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

Amgen

Status and phase: Terminated; Phase 1

Conditions: Higher Risk Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia

Treatments: Drug: AMG 176; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05209152

20200392

Details and patient eligibility

About

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).

Full description

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.

Enrollment: 7 patients

Sex: All

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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:

  1. 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;
  2. 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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7 participants in 3 patient groups

Part 1A - AMG 176 Monotherapy (Dose Exploration)

Experimental group

Description:

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).

Treatment:

Drug: AMG 176

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

Experimental group

Description:

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.

Treatment:

Drug: Azacitidine

Drug: AMG 176

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

Experimental group

Description:

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.

Treatment:

Drug: Azacitidine

Drug: AMG 176