Clinical trial NCT05060432: Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: iTeos Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
name: iTeos Therapeutics
First posted: 2021-09-29
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

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)

Primary outcomes:
measure: Percentage of participants with DLT and Adverse Events
timeFrame: From first study treatment administration through Day 21-28 for DLT / Up to 120 days after the last dose
measure: Recommended Phase 2 dose (RP2D) of EOS884448 in participants with advanced solid tumors
timeFrame: Up to 48 weeks
measure: Percentage of participants with Objective Response as determined by Investigator
timeFrame: Until disease progression - Approximately 48 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Until disease progression or death - Approximately 48 months
measure: Disease Control Rate (DCR)
timeFrame: Until disease progression or death - Approximately 48 months
measure: Progression-free-survival (PFS)
timeFrame: Until disease progression or death - Approximately 48 months
measure: Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level
timeFrame: Up to 48 weeks
measure: Percentage of participants with anti-drug antibodies to EOS884448
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Bergen
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Antwerpen
country: Belgium
facility: GZA Ziekenhuizen campus Sint-Augustinus
state: Antwerp
city: Brussels
country: Belgium
facility: Cliniques universitaires St Luc-UCL
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mons
country: Belgium
facility: CHU Helora
city: Bordeaux
country: France
facility: Hôpital Saint André
city: Caen
country: France
facility: CHU Caen
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Nancy
country: France
facility: Institut de Cancerologie Lorraine (ICL)
city: Nantes
country: France
facility: Institut de Cancérologie de l'Ouest
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Pitié Salpêtrière
city: Poitiers
country: France
facility: CHU de POITIERS
city: Strasbourg
country: France
facility: ICANS
city: Rozzano
country: Italy
facility: IDB Center-Istituto Clinico Humanitas (IRCCS)
state: Milan
city: Candiolo
country: Italy
facility: FPO-IRCCS Candiolo Cancer Insitute
state: Turin
city: Pavia
country: Italy
facility: Universita degli Studi di Pavia - Fondazione IRCCS Policlinico San Matteo
city: Ravenna
country: Italy
facility: AUSL Della Romagna - Ospedale S. Maria delle Croci
city: Manresa
country: Spain
facility: Hospital Althaia Xarxa Assitencial de Manresa
state: Cataluña
city: Badajoz
country: Spain
facility: Hospital Universitario de Badajoz
city: Barcelona
country: Spain
facility: Vall d'Hebron
city: Jaén
country: Spain
facility: Hospital Universitario de Jaen
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz - START Madrid
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Quirón Málaga
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia (IVO)
city: Valencia
country: Spain
facility: Consorci Hospital Gral Univ Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia (Hospital La Fe Bulevar Sur)
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital (Sutton location)
state: Surrey
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital (London location)
city: London
country: United Kingdom
facility: Hammersmith Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
Study officials:
affiliation: iTeos Belgium SA
name: Iteos Clinical Trials
role: STUDY_DIRECTOR
References: