Clinical trial NCT06195527: PEMBRO-K : Evaluation of Pembrolizumab Therapeutic Pharmacological Monitoring Benefit in NSCLC
Official title: PEMBRO-K : Evaluation of Pembrolizumab Therapeutic Pharmacological Monitoring Benefit in Non-small Cell Bronchopulmonary Cancer (NSCLC)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Non Small Cell Lung Cancer
Lead sponsor: University Hospital, Angers
Sponsor class: OTHER_GOV
First posted: 2024-01-08
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This is a population pharmacokinetic study aimed at establishing the PK-PD relationship in patients with NSCLC treated with pembrolizumab (non-comparative descriptive study).

Taking into account the half-life (26 days) and the time necessary to obtain the equilibrium state (16 weeks), the choice was made to take residual and peak samples during administrations. This sampling strategy will allow the construction and validation of the PK model.

Brief summary: Solid cancers and their therapeutic management remain a major public health problem due to their increasing prevalence and associated mortality. Among solid cancers, lung cancer ranks 4th among incident cancers. The prognosis remains poor, 33,117 deaths were recorded in France in 2018. Two histological forms of bronchopulmonary cancer are distinguished: non-small cell lung cancers (NSCLC), which represent 85% of bronchopulmonary cancer, and small cell lung cancers. The most common forms of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.

The emergence of new so-called targeted therapies has considerably modified the management and prognosis of oncology patients and in particular of patients with NSCLC. These new molecules were developed following the molecular characterization of tumors on the one hand and on the other hand the characterization of the role of immunity in anti-tumor defense, particularly the Programmed Death receptor pathway 1 (PD-1). Blocking this pathway restores the anti-tumor potential of these lymphocytes. Pembrolizumab is a humanized monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with the Programmed Death Ligand-1 (PDL1) and Programmed Death Ligand-2 (PDL2), expressed by tumor cells but also by cells in the microenvironment. tumor and by antigen-presenting cells. Pembrolizumab thus potentiates T cell responses, including anti-tumor responses, by blocking the binding of PD-1 with PDL1 and PDL2.

Pembrolizumab currently has marketing authorization (MA) for the treatment of NSCLC. Despite therapeutic progress due, among other things, to the emergence of anti-PD-1 antibodies including pembrolizumab, the prognosis of NSCLC remains poor and the use of pembrolizumab is sometimes limited by the occurrence of adverse effects.

The pharmacokinetics of pembrolizumab was studied pre-marketing in patients with melanoma, NSCLC or metastatic or unresectable carcinomas. However, there are no data relating to the pharmacokinetic (PK) / clinical response (pharmacodynamic / PD) relationship of pembrolizumab, in real life. No prospective pharmacological study has in fact been published to date, especially in patients treated as part of the management of NSCLC. The absence of such studies - in real life - constitutes a pitfall given the existence of a possible association between PK data and the clinical response and/or toxicity of pembrolizumab.


Eligibility criteria: Inclusion Criteria:

* 18 years or more
* patient with NSCLC
* pembrolizumab treatment (monotherapy or not) with a placed line (peripheral catheter, PICC or implantable port)

Exclusion Criteria:

* objection to participate in the study
* patient under judicial protection

Primary outcomes:
measure: Pembrolizumab efficiency Month 2
timeFrame: month 2
Secondary outcomes:
measure: Pembrolizumab efficiency Month 4
timeFrame: month 4
measure: Pembrolizumab efficiency Month 12
timeFrame: month 12
measure: Pembrolizumab toxicity Month 18
timeFrame: month 18
Other outcomes:
Locations:
city: Angers
country: France
facility: Angers University Hospital
city: Le Mans
country: France
facility: CH Le Mans
Study officials:
affiliation: Angers University Hospital
name: Guillaume DREVIN, Doctor
role: STUDY_DIRECTOR
References: