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Other SkinPhase 1/2NCT03747484

Gene-Modified Immune Cells (FH-MCVA2TCR) in Treating Patients With Metastatic or Unresectable Merkel Cell Cancer

A Phase 1/2 study testing Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR, Avelumab and Pembrolizumab in people with Other Skin, run by Fred Hutchinson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I/II trial studies the side effects of gene-modified immune cells (FH-MCVA2TCR) and to see how well they work in treating patients with Merkel cell cancer that has spread to other parts of the body (metastatic) or that cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Other Skin
What is being tested?
Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR, Avelumab and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
1 siteUnited States
Study dates
3 Jul 2019to 9 Jan 2024
Phase
Phase 1/2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • EVALUATION: Metastatic or unresectable Merkel cell polyomavirus (MCPyV)-associated Merkel cell carcinoma (VP-MCC) that has progressed on or after prior treatment with a PD-1 axis immune checkpoint inhibitor.
  • EVALUATION: Individuals that may be consented to undergo evaluation to determine potential eligibility must have a history of metastatic or unresectable Merkel cell carcinoma (MCC) (as documented by medical record).
  • EVALUATION: Be 18 years of age or older.
  • EVALUATION: Be capable of understanding and providing informed consent.
  • Participants must have metastatic or unresectable, histologically confirmed virus-positive MCC. Confirmation of diagnosis must be or have been performed by internal pathology review of initial or subsequent biopsy or other pathologic material at Fred Hutch/Seattle Cancer Care Alliance (SCCA).
  • Approximately 80% of MCCs are caused by Merkel cell polyomavirus (MCPyV) T Antigens and the treatment is expected to only be effective in this population. Merkel cell polyomavirus positivity may be established through one of two means: positive Merkel cell polyomavirus T antigen serology (preferred) or immunohistochemistry of a primary or metastatic MCC tumor lesion (if T antigen seronegative).
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  • MCPyV T Antigen serology will be performed with the anti-Merkel cell panel (AMERK) assay run through the University of Washington Medical Center Laboratory Medicine Clinical Immunology Laboratory. Positivity will be defined as a Merkel oncoprotein antibody titer (MSCTT) of >= 75 standard titer units (STU) at any time point from initial diagnosis onward. Patients with negative T antigen serology but MCPyV positive tumor by other methodologies will be considered for additional MCPyV testing as clinically appropriate, as the T antigen serology assays are highly specific but incompletely sensitive for MCPyV status. In this case, immunohistochemistry of any tumor lesion will be performed with the CM2B4 Merkel cell polyomavirus T antigen antibody. Expression of MCPyV in at least 10% of tumor cells will be considered positive. CM2B4 staining performed at any point clinically and at any clinical laboratory may be accepted. However, if CM2B4 staining has not been previously performed by a clinical pathology laboratory as part of MCC diagnostic workup, it will be performed in a clinical diagnostic pathology laboratory at University of Washington (UW)/Fred Hutchinson Cancer Research Center (FHCRC)/SCCA as per standard staining protocols. Persons are not required to have both CM2B4 positivity and seropositivity; either will be acceptable confirmation of viral status and if one negative and the other positive the patient will remain eligible provided other criteria are met.
  • Patients must have been previously treated with at least one dose of a PD-1 axis inhibitor (e.g. PD-1 or PD-L1 inhibiting monoclonal antibody such as pembrolizumab, nivolumab, avelumab, atezolizumab, durvalumab), developed progression of their MCC tumor on or after treatment, or have biopsy confirmed residual disease following treatment. At least four weeks must have passed between the administration of the first dose of PD-1 axis inhibitor and determination of progression or residual disease. If there is significant clinical concern for pseudoprogression (i.e. progression developed rapidly after checkpoint inhibitor therapy), biopsy must be performed to demonstrate true progression. Patients may have received 1 or more prior systemic regimens for MCC. 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. Patients are also eligible if they have a contraindication to PD-1/PD-L1 axis blockade such as a history of an autoimmune disease.
  • Participants must be HLA-A*02:01 in order for infused transgenic T cells to recognize antigen-MHC complexes. HLA typing for HLA-A2 should be determined through molecular approaches at a clinical laboratory licensed for HLA testing.
  • Life expectancy must be anticipated to be > 3 months at trial entry.
  • 18 years of age or older. Fewer than 0.5% of MCC occur in individuals aged 30 years or younger, thus the protocol includes only adult patients.
  • Capable of understanding and providing a written informed consent.
  • If fertile, willingness to comply with reproductive requirements.
  • Karnofsky performance status of >= 60%.
  • Should there be no tumor tissue that is accessible for biopsy, patients will still be considered for participation, at discretion of the investigator. Similarly, should an investigator determine that a biopsy cannot be performed safely for clinical reasons biopsies may be cancelled or retimed.
  • At least 3 weeks must have passed since any: immunotherapy (for example, T-cell infusions, immunomodulatory agents, interleukins, MCC vaccines, intravenous immunoglobulin, expanded polyclonal tumor infiltrating lymphocyte [TIL] or lymphokine-activated killer cell [LAK] therapy), natural killer (NK) therapy, small molecule or chemotherapy cancer treatment, other investigational agents or other systemic agents that target MCC. There is no washout period for radiation.
  • Serum creatinine < 2.5 or estimated glomerular filtration rate (eGFR) > 30.
  • Total bilirubin (tBili) < 3.0. 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.
  • Oxygen saturation (SaO2) >= 92% on ambient air.
  • If pulmonary function tests (PFTs) are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in one second (FEV1) >= 50% of predicted and diffusion capacity of the lung for carbon monoxide (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 1 year prior to study treatment. LVEF may be established with echocardiogram or multigated acquisition (MUGA) scan, and must be >= 35%. Cardiac evaluation for other patients is at the discretion of the treating physician.
  • Absolute neutrophil count (ANC) > 1000 cells/mm^3.
  • Absolute lymphocyte count (ALC) > 200 cells/mm^3.
  • Hematocrit (HCT) > 30%.
  • Platelet count > 50K.

