Acute Myeloid Leukemia
Conditions
Keywords
AML, FLT3, mutation, relapsed, refractory, gilteritinib, Xospata, MAPK, SHP2, ERK
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.
Interventions
Sponsors
Erasca, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicities (DLT) | Study Day 1 up to Day 29 | Based on adverse events observed during dose escalation |
| Maximum Tolerated Dose (MTD) | Study Day 1 up to Day 29 | Based on adverse events observed during dose escalation |
| Recommended Dose (RD) | Study Day 1 up to Day 29 | Based on adverse events observed during dose escalation |
| Adverse Events | Assessed up to 24 months from time of first dose | Incidence and severity of treatment-emergent AEs and serious AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antileukemic activity | Assessed up to 24 months from time of first dose | Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh); CR rate |
| Plasma concentration (Cmax) | Study Day 1 up to Day 29 | Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies |
| Duration of antileukemic activity | Assessed up to 24 months from time of first dose | Duration of CR/CRh (DOCR/DOCRh) |
| Time to achieve Cmax (Tmax) | Study Day 1 up to Day 29 | Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies |
| Area under the curve | Study Day 1 up to Day 29 | Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies |
| Half-life | Study Day 1 up to Day 29 | Half-life of ERAS-007 or ERAS-601 and other cancer therapies |
Countries
United States
Outcome results
None listed