentage of TCR transduced T cells in peripheral blood will be detected with an established flow cytometric assay.

Time frame
1, 3, 7, 14, 28, 42 and 84 days after cell infusion, then every 3 months, and up to 18 months after cell infusion.
2

Overall survival

The time between cell infusion and the death of patients

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

Other outcomes

Sponsors and contacts

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