Non-Inferiority Study of Reduced Dose Pembrolizumab Versus Standard Dose in Advanced Non-Small Cell Lung Carcinoma for Overall Survival Evaluation
- Trial ID
- 2024-516195-15-00
- Protocol
- 108439
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **non-inferiority** of a reduced dose of pembrolizumab compared to the standard of care dose in the treatment of advanced stage non-small cell lung carcinoma (**NSCLC**), specifically in terms of overall survival. This is clinically relevant as it may offer a more cost-effective treatment option without compromising patient outcomes.
Secondary objectives include:
- Developing immune checkpoint inhibitor response biomarkers, which could enhance personalized treatment strategies.
- Studying the possible effects of co-medication on treatment outcomes, which may provide insights into optimizing therapeutic regimens.
Participants
The clinical trial involves participants diagnosed with **advanced non-small cell lung cancer (NSCLC)**, focusing on individuals eligible for treatment with pembrolizumab according to ESMO guidelines. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a known PD-L1 status, determined through cytology or histology. The trial does not include vulnerable populations. Participants must not be breastfeeding, and both women of childbearing potential and sexually active males must adhere to specific contraceptive guidelines during and after the treatment period. The sponsor has not provided information regarding the total number of participants in the trial. The selection criteria ensure that participants are willing and able to comply with the study's scheduled visits, treatment schedules, and laboratory testing requirements.
Plans and Procedures
The clinical trial is designed to evaluate the **non-inferiority** of a reduced dose of **pembrolizumab** compared to the standard dose for the treatment of advanced non-small cell lung carcinoma (NSCLC). This is a phase III, randomized, double-blind, controlled trial. The trial is expected to run from November 18, 2020, to December 31, 2027. Participants will be randomly assigned to receive either the reduced dose or the standard dose of pembrolizumab, administered as an intravenous solution for infusion. The primary endpoint is the overall survival rate at one year.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, disease stage, and PD-L1 status. Following the screening, participants will attend regular follow-up visits to monitor treatment response and any adverse effects. The end-of-study visit will conclude the participant's involvement, assessing the final outcomes and overall survival. The expected length of participant involvement is up to 24 months, with conditions for early termination including non-compliance with the protocol, withdrawal of consent, or adverse events that necessitate discontinuation of treatment.
Key inclusion criteria require participants to have signed informed consent, be willing to comply with the study protocol, and have confirmed advanced NSCLC. Exclusion criteria are not specified. The trial aims to provide insights into the cost-effectiveness of dose tapering in immunotherapy for NSCLC, potentially influencing future treatment guidelines.
Treatment
The clinical trial involves the administration of **pembrolizumab**, marketed under the name KEYTRUDA, which is a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is intended for intravenous administration. The maximum daily dose of pembrolizumab is 400 mg, with a total maximum dose of 7200 mg over the course of the treatment. The treatment period is capped at 24 months. Pembrolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02, and is produced by Merck Sharp & Dohme B.V. The primary objective of the trial is to assess the non-inferiority of a reduced dose of pembrolizumab compared to the standard-of-care dose in terms of overall survival for patients with advanced stage non-small cell lung carcinoma (NSCLC).
Efficacy
Efficacy in the clinical trial titled "Dose tapering and Early Discontinuation to InCreAse cosT-effictIveness Of immunotherapy for Non-small cell lung carcinoma trial number 1 (NVALT-30 - Dedication-1)" will be assessed primarily through the evaluation of the **overall survival** rate at one year. This parameter serves as the primary endpoint to determine the non-inferiority of a reduced dose of **pembrolizumab** compared to the standard of care dose in the treatment of advanced stage non-small cell lung carcinoma (NSCLC). The trial is designed as a phase III non-inferiority study, focusing on the potential for dose reduction without compromising patient survival outcomes.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal participant care.
- Participants must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
- Subjects with cytologically or histologically confirmed advanced stage or recurrent NSCLC (per the 8th International Association for the Study of Lung Cancer classification), eligible for treatment with pembrolizumab in line with ESMO guidelines.
- Known PD-L1 status (performed on cytology or histology).
- Subjects are aged ≥ 18 years.
- Women must not be breastfeeding.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of 5 months (30 days of ovulatory cycle plus the time required for the investigational drug to undergo five half-lives) after end of pembrolizumab treatment.
- Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of 7 months (90 days plus the time required for pembrolizumab to undergo five half-lives) after the last dose of investigational drug. In addition, male participants must be willing to refrain from sperm donation during this time.
Exclusion Criteria
- Subjects with symptomatic untreated CNS metastases are excluded. i) Subjects are eligible if CNS metastases are asymptomatic or adequately treated and neurological symptoms have returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrolment. ii) In addition, participants must be either off corticosteroids, or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) for at least 2 weeks prior to treatment assignment.
- Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrolment. Inhaled or topical steroids, and steroids for adrenal replacement therapy are permitted.
- A known CD4+ T-cell count of less than 100 cells/μL (CD4+ T cell count measurement is not required for patients without a history of low CD4+ T cell counts or HIV).
- Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Treatment with adjuvant or neoadjuvant chemotherapy 3 months prior to enrolment.
- Non-palliative treatment with chemoradiation for locally advanced disease 3 months prior to enrolment. Palliative radiotherapy is allowed any time.
- Women of childbearing potential (WOCBP) with a known pregnancy or a positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) prior to the start of study treatment.
- History of allergy or hypersensitivity to study drug components.
- Subjects may not have previously received a solid organ transplantation.
- Total body weight <40 or >140 kg.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Not Recruiting | 18 Nov 2020 | — |
| Netherlands | — | — | 750 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 400 | 24 | PRD4323105 |