Clinical trial NCT02989064: MAGE-A10ᶜ⁷⁹⁶T for Urothelial Cancer, Melanoma or Head and Neck Cancers
Official title: Phase 1 Cell Dose Escalation Study to Assess the Safety and Tolerability of Genetically Engineered MAGE-A10ᶜ⁷⁹⁶T in HLA-A2+ Subjects With MAGE-A10 Positive Urothelial, Melanoma or Head and Neck Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Urothelial Carcinoma
Head and Neck Cancer
Melanoma
Bladder Urothelial Carcinoma
Keywords: Cell Therapy
T Cell Therapy
SPEAR T Cell
MAGE-A10
Immuno-oncology
Metastatic
Urothelial Cancer
Previously Treated
T Cell Receptor
Inoperable
Advanced
Cancer
Bladder
Head and neck
Melanoma
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2016-12-12
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This Phase 1 study is designed as a cell dose escalation trial in HLA-A\*02:01 and HLA-A\*02:06 subjects with MAGE-A10 positive urothelial, melanoma or head and neck tumors. The study will enroll subjects between the ages of 18 and 75 using a modified 3+3 cell dose escalation design, to evaluate dose limiting toxicities and determine the target cell dose range. Following the dose escalation phase, additional subjects will be enrolled at the target cell dose range to further characterize safety and the effects at this cell dose.

The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. When the MAGE-A10ᶜ⁷⁹⁶T cells are available, subjects will undergo lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with urothelial, melanoma or head and neck cancer.

Subjects will be seen frequently by the Study Physician after receiving their T cells for the next 6 months. After that, subjects will be seen every 3, 6, or 12 months according to the Schedule of Procedures. All subjects completing or withdrawing from the interventional portion of the study will enter a long term follow-up phase for observation of delayed adverse events and overall survival for 15 years post-infusion.


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 following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
3. Subject is HLA-A\*02:01 and/or HLA-A\*02:06 positive.
4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
5. Subject meets disease-specific requirements per protocol
6. Subject has anticipated life expectancy \> 6 months prior to leukapheresis and \>3 months prior to lymphodepletion.
7. Subject's tumor shows positive MAGE-A10 expression
8. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
9. Subject has a left ventricular ejection fraction ≥50%.
10. Subject is fit for leukapheresis and has adequate venous access for the cell collection.
11. Female subject of childbearing potential (FCBP) must have a negative urine or serum pregnancy test or male subject must be surgically sterile or agree to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential starting at the first dose of chemotherapy and for 4 months thereafter.
12. Subject must have adequate organ function per protocol

Exclusion Criteria:

1. Subject is HLA-A\*02:05 in either allele, HLA-B\*15:01 and/or HLA-B\*46:01 positive. Subject has any A\*02 null allele (designated with an "N", e.g. A\*02:32N) as the sole HLA-A\*02 allele.
2. Subject has received or plans to receive excluded therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy per protocol
3. Subject that has toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 prior to enrollment
4. Subject has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
5. Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
6. Subject has an electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with bundle branch block \[BBB\]) over 3 consecutive ECGs. Either Fridericia's or Bazett's formula may be used to correct the QT interval.
7. Subject has symptomatic CNS metastases.
8. Subject has a history of chronic or recurrent severe autoimmune or immune mediated disease
9. Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening.
10. Subject has uncontrolled intercurrent illness
11. Subject has active infection with HIV, HBV, HCV or HTLV
12. Subject is pregnant or breastfeeding.

Primary outcomes:
measure: Number of subjects with adverse events (AE), including serious adverse events (SAE).
timeFrame: 3 years
measure: Evaluation of the persistence of genetically modified T cells
timeFrame: 3 years
measure: Measurement of RCL in genetically modified T cells.
timeFrame: 3 years
measure: Assessment of dose limiting toxicities to determine optimally tolerated dose range
timeFrame: 3 years
measure: Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).
timeFrame: 3 years
measure: Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.
timeFrame: 3 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 years
measure: Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause.
timeFrame: 3 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 years
measure: Interval between the date of first T cell infusion and date of death due to any cause.
timeFrame: 3 years
measure: Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)
timeFrame: 15 years post last treatment (infusion)
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University - School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
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: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Madrid
country: Spain
facility: Start Madrid-FJD, Fundación Jimѐnez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre Avda. de Córdoba
Study officials:
affiliation: M.D. Anderson Cancer Center
name: David Hong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hong DS, Butler MO, Pachynski RK, Sullivan R, Kebriaei P, Boross-Harmer S, Ghobadi A, Frigault MJ, Dumbrava EE, Sauer A, Brophy F, Navenot JM, Fayngerts S, Wolchinsky Z, Broad R, Batrakou DG, Wang R, Solis LM, Duose DY, Sanderson JP, Gerry AB, Marks D, Bai J, Norry E, Fracasso PM. Phase 1 Clinical Trial Evaluating the Safety and Anti-Tumor Activity of ADP-A2M10 SPEAR T-Cells in Patients With MAGE-A10+ Head and Neck, Melanoma, or Urothelial Tumors. Front Oncol. 2022 Mar 18;12:818679. doi: 10.3389/fonc.2022.818679. eCollection 2022.