Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors (TIG-006)

A Multicenter, Open-Label, Phase I/II Study of EOS884448 (EOS-448) in Combination With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors

This is a multicenter, open-label, phase I/II basket study, evaluating the safety, tolerability, RP2D, pharmacokinetics, pharmacodynamics and antitumor activity of EOS-448 (also known as GSK4428859A or belrestotug) combined with standard of care and/or with investigational therapies in participants with advanced solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma; Head and Neck Cancer; Lung Cancer; Advanced Cancer
• Intervention / Treatment: Drug: EOS-448; Drug: pembrolizumab; Drug: inupadenant; Drug: Dostarlimab; Drug: SOC chemotherapies

Detailed Description

The combinations evaluated will be:

• EOS-448 combined with pembrolizumab, an anti-PD-1 antibody
• EOS-448 combined with inupadenant an investigational adenosine A2A receptor antagonist
• EOS-448 combined with dostarlimab an anti-PD-1 antibody
• inupadenant combined with dostarlimab
• EOS-448 combined with inupadenant and dostarlimab
• EOS-448 combined with dostarlimab and standard of care chemotherapies in participants with NSCLC

• Study Type: Interventional
• Enrollment (Actual): 153
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques universitaires St Luc-UCL
  • Hasselt, Belgium, 3500
    • Jessa Ziekenhuis
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Mons, Belgium, 7000
    • CHU Helora
  • Antwerp
    • Antwerpen, Antwerp, Belgium, 2610
      • GZA Ziekenhuizen campus Sint-Augustinus
• France
  • Bordeaux, France, 33075
    • Hopital Saint André
  • Caen, France, 14033
    • CHU Caen
  • Dijon, France, 21079
    • Centre Georges François Leclerc
  • Le Mans, France, 72000
    • Clinique Victor Hugo
  • Lille, France, 59000
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Nancy, France, 54519
    • Institut de Cancerologie Lorraine (ICL)
  • Nantes, France, 44805
    • Institut de Cancerologie de L'Ouest
  • Nice, France, 06189
    • Centre Antoine Lacassagne
  • Paris, France, 75013
    • Pitié Salpêtrière
  • Poitiers, France, 86000
    • Chu de Poitiers
  • Strasbourg, France, 67033
    • ICANS
• Italy
  • Pavia, Italy, 27100
    • Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
  • Ravenna, Italy, 48121
    • AUSL Della Romagna - Ospedale S. Maria delle Croci
  • Milan
    • Rozzano, Milan, Italy, 20089
      • IDB Center-Istituto Clinico Humanitas (IRCCS)
  • Turin
    • Candiolo, Turin, Italy, 10060
      • FPO-IRCCS Candiolo Cancer Insitute
• Spain
  • Badajoz, Spain, 06006
    • Hospital Universitario de Badajoz
  • Barcelona, Spain, 08035
    • Vall d'Hebron
  • Jaén, Spain, 23007
    • Hospital Universitario de Jaen
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz - START MADRID
  • Málaga, Spain, 29004
    • Hospital Quirón Málaga
  • Pamplona, Spain, 31008
    • Hospital Universitario de Navarra
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46009
    • Fundacion Instituto Valenciano de Oncologia (IVO)
  • Valencia, Spain, 46014
    • Consorci Hospital Gral Univ Valencia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Cataluña
    • Manresa, Cataluña, Spain, 08243
      • Hospital Althaia Xarxa Assitencial de Manresa
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom, W12 0HS
    • Hammersmith Hospital
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden Hospital (London location)
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham City Hospital
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • Royal Marsden Hospital (Sutton location)
• United States
  • California
    • San Diego, California, United States, 92037
      • University of California San Diego
  • New Jersey
    • Bergen, New Jersey, United States, 07601
      • Hackensack University Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provide a signed written informed consent for the trial
• Have measurable disease, per RECIST v1.1
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of Grade 0 or 1.
• Have adequate organ functions
• Part 1A/1B/1C/1D/1E/1F: Have histologically or cytologically confirmed advanced or metastatic solid tumor for whom no standard treatment with survival benefit is available

Part 1G (NSCLC):

