Dose escalation and expansion:

Regimen 1: ASTX029 orally once a day for 21 days of each 21-day cycle.

Dose escalation and expansion:

Regimen 2: ASTX029 orally once a day for 14 days of each 21-day cycle.

ASTX029 at the RP2D of the selected dosing regimen identified in Phase 1 to subjects with tumors characterized by gene aberrations in the MAPK signal pathway that may confer sensitivity to ASTX029.

ASTX029

This study is a first-in-human, open-label, multicenter, Phase 1-2 study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of ASTX029 administered orally to subjects with advanced solid malignancies who are not candidates for approved or available therapies.

ASTX029 is a synthetic small molecule inhibitor of extracellular signal-regulated kinases (ERKs) 1/2. ASTX029 has not been previously evaluated in human subjects. The Phase 1 portion of this study will assess safety and determine the maximum tolerated dose, the recommended Phase 2 dose (RP2D), and the recommended dosing regimen of ASTX029 administered orally. The Phase 2 portion will assess preliminary clinical activity in tumors characterized by gene aberrations in the mitogen-activated protein kinase (MAPK) signal pathway that may confer sensitivity to ASTX029.

Study of ASTX029 in Subjects With Advanced Solid Tumors

A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects With Advanced Solid Tumors

Number of subjects with dose-limiting toxicities

Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

1) Area under the time-concentration curve

6) Analysis of ASTX029 metabolites if applicable

Inhibition of phosphorylated ribosomal s6 kinase protein in response to ASTX029 treatment in fresh tumor biopsies

Astex Pharmaceuticals, Inc.

Symptoms and General Pathology

All Conditions

Blood and Lymph Conditions

Neoplasms

Rare Diseases

Syndrome

Myeloproliferative Disorders

Preleukemia

Myelodysplastic Syndromes

Myelodysplastic-Myeloproliferative Diseases

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

Antineoplastic Agents

All Drugs and Chemicals

Decitabine

Decitabine and cedazuridine drug combination

Antimetabolites

Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX029 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose.

Participants will take ASTX029 daily on days 1-21 of each 28-day cycle. ASTX727 daily on days 1-5 of each 28-day cycle. Both ASTX029 and ASTX727 should be taken with water on an empty stomach, no food 2 hours before and 2 hours after dose.

ASTX727

Guillermo Montalban Bravo, MD

Guillermo Montalban Bravo

The goal of Part 1 of this clinical research study is to find the highest tolerable dose of ASTX029 that can be given in combination with ASTX727 to participants who have RAS-mutant MDS or MDS/MPN. The goal of Part 2 of this clinical research study is to learn if the dose of ASTX029 found in Part 1 can help to control the disease when used in combination with ASTX727.

Primary Objectives:

* Phase 1 dose escalation: to determine safety, tolerability and MTD of ASTX029 in RAS mutant MDS, CMML and other MDS/MPN
* Phase 2 dose expansion: to determine the safety, tolerability and overall response rate (ORR) of ASTX727 in combination with ASTX029 in RAS mutant MDS, CMML and other MDS/MPN
* Incidence of AEs, MTD and changes in clinical laboratory values.
* Measures of efficacy: overall response rate (ORR) defined as sum of CR + complete cytogenetic remission + partial remission + marrow response + clinical benefit for MDS/MPN and defined as CR + mCR + PR + HI in MDS

Secondary Objectives:

* To determine other efficacy outcomes such as duration of response, leukemia-free survival (LFS), progression-free survival (PFS) and overall survival (OS).
* To evaluate differences in response and efficacy outcomes by MDS/MPN IWG response criteria based on disease subtypes and genomic features.
* Correlative studies
* To evaluate changes in clonal composition and VAF of identified mutations with therapy.
* To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ASTX029 and the combination of ASTX727 with ASTX029 in patients with RAS mutant MDS, CMML and other MDS/MPN

Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms

Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of ASTX029 in Subjects With Advanced Solid Tumors	NCT03520075	Solid Tumor, Ad...	ASTX029	18 Years -	Astex Pharmaceuticals, Inc.
Phase I/II Study of a Combination of Decitabine and Cedazuridine (ASTX727) and ASTX029, an ERK Inhibitor, for Patients With RAS Pathway Mutant Myelodysplastic Syndromes and Myelodysplastic/Myeloproliferative Neoplasms	NCT06284460	Pathway Mutant ... Myelodysplastic... Myeloproliferat...	ASTX029 ASTX727	18 Years -	M.D. Anderson Cancer Center
Study of ASTX029 in Subjects With Advanced Solid Tumors	NCT03520075	Solid Tumor, Ad...	ASTX029	18 Years -	Astex Pharmaceuticals, Inc.

Spots Global Cancer Trial Database for astx029

Every month we try and update this database with for astx029 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 astx029

Every month we try and update this database with for astx029 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 astx029 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.