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Metastatic Colorectal CancerPhase 1/2HERKULES-3NCT05039177

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

A Phase 1/2 study testing ERAS-007, Encorafenib and Cetuximab in people with Metastatic Colorectal Cancer and Metastatic Pancreatic Ductal Adenocarcinoma, run by Erasca, Inc. at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ERAS-007, Encorafenib and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
101 participants
Where
14 sitesUnited States
Study dates
20 Sep 2021to 26 Jan 2026
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 14Show fewer
  • 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.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • The Johns Hopkins Hospital

    Baltimore, Maryland, 21287

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

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02215

  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

  • City of Hope

    Duarte, California, 91010

  • Duke Cancer Institute

    Durham, North Carolina, 27710

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Sarah Cannon Research Institute (Tennessee Oncology)

    Nashville, Tennessee, 37203

  • Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • University of California Irvine College of Medicine

    Orange, California, 92868

  • UCSF Mount Zion Medical Ctr

    San Francisco, California, 94158

  • University of Washington - Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • Washington University (Siteman Cancer Center)

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase 1b/2 Study of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Gastrointestinal Malignancies (HERKULES-3)

  • 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.
Read the 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.

Being tested
ERAS-007, Encorafenib, Cetuximab, Palbociclib
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
Medical subject headings
Colorectal Neoplasms, Digestive System Neoplasms, Gastrointestinal Neoplasms, Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ERAS-007Drug

    Administered orally

  • EncorafenibDrug

    Also called Braftovi

    Administered orally

  • CetuximabDrug

    Also called Erbitux

    Administered via intravenous infusion

  • PalbociclibDrug

    Also called Ibrance

    Administered orally

Study groups in NCT05039177
Study groupRoleWhat they receive
Dose Escalation (Parts A1a, A2a, or A3a): ERAS-007 in combination with encorafenib and cetuximabExperimentalERAS-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.
Receives: Drug: ERAS-007; Drug: Encorafenib; Drug: Cetuximab
Dose Escalation (Parts B1a, B2a, B3a or B4a): ERAS-007 in combination with palbociclibExperimentalERAS-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.
Receives: Drug: ERAS-007; Drug: Palbociclib
Dose Expan (Parts A1b, A1c, A2b, A2c, A3b, or A3c): ERAS-007 in combo with encorafenib & cetuximabExperimentalERAS-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.
Receives: Drug: ERAS-007; Drug: Encorafenib; Drug: Cetuximab
Dose Expansion (Parts B1b, B2b, B3b, and B4b): ERAS-007 in combination with palbociclibExperimentalERAS-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.
Receives: Drug: ERAS-007; Drug: Palbociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities (DLT)

    Based on adverse events observed during dose escalation

    Measured: Study Day 1 up to Day 29

  2. Maximum Tolerated Dose (MTD)

    Based on adverse events observed during dose escalation

    Measured: Study Day 1 up to Day 29

  3. Recommended Dose (RD)

    Based on adverse events observed during dose escalation

    Measured: Study Day 1 up to Day 29

  4. Adverse Events

    Incidence and severity of treatment-emergent AEs and serious AEs

    Measured: Assessed up to 24 months from time of first dose

Secondary outcomes (6)

  1. Plasma concentration (Cmax)

    Maximum plasma or serum concentration of ERAS-007 and other cancer therapies

    Measured: Study Day 1 up to Day 29

  2. Time to achieve Cmax (Tmax)

    Time to achieve maximum plasma or serum concentration of ERAS-007 and other cancer therapies

    Measured: Study Day 1 up to Day 29

  3. Area under the curve

    Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies

    Measured: Study Day 1 up to Day 29

  4. Half-life

    Half-life of ERAS-007 and other cancer therapies

    Measured: Study Day 1 up to Day 29

  5. Objective Response Rate (ORR)

    Based on assessment of radiographic imaging per RECIST version 1.1

    Measured: Assessed up to 24 months from time of first dose

  6. Duration of Response (DOR)

    Based on assessment of radiographic imaging per RECIST version 1.1

    Measured: Assessed up to 24 months from time of first dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2021
  2. Study start20 Sep 2021
  3. Primary completion15 Aug 2025
  4. Study completion26 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
101 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05039177
Sponsor's protocol ID
ERAS-007-03
Acronym
HERKULES-3
Status last verified
Mar 2026
First submitted
1 Sep 2021
Last updated
25 Mar 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ERAS-007, Encorafenib and Cetuximab in people with Metastatic Colorectal Cancer and Metastatic Pancreatic Ductal Adenocarcinoma, run by Erasca, Inc. at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicities (DLT) (time frame: Study Day 1 up to Day 29). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05039177.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2026.

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