TP53 R248Q TCR-T Cell Therapy for Advanced Solid Tumor

NCT06619886 | Not Yet Recruiting Early Phase 1

• 1 other identifier: TP53-R248Q-PC
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and efficacy of T cell therapy with mutated TP53 R248Q specific TCR transduction in patients with advanced solid tumor expressing the TP53 R248Q mutation and the HLA-A\*11:01 allele.

Conditions

Solid Tumor, Adult; Lung Adenocarcinoma; Pancreas Cancer; Colorectal Cancer; Other Solid Tumor

Keywords

TP53-R248Q; TCR-T; advanced solid tumor

Outcome Measures

Primary Outcomes (2)

• Short term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors

  Incidence of dose-limiting toxicities (DLTs) after the infusion of TP53-R248Q TCR-T cell injection;

  28 days after infusion

• Long term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors

  Incidence of adverse events and serious adverse events; Treatment-emergent adverse events, and serious adverse events

  28 days after infusion and up to 24 months after infusion

Secondary Outcomes (1)

• Preliminary anti-tumor activity of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors

  Up to 24 months after infusion

Study Arms (1)

TP53 R248Q specific TCR transduction T cell therapy

EXPERIMENTAL

Dose Escalation of TCR T cell product

Biological: Autologous, engineered T Cells targeting TP53 R248Q

Interventions

Autologous, engineered T Cells targeting TP53 R248Q BIOLOGICAL

TP53-R248Q mutant TCR-T Cells Injection, 28 days as a treatment cycle (cycle number N≤3), each cycle was divided into three D0, D7, D14 infusion, a total of 3 dose groups were set up, the single infusion of cells within the range of ±20% all meet the requirements

TP53 R248Q specific TCR transduction 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:

• signed a written informed consent form (ICF), and can comply with protocol-specified visits and related procedures;
• aged ≥ 18 years, and ≤ 75 years, male or female;
• Subject must be pathologically confirmed with one of the histology below:
• Lung carcinoma Colorectal adenocarcinoma Pancreatic adenocarcinoma Any other solid tumor (progression after receiving standard treatment);
• subjects with TP53R248Q mutation in genetic testing, as determined by DNA or RNA sequencing methods;
• if patients with brain metastases are asymptomatic and less than 3 brain lesions less than 3 cm in diameter, they may be eligible;
• ECOG score 0-1;
• Expected survival of no less than 12 weeks;
• According to RECISTv1.1 and mRECIST, subjects have at least 1 measurable lesion (lesions that have received local therapy such as radiotherapy and interventional therapy cannot be used as measurable lesions unless imaging evidence confirms that the lesion has clearly progressed), RECISTv1.1 is non-lymph node lesions with the longest diameter ≥ 10 mm on CT or MRI, and/or lymph node lesions with the short diameter ≥ 15 mm; mRECIST is non-lymph node measurable lesion criteria that meet RECISTv1.1 criteria, and showed intratumoral arterial enhancement in enhanced CT or MRI;
• subjects should provide fresh tumor tissue samples that meet the requirements or within 2 years before signing the ICF;
• Adequate organ and bone marrow function as defined by the following laboratory criteria: (1) bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet (PLT) ≥ 75 × 109/L (transfusion or hematopoietic stimulating factor not acceptable within 14 days prior to Screening); (2) hemoglobin ≥ 90 g/L; (3) liver function: total bilirubin ≤ 2.5 × ULN; alanine aminotransferase ≤ 5 × ULN; aspartate aminotransferase ≤ 5 × ULN; (4) renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); (5) coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (INR between 2.0 and 3.0 is required for subjects receiving prophylactic anticoagulant therapy);
• Males of childbearing potential and females of childbearing potential must agree to use effective contraception from signing the ICF until one year after the last cell infusion and females of childbearing potential must have a negative blood pregnancy test at screening.

You may not qualify if:

• previous bone marrow or organ transplantation (including but not limited to liver transplantation) or waiting for transplantation;
• previous or concurrent history of other malignancies (cured and at least 2 years before screening without recurrence of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or radical treatment of local prostate cancer, radical resection of ductal carcinoma in situ can be enrolled in the study);
• hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and HBV DNA \> 500 IU/mL (lower limit of detection \< HBV DNA ≤ 500 IU/mL, clear lymphocyte conditioning medication before the need for at least 14 days of antiviral therapy and continuous antiviral therapy during the study can be enrolled); hepatitis C virus (HCV) antibody positive and HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
• HLA antibody positive subjects, including weak positive, positive and strong positive (those with different HLA typing sites from TP53R248QTCR-T cell injection can be enrolled in the study);
• previous treatment with other cell products or TP53 targeted drugs;
• treatment with any fluorouracil chemotherapeutic drugs or small molecule targeted drugs within 14 days or 5 half-lives (whichever is shorter) before screening, and any antineoplastic biological agents or non-fluorouracil chemotherapeutic agents; radical radiotherapy or extensive radiotherapy within 28 days before screening (except palliative radiotherapy for non-target lesions performed locally to relieve symptoms); traditional Chinese medicine/Chinese herbal medicine and local interventional therapy with antineoplastic indications within 14 days before screening;
• adverse events caused by previous antineoplastic therapy have not yet recovered to grade 1 or baseline levels, except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy;
• live attenuated vaccination within 28 days before screening, or live attenuated vaccination during the study;
• major surgical treatment (except liver mass biopsy) within 28 days before screening, or major surgical treatment during the study;
• Requirement for chronic systemic corticosteroids (at doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first study drug infusion or during the study, with the exception of inhaled or topical use;
• Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring systemic anti-infective therapy within 14 days prior to screening;
• Patients with active or previous autoimmune diseases that may relapse, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.;
• Previous or current interstitial lung disease, dust disease, radiation pneumonitis, severely impaired pulmonary function and other conditions;
• Third space effusion that is not clinically well controlled before screening, such as pleural effusion and ascites that cannot be controlled by drainage or other methods;
• History of serious cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine: lead

Study Sites (1)

Department of Oncology, Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

MeSH Terms

Conditions

Adenocarcinoma of Lung; Pancreatic Neoplasms; Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Qi Li, Prof.

  Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingyi Zhou, Dr.

CONTACT

15618122509; jingyi_zhou9468@163.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: PRINCIPAL INVESTIGATOR
• PI Title: Shanghai General Hospital

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: October 1, 2024
• Study Start: September 24, 2024
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2027
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)