Neoplasms

Blood and Lymph Conditions

All Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Pharmaceutical Solutions

All Drugs and Chemicals

Amino Acids

Gilteritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Iadademstat

Gilteritinib Oral Tablet

Ana Limón, PhD

Sonia Gutiérrez, MSc

Rajneesh Nath, MD

Sharad Khurana, MD, MSc

Sharad Khurana, MD

Sangeetha Venugopal, MD

Guenther Koehne, MD, PhD

Alexander J Ambiender, MD

Amir Fathi, MD

Neil D Palmisiano, MD, MS

Jonathan Feld, MD

Alice Mims, MD

Theodore P Braun, MD PhD

Robert L. Render, M.D.

Stephen Strickland, MD

Konstantinos Sdrimas, MD

Guru SG Murthy, MD

Douglas Faller, PhD

Iadademstat is being studied as a treatment for subjects with Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) with FMS-like tyrosine kinase mutation (FLT3 mut+). During the trial, iadademstat will be given in combination with gilteritinib, a drug that is already approved to treat patients with FLT3-mutated R/R AML.

This is an escalation/expansion, open label, single arm, study to investigate the safety and the RP2D of the combination of iadademstat with gilteritinib in FLT3-mutated R/R AML.

This study consists of 2 parts. A dose finding part to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and emerging activity of iadademstat and gilteritinib combination, and to determine the pharmacologically-active dose (i.e., the minimum safe and biologically active dose) of iadademstat in combination with gilteritinib, and an expansion part at the specific dose/s selected to evaluate the activity of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)

An Escalation/Expansion, Open Label, Multicenter Study of Iadademstat and Gilteritinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia (R/R AML) With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+): The FRIDA Study

Number of participants with Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

Number of participants with laboratory value abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

Number of participants with vital signs abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

Number of participants with Routine 12-lead electrocardiogram (ECG )abnormalities and/or Adverse Events (AE) after treatment with iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R AML.

Determine the recommended Phase 2 dose (RP2D) of iadademstat in combination with gilteritinib in patients with FLT3-mutated R/R

Measurement of the time it takes for iadademstat to reach the maximum concentration (Cmax) in blood.

Measurement of the highest concentration of iadademstat in the blood after a dose is given.

Measurement of the lowest concentration of iadademstat in the blood, after a dose is given.

Measurement of how much iadadmestat reaches a person's bloodstream in a given period of time after a dose is given.

Percent of drug covalently bound to LSD1 molecule

Proportion of patients achieving complete remission (CR), CR with incomplete hematologic recovery (CRi), and partial remission (PR).

Time from start of treatment to the time of death from any cause.

Time from start of treatment to the date of failure to achieve CR or CRi, relapse from CR/CRi, or death from any cause, whichever occurs first.

Percentage of patients with complete remission (CR), CR with incomplete blood count recovery (CRi), or PR.

Time from the date of initial dosing at RP2D/expansion dose to first documentation of either a type of CR or Partial Response (PR).

Time from the date of first documentation of any type of remission to the date of first documentation of progression of remission for remitters

A patient is defined as red blood cell (RBC) and/or platelet-transfusion independent if he/she receives no RBC and/or platelet transfusions for a period of at least 8 weeks. Rate of transfusion independence is the percentage of patients who become RBC and/or platelet transfusion independent (from the number of patients transfusion dependent at baseline).

Percentage of patients undergoing Hematopoietic Stem Cell Transplantation (HSCT) during the study period.

Oryzon Genomics S.A.

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Neoplasms, Glandular and Epithelial

Small Cell Lung Cancer

Antineoplastic Agents

Atezolizumab

Antibodies

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

Patients in Phase I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Patients in Phase II Arm II continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Patients in Phase II Arm I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Biopsy

Biospecimen Collection

Computed Tomography

Echocardiography

Magnetic Resonance Imaging

Multigated Acquisition Scan

Noura Choudhury

This phase I/II trial tests the safety, side effects, and best dose of iadademstat when given together with atezolizumab or durvalumab, and studies the effect of the combination in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage) who initially received standard of care chemotherapy and immunotherapy. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients with extensive stage small cell lung cancer.

PRIMARY OBJECTIVE:

I. To compare the progression-free survival (PFS) between the combination of iadademstat plus immune checkpoint inhibitor (ICI) versus ICI maintenance alone.

SECONDARY OBJECTIVES:

I. To compare objective response rate (ORR) and overall survival (OS) between treatment arms.

II. To evaluate the safety of combination iadademstat plus ICI.

EXPLORATORY OBJECTIVES:

I. To assess whether detection of circulating tumor DNA (ctDNA) minimal residual disease correlates with disease progression.

II. To assess whether iadademstat impacts the correlation of ICI (atezolizumab or durvalumab) baseline and time varying clearance with clinical outcomes (PFS and OS) and the presence of cachexia.

III. To explore exposure response relationships of iadademstat in combination with ICIs.

IV. To characterize changes to small cell lung cancer (SCLC) subtype throughout treatment.

OUTLINE: This is a phase I dose-escalation study of iadademstat in combination with atezolizumab and durvalumab followed by a randomized phase II study.

