Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors
Phase 1
Active, not recruiting
- Conditions
- Head and Neck CancerAdvanced CancerLung CancerMelanoma
- Interventions
- Registration Number
- NCT05060432
- Lead Sponsor
- iTeos Belgium SA
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 153
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2C - EOS-448 + dostarlimab EOS-448 Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle Part 1F - EOS-448 + dostarlimab + inupadenant HC inupadenant Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis Part 1A - EOS-448 + pembrolizumab pembrolizumab Participants will receive EOS-448 and pembrolizumab at every cycle Part 1C - EOS-448 + inupadenant EOS-448 Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis Part 1B - EOS-448 + inupadenant inupadenant Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis Part 1C - EOS-448 + inupadenant inupadenant Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis Part 1D - EOS-448 + dostarlimab EOS-448 Participants will receive EOS-448 and dostarlimab at every cycle Part 1E - inupadenant HCl + dostarlimab inupadenant Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis Part 1F - EOS-448 + dostarlimab + inupadenant HC Dostarlimab Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis Part 1G - EOS-448 + dostarlimab + chemotherapies Dostarlimab Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle Part 1G - EOS-448 + dostarlimab + chemotherapies SOC chemotherapies Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle Part 2C - EOS-448 + dostarlimab Dostarlimab Participants with 1L mHNSCC CPS ≥ 20 will receive EOS-448 and dostarlimab at every cycle Part 1G - EOS-448 + dostarlimab + chemotherapies EOS-448 Participants with 1L mNSCLC will receive EOS-448 and dostarlimab and chemotherapies at every cycle Part 1B - EOS-448 + inupadenant EOS-448 Participants will receive EOS-448 at every cycle and inupadenant on an ongoing basis Part 1A - EOS-448 + pembrolizumab EOS-448 Participants will receive EOS-448 and pembrolizumab at every cycle Part 1F - EOS-448 + dostarlimab + inupadenant HC EOS-448 Participants will receive EOS-448 and dostarlimab at every cycle and inupadenant on an ongoing basis Part 2D - EOS-448 + dostarlimab EOS-448 Participants with 1L mHNSCC 1 \< CPS \< 20 will receive EOS-448 and dostarlimab at every cycle Part 1D - EOS-448 + dostarlimab Dostarlimab Participants will receive EOS-448 and dostarlimab at every cycle Part 1E - inupadenant HCl + dostarlimab Dostarlimab Participants will receive dostarlimab at every cycle and inupadenant on an ongoing basis Part 2D - EOS-448 + dostarlimab Dostarlimab Participants with 1L mHNSCC 1 \< CPS \< 20 will receive EOS-448 and dostarlimab at every cycle
- Primary Outcome Measures
Name Time Method 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
Name Time Method Duration of Response (DOR) Until disease progression or death - Approximately 48 months Mean and median Maximum concentration (Cmax) of EOS884448 at each dose level Up to 48 weeks Progression-free-survival (PFS) Until disease progression or death - Approximately 48 months Disease Control Rate (DCR) Until disease progression or death - Approximately 48 months Percentage of participants with anti-drug antibodies to EOS884448 Up to 48 weeks
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
What is the molecular mechanism of EOS-448 (belrestotug) in combination with anti-PD-1 antibodies in advanced solid tumors?
How does inupadenant enhance the efficacy of EOS-448 and dostarlimab in A2A receptor-mediated tumor immune evasion?
Which biomarkers are being evaluated to predict response to EOS-448 combinations in head and neck cancer and NSCLC?
What are the potential adverse event profiles of EOS-448 when combined with standard-of-care chemotherapies in lung cancer patients?
How do the therapeutic outcomes of EOS-448 combinations compare to other PRMT5 inhibitors in melanoma and advanced solid tumor trials?
Trial Locations
- Locations (42)
University of California San Diego
🇺🇸San Diego, California, United States
Hackensack University Medical Center
🇺🇸Bergen, New Jersey, United States
GZA Ziekenhuizen campus Sint-Augustinus
🇧🇪Antwerpen, Antwerp, Belgium
Cliniques universitaires St Luc-UCL
🇧🇪Brussels, Belgium
Jessa Ziekenhuis
🇧🇪Hasselt, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
CHU Helora
🇧🇪Mons, Belgium
Hôpital Saint André
🇫🇷Bordeaux, France
CHU Caen
🇫🇷Caen, France
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Scroll for more (32 remaining)University of California San Diego🇺🇸San Diego, California, United States