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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Advanced Cancer, Lung Cancer, Head and Neck Cancer, Melanoma

Intervention / Treatment
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* Drug: EOS-448
* Drug: pembrolizumab
* Drug: inupadenant
* Drug: Dostarlimab
* Drug: SOC chemotherapies


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A - EOS-448 + pembrolizumab<br>Participants will receive EOS-448 and pembrolizumab at every cycle | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: pembrolizumab<br>* Anti-PD-1 monoclonal antibody<br>|
| Experimental: Part 1B - EOS-448 + inupadenant<br>Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: inupadenant<br>* A2A receptor antagonist<br>* Other names: EOS100850;|
| Experimental: Part 1C - EOS-448 + inupadenant<br>Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: inupadenant<br>* A2A receptor antagonist<br>* Other names: EOS100850;|
| Experimental: Part 1D - EOS-448 + dostarlimab<br>Participants will receive EOS-448 and dostarlimab at every cycle | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>|
| Experimental: Part 1E - inupadenant HCl + dostarlimab<br>Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis | Drug: inupadenant<br>* A2A receptor antagonist<br>* Other names: EOS100850;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>|
| Experimental: Part 1F - EOS-448 + dostarlimab + inupadenant HC<br>Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: inupadenant<br>* A2A receptor antagonist<br>* Other names: EOS100850;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>|
| Experimental: Part 1G - EOS-448 + dostarlimab + chemotherapies<br>Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>Drug: SOC chemotherapies<br>* SOC chemotherapies in 1L mNSCLC<br>|
| Experimental: Part 2C - EOS-448 + dostarlimab<br>Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>|
| Experimental: Part 2D - EOS-448 + dostarlimab<br>Participants with 1L mHNSCC 1 < CPS < 20 will receive EOS-448 and dostarlimab at every cycle | Drug: EOS-448<br>* Anti-TIGIT monoclonal antibody<br>* Other names: belrestotug;Drug: Dostarlimab<br>* Anti-PD-1 monoclonal antibody<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EOS884448, GSK4428859A, TIGIT, Anti-TIGIT, EOS-448, pembrolizumab, dostarlimab, inupadenant, A2A Receptor antagonist, EOS-850, EOS100850, Anti-PD-1 monoclonal antibody, belrestotug