Prostatic NeoplasmsPhase 3PSMAforeNCT04689828
177Lu-PSMA-617 vs. Androgen Receptor-Directed Therapy in the Treatment of Progressive Metastatic Castrate Resistant Prostate Cancer
A Phase 3 study testing 177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT in people with Prostatic Neoplasms, run by Novartis Pharmaceuticals at 72 sites in 14 countries.
Trial summary
The purpose of this study is to determine whether 177Lu-PSMA-617 improves the Radiographic progression-free survival (rPFS) or Overall Survival (OS) compared to a change in Androgen receptor-directed therapy (ARDT) in metastatic castrate resistant prostate cancer (mCRPC) participants that were previously treated with… Read more about this study
- Who is it for?
- Ages 18 to 100 years, men only
- Conditions the study is for
- Prostatic Neoplasms
- What is being tested?
- 177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 469 participants
- Where
- 72 sitesin 14 countries
- Study dates
- 15 Jun 2021to 9 Sep 2026
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed consent must be obtained prior to participation in the study.
- Participants must be adults >= 18 years of age.
- Participants must have an ECOG performance status of 0 to 1.
- Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader.
- Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L).
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- Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide).
- First generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy.
- Second generation ARDT must be the most recent therapy received.
- 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 increases in PSA measured at least 1 week apart. The minimal start value is 2.0 ng/mL; 1.0 ng/mL is the minimal starting value if confirmed rise in PSA is the only indication of progression.
- Soft-tissue progression defined [PCWG3-modified RECIST v1.1 (Eisenhauer et al 2009, Scher et al 2016)].
- Progression of bone disease: two new lesions; only positivity on the bone scan defines metastatic disease to bone (PCWG3 criteria (Scher et al 2016)).
- Participants must have >= 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging obtained prior to randomization.
- 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.
- Albumin >= 2.5 g/dL. -. Candidates for change in ARDT as assessed by the treating physician: • Participants cannot have previously progressed nor had intolerable toxicity to both enzalutamide and abiraterone.
Who cannot join
- 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.
- 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. Prior treatment with sipuleucel-T is allowed].
- Any investigational agents within 28 days prior to day of randomization.
- Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes.
- -. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.
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- Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion.
- Participants with a history of CNS metastases who 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.
- Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
- 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.
- 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).
- Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. However, participants with a prior history of malignancy that has been adequately treated and who have been disease free and treatment free for more than 3 years prior to randomization, are eligible, as are participants with adequately treated non-melanoma skin cancer and superficial bladder cancer.
- Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks 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.
- Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: Participant with bladder outflow obstruction or urinary incontinence, which is manageable and controlled with best available standard of care (incl. pads, drainage) are allowed.
- History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.
- Any condition that precludes raised arms position.
- Eligible for treatment(s) other than ARDT based on presence of any mutations or biomarkers that are known as predictors of better response (e.g., AR-V7 or BRCA).
- Not able to understand and to comply with study instructions and requirements.
Trial locations and contacts
72 sites in 14 countries.
