Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Neoplasms

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

All Drugs and Chemicals

Amino Acids

Mitogens

Gilteritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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.

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.

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.

ERAS-007

ERAS-601

Les Brail, Ph.D.

* 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.

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.

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

A Phase 1b/2 Master Protocol of Agents Targeting the Mitogen-Activated Protein Kinase Pathway in Patients With Hematologic Malignancies

Based on adverse events observed during dose escalation

Incidence and severity of treatment-emergent AEs and serious AEs

Maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

Time to achieve maximum plasma concentration of ERAS-007 or ERAS-601 and other cancer therapies

Area under the plasma concentration-time curve of ERAS-007 or ERAS-601 and other cancer therapies

Half-life of ERAS-007 or ERAS-601 and other cancer therapies

Percentage of Participants With Complete Remission and Complete Remission With Partial Hematological Recovery (CR/CRh); CR rate

Erasca, Inc.

Neoplasms by Histologic Type

Antineoplastic Agents

Azacitidine

Cc-486

Antimetabolites

Gilteritinib 120 mg/day, PO by 28 days-cycle

Azacitidine orale (CC-486) 300 mg/day, PO Day 1 to day 14, by 28 days-cycle

AzaCITIDine Oral Tablet

Xospata

Pierre-Yves DUMAS, MD, PhD

Ariane MINEUR

Delphine Lebon, Dr

Mathilde Hunault, Pr

Pierre Arnautou, Dr

Cécile Pautas, Dr

Martin Carré, Dr

Céline Berthon, Dr

Pascal Turlure, Dr

Mael Heiblig, Pr

Emmanuel Raffoux, Prof

Pierre-Yves Dumas, Prof

tony Marchand, Dr

Emilie Lemasle, Dr

Célestine Simand, Dr

Caroline Bonmati, Dr

Juliette Lambert, Dr

Approximately 30% of adult AML subjects are refractory to induction therapy. Furthermore, of those who achieve CR, approximately 75% will relapse. FLT3-mutated AML comprise an especially poor prognosis group.

Until now, there was no established standard for relapsed subjects with FLT3 mutations and less than 20% will achieve CR with subsequent treatment.

In phase 3 Study ADMIRAL Trial, gilteritinib has resulted in CRc in over 25% of subjects receiving 120 mg/day before on study HSCT. With this treatment, the median overall survival is at 9.3 months, furthermore, gilteritinib was well tolerated at the proposed doses. This study has been designed for R/R patients for which gilteritinib as single agent has been showed to be superior to high- and low-intensity chemotherapy (Perl, NEJM 2019, Supp Table S4) and patients included in this study will receive this treatment. Beyond high- or low-intensity chemotherapy, other options available are best supportive car or other clinical trials.

The aim of this study is to assess the efficacy and safety of the addition of oral-azacitidine to salvage treatment by gilteritinib in subjects ≥18 years of age with relapsed/refractory FLT3-mutated acute myeloid leukemia

AML is characterized by the clonal expansion of myeloid blasts in the BM, peripheral blood and extramedullary tissues which disrupts normal hematopoiesis. It is a heterogeneous disease, encompassing a large number of distinctly subtypes that may have different clinical presentations and responses to treatment. AML is defined by the WHO as a myeloid neoplasm with 20% or more blasts in the peripheral blood or BM.

Internal tandem duplication (ITD) in the FLT3 gene is one of the most frequent mutations found in AML. FLT3-ITD is associated with poor prognosis and has emerged as a relevant therapeutic target. FLT3-ITD is usually conserved at relapse, suggesting that FLT3-ITD AML-initiating cells are key targets for long-lasting remission. FLT3-TKI, developed as ATP-competitive inhibitors, are currently the focus of new development strategies in FLT3-mutated AML, particularly in combination with intensive or non-intensive chemotherapies in newly diagnosed (ND) FLT3 mutated AML or in R/R situation. Type I inhibitors, including midostaurin, gilteritinib, and crenolanib, have activity against FLT3-ITD and tyrosine kinase domain (TKD) mutations. Type II inhibitors, including sorafenib and quizartinib, do not have activity against FLT3-TKD mutations. Although first-generation FLT3 inhibitors, such as midostaurin 10 and sorafenib 11, have marginal single-agent activity in active disease, they have shown promising activity as maintenance therapies, notably after HSCT for sorafenib 14. Conversely, several FLT3-TKI, such as quizartinib, crenolanib, and gilteritinib, have single-agent activity that lead to complete or near-complete remission, providing a strong rationale to combine these agents with other chemotherapies.

