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
- RECRUITING
- Sex
- All
- Target Recruitment
- 186
- 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 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 Disease Control Rate [Efficacy] From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months. Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1
Overall Response Rate [Efficacy] From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months. 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. 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. Change in sum of size of target tumors from baseline, per RECIST v1.1
Overall Survival [Efficacy] From randomization to death due to any cause, assessed up to 24 months. Time from randomization to date of death due to any cause.
Efficacy (Patient Reported Outcomes) Duration of intervention (up to 24 months) plus 30 days follow-up Time to definitive deterioration in global health status/quality of life
Peak plasma concentration (Cmax) From first dose of inupadenant through 24 hours Cmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
Time to peak plasma concentration (Tmax) From first dose of inupadenant through 24 hours Tmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
Plasma half-life (T-1/2) At the end of Cycle 12 (each cycle is 3 weeks) T-1/2 for inupadenant and its primary metabolite
Area under the concentration-time curve (AUCinf) At the end of Cycle 12 (each cycle is 3 weeks) AUC from Time 0 extrapolated to infinity for inupadenant and its primary metabolite
Trial Locations
- Locations (67)
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
Innovative Clinical Research Institute (ICRI)
🇺🇸Whittier, California, United States
Mid-Florida Hematology & Oncology Centers, PA
🇺🇸Orange City, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Oncology Hematology West P.C. dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Summit Medical Group PA
🇺🇸Florham Park, New Jersey, United States
Carolina Institute for Clinical Research (Cumberland County Hospital System)
🇺🇸Fayetteville, North Carolina, United States
Gabrail Cancer & Research Center
🇺🇸Canton, Ohio, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
UT Health East Texas HOPE Cancer Center
🇺🇸Tyler, Texas, United States
Algemeen Ziekenhuis Sint-Maarten
🇧🇪Mechelen, Antwerp, Belgium
Algemeen Ziekenhuis Sint-Lucas
🇧🇪Gent, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
C.H.U. Ambroise Paré
🇧🇪Mons, Belgium
CHU UCL Namur - site Sainte-Elisabeth
🇧🇪Namur, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
University of Alberta - Cross Cancer Institute (CCI)
🇨🇦Edmonton, Alberta, Canada
William Osler Health System
🇨🇦Brampton, Ontario, Canada
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Czechia
Vseobecna Fakultni Nemocnice
🇨🇿Praha 3, Czechia
Hopital Saint André - CHU de Bordeaux
🇫🇷Bordeaux, France
Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, France
CHU de Caen
🇫🇷Caen, France
Centre Hospitalier Intercommunal de Creteil
🇫🇷Créteil, France
Centre Georges François Leclerc
🇫🇷Dijon, France
Centre Leon Berard
🇫🇷Lyon, France
Hopital de la Timone Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)
🇫🇷Marseille, France
CHU Nantes
🇫🇷Nantes, France
Hôpital d'Instruction des Armées Bégin (HIA Bégin)
🇫🇷Saint-Mandé, France
Universitätsklinikum Gießen Und Marburg Gmbh (UKGM)
🇩🇪Giessen, Hessen, Germany
Klinikum Chemnitz
🇩🇪Chemnitz, Germany
Evang. Kliniken Essen Mitte GmbH
🇩🇪Essen, Germany
Thoraxklinik-Heidelberg Ggmbh
🇩🇪Heidelberg, Germany
Althaia Hospital
🇪🇸Manresa, Spain
Kliniken der Stadt Köln gGmbH
🇩🇪Köln, Germany
Klinik Loewenstein gGmbH, Klinik für Thorakale Onkologie und Palliativmedizin
🇩🇪Lowenstein, Germany
Azienda Ospedaliera San Giuseppe Moscati
🇮🇹Avellino, Italy
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Italy
Ospedale San Luca
🇮🇹Lucca, Italy
Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico
🇮🇹Milan, Italy
AOU San Luigi Gonzaga - SCDU
🇮🇹Orbassano, Italy
Oncologia Casa Di Cura Polispecialistica Dott Pederzoli
🇮🇹Peschiera del Garda, Italy
Gruppo Humanitas - Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
🇵🇱Warszawa, Mazowieckie, Poland
Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
🇵🇱Olsztyn, Warminsko-Mazurskie, Poland
NZOZ Medpolonia Sp. Z o.o.
🇵🇱Poznan, Wielkopolskie, Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o
🇵🇱Krakow, Poland
Nzoz Formed 2
🇵🇱Oświęcim, Poland
NZOZ Ars Medical Sp. z o.o.
🇵🇱Piła, Poland
Uniwersytet Medyczny w Lodzi Klinika Pulmonologii Ogolnej i Onkologicznej
🇵🇱Łódź, Poland
Hospital Universitari Son Espases
🇪🇸Palma De Mallorca, Illes Balears, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Infanta Cristina (Hospital Universitario de Badajoz)
🇪🇸Badajoz, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Consorcio Hospitalario Provincial de Castellon
🇪🇸Castellón De La Plana, Spain
Centro Oncologico de Galicia
🇪🇸Coruña, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario de Ourense
🇪🇸Ourense, Spain
Complejo Hospitalario de Navarra (CHN)
🇪🇸Pamplona, Spain
Hospital Universitario Marques De Valdecilla
🇪🇸Santander, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland
HFR Fribourg - Cantonal Hospital
🇨🇭Villars-sur-Glâne, Switzerland
Stadtspital Zürich Triemli
🇨🇭Zürich, Switzerland
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom