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

NCT04959981 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-007-02
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

Brief Summary

• 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.

Conditions

Advanced Non-squamous Non-small-cell Lung Cancer

Keywords

EGFR; epidermal growth factor receptor; mutation; biomarker; NSCLC; Tagrisso; osimertinib; ERK; MAPK; sotorasib; Lumakras; KRAS; G12C; SHP2; PTPN11; molecular alterations; Kirsten rat sarcoma; Non-small cell lung cancer; Lung neoplasms; Thoracic neoplasms; ERAS-601; ERAS-007

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities (DLT)

  Based on adverse events observed

  Study Day 1 up to Day 22

• Maximum Tolerated Dose (MTD)

  Based on adverse events observed

  Study Day 1 up to Day 22

• Recommended Dose (RD)

  Based on adverse events observed

  Study Day 1 up to Day 22

• Adverse Events

  Incidence and severity of treatment-emergent AEs and serious AEs

  Assessed up to 24 months from time of first dose

Secondary Outcomes (6)

• Plasma concentration (Cmax)

  Study Day 1 up to Day 22

• Time to achieve Cmax (Tmax)

  Study Day 1 up to Day 22

• Area under the curve

  Study Day 1 up to Day 22

• Half-life

  Study Day 1 up to Day 22

• Objective Response Rate (ORR)

  Assessed up to 24 months from time of first dose

Study Arms (6)

Dose Escalation (Part 1): ERAS-007 plus osimertinib

EXPERIMENTAL

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; Drug: Osimertinib

Dose Escalation (Part 2): ERAS-007 plus sotorasib

EXPERIMENTAL

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; Drug: Sotorasib

Dose Escalation (Part 3): ERAS-601 plus sotorasib

EXPERIMENTAL

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; Drug: Sotorasib

Dose Expansion (Part 4): ERAS-007 plus osimertinib

EXPERIMENTAL

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; Drug: Osimertinib

Dose Expansion (Part 5): ERAS-007 plus sotorasib

EXPERIMENTAL

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; Drug: Sotorasib

Dose Expansion (Part 6): ERAS-601 plus sotorasib

EXPERIMENTAL

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; Drug: Sotorasib

Interventions

ERAS-007 DRUG

Administered orally

Dose Escalation (Part 1): ERAS-007 plus osimertinib; Dose Escalation (Part 2): ERAS-007 plus sotorasib; Dose Expansion (Part 4): ERAS-007 plus osimertinib; Dose Expansion (Part 5): ERAS-007 plus sotorasib

ERAS-601 DRUG

Administered orally

Dose Escalation (Part 3): ERAS-601 plus sotorasib; Dose Expansion (Part 6): ERAS-601 plus sotorasib

Osimertinib DRUG

Administered orally

Also known as: Tagrisso

Dose Escalation (Part 1): ERAS-007 plus osimertinib; Dose Expansion (Part 4): ERAS-007 plus osimertinib

Sotorasib DRUG

Administered orally

Also known as: Lumakras

Dose Escalation (Part 2): ERAS-007 plus sotorasib; Dose Escalation (Part 3): ERAS-601 plus sotorasib; Dose Expansion (Part 5): ERAS-007 plus sotorasib; Dose Expansion (Part 6): ERAS-601 plus sotorasib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (11)

City of Hope

Duarte, California, 91010, United States

Location

UC Irvine, Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

Location

UC Los Angeles

Santa Monica, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Research Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Hackensack University Medical Center (John Theurer Cancer Center)

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Noonan Syndrome; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Thoracic Neoplasms

Interventions

osimertinib; sotorasib

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joyce Antal

  Senior Director, Clinical Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2021
• First Posted: July 13, 2021
• Study Start: September 2, 2021
• Primary Completion: April 27, 2023
• Study Completion: April 27, 2023
• Last Updated: July 25, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)