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

NCT04670679 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-601-01
• Study Type: interventional
• Target: 90
• Locations: 2 countries
• Sites: 14

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.

Conditions

Advanced or Metastatic Solid Tumors

Keywords

SHP2; PTPN11; solid tumor; advanced solid tumor; metastatic solid tumor; neoplasms; solid malignancies; targeted therapy; colorectal cancer; CRC; head and neck squamous cell carcinoma; HPV Negative HNSCC; molecular alterations; cetuximab; Erbitux; Chordoma

Outcome Measures

Primary Outcomes (8)

• Dose Limiting Toxicities (DLT)

  Based on toxicities observed

  Study Day 1 up to Day 29

• Maximum tolerated dose (MTD)

  Based on toxicities observed

  Study Day 1 up to Day 29

• Recommended dose (RD)

  Based on toxicities 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-601 and cetuximab or pembrolizumab (if applicable)

  Study Day 1 up to Day 29

• Time to achieve Cmax (Tmax)

  Time to achieve maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)

  Study Day 1 up to Day 29

• Area under the curve

  Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)

  Study Day 1 up to Day 29

• Half-life

  Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)

  Study Day 1 up to Day 29

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Assessed up to 24 months from time of first dose

• Duration of Response (DOR)

  Assessed up to 24 months from time of first dose

• Time to Response (TTR)

  Assessed up to 24 months from time of first dose

Other Outcomes (1)

• Pharmacodynamic assessment

  Assessed up to 24 months from time of first dose

Study Arms (5)

Dose Escalation (Part A): ERAS-601 monotherapy

EXPERIMENTAL

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.

Drug: ERAS-601

Dose Escalation (Part B): ERAS-601 monotherapy

EXPERIMENTAL

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.

Drug: ERAS-601

Dose Escalation (Part C): ERAS-601 monotherapy

EXPERIMENTAL

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.

Drug: ERAS-601

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

EXPERIMENTAL

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).

Drug: ERAS-601; Drug: Cetuximab

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

EXPERIMENTAL

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).

Drug: ERAS-601; Drug: Pembrolizumab

Interventions

Cetuximab DRUG

Administered via intravenous infusion

Also known as: Erbitux

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

Pembrolizumab DRUG

Administered via intravenous infusion

Also known as: Keytruda

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

ERAS-601 DRUG

Administered orally

Dose Escalation (Part A): ERAS-601 monotherapy; Dose Escalation (Part B): ERAS-601 monotherapy; Dose Escalation (Part C): ERAS-601 monotherapy; Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab; Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Sarah Cannon Research Institute (Florida Cancer Specialists)

Sarasota, Florida, 34232, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89014, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Location

Linear Clinical Research

Perth, Western Australia, Australia

Location

MeSH Terms

Conditions

Noonan Syndrome; Neoplasm Metastasis; Neoplasms; Colorectal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Chordoma

Interventions

Cetuximab; pembrolizumab

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Germ Cell and Embryonal

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Les Brail, PhD

  Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 17, 2020
• Study Start: December 15, 2020
• Primary Completion: February 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (2); US (12)