A Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1)

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of escalating doses of ERAS-801 in study participants with recurrent glioblastoma multiforme (GBM). To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-801. To evaluate the antitumor activity of ERAS-801. To evaluate the PK profile of ERAS-801.

Detailed Description
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This is a Phase 1, open-label, multicenter clinical study evaluating ERAS-801 as a monotherapy. The study will initially commence with dose escalation of ERAS-801 in study participants with recurrent GBM. Once the MTD and/or RD has been determined from dose escalation, then dose expansion of ERAS-801 may commence in study participants with recurrent GBM harboring alterations in epidermal growth factor receptor (EGFR).

Official Title
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A Phase 1 Study to Evaluate the CNS-Penetrant EGFR/ERBB1 Inhibitor ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1)

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: ERAS-801


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Willing and able to give written informed consent Diagnosis of Glioblastoma, IDH WT as defined by the WHO 2021 criteria Adequate organ function Willing to comply with all protocol-required visits, assessments, and procedures Able to swallow oral medication Exclusion Criteria: Prior treatment with an EGFR inhibitor for Glioblastoma Currently enrolled in another therapeutic study History of clinically significant cardiovascular disease Gastrointestinal conditions that may affect administration/absorption of oral medications Have an active infection (bacterial, fungal, or viral) requiring systemic therapy Pregnant or breastfeeding women Any serious underlying medical or psychiatric condition or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study Known allergies, hypersensitivity, or intolerance to ERAS-801 or its excipients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation (Part 1)<br>ERAS-801 will be orally administered to study participants with recurrent GBM in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. | Drug: ERAS-801<br>* Administered orally<br>|
| Experimental: Dose Expansion (Part 2)<br>ERAS-801 will be orally administered at the recommended dose (as determined from Part 1) to study participants with recurrent GBM harboring alterations in EGFR. | Drug: ERAS-801<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT) | Based on adverse events observed during dose escalation | Study Day 1 up to Day 29 | 
| Maximum Tolerated Dose (MTD) | Based on adverse events observed during dose escalation | Study Day 1 up to Day 29 | 
| Recommended Dose (RD) | Based on adverse events observed during dose escalation | Study Day 1 up to Day 29 | 
| Adverse Events | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 24 months from time of first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration (Cmax) | Maximum plasma or serum concentration of ERAS-801 | Study Day 1 up to Day 29 | 
| Time to achieve Cmax (Tmax) | Time to achieve maximum plasma or serum concentration of ERAS-801 | Study Day 1 up to Day 29 | 
| Area under the curve | Area under the plasma concentration-time curve of ERAS-801 | Study Day 1 up to Day 29 | 
| Half-life | Half-life of ERAS-801 | Study Day 1 up to Day 29 | 
| Objective Response Rate (ORR) | Based on assessment of radiographic imaging per modified RANO response assessment | Assessed up to 24 months from time of first dose | 
| Duration of Response (DOR) | Based on assessment of radiographic imaging per modified RANO response assessment | Assessed up to 24 months from time of first dose | 
| Time to Response (TTR) | Based on assessment of radiographic imaging per modified RANO response assessment | Assessed up to 24 months from time of first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GBM, EGFR, epidermal growth factor receptor, alteration, ERBB1