Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
Sponsor: iTeos Belgium SA
ClinicalTrials ID:NCT05060432
This phase I/II study assesses EOS-448 with pembrolizumab, inupadenant, dostarlimab, and SOC chemotherapies in advanced solid tumors. Eligible participants must have measurable disease, ECOG 0-1, and adequate organ function. Specific criteria apply for NSCLC and H&N cancer. Interventions include anti-TIGIT, anti-PD-1 antibodies, and A2A receptor antagonist.
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Program Overview
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.
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)
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