Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
ADP-0022-004
- NCT ID:
NCT02989064
Conditions
- Urothelial Carcinoma
- Head and Neck Cancer
- Melanoma
- Bladder Urothelial Carcinoma
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Autologous genetically modified MAGE A10ᶜ⁷⁹⁶T cells | Experimental | | |
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.
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of subjects with adverse events (AE), including serious adverse events (SAE). |
Time Frame: | 3 years |
Safety Issue: | |
Description: | Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation; and cardiac assessments, including ECG/troponin. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Adaptimmune |
Trial 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
Last Updated
December 19, 2020