A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (HERKULES-3)
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ClinicalTrials.gov Identifier: NCT05039177 |
Recruitment Status :
Recruiting
First Posted : September 9, 2021
Last Update Posted : December 1, 2022
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- 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.
Condition or disease | Intervention/treatment | Phase |
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Metastatic Colorectal Cancer Metastatic Pancreatic Ductal Adenocarcinoma | Drug: ERAS-007 Drug: Encorafenib Drug: Cetuximab Drug: Palbociclib | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 200 participants |
Allocation: | Non-Randomized |
Intervention Model: | Sequential Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase 1b/2 Study of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Gastrointestinal Malignancies (HERKULES-3) |
Actual Study Start Date : | September 20, 2021 |
Estimated Primary Completion Date : | August 2024 |
Estimated Study Completion Date : | December 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: 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.
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Drug: ERAS-007
Administered orally Drug: Encorafenib Administered orally
Other Name: Braftovi Drug: Cetuximab Administered via intravenous infusion
Other Name: Erbitux |
Experimental: 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.
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Drug: ERAS-007
Administered orally Drug: Palbociclib Administered orally
Other Name: Ibrance |
Experimental: 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.
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Drug: ERAS-007
Administered orally Drug: Encorafenib Administered orally
Other Name: Braftovi Drug: Cetuximab Administered via intravenous infusion
Other Name: Erbitux |
Experimental: 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.
|
Drug: ERAS-007
Administered orally Drug: Palbociclib Administered orally
Other Name: Ibrance |
- Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]Based on adverse events observed during dose escalation
- Maximum Tolerated Dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]Based on adverse events observed during dose escalation
- Recommended Dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]Based on adverse events observed during dose escalation
- Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]Incidence and severity of treatment-emergent AEs and serious AEs
- Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]Maximum plasma or serum concentration of ERAS-007 and other cancer therapies
- Time to achieve Cmax (Tmax) [ Time Frame: Study Day 1 up to Day 29 ]Time to achieve maximum plasma or serum concentration of ERAS-007 and other cancer therapies
- Area under the curve [ Time Frame: Study Day 1 up to Day 29 ]Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies
- Half-life [ Time Frame: Study Day 1 up to Day 29 ]Half-life of ERAS-007 and other cancer therapies
- Objective Response Rate (ORR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1
- Duration of Response (DOR) [ Time Frame: Assessed up to 24 months from time of first dose ]Based on assessment of radiographic imaging per RECIST version 1.1

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05039177
Contact: Erasca Clinical Team | +1-858-465-6511 | clinicaltrials@erasca.com |
United States, Alabama | |
University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center) | Recruiting |
Birmingham, Alabama, United States, 35233 | |
United States, California | |
City of Hope | Recruiting |
Duarte, California, United States, 91010 | |
University of California Irvine College of Medicine | Recruiting |
Orange, California, United States, 92868 | |
UCSF Mount Zion Medical Ctr | Recruiting |
San Francisco, California, United States, 94158 | |
United States, Maryland | |
The Johns Hopkins Hospital | Recruiting |
Baltimore, Maryland, United States, 21287 | |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02215 | |
United States, Michigan | |
Henry Ford Cancer Institute | Recruiting |
Detroit, Michigan, United States, 48202 | |
United States, Missouri | |
Washington University (Siteman Cancer Center) | Recruiting |
Saint Louis, Missouri, United States, 63110 | |
United States, North Carolina | |
Duke Cancer Institute | Recruiting |
Durham, North Carolina, United States, 27710 | |
United States, Oklahoma | |
Stephenson Cancer Center | Recruiting |
Oklahoma City, Oklahoma, United States, 73104 | |
United States, Tennessee | |
Sarah Cannon Research Institute (Tennessee Oncology) | Recruiting |
Nashville, Tennessee, United States, 37203 | |
United States, Texas | |
The University of Texas MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
United States, Virginia | |
Virginia Cancer Specialists | Recruiting |
Fairfax, Virginia, United States, 22031 | |
United States, Washington | |
University of Washington - Seattle Cancer Care Alliance | Recruiting |
Seattle, Washington, United States, 98109 |
Study Director: | Wei Lin, M.D. | Chief Medical Officer |
Responsible Party: | Erasca, Inc. |
ClinicalTrials.gov Identifier: | NCT05039177 |
Other Study ID Numbers: |
ERAS-007-03 |
First Posted: | September 9, 2021 Key Record Dates |
Last Update Posted: | December 1, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases |
Intestinal Diseases Rectal Diseases Cetuximab Palbociclib Antineoplastic Agents, Immunological Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |