A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors

Advanced or Metastatic Solid Tumors Clinical Trial

— HERKULES-1  

Official title:

A Phase 1b/2, Open-label, Multi-center Study of ERAS-007 (ERK Inhibitor) Administered as Monotherapy or in Combination With ERAS-601 (SHP2 Inhibitor) in Patients With Advanced or Metastatic Solid Tumors (HERKULES-1)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04866134
• Other study ID #: ERAS-007-01
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 7, 2021
• Est. completion date: November 1, 2024

Study information

• Verified date: June 2023
• Source: Erasca, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

• To evaluate the safety and tolerability of ERAS-007 monotherapy administered once weekly (QW) and twice daily-once weekly (BID-QW).

• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 monotherapy administered BID-QW.

• To characterize the pharmacokinetic (PK) profile of ERAS-007 monotherapy.

• To determine the optimal dose and schedule of ERAS-007 monotherapy.

• To evaluate antitumor activity of ERAS-007 in various solid tumors.

• To evaluate the safety and tolerability of ERAS-007 (BID-QW) and ERAS-601 (twice daily for three weeks on and 1 week off (BID 3/1)) when administered in combination.

• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with ERAS-601.

• To characterize the pharmacokinetic (PK) profile of ERAS-007 and ERAS-601 when administered in combination.

• To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors

• To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors

Description:

This is a Phase 1b/2, open-label, multicenter clinical study of ERAS-007 monotherapy (QW or BID-QW) administered either QW or BID-QWand ERAS-007 (BID-QW) in combination with ERAS-601 (BID 3/1). The monotherapy RD on a weekly schedule has been determined to be 250 mg QW in a previous study. The dose escalation phases of this study will test ERAS-007 monotherapy administered BID-QW as a monotherapy or in combination with ERAS-601 in participants with any solid tumor. The monotherapy RD on a weekly schedule has been determined to be 250 mg QW in a previous study. In parallel, the dose expansion phase of this study will test ERAS-007 monotherapy administered at the RD of 250 mg QW in participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once sufficient safety and PK data are available from the BID-QW dose escalation phase, the Sponsor will then determine the optimal dose and schedule of ERAS-007 administered as a monotherapy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: November 1, 2024
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Age = 18 years.

• Willing and able to give written informed consent.

• Have histologically or cytologically confirmed advanced or metastatic solid tumor with a relevant molecular alteration (as applicable).

• There is no available standard systemic therapy available for the patient's tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy.

• Recovered from all toxicities associated with prior treatment to acceptable baseline status.

• Have ECOG performance status of 0 or 1 with an anticipated life expectancy of > 12 weeks.

• Willing to comply with all protocol-required visits, assessments, and procedures.

• Able to swallow oral medication.

Exclusion Criteria:

• Currently receiving another study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-007.

• Received previous treatment with an ERK inhibitor.

• For participants being considered for ERAS-007 + ERAS-601 (Part D): prior treatment with SHP2 inhibitor.

• For participants being considered for ERAS-007 + ERAS-601 (Part D): documented PTPN11 mutations

• Received prior antineoplastic therapy within < 21 days or 5 half-lives, whichever is shorter.

• Received prior palliative radiation within 7 days of first dose of ERAS 007 or ERAS-601,

• Received previous treatment with a MAPK inhibitor that resulted in discontinuation due to unacceptable toxicity.

• Prior surgery (e.g., gastric bypass surgery, gastrectomy) or gastrointestinal dysfunction (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that may affect drug absorption.

• Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs.

• Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ERAS-007
ERAS-007 will be administered orally as specified in Arm description.
• ERAS-601
ERAS-601 will be administered orally as specified in Arm description.

Locations

Country	Name	City	State
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Sarah Cannon Research Institute (HealthONE)	Denver	Colorado
United States	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee
United States	NEXT Oncology	San Antonio	Texas
United States	Sarah Cannon Research Institute (Florida Cancer Specialists)	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Erasca, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamic assessment	Assessment of phosphorylated ERK (pERK) inhibition in isolated PBMCs or tumor tissue by immunoblot, IHC or immunofluorescence.	Assessed up to 24 months from time of first dose
Primary	Evaluate safety and tolerability of escalating doses of ERAS-007 BID-QW	Based on adverse events observed	Assessed up to 24 months from time of first dose
Primary	Dose Limiting Toxicities (DLT)	Based on adverse events observed	Study Day 1 up to Day 29
Primary	Maximum tolerated dose (MTD)	Based on adverse events observed	Study Day 1 up to Day 29
Primary	Recommended dose (RD)	Based on adverse events observed	Study Day 1 up to Day 29
Primary	Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Primary	Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-007	Study Day 1 up to Day 29
Primary	Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-007 and ERAS-601	Study Day 1 up to Day 29
Primary	Area under the curve	Area under the plasma concentration-time curve of ERAS-007 and ERAS-601	Study Day 1 up to Day 29
Primary	Half-life	Half-life of ERAS-007 and ERAS-601	Study Day 1 up to Day 29
Secondary	Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Time to Response (TTR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose