Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04221542
• Other study ID #: 20180146
• Secondary ID: 2021-005052-1120
• Status: Recruiting
• Phase: Phase 1
• Start date: March 4, 2020
• Est. completion date: July 30, 2028

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: Amgen Call Center
• Phone: 866-572-6436
• Email: medinfo[@]amgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the safety and tolerability of AMG 509 in adult participants and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 461
• Est. completion date: July 30, 2028
• Est. primary completion date: April 15, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Parts 1, 2, and 5: Participants with histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC) who are refractory to a novel antiandrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, or darolutamide) and have failed at least 1 (but not more than 2) taxane regimens including for metastatic hormone-sensitive prostate cancer (mHSPC) (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Note: A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Any NHT that has been administered and has been stopped for reasons other than progression will not be counted as an additional line of treatment.

1. Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.

2. Dose expansion phase: participants must not have had more than 2 NHTs and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-PD1, PARP inhibitors, radioligand therapies, sipuleucel-T, experimental agents) Note: Combinations are considered one systemic anti-cancer treatment.

• Part 3: Participants with histologically or cytologically confirmed mCRPC who are refractory to a NHT (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen.
• Parts 4A and 4B:

1. Participants with histologically or cytologically confirmed mCRPC who have received no or 1/2 prior NHT (given in any disease setting depending on the part), and no or 1 taxane (given for hormone sensitive prostate cancer).

2. Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable.

3. 4A: Participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible). Participants may have had exposure to up to 2 NHTs with a similar mechanism of action (apalutamide, enzalutamide or darolutamide) in the non-mCRPC and mCRPC setting.

4. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).

• All parts:
• Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist.
• Total serum testosterone <= 50 ng/dL or 1.7 nmol/L.
• Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3

(PCWG3) criteria:

1. PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.

2. nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications.

3. appearance of 2 or more new lesions in bone scan.

• Eastern Cooperative Oncology Group performance status of 0-1.
• Adequate organ function, defined as follows:

1. Hematological function:

1. absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment).

2. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment).

3. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).

2. Renal function:

1. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation >= 30 ml/min/1.73 m^2.

3. Hepatic function:

1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement).

2. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases).

4. Cardiac function:

1. left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available).

2. Baseline electrocardiogram (ECG) QTcF <= 470 msec (average of triplicate values).

Exclusion Criteria:

• Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma.
• Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose).
• Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study.
• Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration.
• Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
• History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of AMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation.
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509 with the exception of ischemia or non-ST segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of AMG 509.
• Any anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist/antagonist). Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible.
• Prior PSMA radionuclide therapy within 2 months prior to AMG 509 unless participant received < 2 cycles (Note: a participant cannot have received PSMA radionuclide therapy < 35 days prior to enrollment if 1 cycle was given). Parts 3 and 4: prior PSMA radionuclide therapy is prohibited.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• AMG 509
AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
• Abiraterone
Abiraterone administered as oral tablets.
• Enzalutamide
Enzalutamide administered as oral tablets.

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse	Camperdown	New South Wales
Australia	Monash Medical Centre	Clayton	Victoria
China	Sun Yat-sen University, Cancer Center	Guangzhou	Guangdong
China	Zhejiang Provincial Peoples Hospital	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Centre	Shanghai	Shanghai
Germany	Universitaetsklinikum Essen	Essen
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Klinikum rechts der Isar der TUM	Muenchen
Germany	Universitaetsklinikum Muenster	Muenster
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	The Cancer Institute Hospital of Japanese Foundation for Cancer Research	Koto-ku	Tokyo
Japan	Yokohama City University Hospital	Yokohama-shi	Kanagawa
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Portugal	Hospital da Luz, SA	Lisboa
Portugal	Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE	Porto
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Clinica Universidad de Navarra	Pamplona	Navarra
Switzerland	Istituto Oncologico della Svizzera Italiana	Bellinzona
Switzerland	Kantonsspital Graubuenden	Chur
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	Kantonsspital Sankt Gallen	Sankt Gallen
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation	Taoyuan
United States	Emory University	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers	Aurora	Colorado
United States	Oncology Hematology Care Incorporated	Cincinnati	Ohio
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Virginia Cancer Specialists PC	Fairfax	Virginia
United States	Providence Saint Jude Medical Center	Fullerton	California
United States	Prisma Health Upstate	Greenville	South Carolina
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Alliance for Multispecialty Research	Merriam	Kansas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Tulane Medical Center	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center Cancer Pavillion	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	University of California San Francisco	San Francisco	California
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Sanford Health	Sioux Falls	South Dakota

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Australia,  China,  Germany,  Japan,  Korea, Republic of,  Portugal,  Spain,  Switzerland,  Taiwan, 

References & Publications (1)

Kelly WK, Danila DC, Lin CC, Lee JL, Matsubara N, Ward PJ, Armstrong AJ, Pook D, Kim M, Dorff TB, Fischer S, Lin YC, Horvath LG, Sumey C, Yang Z, Jurida G, Smith KM, Connarn JN, Penny HL, Stieglmaier J, Appleman LJ. Xaluritamig, a STEAP1 x CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study. Cancer Discov. 2024 Jan 12;14(1):76-89. doi: 10.1158/2159-8290.CD-23-0964. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events		3 years
Primary	Incidence of treatment-related adverse events		3 years
Primary	Dose limiting toxicities (DLTs)		3 years
Primary	Number of participants with changes in vital signs		3 years
Primary	Number of participants with changes in the electrocardiogram (ECG) records		3 years
Primary	Number of participants with changes in the clinical laboratory tests results		3 years
Secondary	Maximum serum concentration (Cmax) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Secondary	Time to maximum serum concentration (Tmax) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Secondary	Minimum serum concentration (Cmin) for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Secondary	Area under the concentration-time curve (AUC) over the dosing interval for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Secondary	Accumulation following multiple dosing for AMG 509	To characterize the pharmacokinetics (PK) of AMG 509	3 years
Secondary	Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	Prostate specific antigen (PSA) response	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	PSA decline of at least 50% from baseline at 12 weeks	To evaluate preliminary anti-tumor activity of AMG 509	Week 12
Secondary	Duration of response (DOR) (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	Time to progression (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	Progression-free survival (PFS) (radiographic and PSA)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	6 month radiographic PFS	To evaluate preliminary anti-tumor activity of AMG 509	6 months
Secondary	1, 2, and 3-year radiographic PFS	To evaluate preliminary anti-tumor activity of AMG 509	Year 1, 2, and 3
Secondary	1, 2, and 3-year overall survival (OS)	To evaluate preliminary anti-tumor activity of AMG 509	Year 1, 2, and 3
Secondary	Circulating tumor cells response (CTC0)	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	Rate of circulating tumor cells (CTC) conversion	To evaluate preliminary anti-tumor activity of AMG 509	3 years
Secondary	Time to symptomatic skeletal events	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Secondary	Alkaline phosphatase (total, bone)	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Secondary	Lactate dehydrogenase (LDH)	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Secondary	Hemoglobin	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Secondary	Urine N-telopeptide	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years
Secondary	Neutrophil-to-lymphocyte ratio	To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.	3 years

External Links

•   AmgenTrials clinical trials website