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

September 20, 2023 updated by: iTeos Belgium SA

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

Part 1 of the study determines the optimal dose of inupadenant to be given in combination with carboplatin and pemetrexed to patients that progressed after receiving specific first line treatments for Stage 3 or metastatic non-small cell lung cancer. Part 2 compares the efficacy of inupadenant to placebo when both are combined with carboplatin and pemetrexed for patients that progressed after receiving the same first line treatments for Stage 3 or metastatic non-small cell lung cancer.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In both Part 1 and Part 2, there are two nonsquamous NSCLC patient populations eligible for the study treatment: 1)patients with Stage III, non-resectable cancer that have received chemoradiotherapy, followed by durvalumab, and then have progressed; 2)patients who have received only first-line immunotherapy with anti-PD-L1 therapy, but no chemotherapy, in the metastatic setting, then progressed.

In Part 1, all participants receive open-label inupadenant with standard of care doses of carboplatin and pemetrexed. Carboplatin is given at q3week intervals for no more than 4 cycles; pemetrexed continues at q3week as prescribed by the Investigator. Inupadenant is given orally BID. Dose-limiting toxicities are monitored during the first 21 days of treatment and a modified 3+3 escalation method is utilized to determine the recommended phase 2 dose (RP2D). Imaging and safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

Part 2 is double-blinded, with subjects randomized 1:1 to receive the RP2D of inupadenant or matched placebo. All subjects receive the carboplatin and pemetrexed per standard of care. Imaging, safety and PRO assessments are performed during the treatment and follow-up phase. Treatment continues until progression, withdrawal of consent, start of new anti-cancer treatment, end of study, or death.

In both Parts 1 and 2, blood samples are drawn to further define the pharmacokinetic profile of inupadenant and biosamples are collected for additional exploratory analyses.

Study Type

Interventional

Enrollment (Estimated)

