Solid Tumor, Unspecified, Adult
Conditions
Keywords
ATM, DDR, ATR, protein expression, LoF
Brief summary
This study examines the correlation between ATM alterations identified using NGS profiles with ATM protein expression levels from tumor tissue assessed by IHC.
Detailed description
The purpose of this study is to address whether ATM genomic aberrations could be used to enrich for patients with ATM LoP. Screening of unselected patient populations for ATM protein loss is likely to a lead to high failure rate by IHC testing, as the prevalence of this is expected to be low. This study could allow for identification of the types of ATM aberrations that lead to ATM LoP, and thus significantly decrease IHC failure rate by pre-selecting patients harboring such aberrations. In this study the investigator will be collecting archival tumor tissue or fresh tissue which will be assessed for ATM LoP and compared to NGS data. Additionally, patients whose tumors exhibit ATM LoP within this study could potentially enroll onto the treatment study REFMAL 721/ART0380C001.
Interventions
OTHERDetermination of ATM alteration status.
ATM alterations identified using NGS profiles with ATM protein expression levels from tumor tissue assessed by IHC.
Sponsors
Artios Pharma Ltd
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must meet the following criteria in order to be included in the research study: All patients (Groups A, B, and C) must meet the following criteria: 1. Previous genetic testing of ATM genomic aberrations. 2. ≥18 years of age. All living patients (Groups B and C) must also meet the additional criteria: 3. Signed written informed consent to access archival tissue, if available. All Group C patients must also meet the additional criteria: 4. Provided signed written informed consent to collect a fresh core biopsy. 5. Have a non-irradiated, biopsiable tumor site to allow sampling for analysis via IHC for loss of ATM protein. 6. Potentially eligible for REFMAL 721/ART0380C001: * Have not received a previous treatment targeting the ATR/CHK1 pathway. * If patients have a germline BRCA mutation or a cancer with a somatic BRCA mutation or which is HRD positive and for which there is an approved PARP inhibitor, patients should have received such treatment. * Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator * Advanced or metastatic cancer which is refractory to standard therapies, or for which no standard therapies exist, or for which the investigator feels no other active therapy is required for the duration of the study. * Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale
Exclusion criteria
There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of patients with loss of ATM protein | 12 months | ATM protein expression levels from tumor tissue assessed by immunohistochemistry (IHC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of potential patients with loss of ATM protein eligible for study REFMAL 721/ART0380C001 | 12 months | Patients in Group C are considered for enrolment into study REFMAL 721/ART0380C001 and must meet eligibility based on review of their medical records. REFMAL 721/ART0380C001 is a phase I/IIa open-label trial to assess the safety, tolerability, and preliminary efficacy of the ATR kinase inhibitor, ART0380 administered as a monotherapy as well as in drug combinations with gemcitabine in patients with advanced or metastatic solid tumors. |
| Number of ATM genomic aberrations that lead to ATM LoP | 12 months | Identify types of ATM protein expression from tumor tissue assessed by immunohistochemistry (IHC) |
| Rate of loss of function (LoF) of the ATM gene in patients with genomic aberrations in the ATM gene | 12 months | ATM alterations identified using Next-Generation Sequencing(NGS) profiles |
Countries
United Kingdom, United States
Outcome results
None listed