AFPᶜ³³²T in Advanced HCC

Description

This study will investigate the safety and tolerability of AFP?³³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker, whose liver tumor has the AFP protein and whose noncancerous liver tissue has very little AFP protein. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors.

Study Start Date

May, 08 2017

Estimated Completion Date

May 2019

Interventions

  • Genetic: Autologous genetically modified AFPᶜ³³²T cells

Study ID

Adaptimmune -- ADP-0033-001

Status

Recruiting

Trial ID

NCT03132792

Study Type

Interventional

Trial Phase

Phase 1

Enrollment Quota

30

Sponsor

Adaptimmune

Inclusion Criteria

    1. Subject is ? 18 years and ? 75 years of age and has voluntarily agreed to participate by giving written informed consent 2. Histologically confirmed HCC, not amenable to transplant, resection or locoregional therapy 3. Measurable disease according to RECIST 1.1 criteria. 4. Progressive disease following or intolerant of or refuses sorafenib treatment 5. HLA-A*02:01 positive during the escalation portion of the study. (Eligibility may be broadened to include HLA-A*02:05, *02:06, or *02:07 for the expansion portion of the study based on the accumulated safety experience, and approval of the safety review committee (SRC). 6. Subjects must have a tumor biopsy available for AFP expression evaluation prior to enrollment. Either an archival specimen (taken within the past 6 months from screening) or a new biopsy will be required. Both tumor and noncancerous cells must be present for histological evaluation. Subjects will be eligible for enrollment if their tumors have AFP expression of ?2+ in ?40% tumor cells by immunohistochemistry and if their non-cancerous liver tissue has ?5% cells stained for AFP by immunohistochemistry. Based on the data from dose escalation cohort and with the SRC's approval, subjects in the expansion portion of the study may be enrolled without requiring noncancerous biopsy tissue. Subjects with serum AFP levels within the normal range are unlikely to have AFP expressing tumors and generally should not undergo new tumor biopsy for the purpose of participating in this study. 7. Life expectancy of > 4 months 8. Child-Pugh score ? 6 9. ECOG 0-1 10. 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 maximally 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. 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. 11. Subject must have adequate organ function as indicated by the following laboratory values below:
  • White Blood Cells (WBS) ? 3.0 x10?/L
  • Absolute Neutrophil count (ANC) ? 1.5 x10?/L (without GCSF support)
  • Platelets ? 80 x10?/L (without transfusion support within 7 days from start of leukapheresis)
  • Hemoglobin > 8 g/dL (without transfusion support within 7 days prior to leukapheresis)
  • INR <1.7
  • Partial Thromboplastin Time (PTT) ? 1.5x upper limit of normal (ULN)
  • Calculated or measured creatinine clearance ? 50 mL/min
  • Serum total bilirubin <2.5 mg/dL (42 ?mol/L)
  • Serum Albumin ?3.0 g/dL
  • Alanine aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) ? 3x ULN
  • Left ventricular ejection fraction (LVEF) by ECHO or MUGA ? 50%

Exclusion Criteria

    1. Positive for any of the following alleles: HLA-A*02:02, HLA-C*0404 or HLA-B*5103 2. Prior liver transplant 3. Received the following prior to leukapheresis: 1. Cytotoxic chemotherapy, immune therapy and biological therapy within 3 weeks 2. Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled steroids is not exclusionary. 3. Sorafenib within 1 week 4. Investigational treatment or clinical trial within 4 weeks. 5. Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune study physician. 4. Received the following prior to lymphodepleting chemotherapy: 1. Cytotoxic chemotherapy or loco-regional therapy within 3 weeks, liver directed radiation therapy within three months. 2. Corticosteroids or any other immunosuppressive therapy within 2 weeks. NOTE: Use of inhaled steroids is not exclusionary 3. Bone/soft tissue directed palliative radiotherapy within 4 weeks. 4. Investigational treatment or clinical trial within 4 weeks. 5. Sorafenib within 1 week. 6. Prior cancer-directed immunotherapy within 3 weeks, including monoclonal antibodies against PD-1 receptor or ligand. 7. 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 8. Any previous gene therapy using an integrated vector 9. Duration of treatment free intervals for any other anti-cancer therapies must be discussed with Adaptimmune study physician. 5. Toxicity persisting from previous anti-cancer therapy of ? Grade 2 6. Major surgery within 4 weeks prior to lymphodepletion subjects should have been fully recovered from any surgical related toxicities. 7. Bleeding ? grade 2 in the past 3 months 8. Therapeutic anticoagulation (prophylactic heparin allowed) 9. Clinically detectable ascites or ascites requiring medication 10. Clinically detectable hepatic encephalopathy or hepatic encephalopathy requiring medication 11. Active viral hepatitis Subjects positive for hepatitis B surface antigen not on antiviral treatment/prophylaxis or subjects with detectable hepatitis B DNA 1. Subjects with resolved (surface antigen negative, core antibody positive) or chronic stable (surface antigen positive) hepatitis B on antiviral treatment/prophylaxis with undetectable DNA are allowed 2. Subjects with hepatitis C allowed provided they meet all other eligibility criteria 12. Positive serology for HIV 13. Positive serology for HTLV 1 or 2 14. 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. 15. Subject has known history of brain metastases. 16. Other active malignancy besides HCC within 2 years. 1. Subjects must be in complete remission from prior malignancy in order to be eligible to enter the study. 2. 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. 17. 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). 18. Bacterial or opportunistic infection within 3 months of treatment (URI and uncomplicated UTI allowed) 19. Uncontrolled intercurrent illness considered by the Investigator to add appreciable risk to study participation, including but not limited to: 1. 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 MI) in last 6 months. 2. Oxygen dependent lung disease. 3. Clinically significant psychiatric illness/social situations that would limit compliance with study requirements. 20. Pregnant or breastfeeding 21. Alcohol or illicit drug dependency