192

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Belgium
      • Gent, Belgium, 9000
        • Recruiting
        • Algemeen Ziekenhuis Sint-Lucas
        • Principal Investigator:
          • Elke Govaerts
      • Hasselt, Belgium, 3500
        • Recruiting
        • Jessa Ziekenhuis
        • Principal Investigator:
          • Kristof Cuppens, MD MSc
      • Mechelen, Belgium, 2800
        • Recruiting
        • Algemeen Ziekenhuis Sint-Maarten
        • Principal Investigator:
          • Marc Lambrechts
      • Mons, Belgium, 7000
        • Recruiting
        • C.H.U. Ambroise Pare
        • Principal Investigator:
          • Stephane Hobrechts
      • Namur, Belgium, 5000
        • Recruiting
        • CHU UCL Namur
        • Principal Investigator:
          • Jean-Charles Goeminne, MD
      • Roeselare, Belgium, 8800
        • Recruiting
        • AZ Delta
        • Principal Investigator:
          • Ingel Demedts, MD, PhD
  • Canada
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
        • Recruiting
        • William Osler Health System
        • Principal Investigator:
          • Kristin Perdrizet, MD
  • Czechia
      • Olomouc, Czechia, 77500
        • Recruiting
        • Fakultni nemocnice Olomouc
        • Contact:
        • Principal Investigator:
          • Bohuslav Melichar, MD
      • Praha, Czechia, 116401
        • Recruiting
        • Všeobecná fakultní nemocnice
        • Principal Investigator:
          • Milada Zemanova, MD
      • Praha, Czechia, 1300
        • Recruiting
        • Všeobecná fakultní nemocnice
        • Principal Investigator:
          • Milada Zemanova
  • France
      • Bordeaux, France, 33076
        • Recruiting
        • Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
        • Principal Investigator:
          • Sophie Cousin, MD
        • Contact:
          • Phone Number: 05.56.33.33.33
      • Bordeaux, France, 33075
        • Recruiting
        • Hopital Saint Andre - CHU de Bordeaux
        • Principal Investigator:
          • Charlotte Domblides, MD
      • Caen, France, 14003
        • Recruiting
        • CHU de Caen
        • Contact:
          • Phone Number: 02 31 06 54 37
        • Principal Investigator:
          • Simon DeShayes
      • Dijon, France, 21079
        • Recruiting
        • Centre GEORGES FRANÇOIS LECLERC
        • Principal Investigator:
          • Laure FAVIER, MD
      • Marseille, France, 13385
        • Recruiting
        • Hopital Nord de Marseille
        • Contact:
          • AdmTrials-MultiOnco@ap-hm.fr
        • Principal Investigator:
          • Laurent Greillier, MD, PhD
      • Saint-Mandé, France, 94160
        • Recruiting
        • HIA Begin
        • Principal Investigator:
          • Carole Helissey-Danis, MD
  • Italy
      • Brescia, Italy, 25123
        • Recruiting
        • Azienda Ospedaliera Spedali Civili di Brescia
        • Principal Investigator:
          • Alfredo Berruti
      • Lucca, Italy, 55100
        • Recruiting
        • Ospedale San Luca
        • Principal Investigator:
          • Editta Baldini, MD
      • Milan, Italy, 20133
        • Recruiting
        • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
        • Principal Investigator:
          • claudia Maria Regina Bareggi, MD
      • Milano, Italy, 20133
        • Recruiting
        • Istituto Nazionale dei Tumori
        • Principal Investigator:
          • Giuseppe Lo Russo, MD PhD
      • Peschiera del Garda, Italy, 37019
        • Recruiting
        • Oncologia Casa Di Cura Polispecialistica Dott Pederzoli
        • Principal Investigator:
          • Elisa Roca
      • Rozzano, Italy, 20089
        • Recruiting
        • Gruppo Humanitas - Istituto Clinico Humanitas
        • Principal Investigator:
          • Luca Toschi, MD
  • Poland
      • Krakow, Poland, 31-826
        • Recruiting
        • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie Sp. z o.o
        • Contact:
        • Principal Investigator:
          • Marek Jasiowka, MD
      • Oświęcim, Poland, 32-600
        • Recruiting
        • Nzoz Formed 2
        • Contact:
        • Principal Investigator:
          • Marcin Kowalski, MD
      • Piła, Poland, 64-920
        • Recruiting
        • NZOZ Ars Medical Sp. z o.o.
        • Principal Investigator:
          • Renata Surma-Wlodarczyk, MD
      • Poznan, Poland, 60-693
        • Recruiting
        • NZOZ Medpolonia Sp. Z o.o.
        • Principal Investigator:
          • Rodryg Ramlau
        • Contact:
      • Łódź, Poland, 90-549
        • Recruiting
        • Uniwersytet Medyczny w Lodzi Klinika Pulmonologii Ogolnej i Onkologicznej
        • Contact:
        • Principal Investigator:
          • Adam Antczak
    • Mazowieckie
      • Warszawa, Mazowieckie, Poland, 02-781
        • Recruiting
        • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie
        • Contact:
        • Principal Investigator:
          • Dariusz Kowalski, MD
