Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
1 other identifier
interventional
100
1 country
10
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2024
Longer than P75 for phase_1
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2023
CompletedFirst Posted
Study publicly available on registry
October 27, 2023
CompletedStudy Start
First participant enrolled
March 6, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2029
ExpectedJuly 30, 2025
July 1, 2025
1.7 years
October 9, 2023
July 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
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 Outcomes (6)
Overall Response Rate (ORR)
60 months
Duration of Response (DOR)
60 months
Progression-free Survival (PFS)
60 months
Time to Response (TTR)
60 months
Clinical Benefit Rate (CBR)
60 months
- +1 more secondary outcomes
Study Arms (5)
Dose Escalation
EXPERIMENTALSubjects 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.
Dose Expansion: PDAC
EXPERIMENTAL20 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.
Dose Expansion: CRC
EXPERIMENTAL20 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.
Dose Expansion: NSCLC
EXPERIMENTAL20 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.
Dose Expansion: Adv Solid Tumors
EXPERIMENTAL20 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.
Interventions
Engineered TCR T-Cell
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (10)
USC Norris Comprehensive
Los Angeles, California, 90033, United States
University of California Los Angeles Department of Medicine
Los Angeles, California, 90095, United States
Yale New Haven Hospital
New Haven, Connecticut, 06511, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Providence Cancer Institute Franz Clinic
Portland, Oregon, 97213, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 9, 2023
First Posted
October 27, 2023
Study Start
March 6, 2024
Primary Completion
December 1, 2025
Study Completion (Estimated)
December 1, 2029
Last Updated
July 30, 2025
Record last verified: 2025-07
Data Sharing
- IPD Sharing
- Will not share