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BRIEF TITLE: ATTAMAGE-A1 Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MAGE-A1-Specific T-Cell Receptor (TCR) Combined With Atezolizumab in Patients With Metastatic MAGE-A1 Expressing Cancer

ATTAMAGE-A1.: Phase I/II Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MAGE-A1-Specific T-Cell Receptor (TCR) Combined With Atezolizumab in Patients With Metastatic MAGE-A1 Expressing Cancer


  • Org Study ID: RG1007463
  • Secondary ID: NCI-2020-06602,10420
  • NCT ID: NCT04639245
  • NCT Alias:
  • Sponsor: Fred Hutchinson Cancer Research Center - Other
  • Source: Fred Hutchinson Cancer Research Center

Brief Summary

This phase I/II trial investigates the side effects of genetically engineered cells called FH-MagIC TCR-T cells and how well they work with atezolizumab in treating patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer that has spread to other places in the body (metastatic). T cells are infection fighting blood cells that can kill tumor cells. The T cells given in this study will come from the patient and will have a new gene put in them that makes them able to recognize MAGE-A1, a protein on the surface of tumor cells. These MAGE-A1-specific T cells may help the body's immune system identify and kill MAGE-A1 tumor cells. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving FH-MagIC TCR-T cells with atezolizumab may help treat patients with triple negative breast cancer, urothelial cancer, or non-small cell lung cancer.

Detailed Description


OUTLINE:

This is a phase I, dose escalation study of FH-MagIC TCR-T cells followed by a phase II
study.

LYMPHODEPLETION: Patients receive cyclophosphamide intravenously (IV) and fludarabine IV on
days -4, -3, and -2 before each T-cell infusion.

T-CELL INFUSION: Patients receive FH-MagIC TCR-T cells IV over 15-20 minutes. Six to twelve
weeks after first T-cell infusion, patients with progressive disease and non-persisting
transgenic TCR T cells may receive a second T-cell infusion.

In the Phase 2 portion of the study, atezolizumab will be administered as standard of care
beginning 24-72 hours after T-cell infusion. Atezolizumab will be given IV every 3 weeks for
at least 1 year in the absence of disease progression or unacceptable toxicity. If an
alternative PD1 inhibitor is instead available for a patient, it may be substituted instead.

After completion of study treatment, patients are followed up annually for 15 years after
final infusion of FH-MagIC TCR-T.

Overal Status Start Date Phase Study Type
Recruiting May 12, 2021 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Incidence of treatment-related unexpected grade 3 or higher adverse events

Primary Outcome 1 - Time Frame: Up to 15 years

Primary Outcome 2 - Measure: Best overall response

Primary Outcome 2 - Time Frame: Up to 15 years

Condition:

  • Anatomic Stage IV Breast Cancer AJCC v8
  • Metastatic Lung Non-Small Cell Carcinoma
  • Metastatic Malignant Solid Neoplasm
  • Metastatic Triple-Negative Breast Carcinoma
  • Metastatic Urothelial Carcinoma
  • Prognostic Stage IV Breast Cancer AJCC v8
  • Stage IV Lung Cancer AJCC v8
  • Stage IVA Lung Cancer AJCC v8
  • Stage IVB Lung Cancer AJCC v8

Eligibility

Criteria:
Inclusion Criteria:

- Tissue confirmation of triple negative breast cancer (TNBC), urothelial carcinoma or
non-small cell lung cancer (NSCLC) and expression of MAGEA1: Participants must have
metastatic disease. Confirmation of diagnosis must be or have been performed by
internal pathology review of archival, initial or subsequent biopsy or other
pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer
Care Alliance (SCCA)/University of Washington Medical Center (UWMC). Patients with
TNBC must meet the American Society of Clinical Oncology - College of American
Pathologists (ASCO-CAP) definition of negative estrogen, progesterone and HER2
receptor expression. Baseline tissue will be stained to confirm MAGE-A1 expression

- Measurable disease by RECIST 1.1 criteria: Participants must have measurable disease,
defined as at least one target lesion that can be measured in at least one dimension
(longest diameter to be recorded) as >= 10 mm, unless lymph node in which case short
axis must be >= 15 mm. Baseline imaging (for example diagnostic computed tomography
[CT] chest/abdomen/pelvis and imaging of the affected extremity as appropriate), brain
imaging (magnetic resonance imaging [MRI] or CT scan) must be obtained within 45 days
of prior to start of first planned FH-MAGEA1-A2TCR infusion. MRI can be substituted
for CT in patients unable to have CT contrast

- Previous treatment with standard of care (SOC) Food and Drug Administration
(FDA)-approved therapies. Patients with NSCLC who have actionable somatic mutations or
alterations in EGFR, ROS1 and ALK with FDA-approved drug therapy options will be
eligible for study only after treatment with targeted therapies for those mutations
have been offered or received. Patients with urothelial carcinoma who are candidates
for enfortumab vedotin (enfortumab vedotin-ejfv) will be eligible for study after
prior treatment with enfortumab vedotin-ejfv has been offered or received

- Previous treatment with PD-1 axis inhibitor: Patients in Phase I/2 must have been
offered or been previously treated with at least one dose of a PD-L1 axis inhibitor
(e.g. PD-1 or PD-L1 inhibiting monoclonal antibody such as pembrolizumab, nivolumab,
avelumab, atezolizumab, durvalumab). If received, they must have either developed
progression or still have detectable disease and not have developed Common Terminology
Criteria for Adverse Events (CTCAE) grade 3 or higher toxicity while on treatment.
Patients may have received 1 or more prior systemic regimens for metastatic TNBC or
NSCLC. There is no upper limit on prior regimens. Patients may have received prior
anti-PD-1/anti-PD-L1 in the neoadjuvant or adjuvant setting

