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This arm includes subjects with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).

This arm includes subjects with acute myeloid leukemia (AML).

This arm includes subjects with AML or myelodysplastic syndrome (MDS).

This arm includes subjects with AML in Japan only.

AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

AMG 397

Dexamethasone will be administered intravenously (IV) or orally on Days 1, 8, 15, and 22 of each 28-day cycle.

Azacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle.

Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.

This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study evaluating AMG 397 administered orally once weekly, as part of a 28-day treatment cycle in adult subjects with selected relapsed or refractory hematological malignancies

Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies

A Phase 1 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

DLTs were defined as specific adverse events (AEs) that occurred in a participant during the DLT evaluation period (Day 1 to Day 28), that the investigator assessed as related to AMG 397. The grading and severity of AEs were based on the guidelines provided in the common terminology criteria for adverse events (CTCAE) version 4.03.

A TEAE was defined as any AE starting on or after the first dose of investigational product. Any clinically significant changes in vital signs, physical examinations, electrocardiogram (ECGs) and clinical laboratory test results were recorded as AEs. The grading and severity of adverse events were based on the guidelines provided in the CTCAE version 4.03. Treatment-related TEAEs were any events that the investigator assessed as related to AMG 397.

ORR was assessed for participants with MM using response criteria per International Myeloma Working Group (IMWG).

ORR was defined as the percentage of participants who experienced either one of the following based on investigator assessment:

* partial response (PR)
* very good partial response (VGPR)
* complete response (CR)
* stringent complete response (sCR)

ORR was assessed for participants with NHL using response criteria per Lugano Classification.

ORR was defined as the percentage of participants who experienced either of the following based on investigator assessment:

* partial metabolic response/ PR
* complete metabolic response/ CR

ORR was assessed for participants with AML using response criteria per European Leukemia Network Response Criteria.

ORR was defined as the percentage of participants who experienced either of the following based on investigator assessment:

* PR
* morphological leukemia-free state (MLFS)
* complete remission with incomplete hematologic recovery (CRi)
* complete remission
* complete remission without minimal residual disease (CRmrd-).

PFS was calculated as time from first dose of investigational product date to disease progression date or death due to any cause, whichever was earlier.

PFS time in months: (date of disease progression or death - first dose date +1)/30.4.

OS was defined as the time from first dose of investigational product date until death due to any cause.

OS time in months: (date of death - first dose date +1)/30.4.

TTR was defined as the time from the first dose of investigational product until the first documentation of objective response. Only participants who achieved an objective response were evaluated for TTR.

TTR time in months: (date of the first observation of response - first dose of IP date +1)/30.4.

DOR was only planned to be calculated for participants who achieved response (PR or better). DOR was defined as time from the first observation indicating a response to the subsequent date of disease progression or death, whichever was earlier.

DOR time in months: (date of disease progression or death - date of the first observation of response +1)/30.4.

Predose data for Day 2 were analyzed/included with the Day 1 data.

Amgen

All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for the FAS.

Participants with RR MM and/or NHL received 80 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1a: 80 mg AMG 397

Participants with RR MM and/or NHL received 160 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1a: 160 mg AMG 397

Participants with RR MM received 320 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1a: 320 mg AMG 397

Participants with RR AML received 80 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1b: 80 mg AMG 397

Participants with RR AML received 160 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1b: 160 mg AMG 397

Participants with RR AML received 320 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Part 1b: 320 mg AMG 397

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Full Analysis Set (FAS): All participants who were enrolled and received at least 1 dose of AMG 397.

Study Director

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1.

DLT evaluable set: All participants who experienced a DLT or who received at least 75% of the planned dose in the DLT window (Day 1 to Day 28).

Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

TEAEs

Treatment-related TEAEs

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Participants with MM were only enrolled in part 1a, so therefore data is only presented for part 1a.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Overall Response Rate (ORR) for Participants With Multiple Myeloma (MM)

All participants in part 1a with NHL that received 80 mg AMG 397.

Part 1a: Participants With NHL - 80 mg AMG 397

All participants in part 1a with NHL that received 160 mg AMG 397.

Part 1a: Participants With NHL - 160 mg AMG 397

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Participants with NHL were only enrolled in part 1a, so therefore data is only presented for part 1a.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Overall Response Rate (ORR) for Participants With Non-Hodgkin's Lymphoma (NHL)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Participants with AML were only enrolled in part 1b, so therefore data is only presented for part 1b.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Overall Response Rate (ORR) for Participants With Acute Myeloid Leukemia (AML)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Per the statistical analysis plan (SAP), PFS was only to be calculated if the number of participants who experienced events (disease progression or death) was 10 or more in either part 1 or part 2.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Progression-free Survival (PFS)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Per the SAP, OS was only to be calculated if the number of participants who experienced an event (death) was 10 or more in either part 1 or part 2.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Overall Survival (OS)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Per the SAP, TTR was only to be calculated if the number of participants who experienced an event (objective response) was 10 or more in either part 1 or part 2.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Time to Response (TTR)

Parts 2 and 3 were not initiated and did not enrol any participants, therefore results presented only included participants in part 1. Per the SAP, DOR was only to be calculated if the number of participants who experienced an event (objective response) was 10 or more in either part 1 or part 2.

FAS: All participants who were enrolled and received at least 1 dose of AMG 397.

Duration of Response (DOR)

Day 1

Day 2

The Pharmacokinetic (PK) Analysis Set: All participants who received at least 1 dose of AMG 397 and had at least 1 PK sample collected.

Maximum Observed Concentration (Cmax) of AMG 397

The PK Analysis Set: All participants who received at least 1 dose of AMG 397 and had at least 1 PK sample collected.

Time to Maximum Observed Concentration (Tmax) for AMG 397

Area Under the Concentration Time Curve From Time 0 to 168 Hours (AUC0-168) for AMG 397

Clearance (CL) of AMG 397

Half-life (t1/2) of AMG 397

Participants with relapsed/refractory (RR) multiple myeloma (MM) and/or non-Hodgkin's lymphoma (NHL) received 80 mg AMG 397 once a day for 2 consecutive days followed by a 5 day break at a weekly interval (QD2), as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Participants with RR acute myeloid leukemia (AML) received 80 mg AMG 397 QD2, as part of a 28-day treatment cycle.

Participants could receive AMG 397 until the participant became intolerant to the investigational product, signs and symptoms of clinical progression were evident as determined by the investigator, or the participant withdrew consent.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies	NCT03465540	Multiple Myelom... Acute Myeloid L... Non-Hodgkins Ly... Myelodysplastic... AML MDS NHL	AMG 397 Dexamethasone Azacitidine	18 Years - 65 Years	Amgen
Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies	NCT03465540	Multiple Myelom... Acute Myeloid L... Non-Hodgkins Ly... Myelodysplastic... AML MDS NHL	AMG 397 Dexamethasone Azacitidine	18 Years - 65 Years	Amgen

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