A Study of AMG 340 in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma

Blood samples for pharmacokinetics (PK) analysis were collected at specific time points. PK parameters were estimated using standard non-compartmental approaches.

Time frame: Cohorts 1-5: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 8, and 10; Cohorts 6-10: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 5 (pre-dose to 6 hours post-dose), 6, 7, 8 (pre-dose to 6 hours post-dose), 9, 10

Population: PK analysis set: Included all participants who received at least 1 dose of AMG 340 and had at least 1 PK sample drawn post dose. Summary statistics are presented per dose level as pre-specified in SAP Section 9.7.

A DLT was defined as a TEAE that was not unequivocally due to the participant's underlying malignancy or other extraneous cause, and appeared within 21 days from the first dose of AMG 340. AEs considered DLTs were: * Transient (≤72 hours) grade 3 or 4 electrolyte abnormalities, hyperglycemia, nausea/vomiting/diarrhea responsive to treatment. * Alopecia, vitiligo, and grade 3 fatigue lasting \<10 days. * Grade 3 fever lasting ≤24 hours (outside CRS context). * Grade 3 lab abnormalities resolving within 72 hours (or within 7 days for certain enzymes like ALT, GGT, ALP, and lipase). * Grade 3 CRS or TLS unresolved to ≤ grade 1 within 72 hours or any grade 4 CRS/TLS. * Prolonged grade 4 neutropenia (\>5 days) or febrile neutropenia. * Grade 3 thrombocytopenia with bleeding or any grade 4 thrombocytopenia. * Grade 4 anemia. * Grade 5 adverse events. * Lymphopenia is not considered a DLT.

Time frame: Up to approximately Day 21

Population: DLT evaluable analysis set: All participants who were evaluable for DLTs. A participants was considered DLT evaluable if the participant completed at least the first full treatment cycle or experienced a DLT during the first treatment cycle.

An adverse event (AE) was any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. A treatment-related AE (TRAE) was defined as any TEAE flagged as possibly caused by AMG 340. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were any untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.

Time frame: From enrollment up to and including a maximum of 90 days after last dose of AMG 340; median (min, max) duration was 4.3 (0.5, 27.1) months

Population: SAS: All participants who received at least 1 dose of AMG 340.

DOR was defined as the time from the date of an initial objective response per RECIST 1.1, which was subsequently confirmed, until soft-tissue progression per RECIST 1.1 or death, whichever occurred first in the absence of subsequent anti-cancer therapy. Participants who had not ended their response at the time of analysis had DOR censored at their last evaluable tumor assessment by CT/MRI scan prior to subsequent anti-cancer therapy. This endpoint only applied to participants with an objective response (CR or PR) per RECIST 1.1. No participants achieved CR or PR, therefore, no participants could be analyzed for this outcome measure.

Time frame: Up to approximately 24 months

Population: RECIST 1.1 Evaluable Analysis Set: All participants who received at least one dose of AMG 340, had measurable disease per RECIST 1.1 at baseline, and had the opportunity to be followed for at least six weeks from the start of AMG 340 treatment. Participants who stopped disease assessments prior to six weeks were included in this analysis set if the data snapshot date was at least six weeks after their first study dose date.

SSE was defined as time from study day 1 to the first symptomatic skeletal event, otherwise time to symptomatic skeletal event was censored at the last dose of AMG 340 or end of safety follow-up date, whichever was later.

Time frame: Up to approximately 24 months

Population: SAS: All participants who received at least 1 dose of AMG 340.

OS was defined as the time from the date of study Day 1 until death due to any cause.

Time frame: Up to approximately 24 months

Population: SAS: All participants who received at least 1 dose of AMG 340.

OR was defined as a partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by a repeat assessment at least 4 weeks later. Participants who did not experience a confirmed PR/CR or did not have any follow-up tumor assessments were regarded as non-responders.

Time frame: Up to approximately 24 months

Population: RECIST 1.1 Evaluable Analysis Set: All participants who have received at least 1 dose of AMG 340, had measurable disease per RECIST 1.1 at baseline, and had the opportunity to be followed for at least 6 weeks from start of AMG 340 treatment.

PSA 30 was defined as a ≥ 30% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.

Time frame: Up to approximately 24 months

Population: The PSA response evaluable analysis set was defined as all participants who received at least one dose of AMG 340, had a measurable (i.e., \> 0) PSA at baseline, and had the opportunity to be followed for at least nine weeks from the start of AMG 340 treatment.~Participants who stopped disease assessments prior to nine weeks were included in this analysis set if the data snapshot date was at least nine weeks after their first study dose date.

PSA 50 was defined as a ≥ 50% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.

Time frame: Up to approximately 24 months

Population: The PSA response evaluable analysis set was defined as all participants who received at least one dose of AMG 340, had a measurable (i.e., \> 0) PSA at baseline, and had the opportunity to be followed for at least nine weeks from the start of AMG 340 treatment.~Participants who stopped disease assessments prior to nine weeks were included in this analysis set if the data snapshot date was at least nine weeks after their first study dose date.

PSA 70 was defined as a ≥ 70% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.

Time frame: Up to approximately 24 months

Population: The PSA response evaluable analysis set was defined as all participants who received at least one dose of AMG 340, had a measurable (i.e., \> 0) PSA at baseline, and had the opportunity to be followed for at least nine weeks from the start of AMG 340 treatment.~Participants who stopped disease assessments prior to nine weeks were included in this analysis set if the data snapshot date was at least nine weeks after their first study dose date.

PSA 90 was defined as a ≥ 90% reduction from the baseline PSA. This PSA response had to be confirmed by a second consecutive value obtained at least three weeks later.

Time frame: Up to approximately 24 months

Population: The PSA response evaluable analysis set was defined as all participants who received at least one dose of AMG 340, had a measurable (i.e., \> 0) PSA at baseline, and had the opportunity to be followed for at least nine weeks from the start of AMG 340 treatment.~Participants who stopped disease assessments prior to nine weeks were included in this analysis set if the data snapshot date was at least nine weeks after their first study dose date.

rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.

Time frame: 6 months

Population: SAS: All participants who received at least 1 dose of AMG 340.

PSA PFS was defined as the interval from study day 1 to the earlier of a PSA progression or death from any cause; otherwise, PSA PFS was censored on the date of the last PSA measurement. If a participant had no baseline or post-baseline PSA measurement and a vital status of alive or unknown, PSA PFS was censored at study day 1.

Time frame: Up to approximately 24 months

Population: SAS: All participants who received at least 1 dose of AMG 340.

rPFS was defined as the interval from study day 1 to radiographic progression or death from any cause, whichever occurred first, in the absence of subsequent anti-cancer therapy; otherwise, rPFS was censored at the last evaluable tumor assessment date prior to subsequent anti-cancer therapy. If a participant had no post-baseline radiographic tumor assessment and a vital status of alive or unknown, rPFS was censored at study day 1.

Time frame: Up to approximately 24 months

Population: SAS: All participants who received at least 1 dose of AMG 340.