    • Warminsko-Mazurskie
      • Olsztyn, Warminsko-Mazurskie, Poland, 10-357
        • Recruiting
        • Warminsko Mazurskie Centrum Chorob Pluc w Olsztynie
        • Principal Investigator:
          • Jaroslaw Kolb-Sielecki
  • Spain
      • A Coruña, Spain, 15009
        • Recruiting
        • Centro Oncológico de Galicia
        • Contact:
        • Principal Investigator:
          • Margarita Amenedo Gancedo
      • Alicante, Spain, 03010
        • Recruiting
        • Hospital General Universitario de Alicante
        • Contact:
        • Principal Investigator:
          • Bartomeu Massuti Sureda, MD
      • Badajoz, Spain, 06080
        • Recruiting
        • Hospital Infanta Cristina
        • Principal Investigator:
          • Marta Gonzalez Cordero
        • Contact:
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Quiron Barcelona - Instituto Oncologico Baselga
        • Principal Investigator:
          • Enriqueta Felip, MD PhD
      • Castellón De La Plana, Spain, 12002
      • Lugo, Spain, 27003
        • Recruiting
        • Hospital Universitario Lucus Augusti
        • Principal Investigator:
          • Begona Campos Balea, MD
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
        • Principal Investigator:
          • Manuel Domine Gomez, MD
      • Manresa, Spain, 08243
        • Recruiting
        • Althaia Hospital
        • Principal Investigator:
          • Silvia Catot Tort, MD
        • Contact:
      • Ourense, Spain, 10090
        • Recruiting
        • Complejo Hospitalario Universitario de Ourense
        • Principal Investigator:
          • Maria Carmen Areses Manrique
      • Pamplona, Spain, 37008
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe de Valencia
        • Contact:
        • Principal Investigator:
          • Oscar Juan Vidal, MD
    • Illes Balears
      • Palma De Mallorca, Illes Balears, Spain, 07120
        • Recruiting
        • Hospital Universitario Son Espases
        • Principal Investigator:
          • Raquel Marsé, MD
  • Switzerland
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Centre Hospitalier Universitaire Vaudois
        • Principal Investigator:
          • Solange Peters, MD PhD
      • Villars-sur-Glâne, Switzerland, 1752
        • Recruiting
        • HFR Fribourg
        • Principal Investigator:
          • Alessandra Curioni-Fontecedro
      • Zürich, Switzerland, 8063
        • Recruiting
        • Stadt Zuerich Stadtspital Triemli
        • Principal Investigator:
          • Sebastian Kraus, MD
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Recruiting
        • Highlands Oncology Group
        • Contact:
        • Principal Investigator:
          • Eric Schaefer, MD
    • California
      • Whittier, California, United States, 90603
        • Recruiting
        • Innovative Clinical Research Institute (ICRI)
        • Principal Investigator:
          • Sami Ali
    • Florida
      • Orange City, Florida, United States, 32763
        • Recruiting
        • Mid-Florida Hematology & Oncology Centers, PA
        • Contact:
          • Phone Number: 386-774-1223
        • Principal Investigator:
          • Santosh Nair, MD
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Contact:
          • Clinical Trial Navigator
          • Phone Number: 813-745-6100
        • Principal Investigator:
          • Albert Chiappori, MD
    • Nebraska
      • Omaha, Nebraska, United States, 68310
    • New Jersey
      • Florham Park, New Jersey, United States, 07932
        • Recruiting
        • Summit Medical Group PA
        • Contact:
        • Principal Investigator:
          • William DeRosa, MD
    • North Carolina
      • Fayetteville, North Carolina, United States, 28303
        • Recruiting
        • Carolina Institute for Clinical Research
        • Contact:
        • Principal Investigator:
          • Kenneth Manning, MD
    • Ohio
      • Canton, Ohio, United States, 44718
        • Recruiting
        • Gabrail Cancer & Research Center
        • Principal Investigator:
          • Nashat Gabrail, MD
        • Contact:
    • Pennsylvania
      • Gettysburg, Pennsylvania, United States, 17325
        • Recruiting
        • Gettysburg Cancer Center
        • Principal Investigator:
          • Satish Shah, MD
        • Contact:
    • Texas
      • Tyler, Texas, United States, 75701
        • Recruiting
        • UT Health East Texas HOPE Cancer Center
        • Contact:
          • Phone Number: 903-592-6152
        • Principal Investigator:
          • Arielle S Lee, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable (Stage III) NSCLC of nonsquamous pathology that has relapsed or progressed
  2. Measurable disease as defined by RECIST v1.1 criteria
  3. PD-L1 expression status available at or after the time of diagnosis of advanced or metastatic NSCLC disease
  4. Can provide existing biopsy taken within 2 years prior to entering trial or provide fresh biopsy

