MAGE-A4ᶜ¹º³²T for Multi-Tumor

Phase 1

Active, not recruiting

• Conditions: Urinary Bladder Cancer; Melanoma; Ovarian Cancer; Esophageal Cancer; Synovial Sarcoma; Gastroesophageal Junction; Non-Small Cell Lung Cancer; Head and Neck Cancer; Gastric Cancer; Myxoid Round Cell Liposarcoma
• Interventions: Radiation: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation; Genetic: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells

• Registration Number: NCT03132922
• Lead Sponsor: Adaptimmune

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-25
• Study First Submitted QC: 2017-04-25
• Study First Posted: 2017-04-28
• Study Start: 2017-05-15
• Primary Completion: 2022-12-27
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-19
• Last Update Posted: 2024-01-22
• Study Completion: 2032-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 71

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Radiation Sub-Study: Autologous genetically modified MAGE-A4c1	Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation	-
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells	Autologous genetically modified MAGE-A4ᶜ¹º³²T cells	-

Primary Outcome Measures

Name	Time	Method
Measurement of RCL in genetically modified T cells.	3.5 years	Evaluation of RCL in subject PBMCs using PCR-based assay.
Number of subjects with adverse events (AE), including serious adverse events (SAEs).	3.5 years	Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.
Evaluation of persistence of genetically modified T cells.	3.5 years	Evaluation of persistence of genetically modified T cells in the periphery.
Determining dose limiting toxicities (DLT) and optimally tolerated dose range	3.5 years	Evaluate DLTs and toxicity assessment using NCI CTCAE.

Secondary Outcome Measures

Name	Time	Method
Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.	3.5 years	Evaluation of the efficacy of the treatment by assessment of duration of stable disease.
Interval between the date of first T cell infusion and date of death due to any cause.	3.5 years	Evaluation of the efficacy of the treatment by assessment of overall survival.
Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.	3.5 years	Evaluation of the efficacy of the treatment by assessment of time to first response.
Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).	3.5 years	Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1
Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)	15 years post last treatment (infusion)	* New occurrence of any malignancy; * New occurrence or exacerbation of a pre-existing neurologic disorder; * New occurrence or exacerbation of a prior rheumatologic or other autoimmune disorder; * New occurrence of a hematologic disorder; * New occurrence of any opportunistic and/or serious infections; * New occurrence of any unanticipated illness and/or hospitalization deemed related to gene modified cell therapy
Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.	3.5 years	Evaluation of the efficacy of the treatment by assessment of duration of response.
Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause	3.5 years	Evaluation of the efficacy of the treatment by assessment of progression-free survival.

Trial Locations

Locations (11)

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

Tennessee Oncology - Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Duke University Medical Center, Duke Cancer Institute; 🇺🇸 Durham, North Carolina, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

M.D. Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Miami; 🇺🇸 Miami, Florida, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States