A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies

NCT05039177 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-007-03
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 14

Brief Summary

• To evaluate the safety and tolerability of escalating doses of ERAS-007 in combination with other cancer therapies in study participants with advanced GI malignancies.
• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with other cancer therapies.
• To evaluate the antitumor activity of ERAS-007 in combination with other cancer therapies.
• To evaluate the PK profiles of ERAS-007 and other cancer therapies when administered in combination.

Conditions

Metastatic Colorectal Cancer; Metastatic Pancreatic Ductal Adenocarcinoma

Keywords

BRAF; V600E; KRAS; NRAS; mutation; Braftovi; encorafenib; Erbitux; cetuximab; Ibrance; palbociclib; ERK; MAPK; CDK4/6; CRC; colorectal cancer; EGFR; GI neoplasm; gastrointestinal neoplasm; PDAC; Pancreas Cancer

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities (DLT)

  Based on adverse events observed during dose escalation

  Study Day 1 up to Day 29

• Maximum Tolerated Dose (MTD)

  Based on adverse events observed during dose escalation

  Study Day 1 up to Day 29

• Recommended Dose (RD)

  Based on adverse events observed during dose escalation

  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

Secondary Outcomes (6)

• Plasma concentration (Cmax)

  Study Day 1 up to Day 29

• Time to achieve Cmax (Tmax)

  Study Day 1 up to Day 29

• Area under the curve

  Study Day 1 up to Day 29

• Half-life

  Study Day 1 up to Day 29

• Objective Response Rate (ORR)

  Assessed up to 24 months from time of first dose

Study Arms (4)

Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab

EXPERIMENTAL

ERAS-007 will be orally administered in combination with encorafenib and cetuximab to study participants with BRAFm CRC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: ERAS-007; Drug: Encorafenib; Drug: Cetuximab

Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib

EXPERIMENTAL

ERAS-007 will be orally administered in combination with palbociclib to study participants with KRASm or NRASm CRC and KRASm PDAC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: ERAS-007; Drug: Palbociclib

Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab

EXPERIMENTAL

ERAS-007 will be orally administered at the recommended dose (as determined from Parts A1a, A2a or A3a) in combination with encorafenib and cetuximab to study participants with BRAFm CRC.

Drug: ERAS-007; Drug: Encorafenib; Drug: Cetuximab

Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib

EXPERIMENTAL

ERAS-007 will be orally administered at the recommended dose (as determined from Parts B1a, B2a, B3a or B4a) in combination with palbociclib to study participants with KRASm or NRASm CRC.

Drug: ERAS-007; Drug: Palbociclib

Interventions

ERAS-007 DRUG

Administered orally

Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab; Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib; Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab; Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib

Encorafenib DRUG

Administered orally

Also known as: Braftovi

Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab; Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab

Cetuximab DRUG

Administered via intravenous infusion

Also known as: Erbitux

Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab; Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab

Palbociclib DRUG

Administered orally

Also known as: Ibrance

Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib; Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib

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 metastatic CRC harboring applicable mutation(s) (e.g., BRAF V600E; KRAS or NRAS mutations) or metastatic PDAC harboring KRAS mutation based on an analytically validated assay performed on tumor tissue in a certified testing laboratory.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Adequate bone marrow and organ function.
• Have ECOG performance status of 0 or 1.
• Willing to comply with all protocol-required visits, assessments, and procedures.
• Able to swallow oral medication.

You may not qualify if:

• Prior therapy with a RAS, MEK, or ERK inhibitor. Depending on which treatment arm the patient is assigned, other therapies could also be prohibitive.
• Anti-cancer therapy ≤ 21 days or 4 half-lives prior to first dose of study drug, whichever is shorter.
• Palliative radiation ≤ 7 days prior to first dose of study drug.
• Symptomatic brain metastasis or leptomeningeal disease.
• Gastrointestinal conditions that may affect absorption of oral medications
• Active infection requiring systemic therapy, or a known history of HIV infection, hepatitis B virus, or hepatitis C virus.
• History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to first study drug dose.
• Active, clinically significant interstitial lung disease or pneumonitis.
• Impaired cardiovascular function or clinically significant cardiovascular disease.
• History of thromboembolic or cerebrovascular events ≤ 6 months prior to first dose.
• Major surgery within 28 days of enrollment, or anticipation of major surgery during study treatment.
• Known intolerance or contraindication to encorafenib, cetuximab, or palbociclib.
• Pregnant or breastfeeding women.
• Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the patient inappropriate to participate in the study.

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (14)

University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California Irvine College of Medicine

Orange, California, 92868, United States

Location

UCSF Mount Zion Medical Ctr

San Francisco, California, 94158, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

Location

Washington University (Siteman Cancer Center)

St Louis, Missouri, 63110, United States

Location

Duke Cancer Institute

Durham, North Carolina, 27710, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Digestive System Neoplasms; Gastrointestinal Neoplasms; Pancreatic Neoplasms

Interventions

encorafenib; Cetuximab; palbociclib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Joyce Antal

  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: September 1, 2021
• First Posted: September 9, 2021
• Study Start: September 20, 2021
• Primary Completion: August 15, 2025
• Study Completion: January 26, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)