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

NCT ID: NCT05279859

Last Updated: 2022-06-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-15
• Study Completion Date: 2025-06-01

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.

Detailed Description

This is a Phase 1b/2, open-label, multicenter master protocol evaluating safety, tolerability, and preliminary efficacy of ERAS-007 or ERAS-601 in combination with other cancer therapies in study participants with hematologic malignancies. The study will commence with dose escalation cohorts (ERAS-007 plus gilteritinib and ERAS-601 plus gilteritinib) in study participants with relapsed or refractory (R/R) Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML). Dose expansion will follow and will evaluate ERAS-007 or ERAS-601 drug combinations administered at the RD identified from each respective dose escalation cohort in study participants with R/R FLT-3 mutated AML.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Gilteritinib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Gilteritinib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

ERAS-007

Intervention Type: DRUG

Administered orally

Gilteritinib

Intervention Type: DRUG

Administered orally

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

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.

Group Type: EXPERIMENTAL

ERAS-601

Intervention Type: DRUG

Administered orally

Gilteritinib

Intervention Type: DRUG

Administered orally

Interventions

ERAS-007

Administered orally

Intervention Type: DRUG

ERAS-601

Administered orally

Intervention Type: DRUG

Gilteritinib

Administered orally

Intervention Type: DRUG

Other Intervention Names

Xospata

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• History of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or risk factors to RPED or RVO.
• History of or clinically active interstitial lung disease (ILD), drug induced ILD, or radiation pneumonitis that required steroid treatment.
• Any evidence of severe or uncontrolled systemic disease or evidence of any other significant clinical disorder or laboratory finding that renders the participant inappropriate to participate in the study.
• Pregnant or breastfeeding women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasca, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Les Brail, Ph.D.

Role: STUDY_DIRECTOR

Medical Monitor

Locations

University of California San Francisco

San Francisco, California, United States

Texas Oncology

Dallas, Texas, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology Virginia

Fairfax, Virginia, United States

Countries

United States

Other Identifiers

ERAS-007-04

Identifier Type: -

Identifier Source: org_study_id