First-in-Human Study of EOS100850 in Patients With Cancer

Study Overview
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Brief Summary
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Multicenter, open-label, dose-escalation Phase I/Ib clinical study to evaluate the safety and tolerability, the MTD/RP2D, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of EOS100850 as a Single Agent and in Combination with Pembrolizumab and/or Chemotherapy in Participants with Advanced Cancers.

Official Title
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Phase I/Ib First-in-Human Study of EOS100850 as a Single Agent and in Combination With Pembrolizumab and/or Chemotherapy in Participants With Advanced Cancers

Conditions
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Solid Tumor, Adult

Intervention / Treatment
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* Drug: EOS100850
* Drug: Pembrolizumab
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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For more information regarding participation in the Trial, please refer to your physician Inclusion Criteria: Women and men ≥18 years of age with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Subject with histologically or cytologically confirmed advanced solid tumor for whom no standard treatment is further available. At least 4 weeks since any previous treatment for cancer Subject must consent to pretreatment and on treatment tumor biopsies Adequate organ and marrow function Exclusion Criteria: Patients with primary brain tumors or primary tumors with central nervous system metastases as only location of disease. Controlled brain metastases are permitted Participants with second/other active cancers requiring current treatment Uncontrolled/significant heart disease Known History of chronic hepatitis, Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except participants with liver cancer) or Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome(HIV/AIDS) Active/uncontrolled autoimmune disease Active infection Other protocol defined inclusion/exclusion criteria could apply

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1A Dose escalation EOS100850<br>Dose Escalation- EOS100850 Monotherapy: to confirm RP2D | Drug: EOS100850<br>* Oral administration<br>|
| Experimental: 1B Dose escalation EOS100850 and Pembrolizumab<br>EOS100850 and Pembrolizumab Combination Therapy: to confirm RP2D as combination | Drug: EOS100850<br>* Oral administration<br>Drug: Pembrolizumab<br>* IV Infusion<br>* Other names: MK-3475;|
| Experimental: 2A Dose Expansion- EOS100850<br>Dose Expansion- Monotherapy: to explore safety, PK, PD, and antitumor activity of inupadenant as monotherapy | Drug: EOS100850<br>* Oral administration<br>|
| Experimental: 2B Dose Expansion - EOS100850 and Pembrolizumab<br>Dose Expansion - EOS100850 and Pembrolizumab Combination Therapy: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with pembrolizumab in melanoma and CRPC patients | Drug: EOS100850<br>* Oral administration<br>Drug: Pembrolizumab<br>* IV Infusion<br>* Other names: MK-3475;|
| Experimental: 2D Dose expansion - EOS100850 and Chemotherapy in TNBC<br>Dose expansion - EOS100850 and Chemotherapy: to explore safety, PK, PD, and antitumor activity of inupadenant in combination with chemotherapy SOC carboplatin and paclitaxel in patients with TNBC | Drug: EOS100850<br>* Oral administration<br>Drug: Chemotherapy<br>* Standard of Care<br>* Other names: carboplatin and paclitaxel;|
| Experimental: 3 EOS100850 in BMK-H participants<br>Dose expansion - EOS100850 Monotherapy : to evaluate the safety, PD, and antitumor activity of inupadenant as monotherapy at the mono-RP2D in BMK-H participants in 4 disease-specific cohorts: NSCLC; HNSCC; EC; and other forms of cancer | Drug: EOS100850<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Dose-Limiting Toxicities (DLTs) in patients with advanced solid tumors receiving EOS100850 | To define the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D) of EOS100850 in patients receiving EOS100850 | Up to 15 months | 
| Incidence and severity of AEs in patients receiving EOS100850 | To assess safety and tolerability as measured by incidence and severity of AEs | Up to 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of EOS100850 vs. time profiles | Determined by inspection of the concentration-time profile | Up to 15 months | 
| Maximum observed serum concentration (Cmax) | Determined by inspection of the concentration-time profile | Up to 15 months | 
| Time of maximum observed concentration (Tmax) | Determined by inspection of the concentration-time profile | Up to 15 months | 
| Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] | Determined by inspection of the concentration-time profile | Up to 15 month | 
| Plasma concentration half-life (T-HALF) | Determined by inspection of the concentration-time profile | Up to 15 month | 
| Overall response rate per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 | Assessment of preliminary efficacy of EOS100850 | Up to 15 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid, tumor, advanced cancers, pharmacokinetics, safety, inupadenant, pembrolizumab, chemotherapy