A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Advanced NSCLC
- Conditions
- Advanced Non-squamous Non-small-cell Lung Cancer
- Interventions
- Registration Number
- NCT04959981
- Lead Sponsor
- Erasca, Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (Part 1): ERAS-007 plus osimertinib 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. Dose Escalation (Part 2): ERAS-007 plus sotorasib ERAS-007 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. Dose Expansion (Part 4): ERAS-007 plus osimertinib ERAS-007 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. Dose Expansion (Part 5): ERAS-007 plus sotorasib ERAS-007 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. Dose Expansion (Part 5): ERAS-007 plus sotorasib 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. Dose Escalation (Part 3): ERAS-601 plus sotorasib ERAS-601 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. Dose Expansion (Part 6): ERAS-601 plus sotorasib ERAS-601 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. Dose Escalation (Part 1): ERAS-007 plus osimertinib ERAS-007 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. Dose Escalation (Part 2): ERAS-007 plus sotorasib 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. Dose Escalation (Part 3): ERAS-601 plus sotorasib 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. Dose Expansion (Part 4): ERAS-007 plus osimertinib 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. Dose Expansion (Part 6): ERAS-601 plus sotorasib 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.
- Primary Outcome Measures
Name Time Method Recommended Dose (RD) Study Day 1 up to Day 22 Based on adverse events observed
Dose Limiting Toxicities (DLT) Study Day 1 up to Day 22 Based on adverse events observed
Maximum Tolerated Dose (MTD) Study Day 1 up to Day 22 Based on adverse events observed
Adverse Events Assessed up to 24 months from time of first dose Incidence and severity of treatment-emergent AEs and serious AEs
- Secondary Outcome Measures
Name Time Method Plasma concentration (Cmax) Study Day 1 up to Day 22 Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Time to achieve Cmax (Tmax) Study Day 1 up to Day 22 Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies
Half-life Study Day 1 up to Day 22 Half-life of ERAS-007 or ERAS-601 and other cancer therapies
Objective Response Rate (ORR) Assessed up to 24 months from time of first dose Based on assessment of radiographic imaging per RECIST version 1.1
Duration of Response (DOR) Assessed up to 24 months from time of first dose Based on assessment of radiographic imaging per RECIST version 1.1
Area under the curve Study Day 1 up to Day 22 Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies
Trial Locations
- Locations (11)
Hackensack University Medical Center (John Theurer Cancer Center)
🇺🇸Hackensack, New Jersey, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Research Institute
🇺🇸Boston, Massachusetts, United States
City of Hope
🇺🇸Duarte, California, United States
UC Irvine, Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
UC Los Angeles
🇺🇸Santa Monica, California, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Sarah Cannon Research Institute (Tennessee Oncology)
🇺🇸Nashville, Tennessee, United States