Clinical Trials /

FLAGSHP-1: A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors

NCT04670679

Description:

- To evaluate the safety and tolerability of ERAS-601. - To determine the ERAS-601 Maximum Tolerated Dose (MTD) and/or recommended dose (RD) as a monotherapy and in combination with a MEK inhibitor. - To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with a MEK inhibitor.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: FLAGSHP-1: A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors
  • Official Title: FLAGSHP-1: 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 a MEK Inhibitor in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: ERAS-601-01
  • NCT ID: NCT04670679

Conditions

  • Advanced or Metastatic Solid Tumors

Interventions

DrugSynonymsArms
ERAS-601Dose Escalation (Part A): ERAS-601 Monotherapy, Once daily (QD) dosing
MEK inhibitorDose Escalation (Part C): ERAS-601 in Combination with a MEK Inhibitor

Purpose

- To evaluate the safety and tolerability of ERAS-601. - To determine the ERAS-601 Maximum Tolerated Dose (MTD) and/or recommended dose (RD) as a monotherapy and in combination with a MEK inhibitor. - To characterize the pharmacokinetic (PK) profile of ERAS-601 when administered as a monotherapy and in combination with a MEK inhibitor.

Detailed Description

      This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-601 SHP2
      inhibitor as a monotherapy and in combination with a MEK inhibitor. The study will commence
      with dose escalation of ERAS-601 monotherapy, followed by dose escalation of ERAS-601 in
      combination with a MEK inhibitor. Once the monotherapy maximum tolerated dose (MTD) and/or
      recommended dose (RD) has been determined, then dose expansion of ERAS-601 monotherapy may
      commence. Dose expansion of ERAS-601 in combination with a MEK inhibitor may commence after
      the combination RD has been determined. Dose expansion will enroll participants with advanced
      or metastatic solid tumors harboring specific molecular alterations.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation (Part A): ERAS-601 Monotherapy, Once daily (QD) dosingExperimentalERAS-601 will be administered QD to participants in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.
  • ERAS-601
Dose Escalation (Part B): ERAS-601 Monotherapy, Twice daily (BID) dosingExperimentalERAS-601 will be administered BID to participants in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.
  • ERAS-601
Dose Escalation (Part C): ERAS-601 in Combination with a MEK InhibitorExperimentalERAS-601 will be administered to participants in sequential ascending doses in combination with a MEK inhibitor until unacceptable toxicity, disease progression, or withdrawal of consent.
  • ERAS-601
  • MEK inhibitor
Dose Expansion (Part D): ERAS-601 MonotherapyExperimentalERAS-601 will be administered at the monotherapy recommended dose (as determined from Part A or B) to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.
  • ERAS-601
Dose Expansion (Part E): ERAS-601 in Combination with a MEK InhibitorExperimentalERAS-601 will be administered at the combination therapy recommended dose (as determined from Part C) to participants with advanced or metastatic solid tumors that harbor specific molecular alterations.
  • ERAS-601
  • MEK inhibitor

Eligibility Criteria

        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

          -  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:

          -  Is currently receiving another study therapy or has participated in a study of an
             investigational agent and received study therapy within 4 weeks of Cycle 1, Day 1

          -  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
      
Maximum Eligible Age:99 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLT)
Time Frame:Study Day 1 up to Day 29
Safety Issue:
Description:Based on toxicities observed

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Assessed up to 24 months from time of first dose
Safety Issue:
Description:Based on assessment of radiographic imaging per RECIST version 1.1
Measure:Duration of Response (DOR)
Time Frame:Assessed up to 24 months from time of first dose
Safety Issue:
Description:Based on assessment of radiographic imaging per RECIST version 1.1
Measure:Time to Response (TTR)
Time Frame:Assessed up to 24 months from time of first dose
Safety Issue:
Description:Based on assessment of radiographic imaging per RECIST version 1.1

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Erasca, Inc.

Trial Keywords

  • SHP2
  • PTPN11
  • solid tumor
  • advanced solid tumor
  • metastatic solid tumor
  • neoplasms
  • solid malignancies

Last Updated

December 19, 2020