MAGE-A4ᶜ¹º³²T for Multi-Tumor

Ovarian Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03132922
• Other study ID #: ADP-0044-001/RSS
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 15, 2017
• Est. completion date: September 2032

Study information

• Verified date: January 2024
• Source: Adaptimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 71
• Est. completion date: September 2032
• Est. primary completion date: December 27, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms
• Gastric Cancer
• Gastroesophageal Junction
• Head and Neck Cancer
• Liposarcoma
• Liposarcoma, Myxoid
• Melanoma
• Myxoid Round Cell Liposarcoma
• Non-Small Cell Lung Cancer
• Ovarian Cancer
• Sarcoma
• Sarcoma, Synovial
• Synovial Sarcoma
• Urinary Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Genetic:
• Autologous genetically modified MAGE-A4?¹º³²T cells
Infusion of autologous genetically modified MAGE-A4?¹º³²T on Day 1

Radiation:
• Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation
Up to 10 subjects will be considered for Radiation sub-study. Radiation with an intensity of 1.4Gy for 5 days before infusion of MAGE-A4c1032T cells

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Duke University Medical Center, Duke Cancer Institute	Durham	North Carolina
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida
United States	Tennessee Oncology - Sarah Cannon Research Institute	Nashville	Tennessee
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	MAGE-A4c1032T cell trafficking in tumor lesion(s).	Evaluation of post-infusion T-cell trafficking in irradiated vs non-irradiation lesions	3.5 years
Primary	Number of subjects with adverse events (AE), including serious adverse events (SAEs).	Determine if treatment with autologous genetically modified T cells (MAGE-A4?¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.	3.5 years
Primary	Determining dose limiting toxicities (DLT) and optimally tolerated dose range	Evaluate DLTs and toxicity assessment using NCI CTCAE.	3.5 years
Primary	Evaluation of persistence of genetically modified T cells.	Evaluation of persistence of genetically modified T cells in the periphery.	3.5 years
Primary	Measurement of RCL in genetically modified T cells.	Evaluation of RCL in subject PBMCs using PCR-based assay.	3.5 years
Secondary	Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).	Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to RECIST v1.1	3.5 years
Secondary	Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.	Evaluation of the efficacy of the treatment by assessment of time to first response.	3.5 years
Secondary	Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.	Evaluation of the efficacy of the treatment by assessment of duration of response.	3.5 years
Secondary	Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.	Evaluation of the efficacy of the treatment by assessment of duration of stable disease.	3.5 years
Secondary	Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause	Evaluation of the efficacy of the treatment by assessment of progression-free survival.	3.5 years
Secondary	Interval between the date of first T cell infusion and date of death due to any cause.	Evaluation of the efficacy of the treatment by assessment of overall survival.	3.5 years
Secondary	Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)	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	15 years post last treatment (infusion)