A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- Erasca, Inc.
- 试验地点
- 4
- 主要终点
- Dose Limiting Toxicities (DLT)
研究概览
简要总结
- 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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-
- •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.
研究组 & 干预措施
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.
干预措施: ERAS-007 (Drug)
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.
干预措施: Gilteritinib (Drug)
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.
干预措施: ERAS-601 (Drug)
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.
干预措施: Gilteritinib (Drug)
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.
干预措施: ERAS-007 (Drug)
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.
干预措施: Gilteritinib (Drug)
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.
干预措施: ERAS-601 (Drug)
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.
干预措施: Gilteritinib (Drug)
结局指标
主要结局
Dose Limiting Toxicities (DLT)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Adverse Events
时间窗: Assessed up to 24 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
Maximum Tolerated Dose (MTD)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
Recommended Dose (RD)
时间窗: Study Day 1 up to Day 29
Based on adverse events observed during dose escalation
次要结局
- Time to achieve Cmax (Tmax)(Study Day 1 up to Day 29)
- Plasma concentration (Cmax)(Study Day 1 up to Day 29)
- Area under the curve(Study Day 1 up to Day 29)
- Antileukemic activity(Assessed up to 24 months from time of first dose)
- Duration of antileukemic activity(Assessed up to 24 months from time of first dose)
- Half-life(Study Day 1 up to Day 29)