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

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ClinicalTrials.gov Identifier: NCT04670679
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : November 21, 2022
Sponsor:
Information provided by (Responsible Party):
Erasca, Inc.

Tracking Information
First Submitted Date  ICMJE December 11, 2020
First Posted Date  ICMJE December 17, 2020
Last Update Posted Date November 21, 2022
Actual Study Start Date  ICMJE December 15, 2020
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2022)
  • Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Maximum tolerated dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Recommended dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
    Incidence and severity of treatment-emergent AEs and serious AEs
  • Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]
    Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)
  • Time to achieve Cmax (Tmax) [ Time Frame: 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 [ Time Frame: Study Day 1 up to Day 29 ]
    Area under the plasma concentration-time curve of ERAS-601 and cetuximab or pembrolizumab (if applicable)
  • Half-life [ Time Frame: Study Day 1 up to Day 29 ]
    Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)
Original Primary Outcome Measures  ICMJE
 (submitted: December 15, 2020)
  • Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Maximum tolerated dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Recommended dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed
  • Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
    Incidence and severity of treatment-emergent AEs and serious AEs
  • Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]
    Maximum plasma concentration of ERAS-601 and MEK inhibitor (if applicable)
  • Time to achieve Cmax (Tmax) [ Time Frame: Study Day 1 up to Day 29 ]
    Time to achieve maximum plasma concentration of ERAS-601 and MEK inhibitor (if applicable)
  • Area under the curve [ Time Frame: Study Day 1 up to Day 29 ]
    Area under the plasma concentration-time curve of ERAS-601 and MEK inhibitor (if applicable)
  • Half-life [ Time Frame: Study Day 1 up to Day 29 ]
    Half-life of ERAS-601 and MEK inhibitor (if applicable)
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2020)
  • Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Assessed up to 24 months from time of first dose ]
    Based on assessment of radiographic imaging per RECIST version 1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 6, 2021)
Pharmacodynamic assessment [ Time Frame: Assessed up to 24 months from time of first dose ]
Assessment of phosphorylated ERK (pERK) inhibition in PBMCs or tumor tissue by IHC or immunofluorescence.
Original Other Pre-specified Outcome Measures
 (submitted: December 15, 2020)
Pharmacodynamic assessment [ Time Frame: Assessed up to 24 months from time of first dose ]
Assessment of phosphorylated ERK (pERK) inhibition in isolated PBMCs or tumor tissue by immunoblot, IHC or immunofluorescence.
 
Descriptive Information
Brief Title  ICMJE A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced or Metastatic Solid Tumors
Intervention  ICMJE
  • Drug: ERAS-601
    Administered orally
  • Drug: Cetuximab
    Administered via intravenous infusion
    Other Name: Erbitux
  • Drug: Pembrolizumab
    Administered via intravenous infusion
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: Dose Escalation (Part A): ERAS-601 monotherapy
    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.
    Intervention: Drug: ERAS-601
  • Experimental: Dose Escalation (Part B): ERAS-601 monotherapy
    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.
    Intervention: Drug: ERAS-601
  • Experimental: Dose Escalation (Part C): ERAS-601 monotherapy
    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.
    Intervention: Drug: ERAS-601
  • Experimental: Dose Escalation and Dose Expansion (Part D): ERAS-601 in combination with 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 advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).
    Interventions:
    • Drug: ERAS-601
    • Drug: Cetuximab
  • Experimental: Dose Escalation and Dose Expansion (Part E): ERAS-601 in combination with 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 advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).
    Interventions:
    • Drug: ERAS-601
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 6, 2021)
200
Original Estimated Enrollment  ICMJE
 (submitted: December 15, 2020)
170
Estimated Study Completion Date  ICMJE May 2024
Estimated Primary Completion Date May 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 99 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Erasca Clinical Team +1-858-465-6511 clinicaltrials@erasca.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04670679
Other Study ID Numbers  ICMJE ERAS-601-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Erasca, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Erasca, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Les Brail, PhD Clinical Development
PRS Account Erasca, Inc.
Verification Date November 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP