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

Sponsor

Erasca, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05222802

Collaborator

(none)

Enrollment

Locations

Arms

43.1

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Multiforme	Drug: ERAS-801	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 25, 2022

Anticipated Primary Completion Date :

Jan 31, 2025

Anticipated Study Completion Date :

Sep 30, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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
Recommended Dose (RD) [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

Secondary Outcome Measures

Plasma concentration (Cmax) [Study Day 1 up to Day 29]
Maximum plasma or serum concentration of ERAS-801
Time to achieve Cmax (Tmax) [Study Day 1 up to Day 29]
Time to achieve maximum plasma or serum concentration of ERAS-801
Area under the curve [Study Day 1 up to Day 29]
Area under the plasma concentration-time curve of ERAS-801
Half-life [Study Day 1 up to Day 29]
Half-life 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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Miami Cancer Institute-Baptist Heath South Florida	Miami	Florida	United States	33176
2	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Henry Ford Health System	Detroit	Michigan	United States	48202
4	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10022
5	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee	United States	37203