  5. Have relapsed or progressed after prior anti- PD-(L)1 therapy as follows:

    1. At least 12 weeks of treatment with only 1 line of anti-PD-(L)1 therapy (mono or combo) in the metastatic setting, without concomitant chemotherapy OR
    2. At least 12 weeks of single-agent durvalumab
  6. Adequate organ function
  7. ECOG performance status of 0 to 1.

Exclusion Criteria:

  1. Symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease.
  2. Presence of active second malignancy
  3. EGFR or ALK mutation. Participants with presence of other driver mutations are allowed if targeted therapy is not available as per local standard of care.
  4. Preexisting gastrointestinal disorders/conditions that may interfere with ingestion or absorption of oral medications.
  5. History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis, except for Grade 1 pneumonitis from prior chemoradiation therapy (Stage III patients).
  6. History of or active autoimmune disease requiring systemic treatment in the last 6 months or persistent immune-mediated toxicity caused by checkpoint inhibitor therapy > Grade 2
  7. Known active or chronic hepatitis B or C infection unless adequately treated for at least 4 weeks with no detectable viral load; known infection with human immunodeficiency virus (HIV) unless receiving antiretroviral therapy with well-controlled disease.
  8. History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior therapy.
  9. Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids.
  10. Active infection requiring systemic therapy ≤ 7 days prior to first dose of study treatment.
  11. Any other oncologic treatments administered ≤14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment. Also, ongoing adverse effects from such treatment > Grade 1 with the exception for alopecia and Grade 2 peripheral neuropathy.
  12. Non-study related minor surgical procedure ≤7 days, or major surgical procedure of ≤ 5 weeks prior to first dose of study treatment.
  13. Uncontrolled or significant cardiovascular disease
  14. History of allergy or hypersensitivity to any of the study treatments.
  15. Treatment with a live or live attenuated vaccine.
  16. Treatment with moderate or strong inducers or inhibitor of CYP 3A4, inhibitors of P-glycoprotein, or substrates of breast cancer resistance protein
  17. Pregnant or breast-feeding
  18. Male and Female participants: Lack of agreement to use highly effective method of contraception during treatment and for 6 months after the last administration of chemotherapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Time Frame: At the end of Cycle 1 (each cycle is 21 days)
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]
Time Frame: 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.
Duration of intervention (up to 24 months) plus 30 days follow-up
Progression-free survival [Efficacy]
Time Frame: 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, which ever 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate [Efficacy]
Time Frame: 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
From randomization to first-documented radiological improvement, if applicable, assessed up to 24 months.
Duration of Response [Efficacy]
Time Frame: 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
From first-documented CR or PR to first radiological progression or date of death, whichever comes first, assessed up to 24 months.
Percent Change in Tumor Size [Efficacy]
Time Frame: 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
From randomization to the documented radiological assessment with the smallest tumor size sum, assessed up to 24 months.
Disease Control Rate [Efficacy]
Time Frame: 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
From randomization to second-documented radiological CR, PR or SD, if applicable, assessed up to 24 months.
Overall Survival [Efficacy]
Time Frame: From randomization to death due to any cause, assessed up to 24 months.
Time from randomization to date of death due to any cause.
From randomization to death due to any cause, assessed up to 24 months.
Efficacy (Patient Reported Outcomes)
Time Frame: Duration of intervention (up to 24 months) plus 30 days follow-up
Time to definitive deterioration in global health status/quality of life
Duration of intervention (up to 24 months) plus 30 days follow-up
Peak plasma concentration (Cmax)
Time Frame: From first dose of inupadenant through 24 hours
Cmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
From first dose of inupadenant through 24 hours
Time to peak plasma concentration (Tmax)
Time Frame: From first dose of inupadenant through 24 hours
Tmax for inupadenant and its primary metabolite as observed by assessment of concentration-time profile
From first dose of inupadenant through 24 hours
Plasma half-life (T-1/2)
Time Frame: At the end of Cycle 12 (each cycle is 3 weeks)
T-1/2 for inupadenant and its primary metabolite
At the end of Cycle 12 (each cycle is 3 weeks)
Area under the concentration-time curve (AUCinf)
Time Frame: At the end of Cycle 12 (each cycle is 3 weeks)
AUC from Time 0 extrapolated to infinity for inupadenant and its primary metabolite
At the end of Cycle 12 (each cycle is 3 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

iTeos Belgium SA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 26, 2022

Primary Completion (Estimated)

April 1, 2025

Study Completion (Estimated)

May 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)

September 21, 2023

Last Update Submitted That Met QC Criteria

September 20, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A2A-005

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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