- HLA type HLA-A*02:01: Participants must be HLA-A*02:01 in order for infused transgenic
T cells in order to insure recognition of antigen-MHC complexes. HLA typing should be
determined though a molecular approach in a clinical laboratory licensed for HLA
typing

- Life expectancy must be anticipated to be > 3 months at trial entry

- Capable of understanding and providing a written informed consent

- If fertile, willingness to comply with reproductive requirements

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Tumor tissue amenable to safe biopsy and subject willing to undergo serial tumor
biopsies: Should there be no tumor tissue that is accessible for biopsy, patients will
still be considered for participation, at discretion of the sponsor and in
consultation with the investigator. Similarly, should an investigator determine that a
biopsy cannot be performed safely for clinical reasons biopsies may be cancelled or
retimed after confirming plan with the sponsor

- Participants must be at least three weeks from last systemic treatment: At least 3
weeks must have passed since any: immunotherapy (for example, T-cell infusions,
immunomodulatory agents, interleukins, vaccines), small molecule or chemotherapy
cancer treatment, other investigational agents. There is no washout period for
radiation, so long as radiated lesion is not the lesion being evaluated for RECIST
measurements on the protocol. Bisphosphonates are permitted but the concurrent
treatment with RANK ligand inhibitors (i.e., denosumab) is not permitted within 8
weeks of treatment

- Serum creatine < 2.5 mg/dL or estimated glomerular filtration rate (eGFR) > 30 mL/min

- Total bilirubin (tBili) < 3.0 mg/dL. Patients with suspected Gilbert syndrome may be
included if Tbili > 3 but no other evidence of hepatic dysfunction

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 5 x upper limit
of normal (ULN)

- =< grade 1 dyspnea and oxygen saturation (SaO2) >= 92% on ambient air. If pulmonary
function tests (PFTs) are performed based on the clinical judgement of the treating
physician, patients with forced expiratory volume in 1 second (FEVI) >= 50% of
predicted and carbon monoxide diffusing capability test (DLCO) (corrected) of >= 40%
of predicted will be eligible

- Patients 60 years of age or older are required to have left ventricular ejection
fraction (LVEF) evaluation performed within 60 days prior to enrollment. LVEF may be
established with echocardiogram or multigated acquisition scan (MUGA) scan, and left
ejection fraction must be >= 35%. Cardiac evaluation for other patients is at the
discretion of the treating physician

- Absolute neutrophil count (ANC) > 500 cells/ mm^3

Exclusion Criteria:

- Expression of HLA B*4901: participants will be excluded due to the risk of
alloreactivity

- Participants of childbearing potential must have a negative serum pregnancy test
within 14 days prior to enrollment. Childbearing potential is defined as women who
have not been surgically sterilized and who are not postmenopausal (free of menses for
at least 1 year)

- Patients with active autoimmune disease requiring immunosuppressive therapy are
excluded. Case-by-case exemptions are possible with approval by principal investigator
(PI)

- Prior solid organ transplant or allogenic hematopoietic stem cell transplant: Kidney
transplant patients will be considered on a case-by-case basis requiring discussion
with PI. If kidney transplant, patient must have dialysis access, dialysis plan,
supportive nephrologist, willingness to stop transplant immunosuppression, and express
understanding that rejection is possible outcome. Dialysis or costs related to
transplant kidney will not be supported by the study. Participants having had any
other solid organ transplants will be excluded, as will those with any history of
allogeneic stem cell transplant

- Corticosteroid therapy at a dose equivalent of > 0.5 mg/kg of prednisone-equivalent
per day

- Concurrent use of other investigational anti-cancer agents

- Chronic lymphocytic leukemia (CLL) or other active hematologic malignancy

- Active uncontrolled infection: Human immunodeficiency virus (HIV) positive
participants on highly active anti-retroviral therapy (HAART) with a CD4 count > 500
cells/mm^3 are considered controlled, as are individuals with a history of hepatitis C
who have successfully completed antiviral therapy with an undetectable viral load, and
those with hepatitis B who have, per standard practice, hepatitis well-controlled on
medication (e.g., AST and ALT < 5 x ULN)

- Participants may not have uncontrolled or concurrent illness including, but not
limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Participants with small asymptomatic brain metastases (< 1 cm) or those with brain
metastases previously treated with surgery or radiotherapy will be considered for
inclusion at discretion of principal investigator, so long as other eligibility
criteria are met.

- For patients in phase 1/2, grade 3 or higher immune-mediated toxicity to any prior
PD-L1 axis blocking agent

- Active treatment for prior immune related adverse event to any immunotherapy:
Participants receiving ongoing treatment for prior serious immune related adverse
events are excluded, with exception of hormone supplementation or corticosteroid
therapy at equivalent of up to 0.5 mg/kg prednisone per day, unless otherwise approved
by PI

- Study participants must not have significant active underlying neurologic disease,
unless approved by PI. Neuropathy related to diabetes or prior chemotherapy is
acceptable

- Other medical, social, or psychiatric factor that interferes with medical
appropriateness and/or ability to comply with study, as determined by the PI
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Michael Schweizer

Role: Principal Investigator

Affiliation: Fred Hutch/University of Washington Cancer Consortium

Overall Contact

Name: IMTX Intake Coordinator

Phone: 866-268-6129

Email: immunotherapy@seattlecca.org

Location

Facility Status Contact
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington 98109
United States
Recruiting IMTX Intake Coordinator
866-268-6129
immunotherapy@seattlecca.org