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

NCT ID: NCT04959981

Last Updated: 2023-07-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-02

Study Completion Date

2023-04-27

Brief Summary

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* 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.

Detailed Description

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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.

Conditions

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Advanced Non-squamous Non-small-cell Lung Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

ERAS-007

Intervention Type DRUG

Administered orally

Osimertinib

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

ERAS-007

Intervention Type DRUG

Administered orally

Sotorasib

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

ERAS-601

Intervention Type DRUG

Administered orally

Sotorasib

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

ERAS-007

Intervention Type DRUG

Administered orally

Osimertinib

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

ERAS-007

Intervention Type DRUG

Administered orally

Sotorasib

Intervention Type DRUG

Administered orally

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.

Group Type EXPERIMENTAL

ERAS-601

Intervention Type DRUG

Administered orally

Sotorasib

Intervention Type DRUG

Administered orally

Interventions

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ERAS-007

Administered orally

Intervention Type DRUG

ERAS-601

Administered orally

Intervention Type DRUG

Osimertinib

Administered orally

Intervention Type DRUG

Sotorasib

Administered orally

Intervention Type DRUG

Other Intervention Names

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Tagrisso Lumakras

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Erasca, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Joyce Antal

Role: STUDY_DIRECTOR

Senior Director, Clinical Development

Locations

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City of Hope

Duarte, California, United States

Site Status

UC Irvine, Chao Family Comprehensive Cancer Center

Orange, California, United States

Site Status

UC Los Angeles

Santa Monica, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Research Institute

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Hackensack University Medical Center (John Theurer Cancer Center)

Hackensack, New Jersey, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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ERAS-007-02

Identifier Type: -

Identifier Source: org_study_id

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