Clinical trial NCT04670679: A Dose Escalation/Expansion Study of ERAS-601 in Patients With Advanced or Metastatic Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Keywords: SHP2
PTPN11
solid tumor
advanced solid tumor
metastatic solid tumor
neoplasms
solid malignancies
targeted therapy
colorectal cancer
CRC
head and neck squamous cell carcinoma
HPV Negative HNSCC
molecular alterations
cetuximab
Erbitux
Chordoma
Lead sponsor: Erasca, Inc.
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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
* 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

Primary outcomes:
measure: Dose Limiting Toxicities (DLT)
timeFrame: Study Day 1 up to Day 29
measure: Maximum tolerated dose (MTD)
timeFrame: Study Day 1 up to Day 29
measure: Recommended dose (RD)
timeFrame: Study Day 1 up to Day 29
measure: Adverse Events
timeFrame: Assessed up to 24 months from time of first dose
measure: Plasma concentration (Cmax)
timeFrame: Study Day 1 up to Day 29
measure: Time to achieve Cmax (Tmax)
timeFrame: Study Day 1 up to Day 29
measure: Area under the curve
timeFrame: Study Day 1 up to Day 29
measure: Half-life
timeFrame: Study Day 1 up to Day 29
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Duration of Response (DOR)
timeFrame: Assessed up to 24 months from time of first dose
measure: Time to Response (TTR)
timeFrame: Assessed up to 24 months from time of first dose
Other outcomes:
measure: Pharmacodynamic assessment
timeFrame: Assessed up to 24 months from time of first dose
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute (Florida Cancer Specialists)
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (Tennessee Oncology)
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Perth
country: Australia
facility: Linear Clinical Research
state: Western Australia
Study officials:
affiliation: Clinical Development
name: Les Brail, PhD
role: STUDY_DIRECTOR
References: