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

• ClinicalTrials.gov Identifier: NCT04408898
• Recruitment Status: Recruiting
• First Posted: May 29, 2020
• Last Update Posted: March 1, 2021
• Sponsor: Adaptimmune
• Information provided by (Responsible Party): Adaptimmune

Tracking Information

• First Submitted Date: May 27, 2020
• First Posted Date: May 29, 2020
• Last Update Posted Date: March 1, 2021
• Actual Study Start Date: July 2, 2020
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2020)

Efficacy: Overall Response Rate (ORR) [ Time Frame: 2.5 years ]

ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 27, 2020)

• Best overall response (BOR) [ Time Frame: 2.5 years ]
  BOR defined as the best response recorded from the date of T cell infusion until disease progression.
• Time to response (TTR) [ Time Frame: 2.5 years ]
  TTR defined as the duration between T cell infusion and the initial date of the confirmed response.
• Duration of response (DoR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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.
• Overall survival (OS) [ Time Frame: 2.5 years ]
  OS defined the duration between T cell infusion and death due to any cause.
• To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 15 years ]
  Evaluation of RCL using PCR-based assay in peripheral blood.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: SPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer
• Official Title: A Phase 2 Pilot Study of ADP-A2M4 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Cancer
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Head and Neck Cancer

Intervention

Genetic: ADP-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

Study Arms

Experimental: ADP-A2M4 T cells in combination with pembrolizumab

Intervention: Genetic: ADP-A2M4 in combination with pembrolizumab.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 27, 2020): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2036
• Estimated Primary Completion Date: April 2022 (Final data collection date for primary outcome measure)

Eligibility 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 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 [CPS ≥1]
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Adaptimmune Patient Enquiries; 2158259260; patients@adaptimmune.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04408898
• Other Study ID Numbers: ADP 0044-003
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Adaptimmune
• Study Sponsor: Adaptimmune
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Adaptimmune
• Verification Date: October 2020