Clinical Trials

Inclusion Criteria:

• Age ≥ 18 and ≤ 75 years.
• Diagnosis of head and neck squamous cell carcinoma with metastatic or unresectable, recurrent disease confirmed by cytogenetics.
• Checkpoint inhibitor naïve and may have received prior platinum containing chemotherapy regimen.
• Measurable disease according to RECIST v1.1.  
• HLA-A*02 positive.
• Tumor shows MAGE-A4 expression confirmed by central laboratory.
• Tumors express PD-L1.
•  -ECOG Performance Status of 0 or 1.  
• Left ventricular ejection fraction (LVEF) ≥ 50%.  
• Note: other protocol defined Inclusion criteria may apply  

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.
• Toxicity from previous anti-cancer therapy must have recovered to ≤ Grade 1 or baseline prior to enrollment (except for non-clinically significant toxicities; e.g., alopecia, vitiligo). Subjects with Grade 2 toxicities that are deemed stable or irreversible (e.g., peripheral neuropathy) can be enrolled. For pembrolizumab toxicities; subjects that have terminated pre-study immune checkpoint inhibitor treatment for any reason related to safety are not eligible. Subjects that have reported any Grade 4 toxicity, or a Grade ≥ 3 immune-related adverse event during pre study immune checkpoint inhibitor treatment which was not successfully and rapidly clinically terminated with appropriate 1st-line anti-inflammatory therapy, will not be eligible.
• 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 prior to enrollment. Subjects with hypothyroidism, diabetes, adrenal insufficiency or pituitary insufficiency that are stable on replacement therapy are eligible.
• Subjects with disorders such as asthma, psoriasis or atopic dermatitis that are well controlled without requiring systemic immunosuppression are also eligible.
• Subject had major surgery within 4 weeks prior to lymphodepletion; subjects should have been fully recovered from any surgical related toxicities.
• Leptomeningeal disease, carcinomatous meningitis or CNS metastases.
• Subject has any other prior malignancy that is not considered by the Investigator to be in complete remission. Resectable squamous or basal cell carcinoma of the skin is acceptable.
• Clinically significant cardiovascular disease including, but not limited to, any of the following:
  • Electrocardiogram (ECG) showing clinically significant abnormality at Screening such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block, uncontrolled clinically significant arrhythmias such as rapid atrial fibrillation, or other abnormality considered clinically significant by the investigator;
  • Known family history or congenital history of prolonged QT syndrome or history of Torsade de Pointes;
  • Uncontrolled hypertension despite optimal medical therapy;
  • Acute Coronary Syndrome (ACS) (angina or MI) in the last 6 months;
  • Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class 3 and 4;
  • History of stroke or central nervous system bleeding; transient ischemic attack (TIA) or reversible ischemic neurologic deficit (RIND) within last 6 months.
• Subject has uncontrolled intercurrent illness including, but not limited to:
  • Ongoing or active infection;
  • COVID-19 infection or a positive COVID-19 RT-PCR test within 28 days of leukapheresis or lymphodepleting chemotherapy. If subject has had a positive COVID-19 test, then 2 subsequent negative tests are required, taken at least 7 days apart;
  • Clinically significant pulmonary disease with a requirement for home oxygen;
  • History of pneumonectomy, or of COPD with ≥ 1 exacerbation within 1 year prior to the Screening visit that required treatment with systemic corticosteroids or resulted in hospitalization;
  • Prior interstitial lung disease or pneumonitis requiring systemic corticosteroid therapy;
  • Bleeding ≥ Grade 2 in the past 3 months. 
• Subject has active infection with HIV, HBV, HCV or HTLV as defined below:
  • Positive serology for HIV;
  • Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Subjects who are hepatitis B surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. Prophylaxis should be initiated prior to lymphodepleting therapy and continued for 6 months;
  • Active hepatitis C infection as demonstrated by hepatitis C RNA test. Subjects who are HCV antibody positive will be screened for HCV RNA by any RT-PCR or bDNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value; • Positive serology for HTLV 1 or 2;
  • Re-screening for above infectious disease markers is not required at baseline (prior to lymphodepletion) unless > 6 months has elapsed.
• Subject is pregnant or breastfeeding.
• Subject who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
• Alcohol or illicit drug dependency.
• Has a diagnosis of immunodeficiency.

Additional Eligibility Criteria Prior to T-cell Infusion:

Prior to moving into Part B - Interventional phase (lymphodepletion and receipt of a T cell infusion), all subjects must remain eligible to receive manufactured T cell product and meet the following inclusion criteria:

• Subject has previously received immune checkpoint inhibitor therapy.
• Subject has manufactured T cells available for infusion.
• Subjects coming from Part A of the study only:
  • Subject has stable disease (without clinical benefit per Investigator assessment) at the Week 7 disease assessment, or disease progression at any timepoint post pembrolizumab and has manufactured T cells available for infusion;
  • Any pembrolizumab Immune related adverse events in Part A have resolved to a grade which allows pembrolizumab to be resumed per the guidance in the approved label (if ongoing then patient should stay in Part A of the study until resolved);
  • Subjects with any Grade 4 toxicity, or a Grade 3 immune-related adverse event in Part A which is not successfully and rapidly clinically terminated with appropriate 1st-line antiinflammatory therapy, will not be eligible to proceed to receive T cell infusion in Part B. 
  • These subjects shall be discontinued from the study, but will be followed-up as per protocol. If pembrolizumab is permanently discontinued for any other reasons, the subject may still be allowed to proceed to Part B and receive the T cell infusion only, but once systemic corticosteroids or other immunosuppressive treatments have been discontinued for a minimum of 2 weeks.