The ADMIRAL phase 3 trial, also designed for R/R FLT3-mutated AML patients, recently demonstrated the superiority of gilteritinib as single agent over the control treatment arm, which was determined by investigators prior to 2:1 randomization between mitoxantrone, etoposide, cytarabine; fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin; AZA or LDAC. These regimens are recognized as acceptable salvage strategies in this situation, although other combinations based on intermediate- or high-dose cytarabine or even single-agent cytarabine are also widely used. In the ADMIRAL trial, OS was significantly improved in the gilteritinib arm compared to the control arm with HR at 0.64 (95%CI: 0.49-0.83; p \< 0.001). The median OS was 9.3 months in the gilteritinib arm and 5.6 months in the control arm. The CR and CRi rates were 21.1% and 25.5% in the gilteritinib arm vs. 10.5% and 4.8% in the standard arm 2. Gilteritinib was generally well tolerated but was associated with increased incidence of GI side effects, most frequently diarrhea although nausea has been occasionally observed. Increase in bilirubin and transaminase can be seen with gilteritinib but are usually self-resolving and transient. Posterior reversible encephalopathy and pancreatitis are rare (\<1-2%) but important side effects to be aware of. These results led to the approval of gilteritinib monotherapy in the US and Europe in patients with R/R FLT3 mutated AML and it is now the gold standard treatment in such situation. However, long lasting remission with gilteritinib as single agent are uncommon since various resistance mechanisms allow AML to escape. Innovative strategies have to be established in order to improve these results. In that setting, associations with ICT, HMA, other targeted therapies are currently developed.

AZA was first investigated as a cytotoxic agent in the 1960s and 1970s in R/R AML and a dose- and time-dependent effect of AZA was evident, with higher remission rates and reduced toxicity reported in patients who received lower doses or continuous infusion schedule of AZA

QUAZAR trial used an oral formulation of AZA (oral-AZA) that is not bioequivalent to injectable AZA, as maintenance therapy in patients with AML who were in CR/CRi after ICT 22. Median OS from randomization was significantly longer with oral-AZA than with placebo (24.7 months vs. 14.8 months, respectively; p\<0.001). Median RFS was also significantly longer with oral-AZA than with placebo (10.2 months vs. 4.8 months, respectively; p\<0.001). The most common AE in both groups were grade 1 or 2 GI events. Common grade 3 or 4 AE were neutropenia (in 41% of patients in the oral-AZA group and 24% of patients in the placebo group) and thrombocytopenia (in 22% and 21%, respectively). Overall health-related quality of life was preserved during oral-AZA treatment. Among those who were MRD+ at baseline, patients in the oral-AZA arm had a higher rate of conversion to MRD- status vs. placebo: 37% versus 19%, respectively. These data suggest an effective anti-leukemic therapy and not only an ability to maintain a stable situation, among these MRD responders, 9 of 38 (24%) patients in the oral-AZA arm converted to MRD-negativity after \> 6 months on treatment, vs. only 1of 22 (5%) patients in the placebo arm. Moreover, during the 63rd ASH annual meeting, Döhner et al. confirmed that Oral-AZA, NPM1 and FLT3 mutational status, cytogenetic risk, as well as MRD status at baseline were independent predictors of survival.

In front line situation, LACEWING study was a phase 3, randomized study comparing gilteritinib+AZA vs. AZA for ND FLT3-mutated AML in patients unfit for ICT. In this trial in patients with ND FLT3 mutated AML unfit for ICT, gilteritinib+AZA led to significantly higher CRc rates but similar OS vs. AZA alone. Based on these results, an independent data monitoring committee recommended the study be terminated for futility, citing that the results are unlikely to demonstrate a statistically significant increase in OS. However subsequent therapy after AZA failure, notably with other regimen including FLT3-TKI, could have precluded transition of better CRc results to better OS results

Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia

Open-label, Phase 2 Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia

the rate of composite complete remission (CRc) \[defined by addition of complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and complete remission with incomplete platelet recovery (CRp)\]

description of toxicities according CTCAE v4.0, and death

rate of complete remission (CR), rate of complete remission with incomplete hematologic recovery (CRi), rate of complete remission with incomplete platelet recovery (CRp), rate of complete remission with partial hematologic recovery (CRh)

Acute Leukemia French Association

French Innovative Leukemia Organisation

Patients who receive Xospata® 40 mg tablet in routine clinical practice according to the drug label approved at the time of marketing authorization.

