Clinical trial · Interventional
MAGE-A4ᶜ¹º³²T for Multi-Tumor
Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors
NCT03132922CI-TRIAL-00113684active not recruitingPhase 1Results postedClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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.
Conditions
Conditions (10)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Esophageal Cancer | Malignant Esophageal Neoplasm | CURATED_EXACT | 0.92 |
| Gastric Cancer | Malignant Gastric Neoplasm | CURATED_BROADER | 0.80 |
| Gastroesophageal Junction | — | UNRESOLVED | — |
| Head and Neck Cancer | Malignant Head and Neck Neoplasm | ALIAS | 0.90 |
| Melanoma | Melanoma | ONTOLOGY_EXACT | 0.98 |
| Myxoid Round Cell Liposarcoma | Myxoid Liposarcoma | ALIAS | 0.90 |
| Non-Small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
| Ovarian Cancer | Malignant Ovarian Neoplasm |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation | Radiation | — | UNRESOLVED |
| Autologous genetically modified MAGE-A4ᶜ¹º³²T cells | Genetic | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
- interventionNames
- Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
- type
- EXPERIMENTAL
- label
- Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
- interventionNames
- Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Primary outcomes (3)
- measure
- Adverse Events (AE) Including Serious Adverse Events (SAE)
- timeFrame
- From the start of lymphodepleting chemotherapy until end of interventional phase (up to 3.2 years).
- description
- An AE was defined as any untoward medical occurrence in a clinical study participant who received a pharmaceutical product, regardless of causality. An AE was , therefore, any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants with AEs (including SAEs) are presented.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 75 Years
Show eligibility criteria text
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 7\. 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.
References
Publications (2)
- DERIVEDHong DS, Van Tine BA, Biswas S, McAlpine C, Johnson ML, Olszanski AJ, Clarke JM, Araujo D, Blumenschein GR Jr, Kebriaei P, Lin Q, Tipping AJ, Sanderson JP, Wang R, Trivedi T, Annareddy T, Bai J, Rafail S, Sun A, Fernandes L, Navenot JM, Bushman FD, Everett JK, Karadeniz D, Broad R, Isabelle M, Naidoo R, Bath N, Betts G, Wolchinsky Z, Batrakou DG, Van Winkle E, Elefant E, Ghobadi A, Cashen A, Grand'Maison A, McCarthy P, Fracasso PM, Norry E, Williams D, Druta M, Liebner DA, Odunsi K, Butler MO. Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial. Nat Med. 2023 Jan;29(1):104-114. doi: 10.1038/s41591-022-02128-z. Epub 2023 Jan 9. PMID 36624315
- DERIVEDSanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020. PMID 32002290