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

NCT ID: NCT05039177

Last Updated: 2025-02-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-20
• Study Completion Date: 2025-12-31

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.

Detailed Description

This is a Phase 1b/2, open-label, multicenter clinical study evaluating ERAS-007 in combination with other cancer therapies in study participants with GI malignancies. This study will serve as a platform study, allowing for evaluation of safety/tolerability and efficacy of ERAS-007 in combination with other cancer therapies. The study will initially commence with dose escalation of ERAS-007 administered in combination with encorafenib and cetuximab in study participants with metastatic colorectal cancer (CRC) harboring B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation; and dose escalation of ERAS-007 administered in combination with palbociclib in study participants with metastatic CRC harboring Kirsten rat sarcoma (KRAS) or neuroblastoma rat sarcoma (NRAS) mutations and metastatic pancreatic adenocarcinoma with (PDAC) KRAS mutation. Dose expansion will follow and will test ERAS-007 administered at the RD identified from each dose escalation arm in study participants with metastatic CRC.

Conditions

Metastatic Colorectal Cancer; Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

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

Study Groups

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Encorafenib

Intervention Type: DRUG

Administered orally

Cetuximab

Intervention Type: DRUG

Administered via intravenous infusion

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Palbociclib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Encorafenib

Intervention Type: DRUG

Administered orally

Cetuximab

Intervention Type: DRUG

Administered via intravenous infusion

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Palbociclib

Intervention Type: DRUG

Administered orally

Interventions

ERAS-007

Administered orally

Intervention Type: DRUG

Encorafenib

Administered orally

Intervention Type: DRUG

Cetuximab

Administered via intravenous infusion

Intervention Type: DRUG

Palbociclib

Administered orally

Intervention Type: DRUG

Other Intervention Names

Braftovi; Erbitux; Ibrance

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• 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

Joyce Antal

Role: STUDY_DIRECTOR

Clinical Development

Locations

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

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

University of California Irvine College of Medicine

Orange, California, United States

UCSF Mount Zion Medical Ctr

San Francisco, California, United States

The Johns Hopkins Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Henry Ford Cancer Institute

Detroit, Michigan, United States

Washington University (Siteman Cancer Center)

St Louis, Missouri, United States

Duke Cancer Institute

Durham, North Carolina, United States

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

University of Washington - Seattle Cancer Care Alliance

Seattle, Washington, United States

Countries

United States

Other Identifiers

ERAS-007-03

Identifier Type: -

Identifier Source: org_study_id