A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors

NCT04866134 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-007-01
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 5

Brief Summary

• To evaluate the safety and tolerability of ERAS-007 monotherapy administered once weekly (QW) and twice daily-once weekly (BID-QW).
• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 monotherapy administered BID-QW.
• To characterize the pharmacokinetic (PK) profile of ERAS-007 monotherapy.
• To determine the optimal dose and schedule of ERAS-007 monotherapy.
• To evaluate antitumor activity of ERAS-007 in various solid tumors.
• To evaluate the safety and tolerability of ERAS-007 (BID-QW) and ERAS-601 (twice daily for three weeks on and 1 week off (BID 3/1)) when administered in combination.
• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 administered in combination with ERAS-601.
• To characterize the pharmacokinetic (PK) profile of ERAS-007 and ERAS-601 when administered in combination.
• To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors
• To evaluate antitumor activity of ERAS-007 and ERAS-601 when administered in combination in various solid tumors

Conditions

Advanced or Metastatic Solid Tumors

Keywords

ERK; solid tumor; advanced solid tumor; metastatic solid tumor; neoplasms; solid malignancies; MAPK; SHP2

Outcome Measures

Primary Outcomes (9)

• 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

• Half-life

  Half-life of ERAS-007 and ERAS-601

  Study Day 1 up to Day 29

Secondary Outcomes (3)

• 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

Other Outcomes (1)

• Pharmacodynamic assessment

  Assessed up to 24 months from time of first dose

Study Arms (4)

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.

Drug: ERAS-007

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.

Drug: ERAS-007

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.

Drug: ERAS-007

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.

Drug: ERAS-007; Drug: ERAS-601

Interventions

ERAS-007 DRUG

ERAS-007 will be administered orally as specified in Arm description.

Dose Escalation (Part A): ERAS-007 Monotherapy, BID-QW dosing; Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601; Dose Expansion (Part B): ERAS-007 Monotherapy, QW dosing; Dose Expansion (Part C): ERAS-007 Monotherapy, BID-QW dosing (if necessary)

ERAS-601 DRUG

ERAS-601 will be administered orally as specified in Arm description.

Dose Escalation (Part D): ERAS-007 BID-QW dosing in combination with ERAS-601

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Willing and able to give written informed consent.
• Have histologically or cytologically confirmed advanced or metastatic solid tumor with a relevant molecular alteration (as applicable).
• 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.
• Recovered from all toxicities associated with prior treatment to acceptable baseline status.
• Have ECOG performance status of 0 or 1 with an anticipated life expectancy of \> 12 weeks.
• Willing to comply with all protocol-required visits, assessments, and procedures.
• Able to swallow oral medication.

You may not qualify if:

• 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-007.
• Received previous treatment with an ERK inhibitor.
• For participants being considered for ERAS-007 + ERAS-601 (Part D): prior treatment with SHP2 inhibitor.
• For participants being considered for ERAS-007 + ERAS-601 (Part D): documented PTPN11 mutations
• Received prior antineoplastic therapy within \< 21 days or 5 half-lives, whichever is shorter.
• Received prior palliative radiation within 7 days of first dose of ERAS 007 or ERAS-601,
• Received previous treatment with a MAPK inhibitor that resulted in discontinuation due to unacceptable toxicity.
• 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.

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (5)

Sarah Cannon Research Institute (HealthONE)

Denver, Colorado, 80218, United States

Location

Sarah Cannon Research Institute (Florida Cancer Specialists)

Sarasota, Florida, 34232, United States

Location

Sarah Cannon Research Institute (Tennessee Oncology)

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75251, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Wei Lin, M.D.

  Chief Medical Officer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2021
• First Posted: April 29, 2021
• Study Start: May 7, 2021
• Primary Completion: May 1, 2025
• Study Completion: November 1, 2025
• Last Updated: August 27, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)