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

NCT ID: NCT05060432

Last Updated: 2024-06-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-06
• Study Completion Date: 2025-07-31

Brief Summary

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.

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

Conditions

Advanced Cancer; Lung Cancer; Head and Neck Cancer; Melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A - EOS-448 + pembrolizumab

Participants will receive EOS-448 and pembrolizumab at every cycle

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

pembrolizumab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Part 1B - EOS-448 + inupadenant

Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

inupadenant

Intervention Type: DRUG

A2A receptor antagonist

Part 1C - EOS-448 + inupadenant

Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

inupadenant

Intervention Type: DRUG

A2A receptor antagonist

Part 1D - EOS-448 + dostarlimab

Participants will receive EOS-448 and dostarlimab at every cycle

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Part 1E - inupadenant HCl + dostarlimab

Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis

Group Type: EXPERIMENTAL

inupadenant

Intervention Type: DRUG

A2A receptor antagonist

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Part 1F - EOS-448 + dostarlimab + inupadenant HC

Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

inupadenant

Intervention Type: DRUG

A2A receptor antagonist

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Part 1G - EOS-448 + dostarlimab + chemotherapies

Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

SOC chemotherapies

Intervention Type: DRUG

SOC chemotherapies in 1L mNSCLC

Part 2C - EOS-448 + dostarlimab

Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Part 2D - EOS-448 + dostarlimab

Participants with 1L mHNSCC 1 \< CPS \< 20 will receive EOS-448 and dostarlimab at every cycle

Group Type: EXPERIMENTAL

EOS-448

Intervention Type: DRUG

Anti-TIGIT monoclonal antibody

Dostarlimab

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Interventions

EOS-448

Anti-TIGIT monoclonal antibody

Intervention Type: DRUG

pembrolizumab

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

inupadenant

A2A receptor antagonist

Intervention Type: DRUG

Dostarlimab

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

SOC chemotherapies

SOC chemotherapies in 1L mNSCLC

Intervention Type: DRUG

Other Intervention Names

EOS884448; GSK4428859; belrestotug; EOS100850

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

iTeos Therapeutics

INDUSTRY

Sponsor Role: collaborator

iTeos Belgium SA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Iteos Clinical Trials

Role: STUDY_DIRECTOR

iTeos Belgium SA

Locations

University of California San Diego

San Diego, California, United States

Hackensack University Medical Center

Bergen, New Jersey, United States

GZA Ziekenhuizen campus Sint-Augustinus

Antwerp, Antwerp, Belgium

Cliniques universitaires St Luc-UCL

Brussels, , Belgium

Jessa Ziekenhuis

Hasselt, , Belgium

UZ Leuven

Leuven, , Belgium

CHU Helora

Mons, , Belgium

Hôpital Saint André

Bordeaux, , France

CHU Caen

Caen, , France

Centre Georges Francois Leclerc

Dijon, , France

Clinique Victor Hugo

Le Mans, , France

Centre Oscar Lambret

Lille, , France

Centre Léon Bérard

Lyon, , France

Institut de Cancerologie Lorraine (ICL)

Nancy, , France

Institut de Cancérologie de l'Ouest

Nantes, , France

Centre Antoine Lacassagne

Nice, , France

Pitié Salpêtrière

Paris, , France

CHU de POITIERS

Poitiers, , France

ICANS

Strasbourg, , France

IDB Center-Istituto Clinico Humanitas (IRCCS)

Rozzano, Milan, Italy

FPO-IRCCS Candiolo Cancer Insitute

Candiolo, Turin, Italy

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

AUSL Della Romagna - Ospedale S. Maria delle Croci

Ravenna, , Italy

Hospital Althaia Xarxa Assitencial de Manresa

Manresa, Catalonia, Spain

Hospital Universitario de Badajoz

Badajoz, , Spain

Vall d'Hebron

Barcelona, , Spain

Hospital Universitario de Jaen

Jaén, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz - START Madrid

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Quirón Málaga

Málaga, , Spain

Hospital Universitario de Navarra

Pamplona, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Fundacion Instituto Valenciano de Oncologia (IVO)

Valencia, , Spain

Consorci Hospital Gral Univ Valencia

Valencia, , Spain

Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)

Valencia, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

Royal Marsden Hospital (Sutton location)

Sutton, Surrey, United Kingdom

Addenbrooke's Hospital

Cambridge, , United Kingdom

Royal Marsden Hospital (London location)

London, , United Kingdom

Hammersmith Hospital

London, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Countries

United States; Belgium; France; Italy; Spain; United Kingdom

Other Identifiers

TIG-006

Identifier Type: -

Identifier Source: org_study_id