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

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.

Key Inclusion Criteria:

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

Key Exclusion Criteria:

• 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.
• Any prior gene therapy utilizing an integrating vector
• Previous allogeneic stem cell transplantation or prior organ transplantation
• History of treated primary immunodeficiency, autoimmune, or inflammatory disease including inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, myasthenia gravis, or Grave's disease
• Primary brain tumor
• Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or cord compression.
• Uncontrolled active bacterial, viral, fungal, or mycobacterial infection
• Pregnant or lactating subjects
• Surgery or catheter-based interventions
• Previously identified allergy, hypersensitivity, or known contraindication to cyclophosphamide, fludarabine, or any other agent associated with lymphodepleting chemotherapy (LDC) or AFNT-211 product
• Uncontrolled significant intercurrent or recent illness
• Diagnosis of another malignancy within 2 years prior to screening.
• Seropositive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb)
• Seropositive for hepatitis C antibody.
• Known human immunodeficiency virus (HIV) infection