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

Metastatic Colorectal Cancer Clinical Trial

— HERKULES-3  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05039177
• Other study ID #: ERAS-007-03
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 20, 2021
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: Erasca, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. - 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: December 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer
• Metastatic Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• ERAS-007
Administered orally
• Encorafenib
Administered orally
• Cetuximab
Administered via intravenous infusion
• Palbociclib
Administered orally

Locations

Country	Name	City	State
United States	The Johns Hopkins Hospital	Baltimore	Maryland
United States	University of Alabama at Birmingham (O'Neal Comprehensive Cancer Center)	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Henry Ford Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke Cancer Institute	Durham	North Carolina
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of California Irvine College of Medicine	Orange	California
United States	Washington University (Siteman Cancer Center)	Saint Louis	Missouri
United States	UCSF Mount Zion Medical Ctr	San Francisco	California
United States	University of Washington - Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Erasca, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicities (DLT)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Primary	Maximum Tolerated Dose (MTD)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Primary	Recommended Dose (RD)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Primary	Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Secondary	Plasma concentration (Cmax)	Maximum plasma or serum concentration of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
Secondary	Time to achieve Cmax (Tmax)	Time to achieve maximum plasma or serum concentration of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
Secondary	Area under the curve	Area under the plasma concentration-time curve of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
Secondary	Half-life	Half-life of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
Secondary	Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose