A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors (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 Other Anti-Cancer Therapies in Patients With Advanced or Metastatic Solid Tumors

• 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: ERAS-601; Drug: Cetuximab; Drug: Pembrolizumab

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: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Erasca Clinical Team; Phone Number: +1-858-465-6511; Email: clinicaltrials@erasca.com

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Perth, Western Australia, Australia
      • Linear Clinical Research
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • San Diego, California, United States, 92093
      • University of California, San Diego
  • Florida
    • Sarasota, Florida, United States, 34232
      • Sarah Cannon Research Institute (Florida Cancer Specialists)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute (Tennessee Oncology)
  • Texas
    • Dallas, Texas, United States, 75251
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: ERAS-601; Administered orally
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.	Drug: ERAS-601; Administered orally
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.	Drug: ERAS-601; Administered orally
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 HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC).	Drug: ERAS-601; Administered orally; Drug: Cetuximab; Administered via intravenous infusion; Other Names: Erbitux
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 HPV negative advanced or metastatic head and neck squamous cell carcinoma (HNSCC) or non small cell lung cancer (NSCLC).	Drug: ERAS-601; Administered orally; Drug: Pembrolizumab; Administered via intravenous infusion; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Incidence and severity of treatment-emergent AEs and serious AEs	Assessed up to 24 months from time of first dose
Dose Limiting Toxicities (DLT)	Based on toxicities observed	Study Day 1 up to Day 29
Maximum tolerated dose (MTD)	Based on toxicities observed	Study Day 1 up to Day 29
Recommended dose (RD)	Based on toxicities observed	Study Day 1 up to Day 29
Plasma concentration (Cmax)	Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29
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
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
Half-life	Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable)	Study Day 1 up to Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Erasca, Inc.
• Investigators: Study Director: Les Brail, PhD, Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2020
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 15, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 28, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: colorectal cancer; solid tumor; targeted therapy; SHP2; neoplasms; advanced solid tumor; metastatic solid tumor; solid malignancies; CRC; cetuximab; Erbitux; head and neck squamous cell carcinoma; PTPN11; molecular alterations; Chordoma; HPV Negative HNSCC
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cetuximab
• Other Study ID Numbers: ERAS-601-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No