Clinical trial NCT02636855: Screening Protocol for Tumor Antigen Expression Profiling and HLA Typing for Eligibility Determination
Official title: A Screening Protocol to Determine Tumor Antigen Expression and HLA Sub-Type for Eligibility Determination for Clinical Trials Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs in Subjects With Solid and Hematological Malignancies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Solid and Hematological Malignancies
Keywords: Solid and Hematological Malignancies
Screening
Metastatic
Previously Treated
MAGE-A4
Neoplasms
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 9122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects with confirmed diagnosis of advanced solid or hematologic malignancy or recurrent disease

Brief summary: This screening study is intended for men and women ≥ 18 to ≤ 75 years of age who have advanced solid or hematologic malignancy. The study will assess a subject's human leukocyte antigen (HLA) subtype and tumor antigen expression profile. Based on the results, it will be determined if a subject is eligible to be considered for Adaptimmune sponsored clinical trials testing the safety and efficacy of genetically changed T cells targeting specific tumor antigens. No treatment intervention will occur as part of this screening study.

Upon enrollment, subjects will be required to provide a blood sample for HLA subtype analysis. If the results of the analysis match the HLA-A subtypes noted in the inclusion criteria and do not express the HLA subtypes that are exclusionary for the available interventional clinical trial(s), then the subject will be required to provide either an archival tumor specimen or fresh tumor tissue biopsy. The tumor specimen will be screened at a central laboratory for the expression (protein or gene) of multiple antigens which may include, but are not limited to MAGE-A4. Based upon the results of these diagnostic analyses, if eligible, subjects will be referred to an appropriate available interventional clinical trial(s) at the discretion of the Investigator.

Following screening, tumor samples will be retained by Adaptimmune for the purpose of developing and validating in vitro diagnostic (IVD) assay(s) for antigen expression profiling which is required for regulatory approval of a new therapeutic product indication.

Detailed description: This multicenter screening study will be conducted in order to determine a subject's tumor antigen expression profile and HLA subtype, and subsequent eligibility for Adaptimmune sponsored clinical treatment trials studying the safety and efficacy of autologous genetically modified T-cells engineered with enhanced TCRs targeting specific antigens. No treatment intervention will occur as part of this screening study. Specific Adaptimmune sponsored interventional protocols have been designated to utilize this screening protocol to determine preliminary eligibility. Therefore, details of the available interventional clinical trial(s) (e.g., HLA subtype, tumor antigen, and other eligibility criteria) should be understood before consenting subjects for this screening protocol.

For this screening study, subjects with confirmed advanced solid or hematologic malignancy or recurrent disease, as described in the respective Adaptimmune clinical trial protocol(s), will be required to provide a blood sample for diagnostic analysis. The blood sample will be used for HLA subtype analysis. If the results of the analysis match the HLA subtype specified in the available interventional clinical trial(s), then the subject will be required to provide either an archival tumor specimen or fresh tumor tissue biopsy. The tumor specimen will be screened at a central laboratory for the expression (gene or protein) of multiple antigens using Clinical Trial Assays. The Clinical Trial Assays to be used in this protocol have undergone CLIA validation to establish the sensitivity, specificity and performance of the assays. The antigens to be screened may include, but are not limited to the following: NY-ESO-1 and/or LAGE-1a and MAGE-A10. Based upon both the tumor antigen expression and the HLA subtype, if eligible, subjects will be referred to appropriate available interventional trial(s) at the discretion of the Investigator.

The secondary objective of the study is the collection and analysis of tumor tissue specimens to enable the development and validation of single and/or multiple-marker ('multiplex') IVD assay(s) for antigen expression profiling. It is a regulatory requirement to develop the IVD(s) as a companion diagnostic(s) to accompany a future new indication drug application(s). Therefore all tumor specimens from this study will be retained by Adaptimmune for companion diagnostic validation purposes.

Eligibility criteria: Inclusion Criteria

1. Signed written informed consent;
2. Histologically or cytologically confirmed diagnosis of advanced solid or hematologic malignancy or recurrent disease, as described in the respective Adaptimmune clinical treatment protocol (including, but not limited to myeloma, melanoma, NSCLC, head and neck, gastric and bladder cancer);
3. Male or female ≥ 18 to ≤75 years of age;
4. Life expectancy \> 3 months;
5. Ability to provide a blood sample;
6. Ability to provide one of the following tumor tissue samples:

   i. formalin-fixed, paraffin-embedded (FFPE) tumor block or tissue sections from a current lesion/the most current setting, OR

ii. a fresh biopsy is feasible, OR;

iii. a FFPE archival primary tumor block or tissue sections

Exclusion Criteria:

1. Any bleeding diathesis or coagulopathy, which at the discretion of the Investigator may put the subject at risk.
2. Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the screening study procedures.

Primary outcomes:
measure: Frequency of subjects with the expression (gene or protein) of multiple antigens (including, but are not limited to MAGE-A4 , and others) [ Time Frame: 10 years ]
timeFrame: 10 years
Secondary outcomes:
measure: Retention of screening tumor tissue for the future development and validation of single and/or multi-plex companion diagnostic platforms for the detection of tumor antigen expression. [ Time Frame: 10 years ]
timeFrame: 10 years
Other outcomes:
measure: Incidence of antigen expression in solid and hematological malignancies [ Time Frame: 10 years ]
timeFrame: 10 years
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute (Stanford University)
state: California
city: Boca Raton
country: United States
facility: Boca Raton Regional Hospital, Lynn Cancer Institute, 701 NW 13th Street
state: Florida
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute - Emory University
state: Georgia
city: Rolling Meadows
country: United States
facility: Northwest Oncology and Hematology
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Bel Air
country: United States
facility: Upper Chesapeake Medical Center, Patricia D. and M. Scot Kaufman Cancer Center
state: Maryland
city: Towson
country: United States
facility: UMD St. Joseph Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Duke Cancer Institute
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology- Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Pamplona
country: Spain
facility: University Hospital of Navarra (Pamplona)
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario 12 Octubre Avda. de Córdoba s/n
city: Madrid
country: Spain
facility: Centro Integral Oncológico Clara Campal, HM CIOCC (START MADRID-CIOCC)
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocio, Sevillia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: University College Hospital Macmillan Cancer Centre
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
References: