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

NCT05403385 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: A2A-0052024-515393-27-00
• Study Type: interventional
• Target: 36
• Locations: 8 countries
• Sites: 21

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.

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

Outcome Measures

Primary Outcomes (3)

• Dose-finding to determine recommended Phase 2 dose

  Incidence of dose-limiting toxicities

  At the end of Cycle 1 (each cycle is 21 days)

• 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

• 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.

Secondary Outcomes (5)

• Overall Response Rate [Efficacy]

  From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months or up to database lock.

• 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.

• 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.

• 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.

• Overall Survival [Efficacy]

  From randomization to death due to any cause, assessed up to 24 months or up to database lock.

Study Arms (3)

Part 1, open label

EXPERIMENTAL

Inupadenant will be given at one or more dose levels to determine the recommended Phase 2 dose (RP2D).

Drug: inupadenant; Drug: Carboplatin; Drug: Pemetrexed

Part 2, active treatment

EXPERIMENTAL

Treatment with inupadenant combined with carboplatin and pemetrexed

Drug: inupadenant; Drug: Carboplatin; Drug: Pemetrexed

Part 2, placebo

PLACEBO COMPARATOR

Treatment with matched placebo combined with carboplatin and pemetrexed

Drug: Placebo; Drug: Carboplatin; Drug: Pemetrexed

Interventions

inupadenant DRUG

Adenosine 2a receptor antagonist

Also known as: EOS100850

Part 1, open label; Part 2, active treatment

Placebo DRUG

matched placebo capsule to inupadenant

Part 2, placebo

Carboplatin DRUG

standard of care chemotherapeutic, alkylating agent

Part 1, open label; Part 2, active treatment; Part 2, placebo

Pemetrexed DRUG

standard of care chemotherapeutic, anti-metabolite

Also known as: Alimta

Part 1, open label; Part 2, active treatment; Part 2, placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• iTeos Therapeutics: lead
• iTeos Belgium SA: collaborator

Study Sites (21)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Algemeen Ziekenhuis Sint-Lucas

Ghent, 9000, Belgium

Location

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

AZ Delta

Roeselare, 8800, Belgium

Location

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Vseobecna Fakultni Nemocnice

Prague, 116401, Czechia

Location

CHU de Caen

Caen, 14003, France

Location

Hopital de la Timone Centre d'Essais Précoces en Cancérologie de Marseille (CEPCM)

Marseille, 13005, France

Location

CHU Nantes

Nantes, 44093, France

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Gruppo Humanitas - Istituto Clinico Humanitas

Rozzano, 20089, Italy

Location

Hospital Universitari Son Espases

Palma de Mallorca, Balearic Islands, 07120, Spain

Location

Complejo Hospitalario de Navarra (CHN)

Pamplona, Pamplona, 37008, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Valencia, 46026, Spain

Location

Centro Oncologico de Galicia

A Coruña, 15009, Spain

Location

Hospital Infanta Cristina (Hospital Universitario de Badajoz)

Badajoz, 06080, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Althaia Hospital

Manresa, 08243, Spain

Location

Complejo Hospitalario Universitario de Ourense

Ourense, 10090, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Iteos Clinical Trials

  iTeos Belgium SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple masking : The dose-finding part (Part 1) of this study is open-label whereas the randomized part (Part 2) is double-blinded. Therefore, for Part 2, the subject, the Investigator and Sponsor personnel or delegate(s) who are involved in the treatment administration or clinical evaluation of the subjects will be unaware of the group assignments. The chemotherapy agents administered during Part 2 will be open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group Assignment Part 1 sequential dose escalation. Part 2 randomized double-blind.

Study Record Dates

• First Submitted: May 18, 2022
• First Posted: June 3, 2022
• Study Start: August 26, 2022
• Primary Completion: June 13, 2025
• Study Completion: October 1, 2025
• Last Updated: August 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); US (2); CH (1); ES (8); IT (2); CA (1); BE (3); CZ (1)