Gilteritinib Exposure

Astellas Pharma Korea, Inc.

The objective of this study is to describe the observed safety profile of Xospata® 40 mg tablet when administered in patients with relapsed or refractory AML with FLT3 mutation in routine clinical practice in Korea.

This study is being mandated by Ministry of Food and Drug Safety (MFDS) as a part of the Korea-Risk Management Plan (K-RMP) to assess safety in patients with relapsed or refractory AML with FLT3 mutation in routine clinical practice in Korea. This study collects data for 54 months according to the purpose of this study in routine clinical practice as an observational study.

A Study to Assess the Safety of Xospata in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-Like Tyrosine Kinase 3 (FLT3) Mutation

An Observational Study to Assess the Safety of Xospata® 40 mg Tablet When Administered in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-Like Tyrosine Kinase 3 (FLT3) Mutation

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

An Adverse Drug Reaction refers to any unfavorable and unintended reaction occurring with a normal administration or use of the medicinal product that a causal relationship to the medicinal product cannot be ruled out. Number of ADRs related to important identified risks such as posterior reversible encephalopathy syndrome (PRES), QT prolongation, differentiation syndrome, and/or important potential risks such as pancreatitis, embryo-fetal lethality, suppressed fetal growth and teratogenicity, will be recorded.

An ADR refers to any unfavorable and unintended reaction occurring with a normal administration or use of the medicinal product that a causal relationship to the medicinal product cannot be ruled out. Number of ADRs related to important identified risks such as posterior reversible encephalopathy syndrome (PRES), QT prolongation, differentiation syndrome, and/or important potential risks such as pancreatitis, embryo-fetal lethality, suppressed fetal growth and teratogenicity, will be recorded. An ADR is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires inpatient hospitalization or prolongation of hospitalization, or other medically important event.

An ADR refers to any unfavorable and unintended reaction occurring with a normal administration or use of the medicinal product that a causal relationship to the medicinal product cannot be ruled out. Number of ADRs related to identified risks but considered not important, such as other ADRs described by the Korean package insert, will be recorded. An ADR is considered "serious" if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires inpatient hospitalization or prolongation of hospitalization, or other medically important event.

An AE is defined as any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE is considered "serious" if, in the view of either the investigator or Sponsor, it results in any of the following outcomes: results in death, is life-threatening, results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, results in congenital anomaly or birth defect, requires inpatient hospitalization or prolongation of hospitalization, or other medically important event. Causal relationship between the study drug is judged by medically qualified investigator either as certain, probable/likely, possible, unlikely, conditional/unclassified or unassessable/unclassifiable.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies	NCT05279859	Acute Myeloid L...	ERAS-007 ERAS-601 Gilteritinib	18 Years - 99 Years	Erasca, Inc.
Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia	NCT06022003	AML, Adult Refractory AML Relapsed Adult ... FLT3-TKD Mutati... FLT3-ITD	AzaCITIDine Ora... Xospata	18 Years -	French Innovative Leukemia Organisation
Study Investigating the Efficacy and Safety of the Addition of Oral-azacitidine to Salvage Treatment by Gilteritinib in Subjects ≥18 Years of Age With Relapsed/Refractory FLT3-mutated Acute Myeloid Leukemia	NCT06022003	AML, Adult Refractory AML Relapsed Adult ... FLT3-TKD Mutati... FLT3-ITD	AzaCITIDine Ora... Xospata	18 Years -	French Innovative Leukemia Organisation
A Study of Anti-Cancer Therapies Targeting the MAPK Pathway in Patients With Hematologic Malignancies	NCT05279859	Acute Myeloid L...	ERAS-007 ERAS-601 Gilteritinib	18 Years - 99 Years	Erasca, Inc.
A Study to Assess the Safety of Xospata in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-Like Tyrosine Kinase 3 (FLT3) Mutation	NCT04691648	Acute Myeloid L...	Gilteritinib Ex...	18 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for xospata

Every month we try and update this database with for xospata cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for xospata

Every month we try and update this database with for xospata cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for xospata cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.