Who cannot join

  • Active autoimmune disease requiring immunosuppressive therapy is excluded unless discussed with the principal investigator (PI). Patients with a history of autoimmune disease that was a contra-indication to PD-1 axis blockade treatment will be eligible, but will not receive PD-1 axis blockade treatment on trial.
  • Kidney transplant 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 likely. 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 a history of allogeneic stem cell transplant.
  • Corticosteroid therapy at a dose equivalent of > 10 mg prednisone per day.
  • Concurrent use of other investigational agents or MCC directed therapies.
  • Any medical or psychological condition other than Merkel cell carcinoma that would significantly increase the risk of harm to a subject or interfere with the interpretation of trial endpoints.
  • Active uncontrolled infection. Human immunodeficiency virus (HIV) positive participants on highly active antiretroviral 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 hepatitis well controlled on medication.
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  • Uncontrolled concurrent illness. 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.
  • Untreated brain metastases. 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.
  • Grade 3 or higher immune related adverse event (iRAE) to any prior PD-1 axis blocking agent. iRAEs are persistent T cell mediated inflammatory syndromes caused by PD-1 or PD-L1 inhibitors including colitis, nephritis, pneumonitis, myositis, hepatitis, encephalitis.
  • Participants receiving treatment for prior immune-related adverse event (iRAE) are excluded, with exception of hormone supplementation or corticosteroid therapy at equivalent of up to 10 mg prednisone per day, unless otherwise approved by PI.
  • Study participants must not have significant active underlying neurologic disease, unless approved by PI. Mild 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 PI.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: ATTAC-MCC: Phase I/II Study of Autologous CD8+ and CD4+ Transgenic T Cells Expressing High Affinity MCPyV-specific TCRs Combined With Avelumab and Class I MHC-upregulation in Patients With Metastatic MCC Refractory to PD-1 Axis Blockade

This phase I/II trial studies the side effects of gene-modified immune cells (FH-MCVA2TCR) and to see how well they work in treating patients with Merkel cell cancer that has spread to other parts of the body (metastatic) or that cannot be removed by surgery (unresectable). Placing a gene that has been created in the laboratory into immune cells may improve the body's ability to fight Merkel cell cancer.

Read the detailed description

OUTLINE: This is a dose escalation study of FH-MCVA2TCR autologous T-cells.

Patients receive interferon gamma-1b subcutaneously (SC) on study. Patients receive FH-MCVA2TCR T-cells intravenously (IV) over 60-120 minutes. Beginning 14 days after receiving FH-MCVA2TCR T-cells, patients also receive standard of care avelumab IV over 1 hour every 2 weeks for 1 year or pembrolizumab IV over 30 minutes every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease may then receive an additional cycle of FH-MCVA2TCR T-cells.

After completion of study treatment, patients are followed up periodically for up to 15 years.

Conditions
Other Skin
Being tested
Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR, Avelumab, Pembrolizumab, Interferon Gamma-1b
Keywords
Clinical Stage III Merkel Cell Carcinoma AJCC v8, Clinical Stage IV Merkel Cell Carcinoma AJCC v8, Pathologic Stage III Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIA Merkel Cell Carcinoma AJCC v8, Pathologic Stage IIIB Merkel Cell Carcinoma AJCC v8, Pathologic Stage IV Merkel Cell Carcinoma AJCC v8, Merkel cell carcinoma, metastatic, Merkel cell carcinoma, unresectable, Metastatic Merkel Cell Carcinoma, Unresectable Merkel Cell Carcinoma
Medical subject headings
Carcinoma, Merkel Cell, Neoplasm Metastasis

What participants receive

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

  • Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCRBiological

    Also called Autologous CD8+ and CD4+ T-cells transduced with TCR A2-MCC1, FH-MCVA2TCR, FH-MCVA2TCR Autologous CD8+ and CD4+ T-cells Transduced with TCR A2-MCC1

