MAGE-C2 TCR T cell therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Phenomena and Processes [G] - Cell Physiological Phenomena [G04]

Trial duration

29 Nov 2024 → ongoing

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516922-70-00

EudraCT number

2019-000657-31

ClinicalTrials.gov

NCT04729543

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety

Phase I:
To study the safety and feasibility of AT with autologous MC2 TCR T cells, combined with epigenetic drug treatment, in patients with advanced melanoma or HNSCC. Adverse events (AEs) will be documented according to CTCAE v5.0.
To define the maximum tolerated dose (MTD) of MC2 TCR T cells in the combination treatment.
Phase II:
To assess the efficacy of AT with autologous MC2 TCR T cells at MTD, combined with epigenetic drug treatment, in patients with advanced melanoma or HNSCC.
Tumor response will be evaluated using RECIST v1 .1.

Secondary objectives 7

1. Phase I: To study presence and function of MC2 TCR T cells in peripheral blood samples after treatment.
2. Phase I: To study the systemic release of inflammatory cytokines after administration of autologous MC2 TCR T cells.
3. Phase I: To study immune parameters, in particular T cell parameters, in blood and tumor tissues (when available) prior to and during treatment.
4. Phase I: To document the induction of global DNA hypomethylation and histone acetylation in peripheral blood mononuclear cells (PBMC) by epigenetic drug treatment.
5. Phase II: To determine the following outcomes in patients treated with MC2 TCR T cells at MTD: Progression free survival
6. Phase II: To determine the following outcomes in patients treated with MC2 TCR T cells at MTD: Duration of response
7. Phase II: To determine the following outcomes in patients treated with MC2 TCR T cells at MTD: Overall survival

Conditions and MedDRA coding

advanced melanoma or HNSCC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 18 years of age.
2. inoperable stage Ille or stage IV cutaneous melanoma, including ocular or mucosal melanoma, progressing after standard of care therapy, or recurrent/metastatic HNSCC
3. Patients must be HLA-A2 positive.
4. The primary tumor and/or metastasis have to be positive for MAGE-C2
5. Patients must have a clinical performance status of ECOG O or 1
6. 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 regime
7. Patients must be able to understand and sign the Informed Consent document.

Exclusion criteria 4

1. Life expectancy of less than three months.
2. Requirement for systemic steroid therapy
3. Patients who have active/symptomatic CNS metastases
4. Patients with pleural effusion or ascites.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Phase I: AEs according to CTCAE 5.0
2. Phase I: Recommended Phase II dose
3. Phase I: Feasibility to deliver this sequence of treatmen
4. Phase II: Objective response rate according to RECIST v1 .1
5. Phase II: PFS
6. Phase II: OS

Secondary endpoints 4

1. Phase I and II: Persistence and function of MC2-specific T cells in peripheral blood.
2. Phase I and II: Systemic release of inflammatory cytokines after administration of autologous MC2 TCR T cells
3. Phase I and II: Immune parameters, in particular T cell parameters, in blood and tumor tissues (when available) prior to and during treatmen
4. Phase I and II: Global DNA hypomethylation and histone acetylation in PBMCs after epigenetic treatment and administration of autologous MC2 TCR T cells

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Astrid van der Veldt

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Astrid van der Veldt

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications