Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-06

Study Completion Date

2029-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

This study is open to adult patients with solid tumors who have a KRAS G12V mutation. This mutation is often found in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and other cancers. The study is for patients whose cancer has spread through the body and for whom previous treatments were not successful or treatment does not exist. Patients must also be positive for HLA-A\*11:01. The purpose of this study is to find the best dose of AFNT-211 that is safe and can shrink tumors in patients. AFNT-211 is an investigational therapy and this is the first time that AFNT-211 is being administered to patients. AFNT-211 is an autologous T cell product which means that it is made from a patient's own T cells. These cells are engineered and grown to recognize the KRAS G12V protein on the cell surface of cancer cells. AFNT-211 is infused into patients after a short course of lymphodepleting chemotherapy. Patients will frequently visit the study site. The doctors there will regularly check the size of the cancer and the patient's health. They will also take note of any unwanted effects. Patients may continue in this study for as long as they benefit from the treatment.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Autologous T-cells Genetically Engineered to Express Receptors Reactive Against KRAS Mutations in Conjunction With a Vaccine Directed Against These Antigens in Participants With Metastatic Cancer

NCT06253520

Metastatic Solid Cancers Colorectal Cancer Breast Cancer +4 more

RECRUITING PHASE1

Active Immunotherapy Of Metastatic Renal Cell Carcinoma Using Autologous Dendritic Cells Transfected With Autologous Total Tumor RNA

NCT00006431

Renal Cell Carcinoma

UNKNOWN PHASE1

Vaccine Therapy in Treating Patients With Metastatic Prostate Cancer

NCT00010127

Prostate Cancer

TERMINATED PHASE1

A Safety and Feasibility Study of Active Immunotherapy in Patients With Metastatic Prostate Carcinoma Using Autologous Dendritic Cells Pulsed With Antigen Encoded in Amplified Autologous Tumor RNA

NCT00006430

Prostate Cancer

UNKNOWN PHASE1

Study of Autologous Immune Killer Cells in Patients With Late Stage Hepatocellular Carcinoma or Lung Cancer

NCT03515252

NSCLC Stage IIIB NSCLC Stage IV Hepatocellular Carcinoma by BCLC Stage +2 more

COMPLETED PHASE1

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

AFNT-211 is a cellular therapy consisting of autologous CD4+ and CD8+ T cells engineered to express a human leukocyte antigen-A (HLA-A)\*11:01-restricted Kirsten rat sarcoma (KRAS) G12V-specific transgenic T cell receptor (TCR), the wildtype CD8α/β coreceptor, and a FAS-41BB switch receptor. AFNT-211 is being developed by Affini-T Therapeutics, Inc. (hereafter, "the Sponsor") for the treatment of patients with malignant solid tumors. The primary purpose of this study is to assess the safety and tolerability of AFNT-211 in subjects who are HLA-A\*11:01 positive with advanced or metastatic cancers that harbor a KRAS G12V mutation, as well as determine the optimal biological dose (OBD) and recommended Phase II dose (RP2D) of AFNT-211 in this population. This study will also evaluate the preliminary anti-tumor activity of AFNT-211.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Pancreatic Ductal Adenocarcinoma Non-Small Cell Lung Cancer Colorectal Cancer Solid Tumor KRAS G12V

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

This is a Phase I, FIH, multicenter, open-label study of AFNT-211 consisting of a dose escalation part and a dose expansion part. During dose escalation the optimal biological dose (OBD) will be determined as well as the recommended phase 2 dose (RP2D). Additional subjects will enroll in expansion cohorts treated at OBD/RP2D found in escalation.

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Intervention Type DRUG

Engineered TCR T-Cell

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

AFNT-211

Engineered TCR T-Cell

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Confirmed KRAS G12V mutational status and HLA-A\*11:01 allele
2. Histologically confirmed advanced or metastatic, unresectable solid tumor
3. Progressed on or intolerant of at least one prior line of standard systemic therapy for the current malignancy.
4. Measurable disease per RECIST v1.1.
5. ECOG performance status 0-1
6. Adequate organ and bone marrow function

Exclusion Criteria

1. Any systemic cytotoxic chemotherapy, investigational agents, or any anti-tumor drug from a previous treatment regimen or clinical study (including small molecules and I/O compounds) within 5 half-lives or 14 days of Screening, whichever is shorter.
2. Any prior gene therapy utilizing an integrating vector
3. Previous allogeneic stem cell transplantation or prior organ transplantation
4. History of treated primary immunodeficiency, autoimmune, or inflammatory disease including inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, or Grave's disease
5. Primary brain tumor
6. Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
7. Uncontrolled active bacterial, viral, fungal, or mycobacterial infection
8. Pregnant or lactating subjects
9. Surgery or catheter-based interventions
10. Previously identified allergy, hypersensitivity, or known contraindication to cyclophosphamide, fludarabine, or any other agent associated with lymphodepleting chemotherapy (LDC) or AFNT-211 product
11. Uncontrolled significant intercurrent or recent illness
12. Diagnosis of another malignancy within 2 years prior to screening.
13. Seropositive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb)
14. Seropositive for hepatitis C antibody.
15. Known human immunodeficiency virus (HIV) infection

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No