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

NCT03747484 | Terminated Phase 1 Results DMC FDA Drug

• 5 other identifiers: RG1003611NCI-2018-024839845ATTAC-MCCP01CA225517
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief 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). Placing a gene that has been created in the laboratory into immune cells may improve the body's ability to fight Merkel cell cancer.

Conditions

Other Skin

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

Outcome Measures

Primary Outcomes (2)

• 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%.

  Up to 1 year post infusion

• 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.

  Up to 1 year post infusion

Secondary Outcomes (2)

• Progression-free Survival

  Up to 1 year post infusion

• Overall Survival

  Up to 1 year post infusion

Study Arms (2)

Treatment (TCR-T cells, avelumab or pembrolizumab)

EXPERIMENTAL

Approximated 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.

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)

EXPERIMENTAL

Approximated 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.

Biological: Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR; Drug: Avelumab; Biological: Pembrolizumab; Biological: Interferon Gamma-1b

Interventions

Autologous MCPyV-specific HLA-A02-restricted TCR-transduced CD4+ and CD8+ T-cells FH-MCVA2TCR BIOLOGICAL

Given IV

Also known as: 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

Treatment (TCR-T cells, avelumab or pembrolizumab); Treatment 2 (TCR-T cells, avelumab or pembrolizumab)

Avelumab DRUG

Given IV

Also known as: 1537032-82-8, Bavencio, Immunoglobulin G1-lambda1, Anti-(Homo sapiens CD274 (Programmed Death Ligand 1, PDL1, pd-l1, B7 Homolog 1, B7H1)), Homo sapiens Monoclonal Antibody, MSB-0010718C, MSB0010718C

Treatment (TCR-T cells, avelumab or pembrolizumab); Treatment 2 (TCR-T cells, avelumab or pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Anti-(Human Programmed Cell Death 1), Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (TCR-T cells, avelumab or pembrolizumab); Treatment 2 (TCR-T cells, avelumab or pembrolizumab)

Interferon Gamma-1b BIOLOGICAL

Given SC

Also known as: 98059-61-1, Actimmune, gamma Interferon 1B, IFN-g-1b, IFN-gamma 1b, Recombinant Interferon Gamma-1b

Treatment (TCR-T cells, avelumab or pembrolizumab); Treatment 2 (TCR-T cells, avelumab or pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• Affini-T Therapeutics, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell; Neoplasm Metastasis

Interventions

avelumab; B7-H1 Antigen; pembrolizumab; interferon gamma-1b; Interferon-gamma

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Checkpoint Proteins; Proteins; Amino Acids, Peptides, and Proteins; B7 Antigens; Intercellular Signaling Peptides and Proteins; Membrane Proteins; Antigens, Surface; Antigens; Biological Factors; Interferons; Cytokines; Peptides; Macrophage-Activating Factors; Lymphokines

Results Point of Contact

• Title: Joshua Veatch
• Organization: Fred Hutchinson Cancer Center

jveatch@fredhutch.org

206.667.5108

Study Officials

• Joshua Veatch

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 20, 2018
• Study Start: July 3, 2019
• Primary Completion: January 9, 2024
• Study Completion: January 9, 2024
• Last Updated: March 6, 2025
• Results First Posted: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)