A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC (HERKULES-2)

July 24, 2023 updated by: Erasca, Inc.

A Phase 1b Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Advanced Non-Small-Cell Lung Cancer

  • To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced non-small cell lung cancer (NSCLC).
  • To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
  • To evaluate the antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies.
  • To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 1b, open-label, multicenter master protocol evaluating safety, tolerability, and antitumor activity of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with advanced NSCLC. The study will commence with the following dose escalation cohorts: ERAS-007 plus osimertinib in study participants with advanced NSCLC harboring epidermal growth factor receptor-sensitizing mutation(s) (EGFRm); ERAS-007 or ERAS-601 plus sotorasib in study participants with advanced NSCLC harboring Kirsten rat sarcoma G12C mutation (KRAS G12Cm). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with advanced EGFRm or KRAS G12Cm NSCLC.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

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

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • Orange, California, United States, 92868
        • UC Irvine, Chao Family Comprehensive Cancer Center
      • Santa Monica, California, United States, 90404
        • UC Los Angeles
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Research Institute
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center (John Theurer Cancer Center)
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute (Tennessee Oncology)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists

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.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years.
  • Willing and able to give written informed consent.
  • Have histologically or cytologically confirmed NSCLC, with presence of EGFR mutation(s) sensitive to EGFR inhibitors, or KRAS G12C mutation.
  • 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:

  • Concurrent treatment with any systemic anticancer therapy for NSCLC, including any approved or investigational agent.
  • For participants with EGFRm NSCLC: prior therapy with a RAS, RAF, MEK, or ERK inhibitor.
  • For participants with KRAS G12Cm NSCLC: prior therapy with a SHP2, ERK, or KRAS G12C inhibitor (depending on which cohort is being considered for enrollment).
  • Palliative radiotherapy within 7 days of enrollment.
  • History of unacceptable toxicity to treatment with osimertinib or sotorasib.
  • Major surgery within the 28 days of enrollment.
  • Unresolved toxicities from prior systemic therapy greater than NCI CTCAE grade 1 at time of enrollment, except for toxicities not considered a safety risk (eg, alopecia, vitiligo, and grade 2 neuropathy due to prior chemotherapy).
  • History of another malignancy ≤5 years prior to first dose, except for patients who are disease-free for >2 years after treatment with curative intent or who have carcinoma in situ.
  • Symptomatic and unstable brain metastases, or spinal cord compression, except for patients who have completed definitive therapy (surgery or radiotherapy), are not on steroids, and have a stable neurologic status for a least 2 weeks after completion of the definitive therapy and steroids.
  • History of or clinically active ILD, drug induced ILD, or radiation pneumonitis that required steroid treatment.
  • Impaired cardiovascular function or clinically significant cardiovascular disease.
  • History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO.
  • 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.
  • Pregnant or breastfeeding women.
  • Contraindication to osimertinib or sotorasib use as per local label.

Study Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Escalation (Part 1): ERAS-007 plus osimertinib
ERAS-007 will be orally administered in combination with osimertinib to study participants with EGFRm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-007
Administered orally
Drug: Osimertinib
Administered orally
Other Names:
  • Tagrisso
Experimental: Dose Escalation (Part 2): ERAS-007 plus sotorasib
ERAS-007 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-007
Administered orally
Drug: Sotorasib
Administered orally
Other Names:
  • Lumakras
Experimental: Dose Escalation (Part 3): ERAS-601 plus sotorasib
ERAS-601 will be orally administered in combination with sotorasib to study participants with KRAS G12Cm NSCLC in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-601
Administered orally
Drug: Sotorasib
Administered orally
Other Names:
  • Lumakras
Experimental: Dose Expansion (Part 4): ERAS-007 plus osimertinib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 1) in combination with osimertinib to study participants with EGFRm NSCLC.
Drug: ERAS-007
Administered orally
Drug: Osimertinib
Administered orally
Other Names:
  • Tagrisso
Experimental: Dose Expansion (Part 5): ERAS-007 plus sotorasib
ERAS-007 will be orally administered at the recommended dose (as determined from Part 2) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
Drug: ERAS-007
Administered orally
Drug: Sotorasib
Administered orally
Other Names:
  • Lumakras
Experimental: Dose Expansion (Part 6): ERAS-601 plus sotorasib
ERAS-601 will be orally administered at the recommended dose (as determined from Part 3) in combination with sotorasib to study participants with KRAS G12Cm NSCLC.
Drug: ERAS-601
Administered orally
Drug: Sotorasib
Administered orally
Other Names:
  • Lumakras

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
Assessed up to 24 months from time of first dose
Dose Limiting Toxicities (DLT)
Time Frame: Study Day 1 up to Day 22
Based on adverse events observed
Study Day 1 up to Day 22
Maximum Tolerated Dose (MTD)
Time Frame: Study Day 1 up to Day 22
Based on adverse events observed
Study Day 1 up to Day 22
Recommended Dose (RD)
Time Frame: Study Day 1 up to Day 22
Based on adverse events observed
Study Day 1 up to Day 22

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Assessed up to 24 months from time of first dose
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
Assessed up to 24 months from time of first dose
Plasma concentration (Cmax)
Time Frame: Study Day 1 up to Day 22
Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Study Day 1 up to Day 22
Time to achieve Cmax (Tmax)
Time Frame: Study Day 1 up to Day 22
Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Study Day 1 up to Day 22
Area under the curve
Time Frame: Study Day 1 up to Day 22
Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies
Study Day 1 up to Day 22
Half-life
Time Frame: Study Day 1 up to Day 22
Half-life of ERAS-007 or ERAS-601 and other cancer therapies
Study Day 1 up to Day 22

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Erasca, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Joyce Antal, Senior Director, Clinical Development

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 Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 2, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 27, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 27, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 2, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 2, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 13, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 25, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 24, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ERAS-007-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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