A Study to Evaluate AFPᶜ³³²T in Advanced HCC

Overview

About this study

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.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • 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 or resection. Subjects may undergo loco-regional therapy after enrolment but should not be amenable to further loco-regional therapy at the time of lymphodepletion; OR g-histologically confirmed diagnosis of another AFP expressing tumor (e.g., cholangiocarcinoma).
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (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 HLA-A*02:01 (or any A*02:01 P group allele). The Sponsor will review the results of HLA typing for inclusion alleles, and will adjudicate subject eligibility based on HLA results.
  • Group 1, 2, 3, (HCC) Subjects must have biopsy tissue available for AFP expression evaluation prior to enrollment unless considered unsafe. Either an archival specimen (taken within the past 12 months from Screening) or a new biopsy will be required for AFP expression in tumor tissue. Non-cancerous biopsy is also required prior to enrolment. 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. Subjects with serum AFP levels within the normal range at the time of screening are unlikely to have AFP expressing tumors and generally should not undergo new tumor biopsy for the purpose of participating in this study.
    • Group 4 (other AFP expressing tumor types) Subjects must have biopsy tissue available for AFP expression evaluation prior to enrollment unless considered unsafe. Either an archival specimen (taken within the past 12 months from Screening) or a new biopsy will be required for AFP expression in tumor tissue. Non-cancerous biopsy is also required prior to enrolment, for subjects with underlying liver disease. Subjects will be eligible for enrollment if they meet the following AFP expression criterion:
      • 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. Subjects with serum AFP levels within the normal range at the time of screening are unlikely to have AFP expressing tumors and generally should not undergo new tumor biopsy for the purpose of participating in this study.
  • Life expectancy of > 4 months.
  • Child-Pugh score ≤ 6.
  • Eastern Cooperative Oncology Group (ECOG) 0-1.
  • Female subjects of childbearing potential (FCBP) must have a negative serum pregnancy test.
  • NOTE: FCBP is defined as premenopausal and not surgically sterilized. FCBP must agree to use effective birth control or to abstain from heterosexual activity throughout the study, starting at the first dose of chemotherapy for at least 12 months thereafter or 4 months after there is no evidence of persistence or gene modified cells are in the subject’s blood, whichever is longer. FCBP must also agree to refrain from egg donation, storage, or banking during these same time periods. Effective contraceptive methods include intra-uterine device, oral and injectable hormonal contraception, or 2 adequate barrier methods (e.g., diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide). Spermicides alone are not an adequate method of contraception; OR male subjects must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter. Male subjects must also agree to refrain from sperm donation, storage, or banking during these same time periods.
    Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the subject’s preferred and usual lifestyle and if considered acceptable by local Regulatory Agencies and ERCs/IRBs. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

  • Positive for any 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. The Sponsor will review the results of HLA typing for exclusion alleles, and will adjudicate subject eligibility based on HLA results.
  • 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;
    • 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:
    • Subjects must be in complete remission from prior malignancy in order to be eligible to enter the study;
    • Adequately treated malignancies not likely to require therapy (e.g., completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma) are eligible to enter the study.
  • 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Amit Mahipal, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Mitesh Borad, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20438537

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