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

Sponsor

Adaptimmune (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT04408898

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Genetic: ADP-A2M4 in combination with pembrolizumab.	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 2, 2020

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Efficacy: Overall Response Rate (ORR) [2.5 years]
ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1

Secondary Outcome Measures

Best overall response (BOR) [2.5 years]
BOR defined as the best response recorded from the date of T cell infusion until disease progression.
Time to response (TTR) [2.5 years]
TTR defined as the duration between T cell infusion and the initial date of the confirmed response.
Duration of response (DoR) [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) [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) [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) [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) [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 [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 [15 years]
Evaluation of RCL using PCR-based assay in peripheral blood.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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-A02 allele other than: one of the inclusion alleles, HLA- A02:07P 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Phoenix	Phoenix	Arizona	United States	85054
2	University of California San Diego	San Diego	California	United States	92093
3	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
4	Karmanos Cancer Insitute	Detroit	Michigan	United States	48201
5	Providence Cancer Institute Franz Head and Neck Clinic	Portland	Oregon	United States	97213
6	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37212
7	MD Anderson Cancer Center	Houston	Texas	United States	77030
8	West Virginia University Cancer Institute	Morgantown	West Virginia	United States	26506