Study of Inupadenant (EOS100850) With Chemotherapy as Second Line Treatment for Nonsquamous Non-small Cell Lung Cancer

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic NSCLC - Non-Small Cell Lung Cancer; Locally Advanced NSCLC - Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: inupadenant; Drug: Carboplatin; Drug: Pemetrexed; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Algemeen Ziekenhuis Sint-Lucas
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis
  • Roeselare, Belgium, 8800
    • AZ Delta
• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System
• Czechia
  • Praha 3, Czechia, 116401
    • Vseobecna Fakultni Nemocnice
• France
  • Caen, France, 14003
    • CHU de Caen
  • Marseille, France, 13005
    • Hopital de la Timone Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)
  • Nantes, France, 44093
    • CHU Nantes
• Italy
  • Milano, Italy, 20133
    • Istituto Nazionale dei Tumori
  • Rozzano, Italy, 20089
    • Gruppo Humanitas - Istituto Clinico Humanitas
• Spain
  • Badajoz, Spain, 06080
    • Hospital Infanta Cristina (Hospital Universitario de Badajoz)
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Coruña, Spain, 15009
    • Centro Oncologico de Galicia
  • Manresa, Spain, 08243
    • Althaia Hospital
  • Ourense, Spain, 10090
    • Complejo Hospitalario Universitario De Ourense
  • Pamplona, Spain, 37008
    • Complejo Hospitalario de Navarra (CHN)
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Illes Balears
    • Palma De Mallorca, Illes Balears, Spain, 07120
      • Hospital Universitari Son Espases
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, open label; Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).	Drug: inupadenant; Adenosine 2a receptor antagonist; Other Names: EOS100850; Drug: Carboplatin; standard of care chemotherapeutic, alkylating agent; Drug: Pemetrexed; standard of care chemotherapeutic, anti-metabolite; Other Names: Alimta
Experimental: Part 2, active treatment; Treatment with inupadenant combined with carboplatin and pemetrexed	Drug: inupadenant; Adenosine 2a receptor antagonist; Other Names: EOS100850; Drug: Carboplatin; standard of care chemotherapeutic, alkylating agent; Drug: Pemetrexed; standard of care chemotherapeutic, anti-metabolite; Other Names: Alimta
Placebo Comparator: Part 2, placebo; Treatment with matched placebo combined with carboplatin and pemetrexed	Drug: Carboplatin; standard of care chemotherapeutic, alkylating agent; Drug: Pemetrexed; standard of care chemotherapeutic, anti-metabolite; Other Names: Alimta; Drug: Placebo; matched placebo capsule to inupadenant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-finding to determine recommended Phase 2 dose	Incidence of dose-limiting toxicities	At the end of Cycle 1 (each cycle is 21 days)
Progression-free survival [Efficacy]	Time from first dose to the date of first documented radiologic progression per RECIST v1.1 or time of death, whichever comes first	From randomization to first-documented radiological progression or date of death from any cause, whichever comes first, assessed up to 24 months.
Incidence of treatment-emergent adverse events [Safety and Tolerability]	Incidence of adverse events (AEs), serious adverse events, AEs leading to discontinuation, deaths, and clinically significant laboratory abnormalities.	Duration of intervention (up to 24 months) plus 30 days follow-up or up to database lock

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate [Efficacy]	Proportion of participants with a best overall response of complete (CR) or partial (PR) response as assessed by RECIST v1.1	From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months or up to database lock.
Duration of Response [Efficacy]	Time from first CR or PR to first documented progression or death from any cause, per RECIST v1.1	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.
Percent Change in Tumor Size [Efficacy]	Change in sum of size of target tumors from baseline, per RECIST v1.1	From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months or up to database lock.
Disease Control Rate [Efficacy]	Proportion of participants with CR, PR, or stable disease (SD) sustained over at least 2 consecutive tumor assessments, per RECIST v1.1	From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months or up to database lock.
Overall Survival [Efficacy]	Time from randomization to date of death due to any cause.	From randomization to death due to any cause, assessed up to 24 months or up to database lock.

Collaborators and Investigators

• Sponsor: iTeos Therapeutics
• Collaborators: iTeos Belgium SA
• Investigators: Study Director: Iteos Clinical Trials, iTeos Belgium SA

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2022
• Primary Completion (Actual): June 13, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: May 18, 2022
• First Submitted That Met QC Criteria: May 31, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: July 30, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: immunotherapy; adenosine; non-squamous NSCLC; second line; 2L
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Pemetrexed; Carboplatin
• Other Study ID Numbers: A2A-005; 2024-515393-27-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No