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Trial record 1 of 1 for:    AFNT211-22-101
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Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor

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ClinicalTrials.gov Identifier: NCT06105021
Recruitment Status : Recruiting
First Posted : October 27, 2023
Last Update Posted : May 3, 2024
Sponsor:
Information provided by (Responsible Party):
Affini-T Therapeutics, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Pancreatic Ductal Adenocarcinoma Non-Small Cell Lung Cancer Colorectal Cancer Solid Tumor KRAS G12V Drug: AFNT-211 Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Autologous CD8+ and CD4+ Engineered T Cell Receptor T Cells in Subjects With Advanced or Metastatic Solid Tumor
Actual Study Start Date : March 6, 2024
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Determine the Optimal Biological Dose (OBD) [ Time Frame: 60 months ]
    Quantify the desirability of a dose in terms of toxicity-efficacy tradeoff during the dose escalation portion of the study

  2. Determine the Recommended Phase 2 Dose [ Time Frame: 60 months ]
    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

  3. Incidence of Treatment Emergent Adverse Events [ Time Frame: 60 months ]
    The incidence of TEAEs will be used to determine safety and tolerability of AFNT-211

  4. Incidence of Serious Adverse Events [ Time Frame: 60 months ]
    The incidence of SAEs will be used to determine safety and tolerability of AFNT-211

  5. Incidence of Dose Limiting Toxicities [ Time Frame: 18 months ]
    The incidence of DLTs during Dose Escalation will be used to determine safety and tolerability of AFNT-211


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 60 months ]
    Percentage of subjects who achieved partial response (PR) or complete response (CR) as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  2. Duration of Response (DOR) [ Time Frame: 60 months ]
    Time from first documentation of response of PR or better to first documentation of disease progression or death from any cause, whichever occurs first.

  3. Progression-free Survival (PFS) [ Time Frame: 60 months ]
    From enrollment to first documentation of disease progression or death of any cause, whichever occurs first.

  4. Time to Response (TTR) [ Time Frame: 60 months ]
    Time from first AFNT-211 infusion to first documentation of PR or better.

  5. Clinical Benefit Rate (CBR) [ Time Frame: 60 months ]
    Percentage of subjects who have achieved PR or CR, or had stable disease (SD) for 6 months or more.

  6. Overall Survival (OS) [ Time Frame: 60 months ]
    From time of enrollment to death from any cause


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06105021


Contacts
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Contact: Shaunica Mitchell 617-380-3109 AFNT211info@affinittx.com
Contact: Binaish Khan 617-380-3109 AFNT211info@affinittx.com

Locations
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United States, California
USC Norris Comprehensive Recruiting
Los Angeles, California, United States, 90033
Contact: Xiomara Menendez       Xiomara.menendez@med.usc.edu   
Principal Investigator: Heinz-Josef Lenz         
University of California Los Angeles Department of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Chris Hannigan       CHannigan@mednet.ucla.edu   
Principal Investigator: Joel R Hecht, MD         
United States, New York
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Mark Bond       Mark.Bond@nyulangone.org   
Contact: Jennifer Coffey       Jennifer.Coffey@nyulangone.org   
Principal Investigator: Salman Punekar, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sophie Hieronymi       hierons@mskcc.org   
Principal Investigator: Adam Schoenfeld, MD         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Megan Barrett       SCRI.DDUReferrals@scri.com   
Principal Investigator: Meredith Pelster, MD         
Sponsors and Collaborators
Affini-T Therapeutics, Inc.
More Information
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Responsible Party: Affini-T Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT06105021    
Other Study ID Numbers: AFNT211-22-101
First Posted: October 27, 2023    Key Record Dates
Last Update Posted: May 3, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Affini-T Therapeutics, Inc.:
PDAC
NSCLC
CRC
human leukocyte antigen-A
Kirsten rat sarcoma
 HLA-A*11:01
KRAS
G12V
LDC
Lymphodepleting chemotherapy
Additional relevant MeSH terms:
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Adenocarcinoma
Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type