Clinical trial NCT04408898: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Head and Neck Cancer
Keywords: Cell Therapy
T-cell Therapy
SPEAR T-Cell
Head and Neck Cancer
MAGE-A4
ADP-A2M4
Immuno-oncology
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2020-05-29
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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 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.

Primary outcomes:
measure: Efficacy: Overall Response Rate (ORR)
timeFrame: 2.5 years
Secondary outcomes:
measure: Best overall response (BOR)
timeFrame: 2.5 years
measure: Time to response (TTR)
timeFrame: 2.5 years
measure: Duration of response (DoR)
timeFrame: 2.5 years
measure: Duration of stable disease (DoSD)
timeFrame: 2.5 years
measure: Progression- free survival (PFS)
timeFrame: 2.5 years
measure: Overall survival (OS)
timeFrame: 2.5 years
measure: To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs)
timeFrame: 2.5 years
measure: To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest
timeFrame: 2.5 years
measure: To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells
timeFrame: 15 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Insitute
state: Michigan
city: Portland
country: United States
facility: Providence Cancer Institute Franz Head and Neck Clinic
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
Study officials:
References: