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

• ClinicalTrials.gov Identifier: NCT05222802
• Recruitment Status: Active, not recruiting
• First Posted: February 3, 2022
• Last Update Posted: January 31, 2024
• Sponsor: Erasca, Inc.
• Information provided by (Responsible Party): Erasca, Inc.

Tracking Information

• First Submitted Date: January 24, 2022
• First Posted Date: February 3, 2022
• Last Update Posted Date: January 31, 2024
• Actual Study Start Date: February 25, 2022
• Estimated Primary Completion Date: January 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 24, 2022)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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 Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Glioblastoma Multiforme

Intervention

Drug: ERAS-801

Administered orally

Study Arms

• 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.
  Intervention: Drug: ERAS-801
• 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.
  Intervention: Drug: ERAS-801

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 30, 2024): 52
• Original Estimated Enrollment (submitted: January 24, 2022): 90
• Estimated Study Completion Date: September 30, 2025
• Estimated Primary Completion Date: January 31, 2025 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05222802
• Other Study ID Numbers: ERAS-801-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Erasca, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Erasca, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Les Brail; Medical Director

• PRS Account: Erasca, Inc.
• Verification Date: January 2024