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)

Overview

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.

Primary outcome measures

• Pembrolizumab efficiency Month 2 [Time frame: month 2]

Secondary outcome measures (3)

• Pembrolizumab efficiency Month 4 [Time frame: month 4]
• Pembrolizumab efficiency Month 12 [Time frame: month 12]
• Pembrolizumab toxicity Month 18 [Time frame: month 18]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Case-only

Study locations

France · 2 centers

• Angers University Hospital — Angers
• CH Le Mans — Le Mans

Identifiers

NCT: NCT06195527 · 49RC21_0253 · 2023-A02527-38

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