A Phase 1 First-in-Human Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of ERAS-4001 Monotherapy and in Combination in Patients With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Erasca, Inc.
- Enrollment
- 200
- Locations
- 4
- Primary Endpoint
- Dose Limiting Toxicities (DLT)
Study Overview
Brief Summary
The main purpose of the study is to assess whether the study drug, ERAS-4001, is safe and tolerable when administered to patients with advanced or metastatic solid tumors with certain KRAS mutations. ERAS-4001 will be given alone or in combination with other treatments.
Detailed Description
This is a first-in-human, Phase 1/1b, open-label, multicenter clinical study of ERAS-4001 as a monotherapy and in combination with other cancer therapies. The study will commence with dose optimization of ERAS-4001 monotherapy, followed by dose optimization of ERAS-4001 in combination with other cancer therapies.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 99 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age ≥ 18 years
- •Willing and able to give written informed consent
- •Pathological documentation of tumor type and mutation prior to the first dose of study drug(s)
- •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 RAS inhibitor
- •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-4001
- •Received prior palliative radiation within 14 days of Cycle 1, Day 1
- •Have primary central nervous system (CNS) tumors
- •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
- •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
Arms & Interventions
ERAS-4001 Monotherapy Dose Optimization.
Escalating doses of ERAS-4001 administered orally.
Intervention: ERAS-4001 (Drug)
ERAS-4001 Combination Dose Optimization
ERAS-4001 administered orally with another investigational agent.
Intervention: ERAS-4001 in combination (Drug)
Outcomes
Primary Outcomes
Dose Limiting Toxicities (DLT)
Time Frame: Study Day 1 up to Day 21
Based on toxicities observed
Maximum tolerated dose (MTD)
Time Frame: Study Day 1 up to Day 21
Based on toxicities observed
Recommended dose for expansion (RDE)
Time Frame: Study Day 1 up to Day 21
Based on toxicities observed
Adverse Events
Time Frame: Study Day 1 up to Day 21
Incidence and severity of treatment-emergent AEs and serious AEs
Plasma concentration (Cmax)
Time Frame: Study Day 1 up to Day 65
Maximum plasma concentration of ERAS-4001
Time to achieve Cmax (Tmax)
Time Frame: Study Day 1 up to Day 65
Time of achieve maximum plasma concentration of ERAS-4001
Area under the curve
Time Frame: Study Day 1 up to Day 65
Area under the plasma concentration-time curve of ERAS-4001
Half-life
Time Frame: Study Day 1 up to Day 65
Half-life of ERAS-4001
Secondary Outcomes
- Objective Response Rate (ORR)(Assessed up to 24 months from time of first dose)
- Duration of Response (DOR)(Assessed up to 24 months from time of first dose)
- Time to Response (TTR)(Assessed up to 24 months from time of first dose)