Personalized KSX01-TCRT in Patients With Advanced Solid Tumors

NCT06150365 | Recruiting Early Phase 1

• 1 other identifier: KSX01-R08-102
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is a single arm, open phase I clinical study to investigate the safety and efficacy of personalized KSX01-TCRT in patients with advanced solid tumors. This experiment is divided into two parts: the dose increasing stage (Part A) and the dose expanding stage (Part B). For those enrolled in the planned expansion phase, the dose should have passed the safety assessment during the dose escalation phase.

Conditions

Refractory Solid Tumors; Relapsed Solid Tumors

Outcome Measures

Primary Outcomes (2)

• Subject safety

  Number of participants with treatment-related adverse events assessed by CTCAE v4.0.

  about 2 years

• tumor efficacy

  Changes in overall tumor diameter.

  about 2 years

Study Arms (1)

TCR-T cells

EXPERIMENTAL

KSX01-TCRT cell therapy

Biological: KSX01-TCRT cell therapy

Interventions

KSX01-TCRT cell therapy BIOLOGICAL

Patient autologous T cell therapy

TCR-T cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteer to participate in clinical research; Fully understand this study and voluntarily sign an informed consent form; Willing to follow and capable of completing all testing procedures.
• Age range from 18 to 70 years old (including boundary values).
• Solid tumors that have been confirmed by histological or cytological evaluation as incurable or metastatic, and have failed standard treatment or currently have no available standard treatment.
• Expected survival time\>6 months.
• ECOG score 0 or 1.
• Having sufficient organ function, defined as follows:
• ) Hematology: 6.1.1) Hemoglobin 90 g/L (no blood transfusion received within 14 days prior to examination); 6.1.2) Absolute value of neutrophils 1.5 109/L (did not receive granulocyte colony stimulating factor treatment within 14 days prior to examination); 6.1.3) Platelet count is 100 109/L in the absence of obvious liver lesions (primary or metastatic) (platelet transfusion not received within 14 days before examination), or 75 109/L in the presence of liver lesions (platelet transfusion not received within 14 days before examination); 6.1.4) Absolute lymphocyte count (ALC) 0.7 109/L; 6.2) Liver function: 6.2.1) Total bilirubin (TBIL) ≤ 1.5 in the absence of obvious liver lesions (primary or metastatic) × Upper limit of normal (ULN), subjects with liver lesions or Gilbert disease ≤ 3 × ULN; 6.2.2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (liver metastasis or liver cancer subjects can be ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5) × ULN); 6.3) Renal function: Creatinine clearance rate ≥ 60 mL/min (Cockcroft Fault formula: \[140 age\] × Weight \[kg\] × \[0.85, female only\]/(72 × Creatinine (mg/dl);
• Subjects with a creatinine clearance rate of\<60 mL/min but ≥ 50 mL/min can also be enrolled if all of the following conditions are met:
• Serum creatinine and blood urea nitrogen (BUN) are within the normal range of the research center No clinical evidence showing chronic renal dysfunction (such as acidosis or electrolyte disorders) The urine routine and urine output are within the normal range of the research center Note: It is not recommended to use IL-2 during the treatment period for subjects with a baseline creatinine clearance rate of\<60 mL/min.
• The patient's HLA-I class molecule IHC expression is positive.
• Patients with tumor lesions that can be collected and can screen out TCR sequences that can be used as drugs can enter the study. If the patient has obtained personalized TCR sequences using previously collected and archived tumor tissue in other studies, they can directly enter screening period 2, but the collection time of the archived tissue should be within one year before signing the informed consent for this study.
• The patient agrees to receive peripheral monocyte collection after all tests in screening period 1 meet the standards.
• The organ function and key examination items of the patient at this stage should not have significant changes compared to the examination results in screening period 1. If the patient's examination results during screening period 2 exceed the following criteria, peripheral monocyte collection should not be performed until the abnormal items return to normal range.
• Confirmed screening and locking of tumor specific TCR sequences from the patient's own body. For patients who have obtained TCR sequences through other research projects, they should sign an informed consent form for this research project before entering screening period 2.
• Expected survival time\>6 months.

You may not qualify if:

• Subjects who meet any of the following criteria shall not participate in this clinical study:
• The patient has received systemic chemotherapy on line 3 or above:
• Patients can be enrolled during the first line systemic chemotherapy, during the second line systemic chemotherapy period, or after the end of the second line systemic chemotherapy (enrollment time is screening period 2 and meets the standards and receives clearance chemotherapy), but they cannot receive the third line systemic chemotherapy before enrollment:
• The second and third line systemic chemotherapy is defined as a systematic chemotherapy regimen after the progression of frontline treatment;
• For patients who complete neoadjuvant chemotherapy in the early stage of their disease, their neoadjuvant chemotherapy regimen can include up to two types of chemotherapy;
• Within two years before signing the informed consent, the patient had a medical history of other malignant tumors, except for non melanoma skin cancer, some cancers in situ (such as cervical cancer, bladder cancer, breast cancer), or low-risk prostate cancer.
• Clinically confirmed liver diseases, including active hepatitis virus infection, alcoholic hepatitis, other types of hepatitis, cirrhosis, and hereditary liver diseases; Among them, the subject's
• Hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) are positive, and the hepatitis B virus DNA (HBV DNA) in the peripheral blood is higher than the lower detection limit of the research center;
• HCV-Ab positive and HCV-RNA above the lower detection limit of the research center Patients who can effectively control HBV-DNA and/or HCV-RNA after treatment can also be included in the group after being evaluated and approved by the researcher. HBV-DNA positive subjects should receive hepatitis B treatment after signing the informed consent form and continue to receive KSX01-TCRT infusion for at least 6 months. Such subjects should also monitor their HBV-DNA and hepatitis B related antigen antibodies on Day28 and at each follow-up visit point.
• History of myocardial infarction, history of cardiac bypass surgery, unstable angina, active atrial fibrillation requiring treatment, symptomatic sinus bradycardia (heart rate\<50 beats/min), or other clinically significant heart diseases within 6 months prior to signing the informed consent form.
• Tumor lesions invading the heart or large blood vessels. The patient has permanent percutaneous nephrostomy, catheterization, bile duct, and other indwelling tubes, except for those that the researchers believe can be removed before gonorrhea clearance.
• \) Primary immune deficiency. 8) HIV positive; Active HBV or HCV infection. 9) Received allogeneic stem cell transplantation within 6 months before signing the informed consent form.
• \) Prior to signing the informed consent form, CAR T cell therapy or other genetically modified T cell therapy other than this research technique was received.
• \) Known allergies to dimethyl sulfoxide (DMSO) or any other cellular formulation components and potential therapeutic drugs used during treatment (such as cyclophosphamide, fludarabine, and tolumab).
• \) History of autoimmune diseases, except for the following:

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

Study Officials

• Shuhang Wang

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  STUDY DIRECTOR

Central Study Contacts

clinical trials ksh

CONTACT

18994103369; ksh-clinicalt@tcrximmune.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: KSX01-TCRT cell therapy

Study Record Dates

• First Submitted: November 21, 2023
• First Posted: November 29, 2023
• Study Start: November 7, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

CN (1)