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Hepatocellular CancerPhase 1NCT03132792

AFPᶜ³³²T in Advanced HCC

A Phase 1 study testing Autologous genetically modified AFPᶜ³³²T cells in people with Hepatocellular Cancer and AFP Expressing Tumors, run by Adaptimmune at 21 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Hepatocellular Cancer, AFP Expressing Tumors
What is being tested?
Autologous genetically modified AFPᶜ³³²T cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
21 sitesin 4 countries
Study dates
8 May 2017to 19 Nov 2025
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
Show all 11Show fewer
  • 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.
  • 6. 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.
  • 7. 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.

Who cannot join

  • 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
  • Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled or topical steroids is not exclusionary
  • Sorafenib/Regorafenib/Lenvatinib within 1 week
Show all 43Show fewer
  • 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.
  • Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled or topical steroids is not exclusionary
  • 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
  • Any previous gene therapy using an integrated vector
  • Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune Study Physician.
  • Toxicity persisting from previous anti-cancer therapy of ≥ Grade 2 (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g. peripheral neuropathy) can be enrolled on a case-by-case basis with prior consultation and agreement with the Sponsor Study Physician.
  • Major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
  • Bleeding ≥ Grade 2 in the past 3 months prior to lymphodepletion
  • Therapeutic anticoagulation from lymphodepletion until platelet count recovery (prophylactic heparin allowed)
  • Clinically or radiographically detectable ascites (beyond trace/rim of ascites) or ascites requiring medication
  • Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring medication
  • Active viral hepatitis Subjects positive for hepatitis B surface antigen not on antiviral treatment/prophylaxis or subjects with detectable hepatitis B DNA
  • Subjects with resolved (surface antigen negative, core antibody positive) or chronic stable (surface antigen positive) hepatitis B on antiviral treatment/prophylaxis with DNA levels of ≤100 IU/mL are allowed with HBV DNA monitoring after treatment
  • Subjects with hepatitis C allowed provided they meet all other eligibility criteria
  • Positive serology for HIV
  • Positive serology for HTLV 1 or 2
  • History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. Subjects with history of idiopathic autoimmune hepatitis are excluded. Subjects who experienced hepatitis during treatment with check point inhibiting antibodies are not excluded.
  • Subject has brain metastases.
  • Other active malignancy besides HCC or other eligible AFP expressing tumor types within 3 years.
  • Electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing a QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with Bundle Branch Block (BBB) over consecutive ECGs).
  • Bacterial or opportunistic infection within 3 months of treatment (upper respiratory infection and uncomplicated urinary tract infection allowed)
  • Uncontrolled intercurrent illness considered by the Investigator to add appreciable risk to study participation, including but not limited to:
  • Clinically significant cardiac disease defined by CHF New York Heart Association (NYHA) > Class 1; uncontrolled clinically significant arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or myocardial infarction) in last 6 months.
  • Oxygen dependent lung disease.
  • Clinically significant psychiatric illness/social situations that would limit compliance with study requirements.
  • History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) in last 6 months.
  • Pregnant or breastfeeding
  • Alcohol or illicit drug dependency
  • Known contraindication to cyclophosphamide, fludarabine, mesna, G-CSF or other agents associated with study treatment.

Trial locations and contacts

21 sites in 4 countries.

21 sites in 4 countries

United States12 sites
  • Winship Cancer Institute - Emory University

    Atlanta, Georgia, 30322

  • University of Maryland, Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • UCLA

    Los Angeles, California, 90095

  • University of Miami

    Miami, Florida, 33136

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic Clinical Trial Referral Office

    Rochester, Minnesota, 55905

  • Fred Hutchinson Cancer Research Centre

    Seattle, Washington, 98109

  • SCCA Immunotherapy Trials Intake

    Seattle, Washington, 98109

  • Washington University - School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

United Kingdom4 sites
  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Guy's Hospital

    London, SE1 9RT

  • NIHR UCLH Clinical Research

    London, W1T7HA

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

France3 sites
  • Paoli Calmettes Institute

    Marseille

  • Centre Eugène Marquis

    Rennes

  • Institute Gustave Roussy

    Villejuif

Other trials in France

Spain2 sites
  • University Hospital of Barcelona

    Barcelona, 08036

  • University Hospital of Navarra

    Pamplona, 31008

Other trials in Spain

About this study

Official title: A Phase I Open Label Clinical Trial Evaluating the Safety and Anti-Tumor Activity of Autologous T Cells Expressing Enhanced TCRs Specific for Alpha Fetoprotein (AFPᶜ³³²T) in HLA-A2 Positive Subjects With Advanced Hepatocellular Carcinoma (HCC) or Other AFP Expressing Tumor Types

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.

Read more

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.

