Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer
- Conditions
- Locally Advanced NSCLC - Non-Small Cell Lung CancerMetastatic NSCLC - Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT05403385
- Lead Sponsor
- iTeos Belgium SA
- Brief Summary
The study will first determine the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving first line anti-PD(L)1 treatment for locally advanced or metastatic non-small cell lung cancer. The efficacy and safety of the combination is then compared to standard of care carboplatin and pemetrexed in the same populations.
- Detailed Description
The study is composed of two parts. Part 1 follows an open-label, dose-finding design where individual cohorts are treated with various dose levels of inupadenant combined with standard of care dosing of carboplatin and pemetrexed. The recommended phase 2 dose is determined prior to initiation of Part 2 which then compares inupadenant to placebo with both arms treated in combination with standard of care carboplatin and pemetrexed.
Participants in both parts are enrolled from two populations of patients with nonsquamous NSCLC that have progressed after first line treatment as follows: non-resectable patients treated with chemoradiotherapy followed by anti-PD-(L)1 or metastatic patients treated with anti-PD-(L)1 therapy without chemotherapy.
Imaging, safety and PRO assessments are performed during the treatment and follow-up phase as well as pharmacokinetic and other exploratory analyses.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 36
- Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology
- Measurable disease as defined by RECIST v1.1
- PD-L1 expression status available at or after the time of diagnosis. All levels of expression are eligible.
- Existing biopsy taken within 4 years prior to entering trial or provide fresh biopsy where safe and feasible
- At least 12 weeks of treatment with only 1 anti-PD-(L)1 agent (mono or with IO combo) in the metastatic setting, OR at least 12 weeks of anti-PD-(L)1 agent (mono or with IO combo) following CRT in the unresectable, Stage III setting
- ECOG performance status of 0 to 1.
- Symptomatic central nervous system (CNS) metastases or leptomeningeal disease.
- EGFR, ALK, or ROS1 mutation.
- Autoimmune disease requiring systemic treatment or immunodeficiency requiring concurrent use of systemic immunosuppressants or corticosteroids
- Hepatitis B or C infection unless adequately treated with no detectable viral load; Human immunodeficiency virus (HIV) unless well-controlled disease on therapy.
- History of life-threatening toxicity related to prior immune therapy
- Uncontrolled or significant cardiovascular disease
- Pregnant or breast-feeding
- Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2, active treatment inupadenant Treatment with inupadenant combined with carboplatin and pemetrexed Part 1, open label inupadenant Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D). Part 2, active treatment Pemetrexed Treatment with inupadenant combined with carboplatin and pemetrexed Part 2, placebo Placebo Treatment with matched placebo combined with carboplatin and pemetrexed Part 1, open label Pemetrexed Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D). Part 1, open label Carboplatin Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D). Part 2, active treatment Carboplatin Treatment with inupadenant combined with carboplatin and pemetrexed Part 2, placebo Carboplatin Treatment with matched placebo combined with carboplatin and pemetrexed Part 2, placebo Pemetrexed Treatment with matched placebo combined with carboplatin and pemetrexed
- Primary Outcome Measures
Name Time Method Dose-finding to determine recommended Phase 2 dose At the end of Cycle 1 (each cycle is 21 days) Incidence of dose-limiting toxicities
Incidence of treatment-emergent adverse events [Safety and Tolerability] Duration of intervention (up to 24 months) plus 30 days follow-up or up to database lock Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.
Progression-free survival [Efficacy] From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months. Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, whichever comes first
- Secondary Outcome Measures
Name Time Method Overall Response Rate [Efficacy] From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months or up to database lock. Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1
Duration of Response [Efficacy] From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months or up to database lock. Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1
Percent Change in Tumor Size [Efficacy] From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months or up to database lock. Change in sum of size of target tumors from baseline, per RECIST v1.1
Disease Control Rate [Efficacy] From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months or up to database lock. Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1
Overall Survival [Efficacy] From randomization to death due to any cause, assessed up to 24 months or up to database lock. Time from randomization to date of death due to any cause.
Related Research Topics
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Trial Locations
- Locations (21)
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Algemeen Ziekenhuis Sint-Lucas
🇧🇪Gent, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
William Osler Health System
🇨🇦Brampton, Ontario, Canada
Vseobecna Fakultni Nemocnice
🇨🇿Praha 3, Czechia
CHU de Caen
🇫🇷Caen, France
Hopital de la Timone Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)
🇫🇷Marseille, France
CHU Nantes
🇫🇷Nantes, France
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