Dose Tapering and Early Discontinuation to InCreAse cosT-effectIveness Of Immunotherapy for NSCLC

NCT04909684 | Unknown Phase 3

• 2 other identifiers: NVALT30 / DEDICATION-12020-000493-15
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Immune checkpoint inhibitors have shown to improve the overall survival for patients with metastasized non-small cell lung carcinoma (NSCLC) but the optimal dosing and patient selection are still a matter of discussion. The pembrolizumab dose, for instance, may be reduced significantly without decreasing treatment efficacy. Furthermore, as approximately only half of all patients responds to treatment, there is an urgent need to develop (early) treatment response prediction markers to select those who benefit from treatment. Objective: Primary: to investigate the non-inferiority of pembrolizumab 75% versus pembrolizumab 100% in terms of overall survival. Secondary: to develop biomarkers that predict immunotherapy treatment response. Study design: An open label randomized non-inferiority study. Study population: 750 patients with NSCLC, eligible for treatment with pembrolizumab, in line with the current ESMO clinical practice guidelines. Intervention: Patients will be randomized to standard of care (100%) versus reduced dose (approx. 75%, depending on treatment schedule) pembrolizumab. Main study parameters/endpoints: One-year overall survival rate

Conditions

NSCLC

Keywords

pembrolizumab; immunotherapy; biomarkers; dose tapering

Outcome Measures

Primary Outcomes (1)

• One-year overall survival rate

  Percentage of patients alive after one year.

  At least one year or until death, whichever comes first.

Secondary Outcomes (6)

• Median overall survival

  At least one year or until death, whichever comes first.

• Two-year overall survival rate

  At least one year or until death, whichever comes first.

• Best overall response rate

  At least one year or until death, whichever comes first.

• Disease control rate

  At 3, 6 and 12 months

• Duration of treatment

  At least one year or until death, whichever comes first.

Study Arms (2)

Standard of care

NO INTERVENTION

100% pembrolizumab

Intervention

EXPERIMENTAL

75% pembrolizumab

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

The approved doses of 400 mg every 6 weeks (Q6W) and 200 mg every 3 weeks (Q3W) will be decreased to a 300 mg Q6W dose. The approved dose of 150 mg Q3W will be decreased to a 100 mg Q3W dose.

Intervention

Eligibility Criteria

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

You may qualify if:

• 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 of NSCLC with pembrolizumab in line with ESMO guidelines.
• Prior adjuvant or neoadjuvant chemotherapy is permitted as long as the last administration of the prior regimen occurred at least 3 months prior to enrolment.
• Prior chemoradiation for locally advanced disease is also permitted as long as the last administration of chemotherapy or radiotherapy (which ever was given last) occurred at least 3 months prior to enrolment.
• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Males and Females, ages 18 years (or age of majority) and older.
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study treatment.
• 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).
• 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.

You may not qualify if:

• Subjects with symptomatic untreated CNS metastases are excluded. Subjects are eligible if CNS metastases are asymptomatic and / or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrolment.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 (see list below) within 14 days of enrolment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted.
• a CD4+ T-cell count of less than 100 cells/μL
• 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.
• 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
• Absence of or unknown PD-L1 status

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Society of Physicians for Pulmonology and Tuberculosis: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Gelderland, 6500 HB, Netherlands

RECRUITING

MeSH Terms

Interventions

pembrolizumab

Study Officials

• Michel vd Heuvel, prof.

  Head of Department

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Olinde Hermans

CONTACT

(024) 361 45 79; Researchunit.long@radboudumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: June 2, 2021
• Study Start: November 18, 2020
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: April 11, 2024

Record last verified: 2023-07

Locations

NL (1)