Primary objective:To compose multifaceted predictive signatures for PD-1 or anti-PD-L1 antibody effects with relevant components of integrative omics (histology, immunohistochemistry, genomics, transcriptomics, proteomics, radiomics and molecular…
ID
Source
Brief title
Condition
- Metastases
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A multifaceted predictive signature by combining molecular omics comprising
genomics, transcriptomics, proteomics withradiomics and molecular imaging, that
predicts which patients have a <= 5% chance of responding to PD-1 or anti-PD-L1
antibody.
Secondary outcome
Relationship between a multifaceted signature and toxicity.
Background summary
Immunotherapy is a novel, rapidly evolving field, with several drugs and
combinations under development. Cancer treatment isbeing revolutionized by
these drugs due to broad activity across a variety of cancers, leading to
remarkable and durableresponses. Unfortunately, no validated tools are
available to predict which patients will benefit from these expensive drugs or
willexperience life-threatening toxicity. Patient selection based on factors
such as Programmed Death Ligand 1 (PD-L1) expressionand somatic mutations in
tumor biopsies still undervalues the complexity and dynamics of immune
response.
Study objective
Primary objective:
To compose multifaceted predictive signatures for PD-1 or anti-PD-L1 antibody
effects with relevant components of integrative omics (histology,
immunohistochemistry, genomics, transcriptomics, proteomics, radiomics and
molecular imaging), which predict,which patients have a <= 5% chance of
responding to anti-PD-1 or anti-PD-L1 antibody treatment.
Secondary objective:
Relation between the multifaceted signature and toxicity.
Study design
This is a two-center prospective continuously accruing longitudinal cohort
study in patients with non-small-cell lung carcinoma(NSCLC) or metastatic
melanoma eligible for standard anti-PD-1 or anti-PD-L1 antibody treatment.
After successful eligibility screening, all patients will undergo
i) a biopsy for whole genome sequencing, IHC, DNA and RNA analysis
ii) venous blood sampling for routine assessments and exploratory biomarker
analysis
ii) feces sampling
iv) CD8+ PET-low dose CT scan
Data on medication, side effects of treatment, and results from routine
assessments will be derived from the electronical patiëntdossier. Feces
collection will be performed at home. The tumor biopsy, venous blood sampling
and feces collection will ideally beperformed before, during and at the end of
standard anti-PD-1 antibody treatment.
The data from this prospective longitudinal cohort will be used in the POINTING
(towards patient -tailored cancer immunotherapy supported by a multifaceted
predictive signature composed of integrative omics and molecular imaging) KWF
Kankerbestrijding project. The goal of this project is to develop a
multifaceted predictive signature, by using new techniques on tumor
characteristicsbefore and during treatment with immune therapy. To do so,
researchers will use the *omics* approach. By combining molecularomics
comprising genomics, transcriptomics, proteomics with radiomics and molecular
imaging a set of factors will arise which can accurately predict the outcome of
the treatment.
Intervention
Prior to regular treatment, a CD8+ PET-LDCT scan will be performed, with a Zr89
tracer injection on D0 and a PET-LDCT on D2.
Study burden and risks
All necessary information on the subjects will be extracted from the
(electronic) patient dossier. The risk of blood drawings and stool sampling are
considered negligible. Review of the literature shows that in general tumor
biopsies can be performed with only minor complications and acceptable risks.
The CD8+ PET low-dose radiation exposure is considered responsible under
current regulations. The administration of Zr-CED88004S has been shown to be
safe from previous research. Although patients do notdirectly benefit from this
study, results of this study will be valuable for the understanding of the
tumor immune response and will guide further prospective research and patient
selection thereafter. The purpose of POINTING is to personalize potentially
curative immunotherapy, thereby avoiding possibly harmful exposure by these
drugs of patients who will not benefit.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
1. Histologically or cytological documented locally advanced or metastatic
NSCLC or melanoma.
2. Patients must be eligible for standard treatment with immune checkpoint
inhibitor antibody treatment (monotherapy or in combination with other
anti-cancer treatments).
3. Age >=18 years.
4. Measurable disease, as defined by standard RECIST v1.1. Previously
irradiated lesions should not be counted as target lesions.
5. Metastatic or locally advanced lesion(s) of which a histological biopsy can
safely be obtained according to standard clinical care procedures
6. Ability to comply with protocol.
7. Signed Informed Consent Form.
Exclusion criteria
1. Malignancies other than melanoma or NSCLC within 5 years prior to inclusion,
with the exception of those with a negligible risk of metastasis or death,
treated with expected curative outcome (such as adequately treated carcinoma in
situ of the cervix, basal or squamous cell skin cancer, localized prostate
cancer treated with curative intent or ductal carcinoma in situ treated
surgically with curative intent).
2. Treatment with systemic immunosuppressive medications (including but not
limited to prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to
study inclusion.
• Patients who have received acute, low-dose, systemic immunosuppressant
medications may be enrolled.
• The use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g. fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
3. Signs or symptoms of infection within 2 weeks prior to ZED88082A/CED88004S
injection.
4. Pregnant or lactating women.
5. History of severe allergic, anaphylactic, or other hypersensitivity
reactions to chimeric or humanized antibodies or fusion proteins
6. Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or
condition that contraindicates the use of ZED88082A/CED88004S, or that may
affect the interpretation of the results or render the patient at high risk
from complications.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04193956 |
| CCMO | NL82156.041.22 |