Gender

All

Ages

18 Years to 75 Years

Accepts Healthy Volunteers

No

Study Locations and Contact Information (21)

Study Location Distance Name Phone Email
Massachusetts General Hospital - Boston, Massachusetts 2.8 miles Patricia Lynch RN 617-724-9347 lynch.patricia2@mgh.harvard.edu
Massachusetts General Hospital - Boston, Massachusetts 2.8 miles Patricia Lynch RN 617-724-9347 lynch.patricia2@mgh.harvard.edu
Massachusetts General Hospital - Boston, Massachusetts 2.8 miles Patricia Lynch RN 617-724-9347 lynch.patricia2@mgh.harvard.edu
Massachusetts General Hospital - Boston, Massachusetts 2.8 miles Patricia Lynch RN 617-724-9347 lynch.patricia2@mgh.harvard.edu
University of Maryland Greenebaum Cancer Center - Baltimore, Maryland 358.9 miles Cheryl A Young BSN 410-328-8611 cheryl.young@umm.edu
University of Maryland Greenebaum Cancer Center - Baltimore, Maryland 358.9 miles Cheryl A Young BSN 410-328-8611 cheryl.young@umm.edu
University of Maryland Greenebaum Cancer Center - Baltimore, Maryland 358.9 miles Cheryl A Young BSN 410-328-8611 cheryl.young@umm.edu
University of Maryland Greenebaum Cancer Center - Baltimore, Maryland 358.9 miles Cheryl A Young BSN 410-328-8611 cheryl.young@umm.edu
University of Miami - Miami, Florida 1,259.8 miles Nathalie Luis 305-243-7648 nluis@med.miami.edu
University of Miami - Miami, Florida 1,259.8 miles Nathalie Luis 305-243-7648 nluis@med.miami.edu
USCNorris Comprehensive Cancer Center - Los Angeles, California 2,593.7 miles Ramona Lujan RN 323-409-4366 Lujan_R@med.usc.edu
USCNorris Comprehensive Cancer Center - Los Angeles, California 2,593.7 miles Ramona Lujan RN 323-409-4366 Lujan_R@med.usc.edu
USCNorris Comprehensive Cancer Center - Los Angeles, California 2,593.7 miles Ramona Lujan RN 323-409-4366 Lujan_R@med.usc.edu
USCNorris Comprehensive Cancer Center - Los Angeles, California 2,593.7 miles Ramona Lujan RN 323-409-4366 Lujan_R@med.usc.edu
UCLA - Los Angeles, California 2,605.2 miles Anna Crosetti 310-825-2903 ACrosetti@mednet.ucla.edu
UCLA - Los Angeles, California 2,605.2 miles Anna Crosetti 310-825-2903 ACrosetti@mednet.ucla.edu
UCLA - Los Angeles, California 2,605.2 miles Anna Crosetti 310-825-2903 ACrosetti@mednet.ucla.edu
University of California San Francisco - San Francisco, California 2,699.8 miles Julie McCluggage RN 415-353-2421 Julie.McCluggage@ucsf.edu
University of California San Francisco - San Francisco, California 2,699.8 miles Julie McCluggage RN 415-353-2421 Julie.McCluggage@ucsf.edu
University of California San Francisco - San Francisco, California 2,699.8 miles Julie McCluggage RN 415-353-2421 Julie.McCluggage@ucsf.edu
University of California San Francisco - San Francisco, California 2,699.8 miles Julie McCluggage RN 415-353-2421 Julie.McCluggage@ucsf.edu

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