A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies

NCT05279859 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: ERAS-007-04
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 4

Brief Summary

• To evaluate the safety and tolerability of escalating doses of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
• To determine the Maximum Tolerated Dose (MTD) and/or Recommended Dose (RD) of ERAS-007 or ERAS-601 administered in combination with other cancer therapies.
• To evaluate the preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies.
• To evaluate the PK profiles of ERAS-007 or ERAS-601 and other cancer therapies when administered in combination.

Conditions

Acute Myeloid Leukemia

Keywords

AML; FLT3; mutation; relapsed; refractory; gilteritinib; Xospata; MAPK; SHP2; ERK

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities (DLT)

  Based on adverse events observed during dose escalation

  Study Day 1 up to Day 29

• Maximum Tolerated Dose (MTD)

  Based on adverse events observed during dose escalation

  Study Day 1 up to Day 29

• Recommended Dose (RD)

  Based on adverse events observed during dose escalation

  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

Secondary Outcomes (7)

• Plasma concentration (Cmax)

  Study Day 1 up to Day 29

• Time to achieve Cmax (Tmax)

  Study Day 1 up to Day 29

• Area under the curve

  Study Day 1 up to Day 29

• Half-life

  Study Day 1 up to Day 29

• Antileukemic activity

  Assessed up to 24 months from time of first dose

Study Arms (4)

Dose Escalation (Part 1): ERAS-007 plus gilteritinib

EXPERIMENTAL

ERAS-007 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: ERAS-007; Drug: Gilteritinib

Dose Escalation (Part 2): ERAS-601 plus gilteritinib

EXPERIMENTAL

ERAS-601 will be administered in combination with gilteritinib to study participants with R/R FLT3 mutated AML in sequential ascending doses until unacceptable toxicity, disease progression, or withdrawal of consent.

Drug: ERAS-601; Drug: Gilteritinib

Dose Expansion (Part 3): ERAS-007 plus gilteritinib

EXPERIMENTAL

ERAS-007 will be administered at the recommended dose (as determined from Part 1) in combination with gilteritinib to study participants with R/R FLT3 mutated AML.

Drug: ERAS-007; Drug: Gilteritinib

Dose Expansion (Part 4): ERAS-601 plus gilteritinib

EXPERIMENTAL

ERAS-601 will be administered at the recommended dose (as determined from Part 2) in combination with gilteritinib to study participants with R/R FLT3 mutated AML.

Drug: ERAS-601; Drug: Gilteritinib

Interventions

ERAS-007 DRUG

Administered orally

Dose Escalation (Part 1): ERAS-007 plus gilteritinib; Dose Expansion (Part 3): ERAS-007 plus gilteritinib

ERAS-601 DRUG

Administered orally

Dose Escalation (Part 2): ERAS-601 plus gilteritinib; Dose Expansion (Part 4): ERAS-601 plus gilteritinib

Gilteritinib DRUG

Administered orally

Also known as: Xospata

Dose Escalation (Part 1): ERAS-007 plus gilteritinib; Dose Escalation (Part 2): ERAS-601 plus gilteritinib; Dose Expansion (Part 3): ERAS-007 plus gilteritinib; Dose Expansion (Part 4): ERAS-601 plus gilteritinib

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.
• Diagnosis of primary AML or AML secondary to myelodysplastic syndrome (MDS) according to World Health Organization classification.
• Relapsed after or refractory to first-line AML therapy.
• Positive for FLT3 mutation in bone marrow or whole blood.
• Eastern Cooperative Oncology Group performance status ≤ 2 with no deterioration during screening period.
• Adequate hepatic and renal function.
• Recovery from non-hematologic AEs associated with prior therapy to baseline CTCAE v5 Grade 0 or 1, except for AEs not considered a safety risk (eg, alopecia or vitiligo).
• Able to take oral medication with no medical conditions that prevent swallowing and absorbing oral medications.
• Willing to comply with all protocol-required visits, assessments, and procedures.

You may not qualify if:

• Diagnosis of AML secondary to prior chemotherapy or other neoplasms (except for MDS).
• Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia (chronic myeologenous leukemia in blast crisis).
• Clinically active central nervous system leukemia.
• Second or later hematologic relapse or prior salvage therapy for refractory disease.
• For participants being considered for ERAS-007+gilteritinib treatment: prior therapy with ERK inhibitor.
• For participants being considered for ERAS-601+gilteritinib treatment: prior therapy with SHP2 inhibitor.
• Anticancer therapy ≤14 days prior to first dose (except hydroxyurea given for controlling blast count), or ≤5 half-lives prior to first dose, whichever is shorter.
• Palliative radiation ≤7 days prior to first dose.
• Major surgery within 28 days of enrollment.
• Contraindication to gilteritinib use as per local label.
• Known hypersensitivity to any of the components of ERAS-007 or ERAS-601.
• Clinically active infection, requiring systemic therapy.
• Impaired cardiovascular function or clinically significant cardiovascular disease.
• History of thromboembolic or cerebrovascular events ≤6 months prior to first dose.
• History of other malignancy ≤3 years prior to first dose.

Sponsors & Collaborators

• Erasca, Inc.: lead

Study Sites (4)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Texas Oncology

Dallas, Texas, 75251, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology Virginia

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

gilteritinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Les Brail, Ph.D.

  Medical Monitor

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: March 5, 2022
• First Posted: March 15, 2022
• Study Start: March 15, 2022
• Primary Completion: March 1, 2025
• Study Completion: June 1, 2025
• Last Updated: June 15, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)