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

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.

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.

Eligibility Criteria:
Key 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

Key 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