PHASE I: Patients receive iadademstat orally (PO) on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PHASE II: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

All patients also undergo multi-gated acquisition (MUGA) or echocardiogram (ECHO), brain magnetic resonance imaging (MRI) or brain computed tomography (CT) during screening, and CT scans and blood sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

After completion of study treatment, patients are followed up every 3 months for up to 12 months.

Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer

A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Will be estimated using the method of Kaplan and Meier and will be presented with 95% confidence intervals as measure of effect size.

National Cancer Institute (NCI)

Carcinoma, Neuroendocrine

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Adenocarcinoma

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Iadademstat oralon a 5 day ON and 2-day OFF schedule every week plus Paclitaxel administered intravenously weekly on day 1, 8 and 15 on day 1 of a 21 day treatment cycle.

Patients will be treated with iadademstat given at a dose of 150 microgram PO administered on a 5 day on-2 day off schedule every week (days 1 through 21)

Patients will be treated with Paclitaxel given at a dose of 80 mg/m2 intravenous administration weekly day 1, 8 and 15 (days 1 through 21).

Namrata Vijavergia

Tanu singh

Namrata Vijayvergia, MD

Carolynn Regulatory Coordinator

Heloisa Soares, MD, PhD

This is a non-randomized single-arm, two cohorts, phase II study of iadademstat in combination with weekly paclitaxel in patients with relapse/refractory SCLC or extrapulmonary G3 Neuroendocrine Carcinomas. A total of 42 patients with SCLC (21 patients) and G3 NEC (21 patients) will be enrolled (including those enrolled in the safety lead-in portion).

Patients with SCLC or extrapulmonary high grade neuroendocrine carcinomas with progression on or after platinum-based chemotherapy will be enrolled on this multi-center, single-arm phase II study.

Patients must have histologically proven metastatic/unresectable SCLC or extrapulmonary G3 NEC (Ki-67 index \> 20% with poorly differentiated histology), or metastatic/unresectable prostate or bladder cancer with high-grade neuroendocrine or small cell component. Patients must have received at least 1, but no more than 3 prior lines of therapy, which must include a platinum based agent. Patients will be treated with iadademstat given at a dose of 150 microgram PO administered on a 5 day on-2 day off schedule every week and weekly paclitaxel at a dose of 80 mg/m2 IV). This fix dose of 150 microgram (liquid formulation) is in line with the 90 mg /m2/d BSA adjusted dose selected as RP2D in a 5d on, 2d off weekly schedule for iadademstat liquid formulation in combination with azacitidine per the ALICE AML Ph2 trial that showed to consistently achieve on average 90% target engagement. A safety lead-in phase with 12 patients will be conducted and these patients will be included in the final analysis.

total of 42 patients with SCLC (21 patients) and G3 NEC (21 patients) will be enrolled (including those enrolled in the safety lead-in portion).

Iadademstat in Combination With Paclitaxel in Relapsed/Refractory SCLC and Extrapulmonary High Grade NET

A Phase 2 Study of Iadademstat in Combination With Paclitaxel in Relapsed or Refractory Small Cell Lung Cancer and Extrapulmonary High Grade Neuroendocrine Carcinomas

To determine Overall response rate (ORR) per RECIST1.1 ORR is defined as patients who meet criteria for Complete Response (CR) or Partial response (PR).

To evaluate the safety of iadademstat in combination with paclitaxel in relapsed/refractory SCLC and extrapulmonary high grade neuroendocrine cancers using CTCAE version 5.0

To determine Progression Free Survival as per RECIST 1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)	NCT05546580	Acute Myeloid L... Acute Myeloid L...	Iadademstat Gilteritinib Or...	18 Years -	Oryzon Genomics S.A.
Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer	NCT06287775	Extensive Stage... Stage IV Lung C...	Atezolizumab Biopsy Biospecimen Col... Computed Tomogr... Durvalumab Echocardiograph... Iadademstat Magnetic Resona... Multigated Acqu...	18 Years -	National Cancer Institute (NCI)
Study of Iadademstat and Gilteritinib in Patients With R/R AML With FMS-like Tyrosine Kinase Mutation (FLT3 Mut+)	NCT05546580	Acute Myeloid L... Acute Myeloid L...	Iadademstat Gilteritinib Or...	18 Years -	Oryzon Genomics S.A.
Iadademstat in Combination With Paclitaxel in Relapsed/Refractory SCLC and Extrapulmonary High Grade NET	NCT05420636	Small-cell Lung... Neuroendocrine ...	Iadademstat Paclitaxel	18 Years -	Fox Chase Cancer Center
Iadademstat in Combination With Paclitaxel in Relapsed/Refractory SCLC and Extrapulmonary High Grade NET	NCT05420636	Small-cell Lung... Neuroendocrine ...	Iadademstat Paclitaxel	18 Years -	Fox Chase Cancer Center

Spots Global Cancer Trial Database for iadademstat

Every month we try and update this database with for iadademstat 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 iadademstat

Every month we try and update this database with for iadademstat 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 iadademstat 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.