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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 : January 5, 2022
Sponsor:
Information provided by (Responsible Party):
Erasca, Inc.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: ERAS-007 Drug: Encorafenib Drug: Cetuximab Drug: Palbociclib Phase 1 Phase 2

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. 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.
Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation (Part 1): 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.
 Drug: ERAS-007
Administered orally

Drug: Encorafenib
Administered orally
Other Name: Braftovi

Drug: Cetuximab
Administered via intravenous infusion
Other Name: Erbitux
Experimental: Dose Escalation (Part 2): ERAS-007 in combination with palbociclib
ERAS-007 will be orally administered in combination with palbociclib to study participants with KRASm or NRASm CRC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
 Drug: ERAS-007
Administered orally

Drug: Palbociclib
Administered orally
Other Name: Ibrance
Experimental: Dose Expansion (Part 3): ERAS-007 in combination with encorafenib and cetuximab
ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with encorafenib and cetuximab to study participants with BRAFm CRC.
 Drug: ERAS-007
Administered orally

Drug: Encorafenib
Administered orally
Other Name: Braftovi

Drug: Cetuximab
Administered via intravenous infusion
Other Name: Erbitux
Experimental: Dose Expansion (Part 4): ERAS-007 in combination with palbociclib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with palbociclib to study participants with KRASm or NRASm CRC.
 Drug: ERAS-007
Administered orally

Drug: Palbociclib
Administered orally
Other Name: Ibrance


Outcome Measures
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Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on adverse events observed during dose escalation

  2. Maximum Tolerated Dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on adverse events observed during dose escalation

  3. Recommended Dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on adverse events observed during dose escalation

  4. Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
    Incidence and severity of treatment-emergent AEs and serious AEs


Secondary Outcome Measures :
  1. Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]
    Maximum plasma or serum concentration of ERAS-007 and other cancer therapies

  2. 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

  3. 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

  4. Half-life [ Time Frame: Study Day 1 up to Day 29 ]
    Half-life of ERAS-007 and other cancer therapies

  5. 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

  6. 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


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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) 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 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.
Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Erasca Clinical Team +1-858-465-6511 clinicaltrials@erasca.com

Locations
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United States, Alabama
University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center) Not yet recruiting
Birmingham, Alabama, United States, 35233
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Michigan
Henry Ford Cancer Institute Not yet recruiting
Detroit, Michigan, United States, 48202
United States, Missouri
Washington University (Siteman Cancer Center) Not yet 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
Sponsors and Collaborators
Erasca, Inc.
Investigators
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Study Director: Kimberly Komatsubara, M.D. Senior Medical Director
More Information
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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: January 5, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Erasca, Inc.:
BRAF
V600E
KRAS
NRAS
mutation
Braftovi
encorafenib
Erbitux
cetuximab
Ibrance
 palbociclib
ERK
MAPK
CDK4/6
CRC
colorectal cancer
EGFR
GI neoplasm
gastrointestinal neoplasm
Additional relevant MeSH terms:
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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