A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer

Phase 1

• Conditions: Metastatic Castration-resistant Prostate Cancer; MedDRA version: 21.1Level: LLTClassification code 10076506Term: Castration-resistant prostate cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-001305-23-SE
• Lead Sponsor: Amgen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-08-19
• Last Update Posted: 18 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 136

Inclusion Criteria

All Subprotocols
- Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without pure neuroendocrine differentiation or small cell features
- Subjects must have undergone bilateral orchiectomy or must be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist.
- Total serum testosterone = 50 ng/dL (or 1.7 nmol/L)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 1
- Life expectancy of > 3 months
- Adequate organ function, defined as follows:
• absolute neutrophil count = 1.5 x 10^9/L (without growth factor support within 7 days from screening assessment)
• platelet count = 100 x 10^9/L (without platelet transfusion within 7 days from screening assessment)
• hemoglobin > 9 g/dL (90 g/L) (subprotocol A, C & D) / > 10 g/dL (100g/L) (subprotocol B) (without blood transfusion within 7 days from screening assessment)
• estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 30 mL/min/1.73 m2
• AST and ALT < 3 x upper limit of normal (ULN) (or < 5 x ULN for subjects with liver involvement)
• total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for subjects with liver metastases)
• left ventricular ejection fraction (LVEF)> 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available)
- Baseline electrocardiogram (ECG) QTc = 470 msec

Subprotocol A & B only
- Subjects planning to receive enzalutamide (subprotocol A) / abiraterone (subprotocol B) for the first time for mCRPC (subjects who received prior enzalutamide (subprotocol A) / abiraterone (subprotocol B) are not eligible).

Subprotocol C only
- Subjects who are refractory to a novel antiandrogen therapy (abiraterone, apalutamide, and/or enzalutamide) given for metastatic or non-metastatic prostate cancer. Subjects must be ineligible for or refuse taxane therapy.
- Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
• PSA level of at least 1 ng/mL that has risen on at least 2 successive occasions at least 1 week apart
• nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications
• appearance of 2 or more new lesions in bone scan

Subprotocol D only
- Subjects may have had novel hormonal therapies (NHT; eg,
abiraterone, enzalutamide, apalutamide or darolutamide) for prostate
cancer, but no more than 1 NHT for metastatic prostate cancer.
- Subjects must be ineligible for or refuse taxane therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 69
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 67

Exclusion Criteria

All Subprotocols
- CNS metastases/leptomeningeal disease
- Symptomatic peripheral sensory/motor neuropathy =grade3
- History/presence of clinically relevant CNS pathology
- Confirmed history/current autoimmune disease or other diseases resulting in permanent immunosuppression/requiring permanent immunosuppressive therapy
- Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials (Subprot.A,B&D) /active fungal, bacterial, viral, or other infection requiring systemic therapy (Subprot.C) within 7days of dosing
- History/evidence of inflammatory bowel disease or any other GI disorder causing chronic nausea, vomiting, or diarrhea
- History of arterial/venous thrombosis within 12months of 1st dose
- Myocardial infarction, uncontrolled hypertension (Subprot.A,C&D), unstable angina, cardiac arrhythmia requiring medication, &/or symptomatic congestive heart failure (NYHA > class II) within 12months (Subprot.A,B&D) /within 6months (Subprot.C) of 1st dose of AMG160
- Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE version 5.0 grade 1, except for alopecia or toxicities that are stable and well-controlled & there is agreement to allow by both the investigator & sponsor
- Known HIV infection, hepatitis C or hepatitis B infection
- History of other malignancy within the past 2years, with the following exceptions:
• Malignancy treated with curative intent & with no known active disease present for =3 years before enrollment and felt to be at low risk for recurrence by treating physician
• Adequately treated non-melanoma skin cancer/lentigo maligna without evidence of disease
• Adequately treated urothelial papillary noninvasive carcinoma/carcinoma in situ
- Prior treatment with a taxane for mCRPC
- Radiation therapy within 4weeks of 1st dose (or local or focal radiotherapy within 2weeks)
- Any anticancer therapy/immunotherapy within 4weeks (2weeks Subprot.C) of start of 1st dose, not including LHRH/GnRH analogue. Subjects on a stable bisphosphonate/denosumab regimen for =30 days prior to enrollment are eligible
- Prior PSMAxCD3 bispecific therapy (not subprot.C part3)
- Requiring chronic systemic corticosteroid therapy/any other immunosuppressive therapies. Low dose corticosteroids permitted
- Prior major surgery within 4weeks of 1st dose
- Currently receiving treatment in another investigational device/drug study, or <4 weeks since ending treatment on another investigational device or drug study
- Male subjects with a female partner of childbearing potential/pregnant partner who are unwilling to practice sexual abstinence/use contraception during treatment and for an additional 4months (Subprot.A&B)/8months (Subprot.C) after the last dose
- Male subjects unwilling to abstain from donating sperm during treatment and for an additional 4 months (Subprot.A,B&D)/8months (Subprot.C) after the last dose
- Subject has known sensitivity to any of the products (or components) to be administered during dosing
- Subject likely to not be available to complete all protocol-required study visits/procedures, &/or to comply with all required study procedures
- History/evidence of any other clinically significant disorder, condition or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
- History of SARS-CoV-2 infection unless agreed upon

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified