Clinical trial NCT05403385: Study of Inupadenant (EOS100850) with Chemotherapy As Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer
Official title: A Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating Efficacy and Safety of Inupadenant in Combination with Carboplatin and Pemetrexed in Adults with Nonsquamous Non-small Cell Lung Cancer Who Have Progressed on Immunotherapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer
Locally Advanced NSCLC - Non-Small Cell Lung Cancer
Keywords: non-squamous NSCLC
second line
2L
adenosine
immunotherapy
Lead sponsor: iTeos Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: iTeos Belgium SA
First posted: 2022-06-03
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single Group Assignment Part 1 sequential dose escalation. Part 2 randomized double-blind.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Dose-finding to determine recommended Phase 2 dose
timeFrame: At the end of Cycle 1 (each cycle is 21 days)
measure: Incidence of treatment-emergent adverse events [Safety and Tolerability]
timeFrame: Duration of intervention (up to 24 months) plus 30 days follow-up
measure: Progression-free survival [Efficacy]
timeFrame: From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Secondary outcomes:
measure: Overall Response Rate [Efficacy]
timeFrame: From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months.
measure: Duration of Response [Efficacy]
timeFrame: From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months.
measure: Percent Change in Tumor Size [Efficacy]
timeFrame: From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months.
measure: Disease Control Rate [Efficacy]
timeFrame: From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months.
measure: Overall Survival [Efficacy]
timeFrame: From randomization to death due to any cause, assessed up to 24 months.
measure: Efficacy (Patient Reported Outcomes)
timeFrame: Duration of intervention (up to 24 months) plus 30 days follow-up
measure: Peak plasma concentration (Cmax)
timeFrame: From first dose of inupadenant through 24 hours
measure: Time to peak plasma concentration (Tmax)
timeFrame: From first dose of inupadenant through 24 hours
measure: Plasma half-life (T-1/2)
timeFrame: At the end of Cycle 12 (each cycle is 3 weeks)
measure: Area under the concentration-time curve (AUCinf)
timeFrame: At the end of Cycle 12 (each cycle is 3 weeks)
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Whittier
country: United States
facility: Innovative Clinical Research Institute (ICRI)
state: California
city: Orange City
country: United States
facility: Mid-Florida Hematology & Oncology Centers, PA
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Omaha
country: United States
facility: Oncology Hematology West P.C. dba Nebraska Cancer Specialists
state: Nebraska
city: Florham Park
country: United States
facility: Summit Medical Group PA
state: New Jersey
city: Fayetteville
country: United States
facility: Carolina Institute for Clinical Research (Cumberland County Hospital System)
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer & Research Center
state: Ohio
city: Gettysburg
country: United States
facility: Gettysburg Cancer Center
state: Pennsylvania
city: Tyler
country: United States
facility: UT Health East Texas HOPE Cancer Center
state: Texas
city: Mechelen
country: Belgium
facility: Algemeen Ziekenhuis Sint-Maarten
state: Antwerp
city: Gent
country: Belgium
facility: Algemeen Ziekenhuis Sint-Lucas
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Mons
country: Belgium
facility: C.H.U. Ambroise Paré
city: Namur
country: Belgium
facility: CHU UCL Namur - site Sainte-Elisabeth
city: Roeselare
country: Belgium
facility: AZ Delta
city: Edmonton
country: Canada
facility: University of Alberta - Cross Cancer Institute (CCI)
state: Alberta
city: Brampton
country: Canada
facility: William Osler Health System
state: Ontario
city: Olomouc
country: Czechia
facility: Fakultni nemocnice Olomouc
city: Praha 3
country: Czechia
facility: Vseobecna Fakultni Nemocnice
city: Bordeaux
country: France
facility: Hopital Saint André - CHU de Bordeaux
city: Bordeaux
country: France
facility: Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
city: Caen
country: France
facility: CHU de Caen
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Creteil
city: Dijon
country: France
facility: Centre Georges François Leclerc
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Hopital de la Timone Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)
city: Nantes
country: France
facility: CHU Nantes
city: Saint-Mandé
country: France
facility: Hôpital d'Instruction des Armées Bégin (HIA Bégin)
city: Giessen
country: Germany
facility: Universitätsklinikum Gießen Und Marburg Gmbh (UKGM)
state: Hessen
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz
city: Essen
country: Germany
facility: Evang. Kliniken Essen Mitte GmbH
city: Heidelberg
country: Germany
facility: Thoraxklinik-Heidelberg Ggmbh
city: Köln
country: Germany
facility: Kliniken der Stadt Köln gGmbH
city: Lowenstein
country: Germany
facility: Klinik Loewenstein gGmbH, Klinik für Thorakale Onkologie und Palliativmedizin
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia
city: Lucca
country: Italy
facility: Ospedale San Luca
city: Milano
country: Italy
facility: Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Fondazione Irccs Ca Granda Ospedale Maggiore Policlinico
city: Orbassano
country: Italy
facility: AOU San Luigi Gonzaga - SCDU
city: Peschiera del Garda
country: Italy
facility: Oncologia Casa Di Cura Polispecialistica Dott Pederzoli
city: Rozzano
country: Italy
facility: Gruppo Humanitas - Istituto Clinico Humanitas
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
state: Mazowieckie
city: Olsztyn
country: Poland
facility: Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
state: Warminsko-Mazurskie
city: Poznan
country: Poland
facility: NZOZ Medpolonia Sp. Z o.o.
state: Wielkopolskie
city: Krakow
country: Poland
facility: Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o
city: Oświęcim
country: Poland
facility: Nzoz Formed 2
city: Piła
country: Poland
facility: NZOZ Ars Medical Sp. z o.o.
city: Łódź
country: Poland
facility: Uniwersytet Medyczny w Lodzi Klinika Pulmonologii Ogolnej i Onkologicznej
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Illes Balears
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina (Hospital Universitario de Badajoz)
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Castellón De La Plana
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
city: Coruña
country: Spain
facility: Centro Oncologico de Galicia
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Manresa
country: Spain
facility: Althaia Hospital
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Ourense
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra (CHN)
city: Santander
country: Spain
facility: Hospital Universitario Marques De Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Villars-sur-Glâne
country: Switzerland
facility: HFR Fribourg - Cantonal Hospital
city: Zürich
country: Switzerland
facility: Stadtspital Zürich Triemli
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust
Study officials:
affiliation: iTeos Belgium SA
name: Iteos Clinical Trials
role: STUDY_DIRECTOR
References: