A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors

Advanced or Metastatic Solid Tumors Clinical Trial

— FLAGSHP-1  

Official title:

An Open-Label, Multi-Center Phase 1/1b Dose Escalation and Expansion Study of ERAS-601 SHP2 Inhibitor as a Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04670679
• Other study ID #: ERAS-601-01
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: December 15, 2020
• Est. completion date: May 2024

Study information

• Verified date: November 2023
• Source: Erasca, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: May 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• ERAS-601
Administered orally
• Cetuximab
Administered via intravenous infusion
• Pembrolizumab
Administered via intravenous infusion

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Perth	Western Australia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of North Carolina	Chapel Hill	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
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	Sarah Cannon Research Institute (Tennessee Oncology)	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California, San Diego	San Diego	California
United States	Sarah Cannon Research Institute (Florida Cancer Specialists)	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Erasca, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamic assessment	Assessment of phosphorylated ERK (pERK) inhibition in PBMCs or tumor tissue by IHC or immunofluorescence.	Assessed up to 24 months from time of first dose
Primary	Dose Limiting Toxicities (DLT)	Based on toxicities observed	Study Day 1 up to Day 29
Primary	Maximum tolerated dose (MTD)	Based on toxicities observed	Study Day 1 up to Day 29
Primary	Recommended dose (RD)	Based on toxicities observed	Study Day 1 up to Day 29
Primary	Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Primary	Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29
Primary	Time to achieve Cmax (Tmax)	Time to achieve maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29
Primary	Area under the curve	Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29
Primary	Half-life	Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29
Secondary	Objective Response Rate (ORR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Duration of Response (DOR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose
Secondary	Time to Response (TTR)	Based on assessment of radiographic imaging per RECIST version 1.1	Assessed up to 24 months from time of first dose