MelanomaPhase 1/2MC2TCRNCT04729543
MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer
A Phase 1/2 study testing Adoptive therapy with autologous MC2 TCR T cells in people with Melanoma and Melanoma, Uveal, run by Erasmus Medical Center at 1 site in Netherlands.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Melanoma, Uveal, Head and Neck Cancer
- What is being tested?
- Adoptive therapy with autologous MC2 TCR T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteNetherlands
- Study dates
- 20 Oct 2020to 20 Oct 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- 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;
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- 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:
- Hematology:
- absolute neutrophil count greater than 1.5x10^9/L;
- platelet count greater than 75x10^9/L;
- hemoglobin greater than 5 mmol/L or 8.0 in g/dl;
- Chemistry:
- serum ALAT/ASAT less than 3 times the upper limit of normal (ULN), unless patients have liver metastasis (<5 times ULN);
- serum creatinine < 1.5 ULN;
- total bilirubin ≤ 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin ≤ 50 micromol/L;
- Serology:
- seronegative for HIV antibody;
- seronegative for hepatitis B antigen, and hepatitis C antibody;
- seronegative for lues.
Who cannot join
- 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;
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- 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;
- Women who are pregnant or breastfeeding. A negative pregnancy test before inclusion in the trial is required for all women of child bearing age;
- 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;
- Malignant disease, other than being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to start of study treatment, completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Erasmus Medical Center
Rotterdam, 3015GD
A.A.M. van der Veldt, MD, PhD, +31 107041754, a.vanderveldt@erasmusmc.nl
R. Debets, PhD, Prof., +31 107038307, j.debets@erasmusmc.nl
About this study
Official title: Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer
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).
Read the detailed description
In this patient study, the investigators target the Cancer Germline Antigen (CGA) MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is highly expressed in melanoma (MEL) and head-and-neck squamous cell carcinoma (HNSSC), but not in healthy adult tissues. The investigators isolated MC2-specific TCRs from MEL patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. Following extensive evaluation of in vitro anti-tumor and self-reactivities, the investigators have selected a TCR that recognizes the ALK epitope in the context of HLA-A2 for clinical development. Furthermore, preclinical studies showed that epigenetic pretreatment of tumor cells, but not normal cells, up-regulated MC2 gene expression and resulted in enhanced recognition of MC2 by the selected TCR. In parallel to the above studies, the investigators renewed their GMP protocol to process T cells, using stimulating antibodies and cytokines, to generate T cells with a young phenotype.
In the current phase I/II study, the investigators explore the safety and anti-tumor efficacy of T cells engineered with the selected TCR in patients with MC2-positive MEL and HNSSC. The study contains the following unique elements:
- CGA not targeted before by T cell therapy
- New T cell processing method to generate young T cells
- Pretreatment of patients with epigenetic drugs
- No chemotherapy prior to T cell infusion
Leads:
- Clinical PI: Astrid van der Veldt, MD, PhD
- Clinical logistics: Karlijn de Joode, MD
- T cell production: Monique de Beijer, PhD; and Cor Lamers, PhD
- Coordinator/Preclinical PI: prof. Reno Debets, PhD
- Conditions
- Melanoma, Melanoma, Uveal, Head and Neck Cancer
- Being tested
- Adoptive therapy with autologous MC2 TCR T cells
- Medical subject headings
- Melanoma, Uveal Melanoma, Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adoptive therapy with autologous MC2 TCR T cellsBiological
Also called 5' Azacytidine (AZA), Valproic acid (VP), Interleukin 2 (IL2)
Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: Adoptive therapy with autologous MC2 TCR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2021
- Study start20 Oct 2020
- Primary completion20 Dec 2024 (estimated)
- Study completion20 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research, Dutch Cancer Society, Stichting Coolsingel Rotterdam grant, Jan Ivo Stichting grant
- Responsible party
- Principal investigator, A.A.M. van der Veldt, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04729543
- Sponsor's protocol ID
- NL69011.000.19
- Acronym
- MC2TCR
- Status last verified
- Dec 2023
- First submitted
- 18 Nov 2020
- Last updated
- 4 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 19097774Lamers 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.
PubMed 25423330Kunert 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.
PubMed 27489285Kunert 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.
PubMed 28645940
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT04729543
- Acronym / sponsor ID
- MC2TCR / NL69011.000.19
- Conditions
- Melanoma, Melanoma, Uveal, Head and Neck Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Ludwig Institute for Cancer Research, Dutch Cancer Society, Stichting Coolsingel Rotterdam grant, Jan Ivo Stichting grant
- Study start
- 20 Oct 2020 (actual)
- Primary completion
- 20 Dec 2024 (estimated)
- Study completion
- 20 Oct 2027 (estimated)
- First posted
- 28 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
In this patient study, the investigators target the Cancer Germline Antigen (CGA) MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is highly expressed in melanoma (MEL) and head-and-neck squamous cell carcinoma (HNSSC), but not in healthy adult tissues. The investigators isolated MC2-specific TCRs from MEL patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. Following extensive evaluation of in vitro anti-tumor and self-reactivities, the investigators have selected a TCR that recognizes the ALK epitope in the context of HLA-A2 for clinical development. Furthermore, preclinical studies showed that epigenetic pretreatment of tumor cells, but not normal cells, up-regulated MC2 gene expression and resulted in enhanced recognition of MC2 by the selected TCR. In parallel to the above studies, the investigators renewed their GMP protocol to process T cells, using stimulating antibodies and cytokines, to generate T cells with a young phenotype.
In the current phase I/II study, the investigators explore the safety and anti-tumor efficacy of T cells engineered with the selected TCR in patients with MC2-positive MEL and HNSSC. The study contains the following unique elements:
- CGA not targeted before by T cell therapy
- New T cell processing method to generate young T cells
- Pretreatment of patients with epigenetic drugs
- No chemotherapy prior to T cell infusion
Leads:
- Clinical PI: Astrid van der Veldt, MD, PhD
- Clinical logistics: Karlijn de Joode, MD
- T cell production: Monique de Beijer, PhD; and Cor Lamers, PhD
- Coordinator/Preclinical PI: prof. Reno Debets, PhD
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adoptive therapy with autologous MC2 TCR T cells | Experimental | Biological: Adoptive therapy with autologous MC2 TCR T cells* 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Written informed consent;
- Age ≥ 18 years;
- One of the following three malignancies:
- 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;
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Adoptive therapy with autologous MC2 TCR T cellsAlso: 5' Azacytidine (AZA), Valproic acid (VP), Interleukin 2 (IL2)Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP | Biological | Adoptive therapy with autologous MC2 TCR T cells |
Primary outcome
Maximum Tolerated Dose (MTD) of MC2 TCR T cells
Time frame: 1 year
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
Objective anti-tumor responses of MC2 TCR T cells
Time frame: 2 years
Anti-tumor responses are recorded according to RECIST v1.1 using the MTD from outcome 1
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2023.
- Results publication: PubMed 19097774Eisenhauer 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.
- Results publication: PubMed 25423330Lamers 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.
- Results publication: PubMed 27489285Kunert 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.
- Results publication: PubMed 28645940Kunert 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Adoptive therapy with autologous MC2 TCR T cells in people with Melanoma and Melanoma, Uveal, run by Erasmus Medical Center at 1 site in Netherlands.
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 16 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: looking for participants now, as of the sponsor's last update on 4 Dec 2023. 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 Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact A.A.M. van der Veldt, MD, PhD (+31 107041754, a.vanderveldt@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) of MC2 TCR T cells (time frame: 1 year). 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 NCT04729543, which also lists 4 linked publications.
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 4 Dec 2023.