Head and Neck Cancer
Conditions
Keywords
Cell Therapy, T-cell Therapy, SPEAR T-Cell, Head and Neck Cancer, MAGE-A4, ADP-A2M4, Immuno-oncology
Brief summary
This is a study to investigate the efficacy and safety of ADP-A2M4 in combination with pembrolizumab in HLA-A\*02 eligible and MAGE-A4 positive subjects with recurrent or metastatic Head and Neck cancer.
Interventions
GENETICADP-A2M4 in combination with pembrolizumab.
Single infusion of autologous genetically modified ADP-A2M4 Dose: 1.0 x109 to 10x109 transduced cells by a single intravenous infusion Repeat doses of pembrolizumab every 3 weeks. Dose: 200mg
Sponsors
Adaptimmune
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Age ≥18 and \<75 years * Diagnosis of head and neck squamous cell carcinoma with metastatic or unresectable, recurrent disease. confirmed by histology cytology. * Checkpoint inhibitor naïve and indicated for pembrolizumab or currently receiving pembrolizumab (monotherapy). May have received prior platinum containing chemotherapy regimen or checkpoint inhibitor therapy. * Subjects that have already received pembrolizumab (alone or in combination) and are progressing or have completed immune checkpoint inhibitor therapy for recurrent/metastatic disease, may still be enrolled and will skip Part A of the study. These subjects will enroll into Part B when manufactured T cells are available. * Measurable disease according to RECIST v1.1. * HLA-A\*02 positive by central laboratory. * Tumor shows MAGE-A4 expression confirmed by central laboratory. * ECOG Performance Status of 0 or 1. * Left ventricular ejection fraction (LVEF) ≥50%. Note: other protocol defined Inclusion criteria may apply Key
Exclusion criteria
* Positive for any HLA-A\*02 allele other than: one of the inclusion alleles, HLA- A\*02:07P or HLA-A\*02 null alleles * History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study or history of severe hypersensitivity to another monoclonal antibody. * History of autoimmune or immune mediated disease * Leptomeningeal disease, carcinomatous meningitis or CNS metastases. * Other prior malignancy that is not considered by the Investigator to be in complete remission * Clinically significant cardiovascular disease * Uncontrolled intercurrent illness * Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus * Pregnant or breastfeeding Note: other protocol defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Overall Response Rate (ORR) | 2.5 years | ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to response (TTR) | 2.5 years | TTR defined as the duration between T cell infusion and the initial date of the confirmed response. |
| Duration of response (DoR) | 2.5 years | DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death). |
| Duration of stable disease (DoSD) | 2.5 years | DoSD defined as the duration from the date of T cell infusion to the date of PD (or death). |
| Progression- free survival (PFS) | 2.5 years | PFS defined as the interval between the date T cell infusion and the earliest date of disease progression based on RECIST v1.1 or death due to any cause. |
| Best overall response (BOR) | 2.5 years | BOR defined as the best response recorded from the date of T cell infusion until disease progression. |
| To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs) | 2.5 years | Determination of incidence, severity and duration of adverse events through assessment of adverse events including SAEs. Adverse events will be collected and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest | 2.5 years | Adverse events of special interest will be listed along with duration and toxicity grade. |
| To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells | 15 years | Evaluation of RCL using PCR-based assay in peripheral blood. |
| Overall survival (OS) | 2.5 years | OS defined the duration between T cell infusion and death due to any cause. |
Countries
United States
Outcome results
None listed