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

Phase 1

Active, not recruiting

• Conditions: Glioblastoma Multiforme
• Interventions: Drug: ERAS-801

• Registration Number: NCT05222802
• Lead Sponsor: Erasca, Inc.

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).

Study Timeline

• Study First Submitted: 2022-01-24
• Study First Submitted QC: 2022-01-24
• Study First Posted: 2022-02-03
• Study Start: 2022-02-25
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-30
• Last Update Posted: 2024-01-31
• Primary Completion: 2025-01-31
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 52

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation (Part 1)	ERAS-801	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.
Dose Expansion (Part 2)	ERAS-801	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (8)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

University of California, Los Angeles; 🇺🇸 Los Angeles, California, United States

Miami Cancer Institute-Baptist Heath South Florida; 🇺🇸 Miami, Florida, United States

Huntsman Cancer Institute; 🇺🇸 Salt Lake City, Utah, United States

Sarah Cannon Research Institute (Tennessee Oncology); 🇺🇸 Nashville, Tennessee, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States