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

NCT05060432 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: TIG-006
• Study Type: interventional
• Target: 153
• Locations: 6 countries
• Sites: 42

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.

Conditions

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

Keywords

EOS884448; GSK4428859A; TIGIT; Anti-TIGIT; EOS-448; pembrolizumab; dostarlimab; inupadenant; A2A Receptor antagonist; EOS-850; EOS100850; Anti-PD-1 monoclonal antibody; belrestotug

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• 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

Study Arms (9)

Part 1A - EOS-448 + pembrolizumab

EXPERIMENTAL

Participants will receive EOS-448 and pembrolizumab at every cycle

Drug: EOS-448; Drug: pembrolizumab

Part 1B - EOS-448 + inupadenant

EXPERIMENTAL

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

Drug: EOS-448; Drug: inupadenant

Part 1C - EOS-448 + inupadenant

EXPERIMENTAL

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

Drug: EOS-448; Drug: inupadenant

Part 1D - EOS-448 + dostarlimab

EXPERIMENTAL

Participants will receive EOS-448 and dostarlimab at every cycle

Drug: EOS-448; Drug: Dostarlimab

Part 1E - inupadenant HCl + dostarlimab

EXPERIMENTAL

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

Drug: inupadenant; Drug: Dostarlimab

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

EXPERIMENTAL

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

Drug: EOS-448; Drug: inupadenant; Drug: Dostarlimab

Part 1G - EOS-448 + dostarlimab + chemotherapies

EXPERIMENTAL

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

Drug: EOS-448; Drug: Dostarlimab; Drug: SOC chemotherapies

Part 2C - EOS-448 + dostarlimab

EXPERIMENTAL

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

Drug: EOS-448; Drug: Dostarlimab

Part 2D - EOS-448 + dostarlimab

EXPERIMENTAL

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

Drug: EOS-448; Drug: Dostarlimab

Interventions

EOS-448 DRUG

Anti-TIGIT monoclonal antibody

Also known as: EOS884448, GSK4428859, belrestotug

Part 1A - EOS-448 + pembrolizumab; Part 1B - EOS-448 + inupadenant; Part 1C - EOS-448 + inupadenant; Part 1D - EOS-448 + dostarlimab; Part 1F - EOS-448 + dostarlimab + inupadenant HC; Part 1G - EOS-448 + dostarlimab + chemotherapies; Part 2C - EOS-448 + dostarlimab; Part 2D - EOS-448 + dostarlimab

pembrolizumab DRUG

Anti-PD-1 monoclonal antibody

Part 1A - EOS-448 + pembrolizumab

inupadenant DRUG

A2A receptor antagonist

Also known as: EOS100850

Part 1B - EOS-448 + inupadenant; Part 1C - EOS-448 + inupadenant; Part 1E - inupadenant HCl + dostarlimab; Part 1F - EOS-448 + dostarlimab + inupadenant HC

Dostarlimab DRUG

Anti-PD-1 monoclonal antibody

Part 1D - EOS-448 + dostarlimab; Part 1E - inupadenant HCl + dostarlimab; Part 1F - EOS-448 + dostarlimab + inupadenant HC; Part 1G - EOS-448 + dostarlimab + chemotherapies; Part 2C - EOS-448 + dostarlimab; Part 2D - EOS-448 + dostarlimab

SOC chemotherapies DRUG

SOC chemotherapies in 1L mNSCLC

Part 1G - EOS-448 + dostarlimab + chemotherapies

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• iTeos Belgium SA: lead
• GlaxoSmithKline: collaborator
• iTeos Therapeutics: collaborator

Study Sites (42)

University of California San Diego

San Diego, California, 92037, United States

Location

Hackensack University Medical Center

Bergen, New Jersey, 07601, United States

Location

GZA Ziekenhuizen campus Sint-Augustinus

Antwerp, Antwerp, 2610, Belgium

Location

Cliniques universitaires St Luc-UCL

Brussels, 1200, Belgium

Location

Jessa Ziekenhuis

Hasselt, 3500, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHU Helora

Mons, 7000, Belgium

Location

Hôpital Saint André

Bordeaux, 33075, France

Location

CHU Caen

Caen, 14033, France

Location

Centre Georges Francois Leclerc

Dijon, 21079, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Centre Oscar Lambret

Lille, 59000, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut de Cancerologie Lorraine (ICL)

Nancy, 54519, France

Location

Institut de Cancérologie de l'Ouest

Nantes, 44805, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Pitié Salpêtrière

Paris, 75013, France

Location

CHU de POITIERS

Poitiers, 86000, France

Location

ICANS

Strasbourg, 67033, France

Location

IDB Center-Istituto Clinico Humanitas (IRCCS)

Rozzano, Milan, 20089, Italy

Location

FPO-IRCCS Candiolo Cancer Insitute

Candiolo, Turin, 10060, Italy

Location

Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

AUSL Della Romagna - Ospedale S. Maria delle Croci

Ravenna, 48121, Italy

Location

Hospital Althaia Xarxa Assitencial de Manresa

Manresa, Catalonia, 08243, Spain

Location

Hospital Universitario de Badajoz

Badajoz, 06006, Spain

Location

Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario de Jaen

Jaén, 23007, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundación Jiménez Díaz - START Madrid

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Quirón Málaga

Málaga, 29004, Spain

Location

Hospital Universitario de Navarra

Pamplona, 31008, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Fundacion Instituto Valenciano de Oncologia (IVO)

Valencia, 46009, Spain

Location

Consorci Hospital Gral Univ Valencia

Valencia, 46014, Spain

Location

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

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Royal Marsden Hospital (Sutton location)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Royal Marsden Hospital (London location)

London, SW3 6JJ, United Kingdom

Location

Hammersmith Hospital

London, W12 0HS, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Lung Neoplasms; Head and Neck Neoplasms; Melanoma

Interventions

pembrolizumab; dostarlimab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Iteos Clinical Trials

  iTeos Belgium SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2021
• First Posted: September 29, 2021
• Study Start: September 6, 2021
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2025
• Last Updated: June 21, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4); GB (5); US (2); BE (5); FR (12); ES (14)