An International Prospective Open-label Randomized Phase III Study Comparing 177Lu-PSMA-617 in Combination With Soc Versus SoC Alone in Adult Male Patients With mHSPC

  • End date
    Dec 18, 2025
  • participants needed
  • sponsor
    Novartis Pharmaceuticals
Updated on 28 July 2021


The purpose of this study is to evaluate the efficacy and safety of 177Lu-PSMA-617 in combination with Standard of Care, versus Standard of Care alone, in adult male patients with mHSPC. In this study, the SoC is defined as a combination of Androgen Receptor Directed Therapy + Androgen Deprivation Therapy. Approximately 1126 patients will be randomized in this study.


In this international, open-label, prospective, phase III study, where approximately 1126 patients with treatment nave or minimally treated PSMA-positive mHSPC will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

The primary objective of the study is to determine whether the combination of 177Lu-PSMA-617 + SoC improves rPFS over that obtained by administration of SoC alone in mHSPC patients.

The randomization will be stratified according to the following three factors: disease volume (high v low), age >= 70 years (yes/no), and on Previous or planned treatment (prostatectomy or radiation) to primary (prostate) tumor (yes/no).

Study duration: approximately 50 months. screening period: after signing ICF, patients will be assessed for eligibility and will be scanned with 68Ga PSMA-11 to identify PSMA expression status. Following completion of all required screening procedures and verifying participant eligibility, the participant will be randomized via the interactive response technology (IRT) system.

Prior treatment:

  • Up to 45 days of LHRH agonist/antagonists is allowed prior to ICF signature. If patient did not start the ADT prior randomization, ADT should start as soon as possible and ideally no later than 2 weeks after randomization.
  • Up to 45 days of ARDT is allowed prior ICF signature. If patient did not start the ARDT prior randomization, ARDT should start as soon as possible and ideally no later than 2 weeks after randomization. Patients will received ARDT as per label instructions.

Randomization period:

The participant will be randomized in a 1:1 ratio to receive Standard of Care (SoC) with or without the radioligand 177Lu-PSMA-617.

Treatment period:

Patients randomized to the investigational arm (i.e. SoC+177Lu-PSMA-617): Patients will receive SoC as per label instructions, after randomization, if not started earlier and in the time frame allowed by the protocol. Patients must begin 177Lu-PSMA-617 dosing within 14 days after randomization or as soon as possible after the product is received. 177Lu-PSMA-617 is administered at the dose of 7.4 GBq (+/- 10%), once every 6 weeks (+/- 1 week) for a planned 6 cycles.

Patients randomized to the control arm will begin receiving SoC as per label instructions after randomization, if not started earlier and in the time frame allowed by the protocol.

The primary endpoint of rPFS will be assessed by a centralized blinded image review committee (i.e., BIRC) using radiographic images provided by the treating physician.

An end of treatment (EOT) visit will be performed when participants permanently discontinue study treatment.

Cross-over period:

After patients randomized to the SoC alone (i.e., control) arm experience radiographic progression (the rPFS event) as confirmed by BIRC, they will be allowed to cross-over to receive 177Lu-PSMA-617 +/- SoC per the discretion of the treating physician. If cross-over to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as participants who were initially randomized to receive 177Lu-PSMA-617 as described above. Study cross-over participants for whom 177Lu-PSMA-617 is discontinued must have a second End of Treatment (EOT2) visit performed =< 7 days and enter the Post-treatment Follow-up .

Post-Treatment Follow-Up (Safety, Efficacy):

After treatment discontinuation, all participants will be followed for safety with a 30-day safety follow-up visit (FUP) as well as longer term safety follow-up assessments for a period of approximately 12 months.

Participants who discontinue study treatment without having progressive disease confirmed by BIRC, will continue to be assessed for efficacy (efficacy follow-up) during the post-treatment follow-up period until the occurrence of their BIRC-confirmed radiographic disease progression (rPFS) event , or if the total number of protocol-defined rPFS events has occurred triggering the primary analysis, whichever occurs first.

Survival Follow-Up:

After study treatment discontinuation, or post-treatment follow-up period discontinuation, the participant's status will be collected every 90 days (via phone calls) as part of the survival follow-up. Every effort should be made to comply with the survival follow-up schedule and ensure collection of participant survival. The survival follow-up and the study will end when the number of OS events required for final OS analysis will be reached.

