Trial Outcomes & Findings for AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia (NCT NCT05209152)

NCT ID: NCT05209152

Last Updated: 2025-07-14

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

7 participants

Primary outcome timeframe

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

Results posted on

2025-07-14

Participant Flow

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.

The study was planned to be conducted in 3 parts and was discontinued early after the completion of Part 1A (dose exploration). Part 1B (dose escalation/de-escalation) and Part 3 (dose expansion) were not conducted and did not enroll any participants. Dose level 1 is a low dose and Dose level 2 is a high dose.

Participant milestones

Participant milestones
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 Participants received intravenous (IV) AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Overall Study STARTED	4	3
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 Participants received intravenous (IV) AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Overall Study Sponsor decision	1	2
Overall Study Death	3	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.	Total n=7 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

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

Population: DLT-evaluable participants were those who experienced a DLT during the DLT evaluation period or if they received 75% of the planned doses of AMG 176 and completed the DLT evaluation period.

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: 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

Population: The full analysis set included all enrolled participants who received at least 1 dose of AMG 176.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any TEAE	4 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Any serious TEAE	3 Participants	2 Participants

SECONDARY outcome

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

Population: The full analysis set included all enrolled participants who received at least 1 dose of AMG 176.

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN) Responders	0 Participants	0 Participants
Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN) Non-responders	4 Participants	3 Participants

SECONDARY outcome

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

Population: The full analysis set included all enrolled participants who received at least 1 dose of AMG 176. No participants were responders.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: The full analysis set included all enrolled participants who received at least 1 dose of AMG 176. No participants were responders.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

Population: As pre-specified in Section 10 of the statistical analysis plan, EFS was not analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set included all participants who received at least 1 dose of AMG 176 and had at least 1 PK sample collected.

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Maximum Plasma Concentration (Cmax) of AMG 176 Cycle 1 day 1	18600 ng/mL Standard Deviation 16600	5650 ng/mL Standard Deviation 1790
Maximum Plasma Concentration (Cmax) of AMG 176 Cycle 1 day 8	19500 ng/mL Standard Deviation 6600	14900 ng/mL Standard Deviation 5060

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set included all participants who received at least 1 dose of AMG 176 and had at least 1 PK sample collected.

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Time to Cmax (Tmax) of AMG 176 Cycle 1 day 1	2.4 hours Interval 2.2 to 5.3	2.5 hours Interval 2.3 to 5.1
Time to Cmax (Tmax) of AMG 176 Cycle 1 day 8	2.5 hours Interval 2.3 to 2.7	3.0 hours Interval 2.3 to 3.1

SECONDARY outcome

Timeframe: 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

Population: The PK analysis set included all participants who received at least 1 dose of AMG 176 and had at least 1 PK sample collected. Participants with data available at each time point are included.

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176 Cycle 1 day 1	198000 hour*ng/mL Standard Deviation 148000	75900 hour*ng/mL Standard Deviation 32000
Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176 Cycle 1 day 8	167000 hour*ng/mL Standard Deviation 146000	179000 hour*ng/mL Standard Deviation 85600

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Terminal Half-life of AMG 176 Cycle 1 day 1	27.0 hours Interval 9.93 to 57.2	19.2 hours Interval 10.4 to 27.9
Terminal Half-life of AMG 176 Cycle 1 day 8	19.7 hours Interval 5.1 to 40.8	21.1 hours Interval 9.01 to 22.9

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 Participants Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 Participants Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Clearance (CL) of AMG 176 Cycle 1 day 1	1300 mL/hour/m^2 Standard Deviation 1400	1890 mL/hour/m^2 Standard Deviation 1070
Clearance (CL) of AMG 176 Cycle 1 day 8	1150 mL/hour/m^2 Standard Deviation 788	1540 mL/hour/m^2 Standard Deviation 595

Adverse Events

Part 1A Dose Exploration: AMG 176 Dose Level 1

Serious events: 3 serious events

Other events: 4 other events

Deaths: 3 deaths

Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Part 1A Dose Exploration: AMG 176 Dose Level 1 n=4 participants at risk Participants received IV AMG 176 at dose level 1 once a week in 28-day cycles. Treatment was planned until disease progression or unacceptable toxicity.	Part 1A Dose Exploration: AMG 176 Dose Level 1 Then Dose Level 2 n=3 participants at risk Participants received IV AMG 176 at dose level 1 on cycle 1 day 1 and then dose level 2 from cycle 1 day 8 and once a week thereafter (each cycle = 28 days). Treatment was planned until disease progression or unacceptable toxicity.
Cardiac disorders Ventricular arrhythmia	0.00% 0/4 • 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.	33.3% 1/3 • 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.
General disorders Multiple organ dysfunction syndrome	25.0% 1/4 • 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.	0.00% 0/3 • 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.
Infections and infestations Bacteraemia	0.00% 0/4 • 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.	33.3% 1/3 • 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.
Infections and infestations Penile infection	25.0% 1/4 • 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.	0.00% 0/3 • 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.
Infections and infestations Pneumonia	25.0% 1/4 • 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.	0.00% 0/3 • 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.
Infections and infestations Sepsis	25.0% 1/4 • 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.	33.3% 1/3 • 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.
Metabolism and nutrition disorders Dehydration	0.00% 0/4 • 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.	33.3% 1/3 • 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.

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER