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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Genetic: ADP-A2M4 in combination with pembrolizumab.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • California
    • San Diego, California, United States, 92093
      • University of California San Diego
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Insitute
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute Franz Head and Neck Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ADP-A2M4 T cells in combination with pembrolizumab	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Adaptimmune

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 2, 2020
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: May 27, 2020
• First Submitted That Met QC Criteria: May 27, 2020
• First Posted (ACTUAL): May 29, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 16, 2021
• Last Update Submitted That Met QC Criteria: November 8, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Cell Therapy; Head and Neck Cancer; Immuno-oncology; MAGE-A4; T-cell Therapy; SPEAR T-Cell; ADP-A2M4
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: ADP 0044-003

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No