A Phase 1 interventional study of AMG 176 and Azacitidine in Higher Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia, sponsored by Amgen. Terminated at 1 site in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2025-07-14.
Sponsored by Amgen · Phase 1, Interventional, and Treatment
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).
This study is a Phase 1 clinical trial designed 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 HR-MDS/CMML. Participants will be treated with intravenous (IV) AMG 176 and IV or subcutaneous (SC) azacitidine.
329 studies on the registry are indexed under Leukemia, Myelomonocytic, Chronic; 67 are open to participants now.
This study's enrollment of 7 is below the median of 42 across 297 interventional studies indexed under Leukemia, Myelomonocytic, Chronic.
Browse Leukemia, Myelomonocytic, Chronic studies →Amgen is the lead sponsor of 1,015 studies on the registry; 49 are open to participants now.
Of its 245 completed or terminated interventional studies of FDA-regulated products, 159 (65%) have results posted.
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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:
Exclusion Criteria:
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
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
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
Administered as an intravenous (IV) infusion.
Administered as an IV infusion or subcutaneous (SC) injection.
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.
Time frame: 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.
Time frame: 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
Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN)
A responder was assessed as having complete remission (CR) or partial remission (PR). Non-responders had stable disease, progressive disease or were not evaluable. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline. Progression: ≥ 50% reduction from maximum response levels in granulocytes or platelets, and/or reduction in hemoglobin by ≥ 1.5 g/dL in the absence of another explanation; transfusion dependence.
Time frame: 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
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
Time frame: 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
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
Time frame: 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
Time frame: 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
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: 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
Time to Cmax (Tmax) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Cycle 1: pre-dose, 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
Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Cycle 1: pre-dose, 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
Terminal Half-life of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Cycle 1: pre-dose, 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
Clearance (CL) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Time frame: Cycle 1: pre-dose, 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
A total of 7 participants with higher risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia were enrolled at a single study center in the United States from November 2022 and the last participant's last visit was in December 2023.
| Milestone | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Started | 4 | 3 |
| Completed | 0 | 0 |
| Not completed | 4 | 3 |
| Withdrew: Sponsor decision | 1 | 2 |
| Withdrew: Death | 3 | 1 |
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.
| Participants | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) | 0 | 0 |
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.
| Participants | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Any TEAE | 4 | 3 |
| Any serious TEAE | 3 | 2 |
A responder was assessed as having complete remission (CR) or partial remission (PR). Non-responders had stable disease, progressive disease or were not evaluable. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline. Progression: ≥ 50% reduction from maximum response levels in granulocytes or platelets, and/or reduction in hemoglobin by ≥ 1.5 g/dL in the absence of another explanation; transfusion dependence.
| Participants | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Responders | 0 | 0 |
| Non-responders | 4 | 3 |
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
No measurements were reported for this outcome.
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy. PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but \>5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis.
| ng/mL | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Cycle 1 day 1 | 18600 ± 16600 | 5650 ± 1790 |
| Cycle 1 day 8 | 19500 ± 6600 | 14900 ± 5060 |
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
| hours | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Cycle 1 day 1 | 2.4 (2.2 to 5.3) | 2.5 (2.3 to 5.1) |
| Cycle 1 day 8 | 2.5 (2.3 to 2.7) | 3.0 (2.3 to 3.1) |
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
| hour*ng/mL | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Cycle 1 day 1 | 198000 ± 148000 | 75900 ± 32000 |
| Cycle 1 day 8 | 167000 ± 146000 | 179000 ± 85600 |
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
| hours | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Cycle 1 day 1 | 27.0 (9.93 to 57.2) | 19.2 (10.4 to 27.9) |
| Cycle 1 day 8 | 19.7 (5.10 to 40.8) | 21.1 (9.01 to 22.9) |
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
| mL/hour/m^2 | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Cycle 1 day 1 | 1300 ± 1400 | 1890 ± 1070 |
| Cycle 1 day 8 | 1150 ± 788 | 1540 ± 595 |
Collected over For all-cause mortality, from enrollment through end of study; median (min, max) time on study was 4.1 ( 2.2, 8.61) months. For serious and other AEs, from first dose of AMG 176 to up to 30 days after the last dose or end of study, whichever occurred first; median (min, max) duration was 2.7 ( 2.07, 4.73) months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1A Dose Exploration: AMG 176 Dose Level 1 | 3/4 (75%) | 3/4 (75%) | 4/4 (100%) |
| Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 | 1/3 (33.3%) | 2/3 (66.7%) | 3/3 (100%) |
| Event | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| Ventricular arrhythmiaCardiac disorders | 0/4 | 1/3 |
| BacteraemiaInfections and infestations | 0/4 | 1/3 |
| SepsisInfections and infestations | 1/4 | 1/3 |
| DehydrationMetabolism and nutrition disorders | 0/4 | 1/3 |
| Multiple organ dysfunction syndromeGeneral disorders | 1/4 | 0/3 |
| Penile infectionInfections and infestations | 1/4 | 0/3 |
| PneumoniaInfections and infestations | 1/4 | 0/3 |
| Event | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 |
|---|---|---|
| NauseaGastrointestinal disorders | 3/4 | 3/3 |
| FatigueGeneral disorders | 1/4 | 3/3 |
| CoughRespiratory, thoracic and mediastinal disorders | 4/4 | 1/3 |
| VomitingGastrointestinal disorders | 2/4 | 2/3 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/4 | 2/3 |
| Abdominal painGastrointestinal disorders | 2/4 | 1/3 |
| DiarrhoeaGastrointestinal disorders | 2/4 | 0/3 |
| Non-cardiac chest painGeneral disorders | 2/4 | 0/3 |
| PyrexiaGeneral disorders | 2/4 | 1/3 |
| Decreased appetiteMetabolism and nutrition disorders | 2/4 | 0/3 |
| Age, Categorical(Participants) | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 0 | 1 |
| >=65 years | 3 | 3 | 6 |
| Sex: Female, Male(Participants) | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 2 | 2 | 4 |
| Ethnicity (NIH/OMB)(Participants) | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 4 | 3 | 7 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Part 1A Dose Exploration: AMG 176 Dose Level 1 | Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 | Total |
|---|---|---|---|
| White | 3 | 3 | 6 |
| Black or African American | 1 | 0 | 1 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting information: Study protocol, Sap, Icf, Csr
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Leukemia, Myelomonocytic, Chronic→
Amgen