Advanced Cancer, Head and Neck Cancer, Lung Cancer, Melanoma
Conditions
Keywords
EOS884448, GSK4428859A, TIGIT, Anti-TIGIT, EOS-448, pembrolizumab, dostarlimab, inupadenant, A2A Receptor antagonist, EOS-850, EOS100850, Anti-PD-1 monoclonal antibody, belrestotug
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
Interventions
DRUGEOS-448
Anti-TIGIT monoclonal antibody
DRUGpembrolizumab
Anti-PD-1 monoclonal antibody
DRUGinupadenant
A2A receptor antagonist
DRUGDostarlimab
Anti-PD-1 monoclonal antibody
DRUGSOC chemotherapies
SOC chemotherapies in 1L mNSCLC
Sponsors
GlaxoSmithKline
iTeos Therapeutics
iTeos Belgium SA
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level | Up to 48 weeks |
| Duration of Response (DOR) | Until disease progression or death - Approximately 48 months |
| Percentage of participants with anti-drug antibodies to EOS884448 | Up to 48 weeks |
| Disease Control Rate (DCR) | Until disease progression or death - Approximately 48 months |
| Progression-free-survival (PFS) | Until disease progression or death - Approximately 48 months |
Countries
Belgium, France, Italy, Spain, United Kingdom, United States
Outcome results
None listed