A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies
- Conditions
- Metastatic Pancreatic Ductal AdenocarcinomaMetastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT05039177
- Lead Sponsor
- Erasca, Inc.
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 102
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib ERAS-007 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. Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab ERAS-007 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. Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab Encorafenib 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. Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab ERAS-007 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. Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib ERAS-007 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. Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab Encorafenib 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. Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximab 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. Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclib 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. Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximab 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. Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclib 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.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicities (DLT) Study Day 1 up to Day 29 Based on adverse events observed during dose escalation
Maximum Tolerated Dose (MTD) Study Day 1 up to Day 29 Based on adverse events observed during dose escalation
Adverse Events Assessed up to 24 months from time of first dose Incidence and severity of treatment-emergent AEs and serious AEs
Recommended Dose (RD) Study Day 1 up to Day 29 Based on adverse events observed during dose escalation
- Secondary Outcome Measures
Name Time Method Plasma concentration (Cmax) Study Day 1 up to Day 29 Maximum plasma or serum concentration of ERAS-007 and other cancer therapies
Objective Response Rate (ORR) Assessed up to 24 months from time of first dose Based on assessment of radiographic imaging per RECIST version 1.1
Area under the curve Study Day 1 up to Day 29 Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies
Half-life Study Day 1 up to Day 29 Half-life of ERAS-007 and other cancer therapies
Duration of Response (DOR) Assessed up to 24 months from time of first dose Based on assessment of radiographic imaging per RECIST version 1.1
Time to achieve Cmax (Tmax) Study Day 1 up to Day 29 Time to achieve maximum plasma or serum concentration of ERAS-007 and other cancer therapies
Trial Locations
- Locations (14)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
University of Washington - Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Duke Cancer Institute
🇺🇸Durham, North Carolina, United States
Sarah Cannon Research Institute (Tennessee Oncology)
🇺🇸Nashville, Tennessee, 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
Washington University (Siteman Cancer Center)
🇺🇸Saint Louis, Missouri, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)
🇺🇸Birmingham, Alabama, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States