Clinical trial NCT04866134: A Study of ERAS-007 as Monotherapy or in Combination With ERAS-601 in Patients With Advanced or Metastatic Solid Tumors
Official title: A Phase 1b/2, Open-label, Multi-center Study of ERAS-007 (ERK Inhibitor) Administered as Monotherapy or in Combination With ERAS-601 (SHP2 Inhibitor) in Patients With Advanced or Metastatic Solid Tumors (HERKULES-1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Solid Tumors
Keywords: ERK
solid tumor
advanced solid tumor
metastatic solid tumor
neoplasms
solid malignancies
MAPK
SHP2
Lead sponsor: Erasca, Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-29
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: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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.

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 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Evaluate safety and tolerability of escalating doses of ERAS-007 BID-QW
timeFrame: Assessed up to 24 months from time of first dose
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: Denver
country: United States
facility: Sarah Cannon Research Institute (HealthONE)
state: Colorado
city: Sarasota
country: United States
facility: Sarah Cannon Research Institute (Florida Cancer Specialists)
state: Florida
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: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: Chief Medical Officer
name: Wei Lin, M.D.
role: STUDY_DIRECTOR
References: