Neo-T in Treating Patients With Advanced Solid Tumors(GI-NeoT-03)

NCT05798533 | Unknown Phase 1 DMC

• 1 other identifier: BGI-004
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

The primary objective of this study is to evaluate the safety of Neo-T in combination with anti-PD1 in patients with solid tumors. The secondary objective of this study is to evaluate preliminarily the effect of Neo-T in combination with anti-PD1 in patients with solid tumors.

Conditions

Solid Tumor

Keywords

Melanoma; non-small cell lung cancer; NSCLC; Neoantigen; Adoptive T cell Therapy

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events as assessed by CTCAE v5.0.

  Keep records the adverse events experienced by subjects in 28 days after the first infusion.

  one month

Secondary Outcomes (5)

• Objective Response Rate(ORR)

  one year

• Disease Control Rate(DCR)

  one year

• Overall survival(OS)

  one year

• Progression-free survival(PFS)

  one year

• Duration of Response(DOR)

  one year

Study Arms (1)

Treatment of Neo-T and anti-PD1

EXPERIMENTAL

Dose escalation will use a 3+3 design and will enroll cohorts of 3-6 patients with MEL or NSCLC at escalating doses of 1.2×10\^9 cells and 3.6×10\^9 cells.

Biological: Neo-T; Combination Product: Toripalimab; Combination Product: Tislelizumab

Interventions

Neo-T BIOLOGICAL

Patients will receive Neo-T iv on day 0. Three times of cell infusion with an interval of 7 days constitute a cycle,maximum four cycles of treatment for patients.

Also known as: Neoantigen targeting T cells Suspension for Intravenous Infusion

Treatment of Neo-T and anti-PD1

Toripalimab COMBINATION_PRODUCT

3mg/kg iv; Within 7 days after the first PBMC collection (day-38±3), the first dose was administered, and thereafter every 2 weeks. Toripalimab is recommended for patients with Melanoma.

Also known as: JS001

Treatment of Neo-T and anti-PD1

Tislelizumab COMBINATION_PRODUCT

200mg iv; Within 7 days after the first PBMC collection (day-38±3), the first dose was administered, and thereafter every 3 weeks. Tislelizumab is recommended for patients with NSCLC or other tumor types.

Also known as: BGB-A317

Treatment of Neo-T and anti-PD1

Eligibility Criteria

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

You may qualify if:

• Greater than or equal to 18 years of age and less than or equal to 75 years of age; all genders.
• Advanced solid tumors including but not limited to some high frequency somatic mutations,such as melanoma,driver mutation-negative non-small cell lung cancer.
• Advanced solid tumors patients who are HLA - A0201 /A1101/A2402 subtypes.
• Measurable solid tumors with at least one lesion that is resectable or tumor biopsies for DNA extraction.
• Patients who failed or were intolerant to standard treatment.
• Possess venous access for mononuclear cell collection or intravenous blood collection.
• Patients (or their legal representatives) who are able to understand and sign the Informed Consent Form and willing to sign a durable power of attorney.
• Clinical performance status of ECOG is 0 or 1.
• Patients who are able to cooperate to observe adverse reactions and the effect of the treatment,expected lifetime is greater than six month.
• Patients of both genders must be willing to practice birth control from the time of enrollment to three months after treatment on this study,a fertile woman must have a negative pregnancy test.
• The laboratory test values and the functions of important organs meet the following requirements:1）Serology: HIV antibody(-), hepatitis B DNA(-), hepatitis C antibody(-) and no active syphilis infection; 2）Hematology: Absolute neutrophil count is greater than or equal to 1.5×10\^9/L; WBC is greater than or equal to 3×10\^9/L; lymphocyte count is greater than or equal to 0.8×10\^9/L; Platelet count is greater than or equal to 80×10\^9/L; Hemoglobin is greater than or equal to 90g/L ; 3）Chemistry: Serum ALT/AST is less than or equal to 3 times ULN,except in patients with liver metastasis who must have ALT/AST less than or equal to 5 times ULN; Serum Creatinine is less than or equal to 1.5 times ULN ; Total bilirubin is less than or equal to 1.5 times ULN, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3 times ULN;4）Blood Clotting Parameters:Prothrombin Time(PT) and International Normalised Ratio (INR) are less than or equal to 1.5 times ULN;Activated Partial Thromboplastin Time (APTT) is less than or equal to 1.5 times ULN;For subjects who frequently take anticoagulant drugs,their blood clotting parameters can meet the value range adaptive to this special population;5）Left ventricular ejection fraction（LVEF）is more than or equal to 50%.
• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the first dose of anti-PD1, and toxicities must have recovered to grade 1 or less (except for toxicities such as alopecia or vitiligo).

