Screening Protocol for Tumor Antigen Expression Profiling and HLA Typing for Eligibility Determination

Solid and Hematological Malignancies Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02636855
• Other study ID #: ADP-0000-001
• Status: Recruiting
• Start date: December 2015
• Est. completion date: November 2025

Study information

• Verified date: August 2023
• Source: Adaptimmune
• Contact: Adaptimmune Patient Enquiries Adaptimmune Patient Enquiries
• Email: patients[@]adaptimmune.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10000
• Est. completion date: November 2025
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Neoplasms
• Solid and Hematological Malignancies

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Institut Català d'Oncologia (ICO) L´Hospitalet	Barcelona
Spain	Centro Integral Oncológico Clara Campal, HM CIOCC (START MADRID-CIOCC)	Madrid
Spain	Hospital 12 De Octubre	Madrid
Spain	Hospital Universitario 12 Octubre Avda. de Córdoba s/n	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Start Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	University Hospital of Navarra (Pamplona)	Pamplona	Navarra
Spain	Hospital Virgen del Rocio, Sevillia	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
United Kingdom	University College Hospital Macmillan Cancer Centre	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	Winship Cancer Institute - Emory University	Atlanta	Georgia
United States	University of Maryland, Greenebaum Cancer Center	Baltimore	Maryland
United States	Upper Chesapeake Medical Center, Patricia D. and M. Scot Kaufman Cancer Center	Bel Air	Maryland
United States	Boca Raton Regional Hospital, Lynn Cancer Institute, 701 NW 13th Street	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	City of Hope	Duarte	California
United States	Duke University Medical Center, Duke Cancer Institute	Durham	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	University of Miami, Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Tennessee Oncology- Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Orlando Health	Orlando	Florida
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Northwest Oncology and Hematology	Rolling Meadows	Illinois
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Stanford Cancer Institute (Stanford University)	Stanford	California
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	UMD St. Joseph Medical Center	Towson	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Adaptimmune

Countries where clinical trial is conducted

United States,  Canada,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of antigen expression in solid and hematological malignancies [ Time Frame: 10 years ]	To collect data regarding the frequency of occurrence of antigens in tumor tissue samples of different tumor types.	10 years
Primary	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 ]	To screen subject tumor tissue in order to determine their tumor antigen expression profile, and HLA subtype, for subsequent assessment of eligibility for various Adaptimmune sponsored targeted T cell therapy clinical trials.	10 years
Secondary	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 ]	Following screening for the antigen expression profile, remaining screening tissue will be used for the purpose of developing and validating companion diagnostic assays for antigen screening for regulatory approval. Tumor tissue will be used for the analytical validation (which includes testing for efficiency, sensitivity, specificity, exclusivity, accuracy and precision), as well as the clinical validation of such diagnostic assays.	10 years