A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (HERKULES-1)

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)

• 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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: ERAS-007; Drug: ERAS-601

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute (HealthONE)
  • Florida
    • Sarasota, Florida, United States, 34232
      • Sarah Cannon Research Institute (Florida Cancer Specialists)
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (Tennessee Oncology)
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology

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.
• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Part A): ERAS-007 Monotherapy, BID-QW dosing; ERAS-007 monotherapy will be administered BID-QW in sequential ascending doses to participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.	Drug: ERAS-007; ERAS-007 will be administered orally as specified in Arm description.
Experimental: Dose Expansion (Part B): ERAS-007 Monotherapy, QW dosing; ERAS-007 monotherapy will be administered at 250 mg QW to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.	Drug: ERAS-007; ERAS-007 will be administered orally as specified in Arm description.
Experimental: Dose Expansion (Part C): ERAS-007 Monotherapy, BID-QW dosing (if necessary); Depending on data generated from Part A, ERAS-007 monotherapy may be administered at the BID-QW RD to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.	Drug: ERAS-007; ERAS-007 will be administered orally as specified in Arm description.
Experimental: Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601; Experimental: Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601 ERAS-007 will be administered BID-QW in combination with ERAS-601 administered BID 3/1 to study participants with advanced or metastatic solid tumors that harbor specific molecular targets in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.	Drug: ERAS-007; ERAS-007 will be administered orally as specified in Arm description.; Drug: ERAS-601; ERAS-601 will be administered orally as specified in Arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Dose Limiting Toxicities (DLT)	Based on adverse events observed	Study Day 1 up to Day 29
Maximum tolerated dose (MTD)	Based on adverse events observed	Study Day 1 up to Day 29
Recommended dose (RD)	Based on adverse events observed	Study Day 1 up to Day 29
Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-007	Study Day 1 up to Day 29
Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-007 and ERAS-601	Study Day 1 up to Day 29
Area under the curve	Area under the plasma concentration-time curve of ERAS-007 and ERAS-601	Study Day 1 up to Day 29
Half-life	Half-life of ERAS-007 and ERAS-601	Study Day 1 up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Erasca, Inc.
• Investigators: Study Director: Wei Lin, M.D., Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): May 7, 2021
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: April 24, 2021
• First Submitted That Met QC Criteria: April 27, 2021
• First Posted (Actual): April 29, 2021

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: solid tumor; SHP2; neoplasms; ERK; advanced solid tumor; metastatic solid tumor; solid malignancies; MAPK
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ERAS-007-01

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