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

Overview

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.

Interventions

• Biological 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.
• Procedure 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

Primary outcome measures

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

Eligibility criteria

Inclusion criteria

\- 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.

Exclusion criteria

• 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.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