A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors
- Conditions
- Advanced or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT04670679
- Lead Sponsor
- Erasca, Inc.
- Brief Summary
* To evaluate the safety and tolerability of escalating doses of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies in study participants with advanced or metastatic solid tumors.
* To determine the Maximum Tolerated Dose (MTD) and/or recommended dose (RD) of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
* To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
* To evaluate the antitumor activity of ERAS-601 when administered as a monotherapy and in combination with other cancer therapies.
- Detailed Description
This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 as a monotherapy and in combination with other cancer therapies. The study will commence with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in combination with other cancer therapies. Once the monotherapy MTD and/or RD has been determined, then dose expansion of ERAS-601 monotherapy may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once the combination therapy MTD and/or RD has been determined, then dose expansion of that combination may commence with enrollment of study participants with advanced or metastatic solid tumors harboring specific molecular alterations.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Age ≥ 18 years
- Willing and able to give written informed consent
- Have histologically or cytologically confirmed advanced or metastatic solid tumor
- There is no available standard systemic therapy available for the patient's tumor histology and/or molecular biomarker profile; or standard therapy is intolerable, not effective, or not accessible; or patient has refused standard therapy
- Able to swallow oral medication
- Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Adequate cardiovascular, hematological, liver, and renal function
- Willing to comply with all protocol-required visits, assessments, and procedures
- Previous treatment with a SHP2 inhibitor
- Documented PTPN11 mutations
- Is currently receiving another study therapy or has participated in a study of an investigational agent and received study therapy within 4 weeks of the first dose of ERAS-601
- Received prior palliative radiation within 7 days of Cycle 1, Day 1
- Have primary central nervous system (CNS) disease or known active CNS metastases and/or carcinomatous meningitis
- Prior surgery (e.g., gastric bypass surgery, gastrectomy) or gastrointestinal dysfunction (e.g., Crohn's disease, ulcerative colitis, short gut syndrome) that may affect drug absorption
- Active, clinically significant interstitial lung disease or pneumonitis
- History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to the first dose of study treatment
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
- Have any underlying medical condition, psychiatric condition, or social situation that, in the opinion of the Investigator, would compromise study administration as per protocol or compromise the assessment of AEs
- Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation (Part A): ERAS-601 monotherapy ERAS-601 ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent. Dose Escalation (Part B): ERAS-601 monotherapy ERAS-601 ERAS-601 monotherapy will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent. Dose Escalation (Part C): ERAS-601 monotherapy ERAS-601 ERAS-601 will be administered in sequential ascending doses to study participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab ERAS-601 ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC). Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab ERAS-601 ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC). Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with cetuximab Cetuximab ERAS-601 will be administered in sequential ascending doses with cetuximab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC). Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with pembrolizumab Pembrolizumab ERAS-601 will be administered in sequential ascending doses with pembrolizumab to study participants with advanced metastatic solid tumors until unacceptable toxicity, disease progression or withdrawal of consent. Once the combination therapy recommended dose has been determined, this will be administered to study participants with HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).
- Primary Outcome Measures
Name Time Method Half-life Study Day 1 up to Day 29 Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Plasma concentration (Cmax) Study Day 1 up to Day 29 Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Time to achieve Cmax (Tmax) Study Day 1 up to Day 29 Time to achieve maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Area under the curve Study Day 1 up to Day 29 Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Recommended dose (RD) Study Day 1 up to Day 29 Based on toxicities observed
Dose Limiting Toxicities (DLT) Study Day 1 up to Day 29 Based on toxicities observed
Maximum tolerated dose (MTD) Study Day 1 up to Day 29 Based on toxicities 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 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
Time to Response (TTR) Assessed up to 24 months from time of first dose Based on assessment of radiographic imaging per RECIST version 1.1
Trial Locations
- Locations (29)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Sarah Cannon Research Institute (Florida Cancer Specialists)
🇺🇸Sarasota, Florida, United States
University of California, San Diego
🇺🇸San Diego, California, United States
Sarah Cannon Research Institute (Tennessee Oncology)
🇺🇸Nashville, Tennessee, United States
Linear Clinical Research
🇦🇺Perth, Western Australia, Australia
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Sarah Cannon Research Institute (Florida Cancer Specialists)
🇺🇸Sarasota, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Sarah Cannon Research Institute (Tennessee Oncology)
🇺🇸Nashville, Tennessee, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Henderson, Nevada, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research
🇦🇺Perth, Western Australia, Australia