MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

NCT04729543 | Recruiting Phase 1 DMC

• 1 other identifier: NL69011.000.19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Single-centre, first-in-man phase I/II trial to demonstrate safety and efficacy of MAGE-C2/HLA-A2 TCR T cells (MC2 TCR T cells) in advanced melanoma (MEL) and head-and-neck carcinoma (HNSCC).

Conditions

Melanoma; Melanoma, Uveal; Head and Neck Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of MC2 TCR T cells

  MTD is determined using an accelerated titration phase with T cell doses as described in treatment arm; AEs are recorded according to CTCAE 5.0

  1 year

• Objective anti-tumor responses of MC2 TCR T cells

  Anti-tumor responses are recorded according to RECIST v1.1 using the MTD from outcome 1

  2 years

Study Arms (1)

Adoptive therapy with autologous MC2 TCR T cells

EXPERIMENTAL

* Accelerated titration phase I design and a subsequent single arm phase II study * Prior to T cell transfer (day 0), patients will be treated with valproic acid (dose 50 mg/kg/d, 7d; days -9 to day -3) and 5' azacytidine (dose 75mg/m2/d, 7d; days -9 to day -3) * Phase I: patients will be treated with one single intravenous administration of MC2 TCR T cells at 5 different escalated doses of 5x10E7, 5x10E8, 5x10E9,1.0x10E10, and the total number of cultured TCR T cells (i.e., usually 1.0-5.0 x10E10 TCR T cells). MC2 TCR T cell infusions will be supported by low dose of IL-2 administrations (s.c. 5x10E5 IU/m2 2qd for 5 days) * T cells will be processed using IL-15 and IL-21 to generate young T cells

Biological: Adoptive therapy with autologous MC2 TCR T cells

Interventions

Adoptive therapy with autologous MC2 TCR T cells BIOLOGICAL

Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP

Also known as: 5' Azacytidine (AZA), Valproic acid (VP), Interleukin 2 (IL2)

Adoptive therapy with autologous MC2 TCR T cells

Eligibility Criteria

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

You may qualify if:

• Written informed consent;
• Age ≥ 18 years;
• One of the following three malignancies:
• Previously treated for unresectable or metastatic cutaneous or mucosal melanoma for whom no standard treatment is available (anymore);
• Metastatic uveal melanoma, progressing after standard of care therapy, if available;
• R/M HSNCC for whom no standard treatment is available anymore;
• Patients must be HLA-A2\*0201 positive;
• Primary tumor and/or metastasis (archival or fresh biopsy) is positive for MC2 (\>5% of tumor cells) according to immunohistochemistry;
• Measurable disease according to RECIST v1.1;
• At least one lesion, suitable for sequential mandatory tumor biopsies;
• ECOG performance status of 0 or 1. Life expectancy ≥ 12 weeks;
• Patients with melanoma must have had objective evidence of disease progression while on or after standard systemic therapy. The last dose of prior therapy (e.g. anti- PD-1, chemotherapy) must have been received more than 4 weeks prior to the start of study treatment. For melanoma patients who are treated with BRAF- and MEK inhibitors, an interval of 2 weeks between discontinuation of BRAF- and MEK inhibition and start of study treatment is sufficient;
• Patients with R/M HNSCC must have had objective evidence of disease progression and are ineligible for or unwilling to get platinum-based chemotherapy or for whom no standard treatment is available;
• Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen;
• Patients must meet the following laboratory values at the screening visit in the absence of growth factors and/or transfusion support:

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from participation of this study:
• presence of symptomatic brain metastasis. Note: subjects with symptomatic brain lesions who have been definitively treated with stereotactic radiation therapy, surgery, or gamma knife therapy are eligible;
• Presence of active brain metastasis defined as new or progressive brain metastasis at the time of study entry. Note: subjects with treated or stable brain metastasis are eligible;
• Presence of leptomeningeal metastasis;
• Presence of malignant pleural effusion or ascites;
• Systemic chronic steroid therapy (\>10 mg/day prednisone or equivalent) or any other immunosuppressive therapy within 7 days prior to leukapheresis or 72 hours prior to infusion of the MC2 TCR T cells. Note: local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed;
• Active, known or suspected autoimmune disease or a documented history of autoimmune disease. Note: subjects with vitiligo, controlled type 1 diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted;
• Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune diseases requiring anti-TNF treatment;
• History of myocardial infarction, cardial angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment;
• AEs of previous treatment. Toxicities associated with prior systemic and non- systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or palliative radiotherapy (for non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less;
• Use of any live vaccines against infectious diseases within the last 3 months;
• Active infection requiring systemic antibiotic therapy at start of study treatment;
• Prior allogenic bone marrow or solid organ transplant;
• History of known hypersensitivity to any of the investigational drugs used in this study;

Sponsors & Collaborators

• Erasmus Medical Center: lead
• Ludwig Institute for Cancer Research: collaborator
• Dutch Cancer Society: collaborator
• Stichting Coolsingel Rotterdam grant: collaborator
• Jan Ivo Stichting grant: collaborator

Study Sites (1)

Erasmus Medical Center

Rotterdam, 3015GD, Netherlands

RECRUITING

Related Publications (4)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 RESULT

• Lamers CH, van Steenbergen-Langeveld S, van Brakel M, Groot-van Ruijven CM, van Elzakker PM, van Krimpen B, Sleijfer S, Debets R. T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness. Hum Gene Ther Methods. 2014 Dec;25(6):345-57. doi: 10.1089/hgtb.2014.051.

  PMID: 25423330 RESULT

• Kunert A, van Brakel M, van Steenbergen-Langeveld S, da Silva M, Coulie PG, Lamers C, Sleijfer S, Debets R. MAGE-C2-Specific TCRs Combined with Epigenetic Drug-Enhanced Antigenicity Yield Robust and Tumor-Selective T Cell Responses. J Immunol. 2016 Sep 15;197(6):2541-52. doi: 10.4049/jimmunol.1502024. Epub 2016 Aug 3.

  PMID: 27489285 RESULT

• Kunert A, Obenaus M, Lamers CHJ, Blankenstein T, Debets R. T-cell Receptors for Clinical Therapy: In Vitro Assessment of Toxicity Risk. Clin Cancer Res. 2017 Oct 15;23(20):6012-6020. doi: 10.1158/1078-0432.CCR-17-1012. Epub 2017 Jun 23.

  PMID: 28645940 RESULT

MeSH Terms

Conditions

Melanoma; Uveal Melanoma; Head and Neck Neoplasms

Interventions

Azacitidine; Valproic Acid; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Fatty Acids, Volatile; Fatty Acids; Lipids; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Central Study Contacts

A.A.M. van der Veldt, MD, PhD

CONTACT

+31 107041754; a.vanderveldt@erasmusmc.nl

R. Debets, PhD, Prof

CONTACT

+31 107038307; j.debets@erasmusmc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: January 28, 2021
• Study Start: October 20, 2020
• Primary Completion: December 20, 2024
• Study Completion (Estimated): October 20, 2027
• Last Updated: December 4, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)