SPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 2 Pilot Study of ADP-A2M4 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Cancer

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Genetic: ADP-A2M4 in combination with pembrolizumab.


Participation Criteria
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Eligibility Criteria
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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 Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADP-A2M4 T cells in combination with pembrolizumab<br> | Genetic: ADP-A2M4 in combination with pembrolizumab.<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Overall Response Rate (ORR) | ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1 | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best overall response (BOR) | BOR defined as the best response recorded from the date of T cell infusion until disease progression. | 2.5 years | 
| Time to response (TTR) | TTR defined as the duration between T cell infusion and the initial date of the confirmed response. | 2.5 years | 
| Duration of response (DoR) | DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death). | 2.5 years | 
| Duration of stable disease (DoSD) | DoSD defined as the duration from the date of T cell infusion to the date of PD (or death). | 2.5 years | 
| Progression- free survival (PFS) | 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. | 2.5 years | 
| Overall survival (OS) | OS defined the duration between T cell infusion and death due to any cause. | 2.5 years | 
| To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs) | 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 | 2.5 years | 
| To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest | Adverse events of special interest will be listed along with duration and toxicity grade. | 2.5 years | 
| To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells | Evaluation of RCL using PCR-based assay in peripheral blood. | 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell Therapy, T-cell Therapy, SPEAR T-Cell, Head and Neck Cancer, MAGE-A4, ADP-A2M4, Immuno-oncology