Clinical trial NCT03132922: MAGE-A4ᶜ¹º³²T for Multi-Tumor
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Urinary Bladder Cancer
Melanoma
Head and Neck Cancer
Ovarian Cancer
Non-Small Cell Lung Cancer
Esophageal Cancer
Gastric Cancer
Synovial Sarcoma
Myxoid Round Cell Liposarcoma
Gastroesophageal Junction
Keywords: Cell Therapy
T Cell Therapy
SPEAR T Cell
MAGE-A4
Immuno-oncology
Metastatic
Urothelial Cancer
Previously Treated
T Cell Receptor
Squamous, adenosquamous, adenocarcinoma or large cell NSCLC
Squamous or adenocarcinoma esophageal cancer
Sarcoma
Melanoma
Bladder
Ovarian
Radiation therapy
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2017-04-28
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of subjects with adverse events (AE), including serious adverse events (SAEs).
timeFrame: 3.5 years
measure: Determining dose limiting toxicities (DLT) and optimally tolerated dose range
timeFrame: 3.5 years
measure: Evaluation of persistence of genetically modified T cells.
timeFrame: 3.5 years
measure: Measurement of RCL in genetically modified T cells.
timeFrame: 3.5 years
Secondary outcomes:
measure: Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
timeFrame: 3.5 years
measure: Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
timeFrame: 3.5 years
measure: Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.
timeFrame: 3.5 years
measure: Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.
timeFrame: 3.5 years
measure: Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause
timeFrame: 3.5 years
measure: Interval between the date of first T cell infusion and date of death due to any cause.
timeFrame: 3.5 years
measure: Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
timeFrame: 15 years post last treatment (infusion)
Other outcomes:
measure: MAGE-A4c1032T cell trafficking in tumor lesion(s).
timeFrame: 3.5 years
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology - Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sanderson 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.