A Study Of ERAS-007 In Patients With Advanced Gastrointestinal Malignancies

Study Overview

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

* 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.

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.

Metastatic Colorectal Cancer
Metastatic Pancreatic Ductal Adenocarcinoma

DRUG: ERAS-007
DRUG: Encorafenib
DRUG: Cetuximab
DRUG: Palbociclib

ERAS-007-03

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2021-09-01	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-02-10
First Submitted that Met QC Criteria 2021-09-01	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-02-11
First Posted (ACTUAL) 2021-09-09	Results First Posted N/A	Last Verified 2025-02

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/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.	DRUG: ERAS-007 Administered orally DRUG: Encorafenib Administered orally DRUG: Cetuximab Administered via intravenous infusion
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.	DRUG: ERAS-007 Administered orally DRUG: Palbociclib Administered orally
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.	DRUG: Encorafenib Administered orally DRUG: Cetuximab Administered via intravenous infusion
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: Palbociclib Administered orally

Primary Outcome Measures	Measure Description	Time Frame
Dose Limiting Toxicities (DLT)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Maximum Tolerated Dose (MTD)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Recommended Dose (RD)	Based on adverse events observed during dose escalation	Study Day 1 up to Day 29
Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose

Secondary Outcome Measures	Measure Description	Time Frame
Plasma concentration (Cmax)	Maximum plasma or serum concentration of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
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
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
Half-life	Half-life of ERAS-007 and other cancer therapies	Study Day 1 up to Day 29
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
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Joyce Antal, Clinical Development

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record