Trial Title:
Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
NCT ID:
NCT06105021
Condition:
Pancreatic Ductal Adenocarcinoma
Non-Small Cell Lung Cancer
Colorectal Cancer
Solid Tumor
KRAS G12V
Conditions: Official terms:
Adenocarcinoma
Conditions: Keywords:
PDAC
NSCLC
CRC
human leukocyte antigen-A
Kirsten rat sarcoma
HLA-A*11:01
KRAS
G12V
LDC
Lymphodepleting chemotherapy
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
AFNT-211
Description:
Engineered TCR T-Cell
Arm group label:
Dose Escalation
Arm group label:
Dose Expansion: Adv Solid Tumors
Arm group label:
Dose Expansion: CRC
Arm group label:
Dose Expansion: NSCLC
Arm group label:
Dose Expansion: PDAC
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.
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.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
USC Norris Comprehensive
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Status:
Recruiting
Contact:
Last name:
Xiomara Menendez
Email:
Xiomara.menendez@med.usc.edu
Investigator:
Last name:
Heinz-Josef Lenz
Email:
Principal Investigator
Facility:
Name:
University of California Los Angeles Department of Medicine
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Chris Hannigan
Email:
CHannigan@mednet.ucla.edu
Investigator:
Last name:
Joel R Hecht, MD
Email:
Principal Investigator
Facility:
Name:
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
Address:
City:
New York
Zip:
10016
Country:
United States
Status:
Recruiting
Contact:
Last name:
Salman Punekar, MD
Email:
salman.punekar@nyulangone.org
Investigator:
Last name:
Salman Punekar, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Sophie Hieronymi
Email:
hierons@mskcc.org
Investigator:
Last name:
Adam Schoenfeld, MD
Email:
Principal Investigator
Facility:
Name:
Providence Cancer Institute Franz Clinic
Address:
City:
Portland
Zip:
97213
Country:
United States
Status:
Recruiting
Contact:
Email:
CanRsrchStudies@providence.org
Investigator:
Last name:
Rom S Leidner, MD
Email:
Principal Investigator
Facility:
Name:
Sarah Cannon Research Institute
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Contact:
Last name:
Megan Barrett
Email:
SCRI.DDUReferrals@scri.com
Investigator:
Last name:
Meredith Pelster, MD
Email:
Principal Investigator
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
GI medical Oncology
Email:
GIClinicalTrials@mdanderson.org
Investigator:
Last name:
Dan Zhao, MD
Email:
Principal Investigator
Start date:
March 6, 2024
Completion date:
December 2029
Lead sponsor:
Agency:
Affini-T Therapeutics, Inc.
Agency class:
Industry
Source:
Affini-T Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06105021