You may not qualify if:

• Pregnant or lactating women.
• History of severe immediate hypersensitivity reaction to Neo-T and any of the agents used in this study.
• Subjects with a history of organ transplantation.
• Subjects with brain metastases.
• Any active autoimmune disease or subjects with a history of autoimmune diseases that have been assessed by the investigator to be unsuitable for this study.Including but not limited to the following diseases: such as systemic lupus erythematosus, immune related neuropathy, multiple sclerosis, Guillain Barre syndrome, myasthenia gravis, connective tissue diseases, inflammatory bowel diseases(Crohn's disease and ulcerative colitis), excluding vitiligo, eczema, type I diabetes, rheumatoid arthritis and other joint diseases, Sjogren's syndrome and controlled psoriasis by local medication.
• Active systemic infections,for example, acute infections requiring systemic antibiotic, antiviral, or antifungal treatment occur within 2 weeks before enrollment.
• Subjects plan to receive glucocorticoid(the dose of prednisone or alternative drug is more than 10mg per day) or other immunosuppressant within 4 weeks before the first dose of anti-PD1.Tips: when there is no active autoimmune disease, it is allowed to use prednisone or alternative drug with a dose less than 10 mg per day; Allowing subjects to use topical, ocular, intra articular, intranasal, and inhaled glucocorticoids for treatment.
• Subjects plan to receive immunomodulatory drugs (such as interferon, GM-CSF, thymosin, gamma globulin, excluding IL-2) within 4 weeks before the first dose of anti-PD1.
• The investigator assessed that the subject was unable or unwilling to comply with the requirements of the study protocol.
• The genes correlated to functional defects in antigen presentation, antigen recognition, and cell killing have been detected.
• With a history of other malignant tumors within the past 5 years; Excluding basal cell carcinoma, thyroid papillary carcinoma, cervical carcinoma in situ, or breast ductal carcinoma in situ.
• The subject has any disease or medical condition that may affect the safety or effectiveness evaluation of the study treatment.

Sponsors & Collaborators

• BGI, China: lead
• Fudan University: collaborator
• Shanghai 10th People's Hospital: collaborator

Study Sites (2)

Fudan University Shanghai Cancer Center

Shanghai, China

RECRUITING

Shanghai Tenth People's Hospital

Shanghai, China

RECRUITING

Related Publications (2)

• Li D, Chen C, Li J, Yue J, Ding Y, Wang H, Liang Z, Zhang L, Qiu S, Liu G, Gao Y, Huang Y, Li D, Zhang R, Liu W, Wen X, Li B, Zhang X, Zhang X, Xu RH. A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors. Nat Commun. 2023 Jun 10;14(1):3447. doi: 10.1038/s41467-023-39225-7.

  PMID: 37301885 BACKGROUND

• Guo Z, Yuan Y, Chen C, Lin J, Ma Q, Liu G, Gao Y, Huang Y, Chen L, Chen LZ, Huang YF, Wang H, Li B, Chen Y, Zhang X. Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer. NPJ Precis Oncol. 2022 Jun 3;6(1):34. doi: 10.1038/s41698-022-00279-3.

  PMID: 35661819 BACKGROUND

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

Infusions, Intravenous; toripalimab; tislelizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Administration, Intravenous; Drug Administration Routes; Drug Therapy; Therapeutics; Infusions, Parenteral

Study Officials

• Jian Zhang, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

• Yong Chen, Doctor

  Fudan University

  PRINCIPAL INVESTIGATOR

• Qing Xu, Doctor

  Shanghai 10th People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Zhang, Doctor

CONTACT

021-64175590; syner2000@163.com

Qing Xu, Doctor

CONTACT

021-66300588; xuqingmd@aliyun.com

Study Design

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

Study Record Dates

• First Submitted: March 23, 2023
• First Posted: April 4, 2023
• Study Start: January 10, 2023
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2024
• Last Updated: July 10, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)