A First-in-Human Open-label, Phase I/Ib Dose Escalation and Expansion Cohort Study of EOS006215 as Monotherapy and in Combination With Pembrolizumab or Other Anticancer Treatments in Participants With Advanced Solid Tumors

Phase 1TerminatedNCT06877533

iTeos Belgium SA3 enrolled

Overview

TRM-010 is a first-in-human (FIH) clinical study designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antitumor activity of EOS006215, a fully human monoclonal antibody that binds to the triggering receptor expressed on myeloid cells 2 (TREM2). The study includes EOS006215 monotherapy and combination therapy with other anticancer agents in participants with advanced solid tumors.

The study will be conducted in 2 parts: * Part 1 - Dose Escalation Phase I dose escalation cohorts for EOS006215 as monotherapy and in combination with anticancer treatments in participants with specific tumor types. * Part 2 - Dose Expansion Phase Ib dose expansion cohort(s) may be included to further evaluate the safety, tolerability, efficacy, PK and PD of EOS006215 as monotherapy or in combination with anticancer treatments in participants with specific tumor types.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Selected Advanced Solid Tumors

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Histologically or cytologically confirmed advanced or metastatic unresectable solid tumors for which standard approved treatment is not available or the participant is ineligible or did not tolerate the standard approved treatment. * At least one tumor lesion measurable per RECIST v1.1 * Have an estimated minimum life expectancy of ≥ 12 weeks. * Adequate organ/marrow and liver function * Agree to use adequate highly effective method of contraception during the study is mandatory, if WOCBP or male Exclusion Criteria: * Prior systemic anticancer treatment including investigational agents within 3 weeks (or 5 half-lives, whichever is shorter) before the first dose of study treatment * Major surgery planned or within 5 weeks before the first dose of study treatment, or minor surgical procedure (except tumor biopsy) within 7 days before the first dose of study treatment. * Radiotherapy within 2 weeks before the first dose of study treatment. * Evidence of severe active or chronic infections requiring systemic antibacterial, antiviral, or antifungal treatment, including tuberculosis infection * Known seropositivity for or active infection with human immunodeficiency virus (HIV) * Known seropositivity for hepatitis B virus (HBV), with evidence of active HBV infection * Known seropositivity for hepatitis C virus (HCV), with evidence of active HCV infection * Live or live-attenuated vaccine within 30 days before the first dose of study treatment. * History or current evidence of uncontrolled or significant cardiovascular disease * History or current evidence of significant autoimmune disease that required systemic * treatment * Diagnosis of immunodeficiency or any condition requiring systemic treatment with immunosuppressive medication * Pregnant or breastfeeding.

Outcomes

Primary Outcomes

Incidence of dose-limiting toxicities (DLTs), adverse events (AEs)/serious adverse events (SAEs) [Safety and Tolerability]

Time frame: DLTs - At the end of Cycle 1 AEs/SAES - Duration of intervention (up to 24 months) plus 30 days follow-up

Rate of treatment modifications (interruption or permanent discontinuation) [Safety and Tolerability]

Time frame: Duration of intervention (up to 24 months)

Changes in safety parameters (clinical laboratory tests, vital signs, and electrocardiogram [ECG] / QTcF) [Safety and Tolerability]

Time frame: Duration of intervention (up to 24 months) plus 30 days follow-up

Secondary Outcomes

Overall response rate (ORR) [Efficacy]

Proportion of participants with Best Overall Response (BOR) of complete response (CR) or partial response (PR) confirmed at a minimum of 2 post-baseline radiological assessments, without an intervening response of progressive disease

Time frame: From randomization to confirmed radiological improvement, if applicable, assessed up to 24 months.

Duration of response (DoR)

Time from the date of first confirmed CR or PR (whichever is first recorded) until the date of documented disease progression or death in the absence of disease progression.

Time frame: From first confirmed CR or PR (whichever is first recorded) until the date of documented disease progression or death in the absence of disease progression, assessed up to 24 months.

Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Efficacy]

Time frame: Time from starting treatment until disease progression or death for any reason.

Serum concentrations and PK parameters of EOS006215

Serum concentration-time data will be summarized by descriptive statistics by each treatment cohort and time point. PK parameters, such as Cmax, Cmin, AUC and CL will be derived by non-compartmental analysis and summarized with descriptive statistics.

Time frame: From start of treatment until end of treatment (EOT)

Incidence of antidrug antibody (ADA) against EOS006215

Individual ADA occurrence will be listed, and percentage of occurrence will be summarized by descriptive statistics.