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

• Status: Recruiting
• Trial end date: 2024-11-01
• Target enrollment: 0
• Participant gender: All

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 300 mg Q6W versus pembrolizumab 400 mg Q6W 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 (if applicable): Patients will be randomized to standard of care (400 mg Q6W or 200 mg Q3W dosing of pembrolizumab) versus reduced dose pembrolizumab (300 mg Q6W).

Main study parameters/endpoints: One-year overall survival rate

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Radboud University
• Collaborator: Dutch Society of Physicians for Pulmonology and Tuberculosis
• Treatments: Pembrolizumab

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 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.

Exclusion Criteria:

• 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