Pharmacokinetic Study of Pembrolizumab and Its Impact on Immunity and the Tumor Microenvironment, Which May Explain the Efficacy of Post-immunotherapy Chemotherapy.

Обзор

This is a single-center pharmacokinetic study evaluating the impact of residual pembrolizumab levels on the efficacy of salvage chemotherapy following immunotherapy in patients with non-small cell lung cancer (NSCLC) or recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) not amenable to curative local treatment.

Вмешательства

• Биопрепарат Blood sampling
  Patients will be followed according to standard clinical care. Biological samples collected include: (1) pharmacokinetic and extracellular vesicle analyses: 10 mL blood samples in EDTA tubes at 21±3, 35±3, 49±3, and 63±3 days after the last pembrolizumab administration (P1-P4); (2) pharmacogenetic analysis: one baseline 5 mL EDTA blood sample; (3) cytokine and immune cell analyses: at P1 and P4, collection of 2×4 mL lithium heparin tubes, 1×10 mL EDTA tube, and 1×5 mL dry tube.
• Процедура Tumor biopsies for biobank establishment (optional)
  Depending on feasibility of the procedure, and at the discretion of the investigator, two biopsies will be performed in 20 consenting patients: * Biopsy B1: between the last administration of pembrolizumab (Day 0) and before initiation of standard salvage chemotherapy, * Biopsy B2: after initiation of salvage chemotherapy, at Day 63 ± 7 days after the last administration of pembrolizumab. If chemotherapy is discontinued prematurely, Biopsy B2 may only be performed if the patient has received at

Первичные конечные точки

• Objective response rate (ORR) at 3 months after initiation of salvage chemotherapy (RECIST v1.1) [Срок оценки: 3 months after initiation of salvage chemotherapy]

Критерии участия

Критерии включения

\- Patients over 18 years of age

\- Patients diagnosed with :

• Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma.
• Head and neck squamous cell carcinoma, p16-negative for oropharyngeal tumors.

• Recurrent and/or metastatic tumor not amenable to curative locoregional treatment.
• Disease progression under Pembrolizumab immunotherapy, administered at the standard dose of 200 mg every 3 weeks, as first-line treatment for metastatic disease, regardless of the number of cycles received, either as monotherapy or in combination with chemotherapy, as defined below:

• For pulmonary adenocarcinomas: i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin or Cisplatin) and Pemetrexed

ii. Maintenance therapy with Pembrolizumab, with or without Pemetrexed.

• For pulmonary squamous cell carcinomas: i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin) and Paclitaxel

+/- ii. Maintenance therapy with Pembrolizumab alone.

• For head and neck squamous cell carcinomas : i. First-line treatment with Pembrolizumab in combination with a platinum agent (Carboplatin or Cisplatin) ± 5-Fluorouracil (5-FU) or Paclitaxel

+/- ii. Maintenance therapy with Pembrolizumab alone.

• Eligibility for salvage chemotherapy within standard care:

• For pulmonary adenocarcinomas: weekly Paclitaxel, with or without Bevacizumab.
• For pulmonary squamous cell carcinomas: Gemcitabine monotherapy.
• For head and neck squamous cell carcinomas: weekly Paclitaxel and/or Cetuximab. Standard salvage chemotherapy may be initiated between Day 18 and Day 35 following the last Pembrolizumab injection, at standard doses.
• Measurable disease according to RECIST 1.1 criteria.
• Performance status (PS) 0 to 2.
• Baseline laboratory results meeting the usual criteria permitting initiation of salvage chemotherapy.
• Patients who has voluntarily agreed to participate in the study (including additional blood sampling) and has signed the informed consent form.
• For the subpopulation with accessible tissue biopsy:

• Patient agrees to undergo biopsy,
• INR < 1.5, Platelets > 50000/μL.
• Patients covered by a social security health insurance scheme.

Критерии исключения

• History of cancer, except for cancers in complete remission for more than 3 years, fully resected cutaneous basal cell carcinomas, or treated carcinoma in situ or cervical intraepithelial neoplasia (in situ cervical epithelioma),
• Patients participating in another clinical trial for which an exclusion period is specified,
• Minor patients,
• For the subpopulation with accessible tissue biopsy, patients receiving:

• Clopidogrel (hydrogen sulfate) or Prasugrel (hydrochloride) or Ticlopidine (hydrochloride) without the possibility of discontinuation for 5 days,

• Low-molecular-weight heparin (LMWH) without the possibility of dose suspension prior to the procedure,

• Or Fondaparinux without the possibility of discontinuation,

• Or Abciximab without the possibility of discontinuation for 24 hours and aPTT < 50s and ACT < 150s,

• Or Eptifibatide or Tirofiban hydrochloride monohydrate or Argatroban without the possibility of discontinuation 4 hours before the procedure,
• Or Bivalirudin without the possibility of discontinuation 2-3 hours before the procedure if CrCL > 50 mL/min, or 3-5 hours if CrCL < 50 mL/min,
• Or Dabigatran etexilate without the possibility of discontinuation 2-3 days before the procedure if CrCL > 50 mL/min, or 3-5 days if CrCL < 50 mL/min.
• Vulnerable persons as defined in Articles L1121-5 to L1121-8 :

• Pregnant women, women in labour, and breastfeeding mothers,
• Persons deprived of liberty by judicial or administrative decision, and persons hospitalized without consent under Articles L3212-1 and L3213-1 who do not fall under the provisions of Article L1121-8,
• Persons admitted to a health or social care institution for purposes other than research,
• Adults under legal protection measures or unable to express their consent.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07633613 · 2023/60 · 2026-526866-26-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