AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

NCT05209152 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 20200392
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective is to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia (HR-MDS/CMML).

Conditions

Higher Risk Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia

Keywords

Higher Risk Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

  DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and included the below if considered by the investigator to be related to AMG 176: Grade 3 or higher non-hematological or a Grade 4 hematologic adverse event (AE) during the DLT observation period in Part 1. CTCAE Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 results in death.

  Day 1 to day 28 of cycle 1 (each cycle was 28 days)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  An AE was defined as any untoward medical occurrence in a clinical trial participants. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to 28 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered possibly related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, and clinical laboratory tests were recorded as TEAEs. A serious TEAE resulted in death, was immediately life threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.

  Day 1 cycle 1 to 30 days after the last dose of AMG 176 or end of study, whichever occurred earlier (cycle length = 28 days). Median treatment duration was 2.7 months

Secondary Outcomes (9)

• Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN)

  Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months

• Time to a Response According to the Uniform Response Criteria for MDS/MPN

  Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months

• Duration of Response According to the Uniform Response Criteria for MDS/MPN

  Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months

• Event-free Survival

  Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months

• Maximum Plasma Concentration (Cmax) of AMG 176

  Cycle 1: pre-dose, end of infusion (EOI), 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4

Study Arms (3)

Part 1A - AMG 176 Monotherapy (Dose Exploration)

EXPERIMENTAL

Two dose levels of AMG 176 will be tested in Part 1A to find the optimal biological dose/minimum safe biologically effective dose (OBD/MSBED).

Drug: AMG 176

Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)

EXPERIMENTAL

After the OBD is found in Part 1A, two dose levels of AMG 176 in combination with azacitidine will be tested in Part 1B to find the OBD/MSBED.

Drug: AMG 176; Drug: Azacitidine

Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

EXPERIMENTAL

After the completion of Part 1, the Part 2 dose expansion phase will begin at the OBD/MSBED identified in Part 1. Venetoclax-naïve and venetoclax-exposed R/R HR-MDS participants after HMA failure will be enrolled along with participants with newly diagnosed HR-MDS/CMML.

Drug: AMG 176; Drug: Azacitidine

Interventions

AMG 176 DRUG

Administered as an intravenous (IV) infusion.

Part 1A - AMG 176 Monotherapy (Dose Exploration); Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration); Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

Azacitidine DRUG

Administered as an IV infusion or subcutaneous (SC) injection.

Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration); Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>= 18 years of age
• For Part 1, participants have R/R MDS post-HMA failure, defined as prior receipt of 4 cycles of HMA therapy (including but not limited to decitabine, azacitidine, investigational HMAs such as SGI-110, and oral HMAs such as oral decitabine and cedazuridine \[ASTX727\] and oral azacitidine \[CC-486\]) with failure to attain a response or progression of disease or relapse at any time after prior response to HMA therapy
• a. Note: participants with HR-CMML (CMML-1 or 2 by World Health Organization \[WHO\]) are eligible. Hydroxyurea administration will be allowed on the study to lower the white cell count to \<= 10 000/μL prior to the initiation of therapy
• For Part 2, participants will be divided into 2 cohorts:
• HMA Failure Cohort: participants with R/R MDS post-HMA failure. Participants who have previously received venetoclax are eligible and will be stratified accordingly in the HMA failure cohort;
• Newly Diagnosed Cohort: Participants with treatment-naïve newly diagnosed HR-MDS (revised International Prognostic Scoring System \[IPSS-R\] score \>3.5) are eligible for enrollment only after all prior cohorts have been completed. Hydroxyurea administration will be allowed on the study to lower the white cell count to \<= 10 000/μL prior to the initiation of therapy. Participants with HR-CMML (CMML-1 or 2 by WHO) are eligible

You may not qualify if:

• Participants with newly diagnosed MDS with Revised International Prognostic Scoring System (IPSS-R) lower-risk category (IPSS-R score \< 3.5)
• Participants with CMML-0 by WHO
• History of other malignancy within the past 2 years prior to enrollment (with some exceptions as listed in full list of criteria)
• Excluded prior and/or concomitant therapies as listed in the full list of criteria
• Participants who are fit and deemed eligible by the investigator for intensive salvage therapy

Sponsors & Collaborators

• Amgen: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

tapotoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Limitations and Caveats

The study was planned to be conducted in 3 parts and was discontinued early after the completion of Part 1A due to strategic reasons. No participants enrolled into Parts 1B and 2.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2022
• First Posted: January 26, 2022
• Study Start: November 14, 2022
• Primary Completion: December 19, 2023
• Study Completion: December 19, 2023
• Last Updated: July 14, 2025
• Results First Posted: July 14, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (1)