Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Participants must be adults ≥ 18 years of age
3. Participants must have an ECOG performance status of 0 to 1
4. Participants must have histological pathological, and/or cytological confirmation of
adenocarcinoma of the prostate
5. Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by
the sponsor's central reader
6. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or <
1.7 nmol/L)
7. Participants must have received one prior approved ARDT (for example, abiraterone,
enzalutamide, darolutamide, or apalutamide, etc.) and have documented progression on
therapy
8. Participants must have progressive mCRPC. Documented progressive mCRPC will be based
on at least 1 of the following criteria:
- Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a
previous reference value measured at least 1 week prior. The minimal start value
is 2.0 ng/mL
- Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al
2009, Scher et al 2016)]
- Progression of bone disease: evaluable disease or one or more new bone lesions(s)
by bone scan (PCWG3 criteria (Scher et al 2016))
9. Participants must have ≥ 1 metastatic lesion that is present on screening/baseline CT,
MRI, or bone scan imaging obtained ≤ 28 days prior to beginning study therapy
10. Participants must have recovered to ≤ Grade 2 from all clinically significant
toxicities related to prior therapies (i.e. prior chemotherapy, radiation, etc.)
except alopecia
11. Participants must have adequate organ function:
- Bone marrow reserve:
- ANC ≥ 1.5 x 109/L
- Platelets ≥100 x 109/L
- Hemoglobin ≥ 9 g/dL
- Hepatic:
- Total bilirubin < 2 x the institutional upper limit of normal (ULN). For
participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted
- ALT or AST ≤ 3.0 x ULN OR ≤ 5.0 x ULN for participants with liver metastases
- Renal:
- eGFR ≥ 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD)
equation
12. Albumin ≥ 2.5 g/dL
13. Candidates for change in ARDT as assessed by the treating physician
Exclusion Criteria:
Participants meeting any of the following criteria are not eligible for inclusion in this
study:
1. Previous treatment with any of the following within 6 months of randomization:
Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body
irradiation
2. Previous PSMA-targeted radioligand therapy
3. Prior treatment with cytotoxic chemotherapy for castration resistant or castrate
sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine,
methotrexate, etc.), immunotherapy or biological therapy [including monoclonal
antibodies]) [Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant
setting is allowed if 12 months have elapsed since completion of this adjuvant or
neoadjuvant therapy]
4. Any investigational agents within 28 days prior to day of randomization
5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of
similar classes
6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or
investigational therapy
7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a
participant eligible for study inclusion
8. Patients with a history of CNS metastases that are neurologically unstable,
symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic
integrity. Participants with CNS metastases are eligible if received therapy (surgery,
radiotherapy, gamma knife), asymptomatic and neurologically stable without
corticosteroids. Participants with epidural disease, canal disease and prior cord
involvement are eligible if those areas have been treated, are stable, and not
neurologically impaired.
9. Symptomatic cord compression, or clinical or radiologic findings indicative of
impending cord compression
10. History or current diagnosis of the following ECG abnormalities indicating significant
risk of safety for study participants:
- Concomitant clinically significant cardiac arrhythmias, e.g. sustained
ventricular tachycardia, complete left bundle branch block, high-grade AV block
(e.g., bifascicular block, Mobitz type II and third degree AV block)
- History of familial long QT syndrome or known family history of Torsades de
Pointe
- Cardiac or cardiac repolarization abnormality, including any of the following:
History of myocardial infarction (MI), angina pectoris, or CABG within 6 months
prior to starting study treatment
11. Concurrent serious (as determined by the Principal Investigator) medical conditions,
including, but not limited to New York Heart Association class III or IV congestive
heart failure, history of congenital prolonged QT syndrome, uncontrolled infection,
known active hepatitis B or C or other significant co-morbid conditions that in the
opinion of the investigator would impair study participation or cooperation
- HIV-infected participants who are at a low risk of AIDS-related outcomes may
participate in this trial.
- Participants with an active documented COVID-19 infection (any grade of disease
severity) at time of informed consent may be included only when completely
recovered (in accordance with local guidance) and had no symptoms for at least 28
days before the first dose of study medication.
12. Diagnosed with other malignancies that are expected to alter life expectancy or may
interfere with disease assessment. Participants with a prior history of malignancy
that has been adequately treated and who have been disease free for more than 3 years
are eligible, as are participants with adequately treated non-melanoma skin cancer,
superficial bladder cancer
13. Sexually active males unwilling to use a condom during intercourse while taking study
treatment and for 6 months after stopping study treatment. A condom is required for
all sexually active male participants to prevent them from fathering a child AND to
prevent delivery of study treatment via seminal fluid to their partner. In addition,
male participants must not donate sperm for the time period specified above. If local
regulations deviate from the contraception methods listed above to prevent pregnancy,
local regulations apply and will be described in the ICF
14. Concurrent bladder outflow obstruction or unmanageable urinary incontinence
15. History of somatic or psychiatric disease/condition that may interfere with the
objectives and assessments of the study
16. Any condition that precludes raised arms position
17. Presence of any mutations or biomarkers that are known as predictors of better
response to treatments other than ARDT (e.g., AR-V7 or BRCA) as assessed by the
investigator
18. Not able to understand and to comply with study instructions and requirements