A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors

NCT ID: NCT04670679

Last Updated: 2025-02-12

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-15
• Study Completion Date: 2026-02-28

Brief Summary

• To evaluate the safety and tolerability of escalating doses of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies in study participants with advanced or metastatic solid tumors.
• To determine the Maximum Tolerated Dose (MTD) and/or recommended dose (RD) of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
• To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
• To evaluate the antitumor activity of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.

Detailed Description

This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other cancer therapies. The study will commence with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in combination with other cancer therapies. Once the monotherapy MTD and/or RD has been determined, then dose expansion of ERAS-601 monotherapy may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once the combination therapy MTD and/or RD has been determined, then dose expansion of that combination may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations.

Conditions

Advanced or Metastatic Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dose Escalation (Part A): ERAS-601 monotherapy

ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Dose Escalation (Part B): ERAS-601 monotherapy

ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent.

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Dose Escalation (Part C): ERAS-601 monotherapy

ERAS-601 will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent.

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab

ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Cetuximab

Intervention Type: DRUG

Administered via intravenous infusion

Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab

ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Pembrolizumab

Intervention Type: DRUG

Administered via intravenous infusion

Interventions

ERAS-601

Administered orally

Intervention Type: DRUG

Cetuximab

Administered via intravenous infusion

Intervention Type: DRUG

Pembrolizumab

Administered via intravenous infusion

Intervention Type: DRUG

Other Intervention Names

Erbitux; Keytruda

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 years
• Willing and able to give written informed consent
• Have histologically or cytologically confirmed advanced or metastatic solid tumor
• 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
• Able to swallow oral medication
• Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• Adequate cardiovascular, hematological, liver, and renal function
• Willing to comply with all protocol-required visits, assessments, and procedures

Exclusion Criteria

• Previous treatment with a SHP2 inhibitor
• Documented PTPN11 mutations
• Is 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-601
• Received prior palliative radiation within 7 days of Cycle 1, Day 1
• Have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis
• 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
• Active, clinically significant interstitial lung disease or pneumonitis
• History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasca, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Les Brail, PhD

Role: STUDY_DIRECTOR

Clinical Development

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Sarah Cannon Research Institute (Florida Cancer Specialists)

Sarasota, Florida, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Washington University

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

University of North Carolina

Chapel Hill, North Carolina, United States

University of Cincinnati

Cincinnati, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, United States

Mary Crowley Cancer Research

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Linear Clinical Research

Perth, Western Australia, Australia

Countries

United States; Australia

Other Identifiers

ERAS-601-01

Identifier Type: -

Identifier Source: org_study_id