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

• ClinicalTrials.gov Identifier: NCT05060432
• Recruitment Status: Recruiting
• First Posted: September 29, 2021
• Last Update Posted: December 27, 2023
• Sponsor: iTeos Belgium SA
• Collaborators: GlaxoSmithKline; iTeos Therapeutics
• Information provided by (Responsible Party): iTeos Therapeutics ( iTeos Belgium SA )

Tracking Information

• First Submitted Date: September 6, 2021
• First Posted Date: September 29, 2021
• Last Update Posted Date: December 27, 2023
• Actual Study Start Date: September 6, 2021
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2021)

• Percentage of participants with DLT and Adverse Events [ Time Frame: 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 [ Time Frame: Up to 48 weeks ]
• Percentage of participants with Objective Response as determined by Investigator [ Time Frame: Until disease progression - Approximately 48 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 27, 2021)

• Duration of Response (DOR) [ Time Frame: Until disease progression or death - Approximately 48 months ]
• Disease Control Rate (DCR) [ Time Frame: Until disease progression or death - Approximately 48 months ]
• Progression-free-survival (PFS) [ Time Frame: Until disease progression or death - Approximately 48 months ]
• Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level [ Time Frame: Up to 48 weeks ]
• Percentage of participants with anti-drug antibodies to EOS884448 [ Time Frame: Up to 48 weeks ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: September 27, 2021)

• Change from baseline in absolute cell count in the tumor and in peripheral blood [ Time Frame: Up to 48 weeks ]
• Frequency of activation/exhaustion markers in the tumor and in peripheral blood [ Time Frame: Up to 48 weeks ]

Descriptive Information

• Brief Title: Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
• Official Title: 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
• 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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Cancer
• Lung Cancer
• Head and Neck Cancer
• Melanoma

Intervention

• Drug: EOS-448
  Anti-TIGIT monoclonal antibody
  Other Names:

  • EOS884448
  • GSK4428859
  • belrestotug
• Drug: pembrolizumab
  Anti-PD-1 monoclonal antibody
• Drug: inupadenant
  A2A receptor antagonist
  Other Name: EOS100850
• Drug: Dostarlimab
  Anti-PD-1 monoclonal antibody
• Drug: SOC chemotherapies
  SOC chemotherapies in 1L mNSCLC

Study Arms

• Experimental: Part 1A - EOS-448 + pembrolizumab
  Participants will receive EOS-448 and pembrolizumab at every cycle
  Interventions:

  • Drug: EOS-448
  • Drug: pembrolizumab
• Experimental: Part 1B - EOS-448 + inupadenant
  Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
  Interventions:

  • Drug: EOS-448
  • Drug: inupadenant
• Experimental: Part 1C - EOS-448 + inupadenant
  Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis
  Interventions:

  • Drug: EOS-448
  • Drug: inupadenant
• Experimental: Part 1D - EOS-448 + dostarlimab
  Participants will receive EOS-448 and dostarlimab at every cycle
  Interventions:

  • Drug: EOS-448
  • Drug: Dostarlimab
• Experimental: Part 1E - inupadenant HCl + dostarlimab
  Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis
  Interventions:

  • Drug: inupadenant
  • Drug: Dostarlimab
• Experimental: Part 1F - EOS-448 + dostarlimab + inupadenant HC
  Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis
  Interventions:

  • Drug: EOS-448
  • Drug: inupadenant
  • Drug: Dostarlimab
• Experimental: Part 1G - EOS-448 + dostarlimab + chemotherapies
  Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle
  Interventions:

  • Drug: EOS-448
  • Drug: Dostarlimab
  • Drug: SOC chemotherapies
• Experimental: Part 2C - EOS-448 + dostarlimab
  Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle
  Interventions:

  • Drug: EOS-448
  • Drug: Dostarlimab
• Experimental: Part 2D - EOS-448 + dostarlimab
  Participants with 1L mHNSCC 1 < CPS < 20 will receive EOS-448 and dostarlimab at every cycle
  Interventions:

  • Drug: EOS-448
  • Drug: Dostarlimab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 20, 2023): 254
• Original Estimated Enrollment (submitted: September 27, 2021): 276
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: September 2024 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: iTeos Belgium SA; +32 71 91 99 33; clinical_info@iteostherapeutics.com

• Listed Location Countries: Belgium, France, Italy, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05060432
• Other Study ID Numbers: TIG-006
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: iTeos Therapeutics ( iTeos Belgium SA )
• Original Responsible Party: Same as current
• Current Study Sponsor: iTeos Belgium SA
• Original Study Sponsor: Same as current

Collaborators

• GlaxoSmithKline
• iTeos Therapeutics

Investigators

• Study Director: Iteos Clinical Trials; iTeos Belgium SA

• PRS Account: iTeos Therapeutics
• Verification Date: December 2023