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

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

• 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Glioblastoma Multiforme
• Intervention / Treatment: Drug: 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 Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute-Baptist Heath South Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (Tennessee Oncology)
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Part 1); 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; Administered orally
Experimental: Dose Expansion (Part 2); 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; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
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

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

Collaborators and Investigators

• Sponsor: Katmai Pharmaceuticals Inc.
• Collaborators: Erasca, Inc.
• Investigators: Study Director: Les Brail, Medical director

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2022
• Primary Completion (Estimated): August 31, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: January 24, 2022
• First Posted (Actual): February 3, 2022

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: GBM; EGFR; epidermal growth factor receptor; alteration; ERBB1
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: ERAS-801-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No