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

Inclusion Criteria:

\- Patients over 18 years of age

\- Patients diagnosed with :

1. Non-small cell lung cancer (NSCLC), including adenocarcinoma and squamous cell carcinoma.
2. 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.