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

NCT07633613 | Not Yet Recruiting Phase 4

• 2 other identifiers: 2023/602026-526866-26-00
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Non-Small Cell Lung Carcinoma (NSCLC); Metastatic Head and Neck Squamous Cell Carcinoma

Keywords

Pembrolizumab; immunotherapy; salvage chemotherapy; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) at 3 months after initiation of salvage chemotherapy (RECIST v1.1)

  Objective response rate (ORR) includes the proportion of patients achieving complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. Tumor response will be assessed using routine imaging performed during standard clinical follow-up care. ORR will be analyzed in relation to residual pembrolizumab (anti-PD-1) serum concentration measured 21 days after the last administration of pembrolizumab (P1), immediately prior to initiation of salvage chemotherapy.

  3 months after initiation of salvage chemotherapy

Study Arms (1)

Residual Pembrolizumab Exposure Assessment

EXPERIMENTAL

Biological: Blood sampling; Procedure: Tumor biopsies for biobank establishment (optional)

Interventions

Blood sampling BIOLOGICAL

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.

Residual Pembrolizumab Exposure Assessment

Tumor biopsies for biobank establishment (optional) PROCEDURE

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 least 3 weeks of chemotherapy exposure. Due to logistical constraints, these biopsies will be proposed to patients followed at CAL. They will be performed primarily in the interventional radiology department of CAL.

Residual Pembrolizumab Exposure Assessment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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.

You may not qualify if:

• 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),
• 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.

Sponsors & Collaborators

• Centre Antoine Lacassagne: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Marine SIRVENT

CONTACT

+33 4 92 03 17 78; DRCI-Promotion@nice.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 8, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 8, 2026

Record last verified: 2026-05