NCT05255302

De-escalation Immunotherapy mAintenance Duration Trial for Stage IV Lung Cancer Patients With Disease Control After Chemo-immunotherapy Induction

A Phase II-III Randomized Trial Evaluating Maintenance Pembrolizumab (± Pemetrexed) Until Progression Versus Observation (± Pemetrexed) After 6 Months of Platinum-based Doublet Chemotherapy Plus Pembrolizumab Induction Treatment in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC)

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 1,360 (estimated)
• Sponsor: Intergroupe Francophone de Cancerologie Thoracique · Academic / Other
• Sex: All
• Age: 18 Years – 74 Years
• Healthy volunteers: Not accepted

Summary

Immunotherapeutic approaches recently have demonstrated clinical efficacy in several cancer types, including melanoma and NSCLC. As a matter of fact, first registration trials of immune-checkpoints inhibitors (ICI) in second-line settings (pembrolizumab as well as nivolumab or atezolizumab) had stated that ICI could be continued until disease progression or not tolerable toxicity, up to 5 years. This is only for the first-line registration studies that the arbitrary maximal duration of treatment of 2 years was set up by the Companies sponsoring such trials. The aim is to study a de-escalation scheme of treatment from 2 years of immunotherapy to 6 months (27-weeks), in patients with controlled disease.

Detailed description

This is a phase II-III randomized, open-labelled, multicentre study for NSCLC patients who are naive of treatment for advanced disease. Patients will be given first-line chemotherapy + pembrolizumab: platinum doublet for at least 3 cycles, either paclitaxel-carboplatin for patient with SCC or 3 cycles of pemetrexed-platinum salt followed by 2 cycles of pemetrexed and 6 cycles of pembrolizumab. Only patients with disease control, confirmed at 6 months (27-weeks) without drug-related toxicity imposing treatment discontinuation will be randomized 1:1 either to continuation of pembrolizumab (± pemetrexed for non-SCC) until disease progression or unacceptable toxicity or 2 years, or observation (± pemetrexed for non-SCC). Patients will be stratified by performance status (0 versus 1), histology (SCC versus non-SCC), PD-L1 (PD-L1 \< 1% versus 49%≥PD-L1 ≥ 1% versus PD-L1\>49%), sex and response at randomization (partial response versus stabilisation).

Conditions

• Metastatic NSCLC

Interventions

Type	Name	Description
DRUG	Pembrolizumab before randomization	Pembrolizumab 200 mg every 3 weeks before randomization
DRUG	Chemotherapy	Platinum doublet - 4 cycles: either paclitaxel-carboplatin for patient with SCC or pemetrexed-platinum salt followed by 2 cycles of pemetrexed until reaching the 6 months time-point for randomization Carboplatin AUC 5 for non-squamous cell carcinoma and AUC6 for squamous cell carcinoma every 3 weeks or cisplatin 75 mg/m² every 3 weeks Pemetrexed 500 mg/m² every 3 weeks or paclitaxel 175 mg/m² every 3 weeks
DRUG	Pemetrexed	Maintenance pemetrexed after randomization Pemetrexed 500 mg/m² every 3 weeks
DRUG	Pembrolizumab after randomization	Pembrolizumab 200 mg every 3 weeks after randomization

Timeline

• Start date: 2022-05-02
• Primary completion: 2025-05-01
• Completion: 2029-06-01
• First posted: 2022-02-24
• Last updated: 2025-04-01

Locations

44 sites across 1 country: France