Advanced or Metastatic Solid Tumors
Conditions
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
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.
Interventions
DRUGERAS-601
Administered orally
DRUGCetuximab
Administered via intravenous infusion
DRUGPembrolizumab
Administered via intravenous infusion
Sponsors
Erasca, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | Study Day 1 up to Day 29 | Based on toxicities observed |
| Maximum tolerated dose (MTD) | Study Day 1 up to Day 29 | Based on toxicities observed |
| Recommended dose (RD) | Study Day 1 up to Day 29 | Based on toxicities observed |
| Adverse Events | Assessed up to 24 months from time of first dose | Incidence and severity of treatment-emergent AEs and serious AEs |
| Plasma concentration (Cmax) | Study Day 1 up to Day 29 | Maximum plasma concentration of ERAS-601 and cetuximab or pembrolizumab (if applicable) |
| Time to achieve Cmax (Tmax) | 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 | 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 | Study Day 1 up to Day 29 | Half-life of ERAS-601 and cetuximab or pembrolizumab (if applicable) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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) | 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) | Assessed up to 24 months from time of first dose | Based on assessment of radiographic imaging per RECIST version 1.1 |
Countries
Australia, United States
Contacts
STUDY_DIRECTORLes Brail, PhD
Clinical Development
Outcome results
None listed