Study of AMG 330 in Combination With Pembrolizumab in Adult With Relapsed or Refractory Acute Myeloid Leukemia

Phase 1

Terminated

• Conditions: Relapsed or Refractory Acute Myeloid Leukemia
• Interventions: Drug: AMG 330; Drug: Pembrolizumab

• Registration Number: NCT04478695
• Lead Sponsor: Amgen

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of AMG 330, administered in combination with pembrolizumab, in participants with relapsed or refractory acute myeloid leukemia (R/R AML).

Detailed Description

This study will assess the safety and tolerability of AMG 330 in combination with pembrolizumab and whether pembrolizumab will enhance the anti-AML activity of AMG 330. Both cohort 1 and 2 will include AMG 330 and pembrolizumab with the difference being the initiation date for pembrolizumab treatment.

Study Timeline

• Study First Submitted: 2020-07-16
• Study First Submitted QC: 2020-07-16
• Study First Posted: 2020-07-21
• Study Start: 2020-09-29
• Primary Completion: 2020-10-23
• Study Completion: 2020-10-23
• Status Verified: 2023-06
• Results First Submitted: 2023-08-11
• Results First Submitted QC: 2023-08-11
• Last Update Submitted: 2023-08-11
• Results First Posted: 2024-03-08
• Last Update Posted: 2024-03-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 1	AMG 330	-
Cohort 2	AMG 330	-
Cohort 1	Pembrolizumab	-
Cohort 2	Pembrolizumab	-

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)	28 days	A DLT was defined as any of the events described below occurring in a participant during the DLT window, unless clearly attributable to causes other than investigational product: Any treatment-related death, Grade 4 neutropenia, Grade 3-4 non hematologic toxicity not clearly resulting from the underlying leukemia, with some exceptions, cytokine release syndrome, and any Grade 5 toxicity.
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	A TEAE was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment that occurred after first dose. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests that occurred after first dose were recorded as TEAEs.
Number of Participants Who Experienced Treatment-related Adverse Events (TRAEs)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	A TRAE was defined as any untoward medical occurrence in a clinical study participant considered to have a possible causal relationship with the study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests that were considered to have a possible causal relationship with the study treatment were recorded as TRAEs.

Secondary Outcome Measures

Name	Time	Method
Volume of Distribution of AMG 330	Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Complete Remission Without Minimal Residual Disease (CRMRD-)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	CRMRD- was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CRMRD- was defined as complete remission (CR) with negativity for a genetic marker by quantitative reverse transcription polymerase chain reaction (RT-qPCR), or CR with negativity by multiparametric flow cytometry (MFC). CR was defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/μL); platelet count ≥ 100 x 109/L (100 000/μL).
Complete Remission (CR)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	CR was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CR was defined as bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/μL); platelet count ≥ 100 x 109/L (100 000/μL).
CR With Incomplete Recovery (CRi)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	CRi was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). CRi was defined as all CR criteria (bone marrow blasts \<5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥ 1.0 x 109/L (1000/μL); platelet count ≥ 100 x 109/L \[100 000/μL\]), except for residual neutropenia (\< 1.0 x 109/L \[1000/μL\]) or thrombocytopenia (\< 100 x 109/L \[100 000/μL\]).
Morphological Leukemia-free State (MLFS)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	MLFS was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). MLFS was defined as bone marrow blasts \< 5%; absence of blasts with Auer rods; absence of extramedullary disease; no hematologic recovery required.
Partial Remission (PR)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	PR was measured according to the 2017 European Leukemia Net (ELN) criteria (Döhner et al, 2017). PR was defined as all hematologic criteria of CR; decrease of bone marrow blast percentage to 5 to 25%; and decrease of pre-treatment bone marrow blast percentage by at least 50%.
Duration of Response (DoR)	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.	DoR was calculated for participants who achieved overall response (CRMRD-, CR, CRi, PR or MLFS). DoR was defined as time from the first observation indicating an objective response to the subsequent date of disease progression or death, whichever is earlier.
Plasma Concentration of AMG 330	Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Number of Participants With Anti-AMG 330 Antibody Formation	From first dose of study treatment until 30 days after last dose, or end of study, whichever was earlier; median (min, max) duration was 0.79 (0.79, 0.79) months.
Half-life of AMG 330	Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Clearance of AMG 330	Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively
Steady State Concentration of AMG 330	Pre-dose, 6hrs post-dose Day 1 to 71 of Cycle 1 (Cycle 1=77 days), pre-dose, 6hrs post-dose Day 1 to 50 of Cycles 2+ (Cycle 2+=57 days); end of infusion,0.5,2,4 and 8hrs post-infusion on Days 78 and 57 of Cycle 1 and 2 infusion-free periods respectively

Trial Locations

Locations (2)

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States