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

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.

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)