    Given IV

  • AvelumabDrug

    Also called 1537032-82-8, Bavencio, Immunoglobulin G1-lambda1, Anti-(Homo sapiens CD274 (Programmed Death Ligand 1, PDL1, pd-l1, B7 Homolog 1, B7H1))

    Given IV

  • PembrolizumabBiological

    Also called Anti-(Human Programmed Cell Death 1), Keytruda, Lambrolizumab, MK-3475

    Given IV

  • Interferon Gamma-1bBiological

    Also called 98059-61-1, Actimmune, gamma Interferon 1B, IFN-g-1b

    Given SC

Study groups in NCT03747484
Study groupRoleWhat they receive
Treatment (TCR-T cells, avelumab or pembrolizumab)ExperimentalApproximated 5-7 days prior to receiving FH-MCVA2TCR T-cells, patients receive interferon gamma administered at the FDA-approved dosing of 50mcg/m2, 3 times weekly for a total of 4 weeks. Patients receive FH-MCVA2TCR T-cells IV over 60-120 minutes. Beginning 14 days after receiving FH-MCVA2TCR T-cells, patients also receive standard of care avelumab IV over 1 hour every 2 weeks for 1 year or pembrolizumab IV over 30 minutes every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease may then receive an additional cycle of FH-MCVA2TCR T-cells.
Receives: Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Biological: Pembrolizumab; Biological: Interferon Gamma-1b
Treatment 2 (TCR-T cells, avelumab or pembrolizumab)ExperimentalApproximated 5-7 days prior to receiving FH-MCVA2TCR T-cells, patients receive interferon gamma administered at the FDA-approved dosing of 50mcg/m2, 3 times weekly for a total of 4 weeks. Patients receive FH-MCVA2TCR T-cells IV over 60-120 minutes. Beginning 14 days after receiving FH-MCVA2TCR T-cells, patients also receive standard of care avelumab IV over 1 hour every 2 weeks for 1 year or pembrolizumab IV over 30 minutes every 3 weeks for 1 year in the absence of disease progression or unacceptable toxicity. Patients with partial response or stable disease may then receive an additional cycle of FH-MCVA2TCR T-cells.
Receives: Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Biological: Pembrolizumab; Biological: Interferon Gamma-1b

What is being measured

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

  1. Incidence of Adverse Events Grade 3 or Higher Determined to be Possibly, Probably or Definitely Secondary to Study Treatments.

    Assessed per Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. Evidence of excessive toxicity will be an observed proportion of toxicities for which the associated lower 80% confidence limit exceeds 40%.

    Measured: Up to 1 year post infusion

  2. Best Overall Response

    Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 of complete or partial response. Irradiated and non-irradiated lesions will be separately tracked but response determined in totality.

    Measured: Up to 1 year post infusion

Secondary outcomes (2)

  1. Progression-free Survival

    Will be estimated using the method of Kaplan and Meier, with time zero the time of first T cell infusion.

    Measured: Up to 1 year post infusion

  2. Overall Survival

    Will be estimated using the method of Kaplan and Meier, with time zero the time of first T cell infusion.

    Measured: Up to 1 year post infusion

Timeline

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

  1. First posted20 Nov 2018
  2. Study start3 Jul 2019
  3. Primary completion9 Jan 2024
  4. Study completion9 Jan 2024

Why it stopped: Terminated due to insufficient funding

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 1/2
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03747484
Sponsor's protocol ID
RG1003611
Other IDs
NCI-2018-02483, 9845, ATTAC-MCC, P01CA225517
Status last verified
Mar 2025
First submitted
16 Nov 2018
Last updated
6 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Asano Y, Veatch JR, Sung CJ, Tang TH, Mazziotta F, Natsuki S, McAfee M, Bakhtiari J, Lee B, Martin L, Rizzi A, Zhang T, Smith CW, Paulson KG, Schmitt TM, Newell EW, Elz AE, Chen DG, Su Y, Gustafson HH, Yeung CCS, Seaton B, Hunter D, Koelle DM, Bhatia S, Hall ET, Voillet V, Cao J, Gooley T, Greenberg PD, Gottardo R, Oda SK, Nghiem P, Chapuis AG. Reprogramming engineered autologous T cells to overcome resistance in patients with Merkel cell carcinoma. Sci Transl Med. 2026 Sep 9;18(866):eaea8773. doi: 10.1126/scitranslmed.aea8773. Epub 2026 Sep 9.

    PubMed 42715345

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR, Avelumab and Pembrolizumab in people with Other Skin, run by Fred Hutchinson Cancer Center at 1 site in United States.

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 27 inclusion and 12 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: stopped early, as of the sponsor's last update on 6 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 6 Mar 2025). 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 Adverse Events Grade 3 or Higher Determined to be Possibly, Probably or Definitely Secondary to Study Treatments. (time frame: Up to 1 year post infusion). The study lists 2 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 NCT03747484, 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 6 Mar 2025.

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