Trial Outcomes & Findings for Study of AMG 330 in Combination With Pembrolizumab in Adult With Relapsed or Refractory Acute Myeloid Leukemia (NCT NCT04478695)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

1 participants

Primary outcome timeframe

28 days

Results posted on

2024-03-08

Participant Flow

1 participant was enrolled into this study at 1 center in the United States.

Screening tests and procedures were performed within the 14 days preceding administration of the first dose.

Participant milestones

Participant milestones
Measure	Cohort 1 Cohort 1 were planned to receive escalating doses of AMG 330 via continuous intravenous infusion (cIV) from Day 1 of Cycle 1 (Cycle 1 was 77 days; subsequent cycles were 57 days) for up to 6 months. The starting dose of AMG 330 was 10 μg/day, increasing up to a maximum of 600 μg/day. Cohort 1 were planned to receive 8 mg of dexamethasone 1 hour prior to each step dose of AMG 330. If the participant did not experience a dose-limiting toxicity (DLT) by Day 14, they then were also planned to receive 200 mg of pembrolizumab once every 3 weeks (Q3W) by a 30-minute intravenous (IV) infusion from Day 15 onwards. At the end of Cycle 1, there was a planned 1-week interval without administration of AMG 330, known as the infusion-free period.	Cohort 2 Cohort 2 were planned to receive escalating doses of AMG 330 via cIV from Day 1 of Cycle 1 (cycles were 57 days) for up to 6 months. The starting dose of AMG 330 was planned to be 10 μg/day, increasing up to a maximum of 600 μg/day. The participants were also planned to receive 8 mg of dexamethasone 1 hour prior to each step dose of AMG 330, and 200 mg of pembrolizumab Q3W by a 30-minute IV infusion from Day 1 onwards. At the end of Cycle 1, there was planned to be a 1-week interval without administration of AMG 330 known as the infusion-free period.. The trial was terminated early and 0 participants were enrolled into Cohort 2.
Overall Study STARTED	1	0
Overall Study Received AMG 330	1	0
Overall Study Received Pembrolizumab	0	0
Overall Study Received Dexamethasone	1	0
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 Cohort 1 were planned to receive escalating doses of AMG 330 via continuous intravenous infusion (cIV) from Day 1 of Cycle 1 (Cycle 1 was 77 days; subsequent cycles were 57 days) for up to 6 months. The starting dose of AMG 330 was 10 μg/day, increasing up to a maximum of 600 μg/day. Cohort 1 were planned to receive 8 mg of dexamethasone 1 hour prior to each step dose of AMG 330. If the participant did not experience a dose-limiting toxicity (DLT) by Day 14, they then were also planned to receive 200 mg of pembrolizumab once every 3 weeks (Q3W) by a 30-minute intravenous (IV) infusion from Day 15 onwards. At the end of Cycle 1, there was a planned 1-week interval without administration of AMG 330, known as the infusion-free period.	Cohort 2 Cohort 2 were planned to receive escalating doses of AMG 330 via cIV from Day 1 of Cycle 1 (cycles were 57 days) for up to 6 months. The starting dose of AMG 330 was planned to be 10 μg/day, increasing up to a maximum of 600 μg/day. The participants were also planned to receive 8 mg of dexamethasone 1 hour prior to each step dose of AMG 330, and 200 mg of pembrolizumab Q3W by a 30-minute IV infusion from Day 1 onwards. At the end of Cycle 1, there was planned to be a 1-week interval without administration of AMG 330 known as the infusion-free period.. The trial was terminated early and 0 participants were enrolled into Cohort 2.
Overall Study Death	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline data not reported

PRIMARY outcome

Timeframe: 28 days

Population: Measured in the Dose-limiting Toxicity Evaluable Analysis Set, which was defined as DLT-evaluable participants in the Safety Analysis Set. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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 \[100 000/μL\]).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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%.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: Measured in the Pharmacokinetic (PK) Analysis Set which contained all participants who received at least 1 dose of AMG 330 or pembrolizumab and had at least 1 PK sample collected. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: Measured in the Pharmacokinetic (PK) Analysis Set which contained all participants who received at least 1 dose of AMG 330 or pembrolizumab and had at least 1 PK sample collected. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: Measured in the Pharmacokinetic (PK) Analysis Set which contained all participants who received at least 1 dose of AMG 330 or pembrolizumab and had at least 1 PK sample collected. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: Measured in the Pharmacokinetic (PK) Analysis Set which contained all participants who received at least 1 dose of AMG 330 or pembrolizumab and had at least 1 PK sample collected. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Population: Measured in the Pharmacokinetic (PK) Analysis Set which contained all participants who received at least 1 dose of AMG 330 or pembrolizumab and had at least 1 PK sample collected. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: Measured in the Safety Analysis Set, which was defined as all participants that were enrolled and received at least 1 dose of AMG 330 or pembrolizumab. The study was terminated with only 1 participant enrolled into Cohort 1 (0 participants were enrolled into Cohort 2). No data is reported here to maintain participant confidentiality.

Outcome measures

Outcome data not reported

Adverse Events

Cohort 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

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