Clinical trial NCT05222802: A Study to Evaluate ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1)
Official title: A Phase 1 Study to Evaluate the CNS-Penetrant EGFR/ERBB1 Inhibitor ERAS-801 in Patients With Recurrent Glioblastoma (THUNDERBBOLT-1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Glioblastoma Multiforme
Keywords: GBM
EGFR
epidermal growth factor receptor
alteration
ERBB1
Lead sponsor: Erasca, Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-03
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: * 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Study Day 1 up to Day 29
measure: Maximum Tolerated Dose (MTD)
timeFrame: Study Day 1 up to Day 29
measure: Recommended Dose (RD)
timeFrame: Study Day 1 up to Day 29
measure: Adverse Events
timeFrame: Assessed up to 24 months from time of first dose
Secondary outcomes:
measure: Plasma concentration (Cmax)
timeFrame: Study Day 1 up to Day 29
measure: Time to achieve Cmax (Tmax)
timeFrame: Study Day 1 up to Day 29
measure: Area under the curve
timeFrame: Study Day 1 up to Day 29
measure: Half-life
timeFrame: Study Day 1 up to Day 29
measure: Objective Response Rate (ORR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Duration of Response (DOR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Time to Response (TTR)
timeFrame: Assessed up to 24 months from time of first dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Miami
country: United States
facility: Miami Cancer Institute-Baptist Heath South Florida
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Tennessee Oncology)
state: Tennessee
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
Study officials:
affiliation: Medical Director
name: Les Brail
role: STUDY_DIRECTOR
References: