Clinical trial

POSITive: Prospective Observational Study for the Multidimensional Analyses of Resistance and Toxicity to Immune- and Targeted-therapies

Name

IEO 1777

Description

Novel treatment modalities like targeted therapies and Immune checkpoint inhibitors have revolutionised the therapeutic landscape in oncology and hematology, significantly improving outcomes even in clinical contexts in which little improvement had been observed for decades such as metastatic melanoma, lung cancer, and lymphoproliferative neoplasms such as chronic lymphoid leukemia or Hodgkin lymphoma. However, major issues remain unsolved, given the frequent occurrence of primary or secondary resistance and the still incomplete understanding of the physiopathology of adverse events, which represent a major cause of morbidity and treatment interruption and often remain difficult to treat and diagnose. In this complex landscape, identifying the best treatment option for each patient remains challenging. For both targeted therapies and Immune checkpoint inhibitors, several biomarkers have been reported, but their implementation in clinical practice is still uncommon, and most of the decision-making process remains based on purely clinical considerations or constraints dictated by the regulatory bodies. Obstacles to biomarker-driven decision making are manifold and include insufficient understanding of the underlying biology, lack of strong evidence on their predictive power and limited tumor sampling, which may be circumvented by non-invasive techniques such as liquid biopsies.

Trial arms

Trial start

2022-07-08

Estimated PCD

2024-12-31

Trial end

2025-12-31

Status

Recruiting

Treatment

Cohort A: primarily operable disease, candidate to adjuvant

This cohort includes any patient with nonmetastatic disease, candidate to surgery as primary treatment, for whom adjuvant therapy with targeted or immune therapy is recommended based on prior information obtained on the diagnostic biopsy. This cohort represents a control group, for whom high-throughput DNA/RNA sequencing is considered feasible in the vast majority of cases, and will not be considered in the computation of the primary endpoint

Arms:

Cohort A: primarily operable disease, candidate to adjuvant

Cohort B: locally advanced disease

Patients in this cohort are eligible if diagnosed with or highly suspected of locally advanced (nonmetastatic) neoplasm and candidate to a diagnostic/confirmatory biopsy and subsequent treatment with targeted therapy, immune therapy or radiotherapy, where the treatment is administered with potentially curative intent. Patients in this cohort may be considered for enrolment prior to a formal diagnosis, so the study should be offered on the basis of a high suspicion of invasive cancer upon radiological evidence.

Arms:

Cohort B: locally advanced disease

Cohort C: metastatic disease

In this cohort, patients are eligible if diagnosed with invasive cancer with radiologically proven metastatic localization and candidate to treatment with targeted or immune therapy.

Arms:

Cohort C: metastatic disease

Cohort D: Progressive disease

In this cohort, patients are eligible if a tumor biopsy is considered indicated by the referring physician upon disease progression to prior treatment in the metastatic setting or for hematological neoplasms. Definition of progression is based on the investigator's judgement and does not strictly require RECIST 1.1 definition, although all relevant radiological data will be collected whenever possible. Tumor biopsy must be collected no more than 6 months after the documented date of progression.

Arms:

Cohort D: Progressive disease

Cohort E: Hematological neoplasms

Any patient that is expected to be treated with targeted agents. Special consideration will be given to patients affected by chronic lymphoid leukemia and follicular lymphoma treated with BTKi, PI3Ki, BCL-2i +/- monoclonal antibodies. Any patient that is expected to be treated with immunotherapy. Special consideration will be given to patients affected by Hodgkin lymphoma and Diffuse Large B-cell lymphoma treated with ICIs, Tafasitamab/Lenalidomide, immunoconjugates.

Arms:

Cohort E: Hematological neoplasms

Cohort F: Toxicity

In this cohort, patients are enrolled upon experiencing an adverse event of grade 3/4 as per CTCAE v 5.0 that, in the opinion of the investigator, is unequivocally caused by a targeted or immune therapeutic. The event may occur at any time after the last dose of the drug. Events may be of any nature but particular attention will be given to those events for which pathophysiology is currently poorly understood (severe myocardial or neurologic Immune-related events or DS-8201-induced pneumonitis)

Arms:

Cohort F: Toxicity

Size

265

Primary endpoint

Percentage of patients in each cohort that will obtain a full "core" omic characterization.

2 months

Eligibility criteria

Inclusion Criteria: * age\>18 yrs old * histological diagnosis of any cancer * signed informed consent * fulfills criteria described in cohort definition * Clinical indication for a diagnostic biopsy Exclusion Criteria: Performance Status (ECOG) \>2 * life expectancy \< 3 months * unwilling to receive treatment at IEO for at least 6 months after enrolment * active pregnancy at the moment of enrolment * for cohort F: use of steroids (higher than 10 mg prednisone-equivalent) or other major immunosuppressive drug (e.g. tocilizumab) in the 14 days prior to the baseline sample collection.

Protocol

{'studyType': 'OBSERVATIONAL', 'patientRegistry': False, 'designInfo': {'observationalModel': 'COHORT', 'timePerspective': 'PROSPECTIVE'}, 'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'A surgical specimen will be collected. The sample will be processed regularly for diagnostic histopathology.One additional tumor specimen beyond the diagnostic biopsy will be collected using a single-pass technique. If a single additional specimen is collected, it will be processed in formalin according to the standard pathology procedure.Peripheral blood (18 ml in total) and Bone Marrow Aspirate (10 ml) will be collected.A biological specimen relevant for the toxic event will be collected.'}, 'enrollmentInfo': {'count': 265, 'type': 'ESTIMATED'}}

Updated at

2024-03-20

1 organization

Organization

European Institute of Oncology