Being tested
Autologous genetically modified AFPᶜ³³²T cells
Keywords
Alpha-fetoprotein, Cell Therapy, T Cell Therapy, SPEAR T Cell, Immuno-oncology, Metastatic, Previously treated, T Cell Receptor
Medical subject headings
Liver Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous genetically modified AFPᶜ³³²T cellsGenetic

    Infusion of autologous genetically modified AFPᶜ³³²T cells

Study groups in NCT03132792
Study groupRoleWhat they receive
Autologous genetically modified AFPᶜ³³²T cellsExperimentalNot described
Receives: Genetic: Autologous genetically modified AFPᶜ³³²T cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of Dose-limiting Toxicities (DLTs)

    Number of participants experiencing at least one dose-limiting toxicity (DLT) following administration of autologous genetically modified AFPᶜ³³²T cells, assessed during the protocol-defined DLT evaluation period.

    Measured: The DLT observation period was from the time of chemotherapy until 30 days following the infusion of AFPc332T cells for each participant in all groups.

  2. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Number of participants experiencing at least one treatment-emergent adverse event (TEAE) following administration of lymphodepleting chemotherapy and autologous genetically modified AFPᶜ³³²T cells.

    Measured: From first lymphodepleting chemotherapy through end of safety follow-up. Assessed at Days 9, 11, Weeks 2, 3, 4, 8, 12, 16, 24, then every 3 months until progression or withdrawal, up to approximately 4 years (data cut-off: 08 November 2022).

  3. Number of Participants With Serious Adverse Events (SAEs)

    Number of participants experiencing at least one serious adverse event (SAE) following administration of lymphodepleting chemotherapy and autologous genetically modified AFPᶜ³³²T cells

    Measured: From first lymphodepleting chemotherapy through end of safety follow-up. Assessed at Days 9, 11, Weeks 2, 3, 4, 8, 12, 16, 24, then every 3 months until progression or withdrawal, up to approximately 4 years (data cut-off: 08 November 2022).

Secondary outcomes (5)
  1. Overall Response Rate (ORR)

    Overall Response Rate (ORR) defined as the proportion of participants with a confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR = disappearance of all target lesions; PR = at least 30% decrease in the sum of diameters of target lesions. Response confirmation required a repeat assessment no less than 4 weeks after the criteria for response were first met.

    Measured: From first T-cell infusion; tumour assessments at Baseline, Weeks 4, 8, 16, 24, then every 3 months until disease progression or withdrawal, up to approximately 2 years (data cut-off: 08 November 2022).

  2. Interval Between Date of First Documented Evidence of CR or PR Until First Documented Disease Progression or Death Due to Any Cause

    Duration of response (DoR) was measured from the date of first documented confirmed Complete Response (CR) or Partial Response (PR) per RECIST v1.1 until the date of first documented disease progression or death due to any cause. Only participants achieving a confirmed CR or PR were included in this analysis.

    Measured: From date of first confirmed CR or PR until disease progression or death due to any cause, assessed at Weeks 4, 8, 16, 24 and every 3 months thereafter, up to approximately 2 years (data cut-off: 08 November 2022).

  3. Interval Between the Date of First Documented Evidence of SD Until First Documented Disease Progression or Death Due to Any Cause

    Duration of stable disease (DoSD) was measured from the date of first documented Stable Disease (SD) per RECIST v1.1 until the date of first documented disease progression or death due to any cause. Only participants achieving SD were included in this analysis.

    Measured: From date of first documented SD until disease progression or death due to any cause, assessed at Weeks 4, 8, 16, 24 and every 3 months thereafter, up to approximately 2 years (data cut-off: 08 November 2022).

  4. Interval Between the Date of First T Cell Infusion and the Earliest Date of Disease Progression or Death Due to Any Cause

    Progression-free survival (PFS) was measured from the date of first T-cell infusion until the date of first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurred first. Participants without a PFS event were censored at the date of last tumour assessment.

    Measured: From date of first T-cell infusion until disease progression or death due to any cause, assessed at Weeks 4, 8, 16, 24 and every 3 months thereafter, up to approximately 2 years (data cut-off: 08 November 2022).

  5. Interval Between the Date of First T-Cell Infusion and Date of Death Due to Any Cause

    Overall survival (OS) was measured from the date of first T-cell infusion until the date of death due to any cause. Participants who had not died at the data cut-off were censored at the date last known to be alive.

    Measured: From date of first T-cell infusion until death due to any cause, assessed every 3 months until disease progression and every 6 months thereafter during long-term follow-up, up to approximately 4 years (data cut-off: 08 November 2022).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2017
  2. Study start8 May 2017
  3. Primary completion7 Jul 2021
  4. Study completion19 Nov 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03132792
Sponsor's protocol ID
ADP-0033-001
Other IDs
2017-000778-12, 2017
Status last verified
May 2026
First submitted
25 Apr 2017
Last updated
17 Jun 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Not Applicable. Enrollment started before 2019.

Publications

  • 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.

    PubMed 40812667

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous genetically modified AFPᶜ³³²T cells in people with Hepatocellular Cancer and AFP Expressing Tumors, run by Adaptimmune at 21 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, United Kingdom, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Jun 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of Dose-limiting Toxicities (DLTs) (time frame: The DLT observation period was from the time of chemotherapy until 30 days following the infusion of AFPc332T cells for each participant in all groups.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03132792, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.

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