First-in-Human Study of EOS100850 (Inupadenant) in Patients with Cancer (IO-001)

Phase I/Ib First-in-Human Study of EOS100850 (Inupadenant) As a Single Agent and in Combination with Pembrolizumab And/or Chemotherapy in Participants with Advanced Cancers

Multicenter, open-label, dose-escalation Phase I/Ib clinical study to evaluate the safety and tolerability, the MTD/RP2D, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of EOS100850 (Inupadenant) as a Single Agent and in Combination with Pembrolizumab and/or Chemotherapy in Participants with Advanced Cancers.

Study Overview

• Status: Completed
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: Pembrolizumab; Drug: EOS100850; Drug: Chemotherapy

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • UCL Saint-Luc
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
      • Hospital GZA Sint-Augustinus
  • Brussels
    • Anderlecht, Brussels, Belgium, 1070
      • Institut Jules Bordet
  • East-Flanders
    • Ghent, East-Flanders, Belgium, 9000
      • UZ Ghent
• France
  • Lyon, France, 69008
    • Centre de Lutte Contre le Cancer (CLCC) - Universite de Lyon - Centre Leon-Berard
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers - Hopital la Miletrie- Pôle Régional de Cancérologie
  • Saint-Herblain, France, 44805
    • Centre de Lutte Contre Le Cancer - Institut de Cancerologie de L'Ouest - Rene Gauducheau
  • Villejuif, France, 94805
    • Gustave Roussy
• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03722
    • Yonsei University Severance Hospital
  • Seoul, Korea, Republic of, 06591
    • St Mary's Hospital, The Catholic University of Korea
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Madrid, Spain, 28050
    • START Madrid-HM CIOCC Hospital Universitario HM Sanchinarro
  • Pamplona, Spain, 31008
    • Universidad de Navarra - Clinica Universitaria de Navarra
  • San Sebastián, Spain, 20014
    • Onkologikoa
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital
• United States
  • Michigan
    • Michigan Center, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center, Hackensack University Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

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

Description

For more information regarding participation in the Trial, please refer to your physician

Inclusion Criteria:

• Women and men ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Subject with histologically or cytologically confirmed advanced solid tumor for whom no standard treatment is further available.
• At least 4 weeks since any previous treatment for cancer
• Subject must consent to pretreatment and on treatment tumor biopsies
• Adequate organ and marrow function

Exclusion Criteria:

• Patients with primary brain tumors or primary tumors with central nervous system metastases as only location of disease. Controlled brain metastases are permitted
• Participants with second/other active cancers requiring current treatment
• Uncontrolled/significant heart disease
• Known History of chronic hepatitis, Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except participants with liver cancer) or Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome(HIV/AIDS)
• Active/uncontrolled autoimmune disease
• Active infection

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1A Dose escalation EOS100850; Dose Escalation- EOS100850 Monotherapy: to confirm RP2D	Drug: EOS100850; Oral administration; Other Names: Inupadenant
Experimental: 1B Dose escalation EOS100850 and Pembrolizumab; EOS100850 and Pembrolizumab Combination Therapy: to confirm RP2D as combination	Drug: Pembrolizumab; IV Infusion; Other Names: Keytruda; MK-3475; Drug: EOS100850; Oral administration; Other Names: Inupadenant
Experimental: 2B Dose Expansion - EOS100850 and Pembrolizumab; Dose Expansion - EOS100850 and Pembrolizumab Combination Therapy: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with pembrolizumab in melanoma and CRPC patients	Drug: Pembrolizumab; IV Infusion; Other Names: Keytruda; MK-3475; Drug: EOS100850; Oral administration; Other Names: Inupadenant
Experimental: 3 EOS100850 in BMK-H participants; Dose expansion - EOS100850 Monotherapy : to evaluate the safety, PD, and antitumor activity of inupadenant as monotherapy at the mono-RP2D in BMK-H participants in 4 disease-specific cohorts: NSCLC; HNSCC; EC; and other forms of cancer	Drug: EOS100850; Oral administration; Other Names: Inupadenant
Experimental: 2A Dose Expansion- EOS100850; Dose Expansion - EOS100850 Monotherapy: to explore safety, PK, PD, and antitumor activity of inupadenant as monotherapy	Drug: EOS100850; Oral administration; Other Names: Inupadenant
Experimental: 2D Dose expansion - EOS100850 and Chemotherapy in TNBC; Dose expansion - EOS100850 and Chemotherapy Combination: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with chemotherapy SOC carboplatin and paclitaxel in patients with TNBC	Drug: EOS100850; Oral administration; Other Names: Inupadenant; Drug: Chemotherapy; Standard of Care IV Infusion; Other Names: carboplatin and paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLTs) in patients with advanced solid tumors receiving EOS100850	To define the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) of EOS100850 in patients receiving EOS100850	During the DLT evaluation period that is cycle 1 (each cycle is 3 or 4 weeks)
Incidence and severity of AEs in patients receiving EOS100850	To assess safety and tolerability as measured by incidence and severity of AEs	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of EOS100850 vs. time profiles	Determined by inspection of the concentration-time profile	Up to 30 months
Maximum observed serum concentration (Cmax)	Determined by inspection of the concentration-time profile	Up to 30 months
Time of maximum observed concentration (Tmax)	Determined by inspection of the concentration-time profile	Up to 30 months
Area under the concentration-time curve in 1 dosing interval [AUC(TAU)]	Determined by inspection of the concentration-time profile	Up to 30 months
Plasma concentration half-life (T-HALF)	Determined by inspection of the concentration-time profile	Up to 30 months
Overall response rate per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1	Assessment of preliminary efficacy of EOS100850	Up to 30 months

Collaborators and Investigators

• Sponsor: iTeos Therapeutics
• Collaborators: Merck Sharp & Dohme LLC; iTeos Belgium SA
• Investigators: Study Director: Iteos Clinical Trials, iTeos Belgium SA

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2019
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: March 6, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 14, 2019

Study Record Updates

• Last Update Posted (Actual): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 13, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: chemotherapy; safety; pharmacokinetics; pembrolizumab; tumor; advanced cancers; solid; inupadenant
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Paclitaxel; Pembrolizumab
• Other Study ID Numbers: IO-001; Keynote A45 (Other Identifier: Merck and Co.); 2018-003173-10 (EudraCT Number)

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