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

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Erasca, Inc.

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.