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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 : July 23, 2021
Sponsor:
Information provided by (Responsible Party):
Erasca, Inc.

Brief Summary:
  • 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.

Condition or disease Intervention/treatment Phase
Advanced or Metastatic Solid Tumors Drug: ERAS-601 Drug: MEK inhibitor Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 15, 2020
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2024

Arm Intervention/treatment
Experimental: Dose Escalation (Part A): ERAS-601 Monotherapy, Once daily (QD) dosing
ERAS-601 will be administered QD to participants in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-601
ERAS-601 will be administered orally as specified in Arm description

Experimental: Dose Escalation (Part B): ERAS-601 Monotherapy, Twice daily (BID) dosing
ERAS-601 will be administered BID to participants in sequential ascending doses as a monotherapy until unacceptable toxicity, disease progression, or withdrawal of consent.
Drug: ERAS-601
ERAS-601 will be administered orally as specified in Arm description

Experimental: Dose Escalation (Part C): ERAS-601 in Combination with a MEK Inhibitor
ERAS-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.
Drug: ERAS-601
ERAS-601 will be administered orally as specified in Arm description

Drug: MEK inhibitor
MEK inhibitor will be administered orally as specified in Arm description.

Experimental: Dose Expansion (Part D): ERAS-601 Monotherapy
ERAS-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.
Drug: ERAS-601
ERAS-601 will be administered orally as specified in Arm description

Experimental: Dose Expansion (Part E): ERAS-601 in Combination with a MEK Inhibitor
ERAS-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.
Drug: ERAS-601
ERAS-601 will be administered orally as specified in Arm description

Drug: MEK inhibitor
MEK inhibitor will be administered orally as specified in Arm description.




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLT) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed

  2. Maximum tolerated dose (MTD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed

  3. Recommended dose (RD) [ Time Frame: Study Day 1 up to Day 29 ]
    Based on toxicities observed

  4. Adverse Events [ Time Frame: Assessed up to 24 months from time of first dose ]
    Incidence and severity of treatment-emergent AEs and serious AEs

  5. Plasma concentration (Cmax) [ Time Frame: Study Day 1 up to Day 29 ]
    Maximum plasma concentration of ERAS-601 and MEK inhibitor (if applicable)

  6. 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)

  7. 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)

  8. Half-life [ Time Frame: Study Day 1 up to Day 29 ]
    Half-life of ERAS-601 and MEK inhibitor (if applicable)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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


Other Outcome Measures:
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04670679


Contacts
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Contact: Erasca Clinical Team +1-858-465-6511 clinicaltrials@erasca.com

Locations
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United States, Florida
Sarah Cannon Research Institute (Florida Cancer Specialists) Recruiting
Sarasota, Florida, United States, 34232
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute (Tennessee Oncology) Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75251
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Australia, Western Australia
Linear Clinical Research Recruiting
Perth, Western Australia, Australia
Sponsors and Collaborators
Erasca, Inc.
Investigators
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Study Director: Les Brail, PhD Clinical Development
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Responsible Party: Erasca, Inc.
ClinicalTrials.gov Identifier: NCT04670679    
Other Study ID Numbers: ERAS-601-01
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: July 23, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Erasca, Inc.:
SHP2
PTPN11
solid tumor
advanced solid tumor
metastatic solid tumor
neoplasms
solid malignancies
Additional relevant MeSH terms:
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Neoplasms