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.

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer; Solid Tumor; Pancreatic Ductal Adenocarcinoma; KRAS G12V
• Intervention / Treatment: Drug: AFNT-211

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles Department of Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale New Haven Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Subjects will be given a one-time infusion of AFNT-211 starting at dose level 1 and monitored for 28 days (DLT period). Each cohort will enroll 2-4 subjects at different dose levels for a total of 20 subjects in the escalation portion. The optimal biological dose and recommended phase 2 dose will be determined.	Drug: AFNT-211; Engineered TCR T-Cell
Experimental: Dose Expansion: PDAC; 20 subjects with pancreatic ductal adenocarcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.	Drug: AFNT-211; Engineered TCR T-Cell
Experimental: Dose Expansion: CRC; 20 subjects with colorectal carcinoma will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.	Drug: AFNT-211; Engineered TCR T-Cell
Experimental: Dose Expansion: NSCLC; 20 subjects with non-small cell cancer will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.	Drug: AFNT-211; Engineered TCR T-Cell
Experimental: Dose Expansion: Adv Solid Tumors; 20 subjects with solid tumors will be given a one-time infusion of AFNT-211 at the optimal biological dose / recommended phase 2 dose determined in the escalation portion. Subjects will be monitored for safety for 28 days.	Drug: AFNT-211; Engineered TCR T-Cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the Optimal Biological Dose (OBD)	Quantify the desirability of a dose in terms of toxicity-efficacy tradeoff during the dose escalation portion of the study	60 months
Determine the Recommended Phase 2 Dose	This will be selected based on Bayesian optimal interval Phase I/II (BOIN12) design recommendation and the totality of benefit-risk evidence during dose escalation	60 months
Incidence of Treatment Emergent Adverse Events	The incidence of TEAEs will be used to determine safety and tolerability of AFNT-211	60 months
Incidence of Serious Adverse Events	The incidence of SAEs will be used to determine safety and tolerability of AFNT-211	60 months
Incidence of Dose Limiting Toxicities	The incidence of DLTs during Dose Escalation will be used to determine safety and tolerability of AFNT-211	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Percentage of subjects who achieved partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	60 months
Duration of Response (DOR)	Time from first documentation of response of PR or better to first documentation of disease progression or death from any cause, whichever occurs first.	60 months
Progression-free Survival (PFS)	From enrollment to first documentation of disease progression or death of any cause, whichever occurs first.	60 months
Time to Response (TTR)	Time from first AFNT-211 infusion to first documentation of PR or better.	60 months
Clinical Benefit Rate (CBR)	Percentage of subjects who have achieved PR or CR, or had stable disease (SD) for 6 months or more.	60 months
Overall Survival (OS)	From time of enrollment to death from any cause	60 months

Collaborators and Investigators

• Sponsor: Affini-T Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: October 9, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 28, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: NSCLC; KRAS; CRC; PDAC; Kirsten rat sarcoma; G12V; human leukocyte antigen-A; HLA-A*11:01; LDC; Lymphodepleting chemotherapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Adenocarcinoma
• Other Study ID Numbers: AFNT211-22-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No