AFPᶜ³³²T in Advanced HCC

NCT03132792 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: ADP-0033-0012017-000778-12
• Study Type: interventional
• Target: 45
• Locations: 4 countries
• Sites: 21

Brief Summary

This first time in human study is intended for men and women between 18 and 75 years of age who have advanced liver cancer which has grown or returned after being treated or another AFP expressing tumor. Those who did not tolerate or refused other therapies may also participate. The purpose of this study is to test the safety of genetically changed T cells that target alpha-fetoprotein (AFP) and find out what effects, if any, they have in subjects with liver cancer or other AFP expressing tumor types. This study is for subjects who have a blood test positive for appropriate HLA-A\*02 P Group and have adequate AFP protein in blood or tumor, and whose noncancerous liver tissue has very little AFP protein (Liver only). The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion after 3 days of chemotherapy. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose. Subjects will be hospitalized for at least 1 week after receiving their T cells back and then seen frequently by the Study Physician for the next 6 months. After that, subjects will be seen every three months. If subjects have disease progression or withdraw from the study, they will then be entered into a long-term follow up for safety monitoring. In long-term follow up, subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion and annually for the next 10 years.

Conditions

Hepatocellular Cancer; AFP Expressing Tumors

Keywords

Alpha-fetoprotein; Cell Therapy; T Cell Therapy; SPEAR T Cell; Immuno-oncology; Metastatic; Previously treated; T Cell Receptor

Outcome Measures

Primary Outcomes (1)

• Number of subjects with dose-limiting toxicity (DLT) and adverse events (AEs) and determination of optimally tolerated dose range, including serious adverse events (SAE).

  Determine if treatment with autologous genetically modified T cells, (AFPᶜ³³²T) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments including chemistry, hematology, coagulation, cardiac assessments including ECG, and cardiac Troponin

  2 years

Secondary Outcomes (6)

• Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR)

  2 years

• Interval between the date of first T cell infusion dose and first documented evidence of CR or PR

  2 years

• Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause

  2 years

• Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause

  2 years

• Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause

  2 years

Study Arms (1)

Autologous genetically modified AFPᶜ³³²T cells

EXPERIMENTAL

Genetic: Autologous genetically modified AFPᶜ³³²T cells

Interventions

Autologous genetically modified AFPᶜ³³²T cells GENETIC

Infusion of autologous genetically modified AFPᶜ³³²T cells

Autologous genetically modified AFPᶜ³³²T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is ≥ 18 years and ≤ 75 years of age and has voluntarily agreed to participate by giving written informed consent in accordance with ICH GCP Guidelines and applicable local regulations.
• Histologically confirmed HCC, not amenable to transplant, resection. Subjects may undergo loco-regional therapy after enrollment but not at time of lymphodepletion. Or Histologically confirmed diagnosis of another AFP expressing tumor (e.g. cholangiocarcinoma).
• Measurable disease according to RECIST 1.1 criteria prior to lymphodepletion.
• Progressive disease following or intolerant of or refuses standard of care systemic therapy prior to lymphodepletion.
• Positive for any A\*02:01 P group allele.
• a) Group 1, 2, 3, (HCC) Subjects will be eligible for enrollment if they meet either one of these AFP expression criteria:
• AFP expression of ≥1+ in ≥20% of tumor cells by immunohistochemistry and their non-cancerous liver tissue has ≤5% cells stained for AFP at any intensity by immunohistochemistry.
• Serum AFP levels of ≥100ng/mL and their non-cancerous liver tissue has ≤5% cells stained for AFP at any intensity by immunohistochemistry.
• \. b) Group 4 (other AFP expressing tumor types) Subjects will be eligible for enrollment if they meet either one of these AFP expression criteria:
• o Serum AFP levels of ≥100ng/mL and their non-cancerous liver tissue (if applicable) has ≤5% cells stained for AFP at any intensity by immunohistochemistry.
• \. Life expectancy of \> 4 months 8. Child-Pugh score ≤ 6 9. Eastern Cooperative Oncology Group (ECOG) 0-1 10. Subject must have adequate organ function as defined in the protocol.

You may not qualify if:

• Positive for any of the HLA-A\*02 allele other than HLA-A\*02:01 P Group, HLA-A\*02:03 P group or null alleles or positive for the following alleles: HLA-C\*04:04 or HLA-B\*51:03.
• Prior liver transplant
• Received the following prior to leukapheresis:
• Cytotoxic chemotherapy, immune therapy and biological therapy within 3 weeks
• Sorafenib/Regorafenib/Lenvatinib within 1 week
• Cabozantinib within 2 weeks
• Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune Study Physician.
• Received the following prior to lymphodepleting chemotherapy :
• Cytotoxic chemotherapy or loco-regional therapy within 3 weeks, liver directed radiation therapy within three months.
• Bone/soft tissue directed palliative radiotherapy within 4 weeks.
• Investigational treatment or clinical trial within 4 weeks.
• Sorafenib/Regorafenib/Lenvatinib within 1 week.
• Cabozantinib within 2 weeks
• Prior cancer-directed immunotherapy within 4 weeks, including monoclonal antibodies against PD-1 receptor or ligand.
• Use of an experimental vaccine within 2 months in the absence of tumor response. The subject should be excluded if their disease is responding to an experimental vaccine given within 6 months

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (21)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

UCLA

Los Angeles, California, 90095, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Winship Cancer Institute - Emory University

Atlanta, Georgia, 30322, United States

Location

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic Clinical Trial Referral Office

Rochester, Minnesota, 55905, United States

Location

Washington University - School of Medicine

St Louis, Missouri, 63110, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Centre

Seattle, Washington, 98109, United States

Location

SCCA Immunotherapy Trials Intake

Seattle, Washington, 98109, United States

Location

Paoli Calmettes Institute

Marseille, France

Location

Centre Eugène Marquis

Rennes, France

Location

Institute Gustave Roussy

Villejuif, France

Location

University Hospital of Barcelona

Barcelona, 08036, Spain

Location

University Hospital of Navarra

Pamplona, 31008, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

NIHR UCLH Clinical Research

London, W1T7HA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (1)

• Meyer T, Finn RS, Borad M, Mahipal A, Edeline J, Houot R, Hausner PF, Hollebecque A, Goyal L, Frigault M, Evans TRJ, Wong KM, Tan BR, Mitry E, Sarker D, Feun L, El-Rayes B, Thistlethwaite F, Kaseb A, Alese O, Jin Z, Cirillo C, Bruix J, Roddie C, Noto P, Fayngerts S, Cristiani S, Sampson J, Bai J, Isabelle M, Broad R, Sun A, Norry E, Sangro B. Phase I trial of ADP-A2AFP TCR T-cell therapy in patients with advanced hepatocellular or gastric hepatoid carcinoma. J Hepatol. 2026 Jan;84(1):113-121. doi: 10.1016/j.jhep.2025.07.033. Epub 2025 Aug 12.

  PMID: 40812667 DERIVED

MeSH Terms

Conditions

Liver Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Richard S Finn, MD

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: April 28, 2017
• Study Start: May 8, 2017
• Primary Completion: July 7, 2021
• Study Completion: December 7, 2025
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (12); ES (2); FR (3); GB (4)