Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors (TIG-006)

iTeos Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Advanced Cancer; Melanoma; Lung Cancer; Head and Neck Cancer

Treatments: Drug: inupadenant; Drug: Dostarlimab; Drug: SOC chemotherapies; Drug: pembrolizumab; Drug: EOS-448

Study type: Interventional

Funder types: Industry

Identifiers

NCT05060432

TIG-006

Details and patient eligibility

About

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.

Full 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

Enrollment: 153 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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153 participants in 9 patient groups

Part 1A - EOS-448 + pembrolizumab

Experimental group

Description:

Participants will receive EOS-448 and pembrolizumab at every cycle

Treatment:

Drug: EOS-448

Drug: pembrolizumab

Part 1B - EOS-448 + inupadenant

Experimental group

Description:

Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis

Treatment:

Drug: EOS-448

Drug: inupadenant

Part 1C - EOS-448 + inupadenant

Experimental group

Description:

Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis

Treatment:

Drug: EOS-448

Drug: inupadenant

Part 1D - EOS-448 + dostarlimab

Experimental group

Description:

Participants will receive EOS-448 and dostarlimab at every cycle

Treatment:

Drug: EOS-448

Drug: Dostarlimab

Part 1E - inupadenant HCl + dostarlimab

Experimental group

Description:

Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis

Treatment:

Drug: Dostarlimab

Drug: inupadenant

Part 1F - EOS-448 + dostarlimab + inupadenant HC

Experimental group

Description:

Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis

Treatment:

Drug: EOS-448

Drug: Dostarlimab

Drug: inupadenant

Part 1G - EOS-448 + dostarlimab + chemotherapies

Experimental group

Description:

Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle

Treatment:

Drug: EOS-448

Drug: SOC chemotherapies

Drug: Dostarlimab

Part 2C - EOS-448 + dostarlimab

Experimental group

Description:

Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle

Treatment:

Drug: EOS-448

Drug: Dostarlimab

Part 2D - EOS-448 + dostarlimab

Experimental group

Description:

Participants with 1L mHNSCC 1 \< CPS \< 20 will receive EOS-448 and dostarlimab at every cycle

Treatment:

Drug: EOS-448

Drug: Dostarlimab