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This is a Phase 1b/2, open-label, multicenter clinical study of ERAS-007 monotherapy (QW or BID-QW) administered either QW or BID-QWand ERAS-007 (BID-QW) in combination with ERAS-601 (BID 3/1). The monotherapy RD on a weekly schedule has been determined to be 250 mg QW in a previous study. The dose escalation phases of this study will test ERAS-007 monotherapy administered BID-QW as a monotherapy or in combination with ERAS-601 in participants with any solid tumor. The monotherapy RD on a weekly schedule has been determined to be 250 mg QW in a previous study. In parallel, the dose expansion phase of this study will test ERAS-007 monotherapy administered at the RD of 250 mg QW in participants with advanced or metastatic solid tumors harboring specific molecular alterations. Once sufficient safety and PK data are available from the BID-QW dose escalation phase, the Sponsor will then determine the optimal dose and schedule of ERAS-007 administered as a monotherapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation (Part A): ERAS-007 Monotherapy, BID-QW dosing | Experimental | ERAS-007 monotherapy will be administered BID-QW in sequential ascending doses to participants with advanced or metastatic solid tumors until unacceptable toxicity, disease progression, or withdrawal of consent. |
|
| Dose Expansion (Part B): ERAS-007 Monotherapy, QW dosing | Experimental | ERAS-007 monotherapy will be administered at 250 mg QW to participants with advanced or metastatic solid tumors that harbor specific molecular alterations. |
|
| Dose Expansion (Part C): ERAS-007 Monotherapy, BID-QW dosing (if necessary) | Experimental | Depending on data generated from Part A, ERAS-007 monotherapy may be administered at the BID-QW RD to participants with advanced or metastatic solid tumors that harbor specific molecular alterations. |
|
| Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601 | Experimental | Experimental: Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601 ERAS-007 will be administered BID-QW in combination with ERAS-601 administered BID 3/1 to study participants with advanced or metastatic solid tumors that harbor specific molecular targets in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ERAS-007 | Drug | ERAS-007 will be administered orally as specified in Arm description. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate safety and tolerability of escalating doses of ERAS-007 BID-QW | Based on adverse events observed | Assessed up to 24 months from time of first dose |
| Dose Limiting Toxicities (DLT) | Based on adverse events observed | Study Day 1 up to Day 29 |
| Maximum tolerated dose (MTD) | Based on adverse events observed | Study Day 1 up to Day 29 |
| Recommended dose (RD) | Based on adverse events observed | Study Day 1 up to Day 29 |
| Adverse Events | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 24 months from time of first dose |
| Plasma concentration (Cmax) | Maximum plasma concentration of ERAS-007 | Study Day 1 up to Day 29 |
| Time to achieve Cmax (Tmax) | Time to achieve maximum plasma concentration of ERAS-007 and ERAS-601 | Study Day 1 up to Day 29 |
| Area under the curve | Area under the plasma concentration-time curve of ERAS-007 and ERAS-601 | Study Day 1 up to Day 29 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacodynamic assessment | Assessment of phosphorylated ERK (pERK) inhibition in isolated PBMCs or tumor tissue by immunoblot, IHC or immunofluorescence. | Assessed up to 24 months from time of first dose |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Wei Lin, M.D. | Chief Medical Officer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sarah Cannon Research Institute (HealthONE) | Denver | Colorado | 80218 | United States | ||
| Sarah Cannon Research Institute (Florida Cancer Specialists) |
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| ERAS-601 | Drug | ERAS-601 will be administered orally as specified in Arm description. |
|
| Half-life | Half-life of ERAS-007 and ERAS-601 | Study Day 1 up to Day 29 |
| 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 |
| Sarasota |
| Florida |
| 34232 |
| United States |
| Sarah Cannon Research Institute (Tennessee Oncology) | Nashville | Tennessee | 37203 | United States |
| Mary Crowley Cancer Research | Dallas | Texas | 75251 | United States |
| NEXT Oncology | San Antonio | Texas | 78229 | United States |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D009369 | Neoplasms |
| ID | Term |
|---|---|
| D009385 | Neoplastic Processes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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