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

NCT04740034 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: TNB585.00120210249
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 7

Brief Summary

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of AMG 340, a PSMA x CD3 T-cell engaging bispecific antibody, in subjects with metastatic castrate-resistant prostate cancer (mCRPC) who have received 2 or more prior lines of therapy. The study consists of 2 parts, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of AMG 340 monotherapy in subjects with mCRPC.

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Prostate specific membrane antigen; PSMA; Prostate cancer; Metastatic; Castrate-resistant

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  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.

  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

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

  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.

  Up to approximately Day 21

• Median Concentration of AMG 340

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

  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

Secondary Outcomes (11)

• Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Up to approximately 24 months

• Overall Survival (OS)

  Up to approximately 24 months

• Prostate Specific Antigen (PSA) Progression Free Survival (PFS)

  Up to approximately 24 months

• Radiographic PFS (rPFS)

  Up to approximately 24 months

• Percentage of Participants With rPFS at 6 Months

  6 months

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.

Drug: AMG 340

Dose Expansion

EXPERIMENTAL

An expansion cohort in subjects with mCRPC will be enrolled after RP2D is established.

Drug: AMG 340

Interventions

AMG 340 DRUG

AMG 340 is a bispecific antibody targeting prostate-specific membrane antigen (PSMA) on tumor cells and CD3 on T-cells

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically confirmed prostatic adenocarcinoma.
• History of metastatic disease.
• Chemically or surgically castrate.
• Subject has received at least 2 lines of systemic therapy approved for mCRPC, with disease progression on the most recent systemic therapy as defined in Prostate Cancer Working Group 3 (PCWG3) recommendations.
• Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)-infected subjects that have been cured or who are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
• An Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
• Subject must have adequate heart, liver, bone marrow and kidney function (e.g. estimated glomerular filtration rate \[eGFR\] ≥ 50 mL/min, aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\] ≤ 3 x upper limit of normal \[ULN\], hemoglobin \[Hgb\] ≥ 9 g/dL (without blood transfusion within 7 days from screening assessment), platelets ≥ 100,000 / mm\^3 (without platelet transfusion within 7 days from screening assessment), absolute neutrophil count \[ANC\] ≥ 1500 / mm\^3).

You may not qualify if:

• Subject has been diagnosed with or treated for another malignancy within the past 2 years whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
• History of neuroendocrine differentiation in the subject's disease.
• Subject has a history of central nervous system (CNS) involvement by their mCRPC. Metastases stemming from bone are allowed.
• Subject has clinically significant CNS pathology.
• Subject requires chronic immunosuppressive therapy.
• Subject has a history of major cardiac abnormalities.

Sponsors & Collaborators

• Amgen: lead

Study Sites (7)

UCSF

San Francisco, California, 94158, United States

Location

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Tulane Cancer Center

New Orleans, Louisiana, 70112, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10128, United States

Location

Thomas Jefferson University - Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2021
• First Posted: February 5, 2021
• Study Start: April 29, 2021
• Primary Completion: June 24, 2024
• Study Completion: June 24, 2024
• Last Updated: June 17, 2025
• Results First Posted: June 17, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)