MAGE-A4ᶜ¹º³²T for Multi-Tumor

Adaptimmune

Status and phase: Active, not recruiting; Phase 1

Conditions: Urinary Bladder Cancer; Melanoma; Gastric Cancer; Esophageal Cancer; Synovial Sarcoma; Ovarian Cancer; Head and Neck Cancer; Gastroesophageal Junction; Non-Small Cell Lung Cancer; Myxoid Round Cell Liposarcoma

Treatments: Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells; Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation

Study type: Interventional

Funder types: Industry

Identifiers

NCT03132922

ADP-0044-001/RSS

Details and patient eligibility

About

This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.

Enrollment: 71 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Subject is ≥18 to 75 years of age at the time of signing the study informed consent.

2. Subject has histologically confirmed diagnosis of any one of the indicated tumor types

3. Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).

4. Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).

5. Adequate organ function as indicated in the study protocol

6. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion

7. Subject meets disease-specific requirements per protocol

8. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.

Exclusion criteria

1. Subject does not express appropriate HLA-A genotype
2. Subject is receiving excluded therapy/treatment per protocol
3. Subject has symptomatic CNS metastases.
4. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
5. Subject has active infection with HIV, HBV, HCV or HTLV
6. Subject is pregnant or breastfeeding.

Additional Exclusion Criteria for the Radiation Substudy:

• Subject does not meet eligibility criteria for the main study (ADP-0044-001).
• Subject does not have at least one target lesion amenable to radiation.
• Certain radiation therapy within 6 months of clinical trial are an exclusion.
• Metastatic disease impinging on the spinal cord or threatening spinal cord compression.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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71 participants in 2 patient groups

Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

Experimental group

Treatment:

Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

Radiation Sub-Study: Autologous genetically modified MAGE-A4c1

Experimental group

Treatment:

Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation