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

Head and Neck Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04408898
• Other study ID #: ADP 0044-003
• Status: Withdrawn
• Phase: Phase 2
• Start date: July 2, 2020
• Est. completion date: December 2021

Study information

• Verified date: November 2021
• Source: Adaptimmune
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

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

Locations

Country	Name	City	State
United States	Karmanos Cancer Insitute	Detroit	Michigan
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	West Virginia University Cancer Institute	Morgantown	West Virginia
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	Providence Cancer Institute Franz Head and Neck Clinic	Portland	Oregon
United States	University of California San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Best overall response (BOR)	BOR defined as the best response recorded from the date of T cell infusion until disease progression.	2.5 years
Secondary	Time to response (TTR)	TTR defined as the duration between T cell infusion and the initial date of the confirmed response.	2.5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	Overall survival (OS)	OS defined the duration between T cell infusion and death due to any cause.	2.5 years
Secondary	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
Secondary	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
Secondary	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