Condition Malignant neoplasm of prostate, Prostatic disorder, prostate tumor, prostate tumors
Treatment ADT, 177Lu-PSMA-617, 68Ga-PSMA-11, ARDT
Clinical Study IdentifierNCT04720157
SponsorNovartis Pharmaceuticals
Last Modified on28 July 2021


Yes No Not Sure

Inclusion Criteria

Participants eligible for inclusion in this study must meet all of the
following criteria
Signed informed consent must be obtained prior to participation in the study
Patients must be adults 18 years of age
Patients must have an ECOG performance status of 0 to 2
Patients must have a life expectancy >9 months as determined by the study investigator
Patients must have metastatic prostate cancer with histologically or cytologically confirmed adenocarcinoma (current or prior biopsy of the prostate and/or metastatic site)
Patients must have evidence of PSMA-positive disease as seen on a 68Ga-PSMA-11 PET/CT scan, and eligible as determined by the sponsor's central reader
Patients must have documented metastatic disease to bone and/or soft tissue/visceral sites documented in one of the following manners within 28 days prior randomization
Metastatic disease to the bone (in any distribution) visible on 99Tc-MDP bone scintigraphy on either pre-ADT scans or baseline scans. OR
Lymph node metastases of any size or distribution. If lymph nodes are the only site of metastasis, then at least one must be at least 1.5 cm in short axis AND outside of the pelvis. OR
Visceral metastases of any size or distribution. If a subject has a history of visceral metastases at any time prior to registration, he should be coded as having visceral metastases at baseline (i.e., patients with visceral metastases prior to ADT that disappear at baseline will be counted as having visceral metastases and would therefore have high volume disease for stratification purposes)
Patients 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 patients with known Gilbert's Syndrome 3 x ULN is permitted Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 3.0 x ULN OR 5.0 x ULN for patients with liver metastases
Renal eGFR 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation
Albumin 2.5 g/dL
Human immunodeficiency virus (HIV)-infected patients who are healthy and have a low risk of acquired immune deficiency syndrome (AIDS)-related outcomes can participate in this trial
Patients must be
Treatment nave OR minimally treated with
Up to 45 days of luteinizing hormone-releasing hormone (LHRH) agonist /antagonists or bilateral orchiectomy with or without first generation anti-androgen (e.g. bicalutamide, flutamide) for metastatic prostate cancer is allowed prior to ICF signature. If given, first generation anti-androgen must be discontinued prior to start of therapy
If received, prior LHRH agonist/antagonist use in the adjuvant/neo-adjuvant setting must have been discontinued > 12 months prior to ICF signature AND must not have exceeded 24 months of therapy AND must not have shown disease progression within 12 months of completing adjuvant/neo-adjuvant therapy
Up to 45 days of CYP17 inhibitor or ARDT exposure for metastatic prostate cancer is allowed prior to ICF signature. No exposure for earlier stages of prostate cancer is allowed

Exclusion Criteria

Participants meeting any of the following criteria are not eligible for
inclusion in this study
Patients with rapidly progressing tumor that requires urgent exposure to taxane-based chemotherapy
Any systemic anti-prostate cancer therapy (with the exception of the drugs listed on inclusion criteria 11), including chemotherapy, PARP inhibitors, immunotherapy or biological therapy (including monoclonal antibodies)
Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, or investigational therapy
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. Previous PSMA-targeted radioligand therapy is not allowed
Ongoing participation in any other clinical trial
Use of other investigational drugs within 30 days prior to day of randomization
Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes
Transfusion for the sole purpose of making a subject eligible for study inclusion
Patients with CNS metastases that are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable, and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (magnetic resonance imaging (MRI) preferred or CT with contrast)
Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, patients 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 patients with adequately treated non-melanoma skin cancer, superficial bladder cancer. Note: Patients with a history of CNS metastases that have received prior therapy and are neurologically stable, asymptomatic and not receiving corticosteroids are allowed
Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, 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. 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
No active clinically significant cardiac disease defined as any of the following
NYHA class 3/4 congestive heart failure within 6 months prior to ICF signature unless treated with improvement and echocardiogram or MUGA demonstrates EF > 45% with improvement in symptoms to class < 3\
History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants in the study such as: Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade atrioventricular (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 Pointes
Cardiac or cardiac repolarization abnormality, including any of the following: History of myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature
History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression
Any condition that precludes raised arms position
Concurrent bladder outflow obstruction or unmanageable urinary incontinence
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
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