• Have a histologically confirmed or cytologically confirmed previously untreated stage IV OR stage III not amenable to curative chemoradiotherapy or surgery (AJCC 8th edition) nonsquamous NSCLC OR squamous NSCLC.
• Are eligible to receive anti-PD(L)1 therapy combined with chemotherapy in first line metastatic setting

Part 2 (H&N cancer)

• Have histologically or cytologically confirmed recurrent advanced or metastatic head and neck squamous cell carcinoma considered incurable by local therapies
• PD-L1 status positive

Exclusion Criteria:

• Have received any anti-cancer therapy within 4 weeks prior to the first dose
• Have received a live vaccine within 30 days prior to the first dose
• Have known primary CNS cancer.
• Have known CNS metastases unless previously treated and well controlled for at least 1 month
• Have concomitant second malignancies unless a complete remission was achieved at least 2 years before study entry
• Have a history of Grade ≥ 2 pneumonitis, active autoimmune disease, or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2
• Have toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery unless the toxicity is either resolved, returned to baseline or Grade 1, or deemed irreversible.
• Have uncontrolled or significant cardiovascular disease
• Part 1: major surgery within 3 weeks before initiating treatment
• Part 1: Have received prior radiotherapy within 2 weeks of start of study treatment
• Part 2 (H&N cancer):
• Have received prior immunotherapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Have received prior chemotherapy administered in the recurrent advanced or metastatic setting (except for systemic therapy completed > 6 months prior to screening if given as part of multimodal treatment for locally advanced disease)

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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1D - EOS-448 + dostarlimab; Participants will receive EOS-448 and dostarlimab at every cycle	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody
Experimental: Part 1A - EOS-448 + pembrolizumab; Participants will receive EOS-448 and pembrolizumab at every cycle	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: pembrolizumab; Anti-PD-1 monoclonal antibody
Experimental: Part 1B - EOS-448 + inupadenant; Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: inupadenant; A2A receptor antagonist; Other Names: EOS100850
Experimental: Part 1C - EOS-448 + inupadenant; Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: inupadenant; A2A receptor antagonist; Other Names: EOS100850
Experimental: Part 1E - inupadenant HCl + dostarlimab; Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis	Drug: inupadenant; A2A receptor antagonist; Other Names: EOS100850; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody
Experimental: Part 1F - EOS-448 + dostarlimab + inupadenant HC; Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: inupadenant; A2A receptor antagonist; Other Names: EOS100850; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody
Experimental: Part 1G - EOS-448 + dostarlimab + chemotherapies; Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody; Drug: SOC chemotherapies; SOC chemotherapies in 1L mNSCLC
Experimental: Part 2C - EOS-448 + dostarlimab; Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody
Experimental: Part 2D - EOS-448 + dostarlimab; Participants with 1L mHNSCC 1 < CPS < 20 will receive EOS-448 and dostarlimab at every cycle	Drug: EOS-448; Anti-TIGIT monoclonal antibody; Other Names: EOS884448; GSK4428859; belrestotug; Drug: Dostarlimab; Anti-PD-1 monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of participants with DLT and Adverse Events	From first study treatment administration through Day 21-28 for DLT / Up to 120 days after the last dose
Recommended Phase 2 dose (RP2D) of EOS884448 in participants with advanced solid tumors	Up to 48 weeks
Percentage of participants with Objective Response as determined by Investigator	Until disease progression - Approximately 48 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of Response (DOR)	Until disease progression or death - Approximately 48 months
Disease Control Rate (DCR)	Until disease progression or death - Approximately 48 months
Progression-free-survival (PFS)	Until disease progression or death - Approximately 48 months
Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level	Up to 48 weeks
Percentage of participants with anti-drug antibodies to EOS884448	Up to 48 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2021
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2025

Study Registration Dates

• First Submitted: September 6, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: dostarlimab; pembrolizumab; TIGIT; Anti-PD-1 monoclonal antibody; GSK4428859A; EOS884448; Anti-TIGIT; EOS-448; inupadenant; A2A Receptor antagonist; EOS-850; EOS100850; belrestotug
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Dostarlimab
• Other Study ID Numbers: TIG-006

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