Clinical trial NCT04221542: Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer
Official title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: AMG 509
mCRPC
Metastatic Castration-resistant Prostate Cancer
Prostate cancer
PSMA
STEAP1
STEAP1 targeted therapy
Solid tumor
Immunotherapy
Immuno-oncology
Immunooncology
Bispecific T-Cell engager®
BiTE®
XmAb®
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-01-09
Enrollment: 470
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).

Part 2 is now closed to accrual.


Eligibility criteria: 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 have received no or 1-2 prior NHTs (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 (unless taxane treatment was administered in HSPC setting). 0 1 prior PARP inhibitors or sipuleucel T treatments are acceptable. Subjects who received prior investigational therapy for the treatment of metastatic disease are not eligible.
* Parts 4A and 4B:

  1. Participants with histologically or cytologically confirmed mCRPC who have received no or 1-2 prior NHTs (given in any disease setting depending on the part), and no or 1 taxane regimen (for HSPC).
  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.
* Dose expansion phase: up to approximately 10 subjects with prior exposure to abiraterone acetate may be enrolled into Part 4A expansion cohort.

  d. 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).

Part 3-Retreatment group:

* Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following:

  1. confirmed PSA50 response.
  2. radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with AMG 509 and without progression during the first 6 cycles.
* No discontinuation for toxicity during the initial treatment with 6 cycles of AMG 509.
* Progressive disease as defined in I106 within 12 months of final dose in their initial treatment with 6 cycles (EOT_1).
* Willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator.

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).
* 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. Participants on a stable bisphosphonate or denosumab regimen for \>= 30 days prior to enrollment are eligible (exception: part 3 retreatment).
* Part 3-Retreatment only: Any anticancer therapy or immunotherapy, not including luteinizing hormone-releasing hormone/gonadotropin releasing hormone (LHRH/GnRH) analogue (agonist/antagonist), and/or bisphosphonate or denosumab regimen after last dose of AMG 509 initial course of treatment.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events
timeFrame: 3 years
measure: Incidence of treatment-related adverse events
timeFrame: 3 years
measure: Dose limiting toxicities (DLTs)
timeFrame: 3 years
measure: Number of participants with changes in vital signs
timeFrame: 3 years
measure: Number of participants with changes in the electrocardiogram (ECG) records
timeFrame: 3 years
measure: Number of participants with changes in the clinical laboratory tests results
timeFrame: 3 years
Secondary outcomes:
measure: Maximum serum concentration (Cmax) for AMG 509
timeFrame: 3 years
measure: Time to maximum serum concentration (Tmax) for AMG 509
timeFrame: 3 years
measure: Minimum serum concentration (Cmin) for AMG 509
timeFrame: 3 years
measure: Area under the concentration-time curve (AUC) over the dosing interval for AMG 509
timeFrame: 3 years
measure: Accumulation following multiple dosing for AMG 509
timeFrame: 3 years
measure: Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications
timeFrame: 3 years
measure: Prostate specific antigen (PSA) response
timeFrame: 3 years
measure: PSA decline of at least 50% from baseline at 12 weeks
timeFrame: Week 12
measure: Duration of response (DOR) (radiographic and PSA)
timeFrame: 3 years
measure: Time to progression (radiographic and PSA)
timeFrame: 3 years
measure: Progression-free survival (PFS) (radiographic and PSA)
timeFrame: 3 years
measure: 6 month radiographic PFS
timeFrame: 6 months
measure: 1, 2, and 3-year radiographic PFS
timeFrame: Year 1, 2, and 3
measure: 1, 2, and 3-year overall survival (OS)
timeFrame: Year 1, 2, and 3
measure: Circulating tumor cells response (CTC0)
timeFrame: 3 years
measure: Rate of circulating tumor cells (CTC) conversion
timeFrame: 3 years
measure: Time to symptomatic skeletal events
timeFrame: 3 years
measure: Alkaline phosphatase (total, bone)
timeFrame: 3 years
measure: Lactate dehydrogenase (LDH)
timeFrame: 3 years
measure: Hemoglobin
timeFrame: 3 years
measure: Urine N-telopeptide
timeFrame: 3 years
measure: Neutrophil-to-lymphocyte ratio
timeFrame: 3 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Fullerton
country: United States
facility: Providence Saint Jude Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Merriam
country: United States
facility: Alliance for Multispecialty Research
state: Kansas
city: New Orleans
country: United States
facility: Tulane Medical Center
state: Louisiana
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Incorporated
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Oncology Clinic and Pharmacy
state: South Dakota
city: Nashville
country: United States
facility: United States Oncology Regulatory Affairs Corporate Office
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: US Oncology Research Investigational Products Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Fairfax
country: United States
facility: Virginia Cancer Specialists PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Guangzhou
country: China
facility: Sun Yat-sen University, Cancer Center
state: Guangdong
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Centre
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Provincial Peoples Hospital
state: Zhejiang
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Muenchen
country: Germany
facility: Klinikum rechts der Isar der TUM
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Yokohama-shi
country: Japan
facility: Yokohama City University Hospital
state: Kanagawa
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Lisboa
country: Portugal
facility: Hospital da Luz, SA
city: Lisboa
country: Portugal
facility: Unidade Local de Saude de Santa Maria, EPE - Hospital de Santa Maria
city: Porto
country: Portugal
facility: Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Chur
country: Switzerland
facility: Kantonsspital Graubuenden
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Sankt Gallen
country: Switzerland
facility: Kantonsspital Sankt Gallen
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.