72 sites in 14 countries
United States20 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, 02215
The Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43221
Rocky Mountain Cancer Centers
Denver, Colorado, 80218
Duke Univ Medical Center
Durham, North Carolina, 27710
University of Florida
Gainesville, Florida, 32610
Uni Of TX MD Anderson Cancer Cntr
Houston, Texas, 77030
Medical College Of Wisconsin
Milwaukee, Wisconsin, 53226
Tennessee Oncology
Nashville, Tennessee, 37203
Tulane Uni Health Sciences Center
New Orleans, Louisiana, 70112
NYU Laura and Isaac Perlmutter Cancer Center
New York, New York, 10016
Mount Sinai Hosp Med School
New York, New York, 10029
Memorial Sloan Kettering Cancer Ctr
New York, New York, 10065
Virginia Oncology Associates
Norfolk, Virginia, 23502
Urology Cancer Center PC
Omaha, Nebraska, 68130
Nebraska Cancer Specialists
Omaha, Nebraska, 68154
Onco Hemato Asso of SW Virginia
Roanoke, Virginia, 24014
Utah Cancer Specialists
Salt Lake City, Utah, 84106
Seattle Cancer Care Alliance
Seattle, Washington, 98109
WA Uni School Of Med
St Louis, Missouri, 63110
Spain15 sites
Novartis Investigative Site
Barcelona, 08035
Novartis Investigative Site
Barcelona, 08036
Novartis Investigative Site
Barcelona, 08041
Novartis Investigative Site
El Palmar, Murcia, 30120
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Madrid, 28009
Novartis Investigative Site
Madrid, 28040
Novartis Investigative Site
Madrid, 28041
Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Málaga, 29010
Novartis Investigative Site
Pamplona, Navarre, 31008
Novartis Investigative Site
Santiago Compostela, A Coruna, 15706
Novartis Investigative Site
Seville, 41013
Novartis Investigative Site
Valencia, Valencia, 46009
Novartis Investigative Site
Valencia, 46026
United Kingdom7 sites
Novartis Investigative Site
Coventry, CV2 2DX
Novartis Investigative Site
Guildford, Surrey, GU2 7XX
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
London, NW1 2BU
Novartis Investigative Site
London, NW3 2QG
Novartis Investigative Site
Middlesbrough, TS4 3BW
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
France6 sites
Novartis Investigative Site
Angers, 49055
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Clermont-Ferrand, 63011
Novartis Investigative Site
Lyon, 69373
Novartis Investigative Site
Paris, 75970
Novartis Investigative Site
Villejuif, 94800
Belgium4 sites
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Liège, 4000
Novartis Investigative Site
Roeselare, West-Vlaanderen, 8800
Austria3 sites
Novartis Investigative Site
Innsbruck, Tyrol, 6020
Novartis Investigative Site
Linz, 4020
Novartis Investigative Site
Vienna, 1090
Canada3 sites
Novartis Investigative Site
Montreal, Quebec, H2X 1R9
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Vancouver, British Columbia, V5Z 4E6
Netherlands3 sites
Novartis Investigative Site
Maastricht, Limburg, 6229 HX
Novartis Investigative Site
Nijmegen, 6525 GA
Novartis Investigative Site
Utrecht, 3584 CX
Sweden3 sites
Novartis Investigative Site
Gothenburg, 413 45
Novartis Investigative Site
Lund, 221 85
Novartis Investigative Site
Stockholm, 17176
Switzerland3 sites
Novartis Investigative Site
Baden, 5404
Novartis Investigative Site
Lausanne, 1011
Novartis Investigative Site
Zurich, 8091
Germany2 sites
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
München, 80377
About this study
Official title: PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-Directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer
The purpose of this study is to determine whether 177Lu-PSMA-617 improves the Radiographic progression-free survival (rPFS) or Overall Survival (OS) compared to a change in Androgen receptor-directed therapy (ARDT) in metastatic castrate resistant prostate cancer (mCRPC) participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings.
469 participants were randomized (235 in the 177Lu-PSMA-617 group and 234 in the ARDT group.
Read the detailed description
This is a phase III, open label, multicenter randomized study evaluating the superiority of 177Lu-PSMA-617 over a change of ARDT treatment in prolonging rPFS. The primary endpoint of rPFS is to assess via blinded independent centralized review (BICR) of radiographic images provided by the treating physician and as outlined in PCWG3 modified RECIST v 1.1 Guidelines.
The study also evaluates whether 177Lu-PSMA-617 improves the overall survival (OS) in participants with progressive PSMA-positive mCRPC compared to participants treated with a change in ARDT treatment. OS is defined as the time from randomization to death due to any cause.
Treatment duration: approximately 43 months.
Screening period At screening, the participants are assessed for eligibility and undergo a 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria are randomized.
Randomization period The participants are randomized 1:1 to receive 177Lu-PSMA-617 or a change of the ARDT treatment. The ARDT change includes approved Androgen Receptor (AR) axis targeted therapy (abiraterone or enzalutamide). Supportive care is allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT). Investigational agents, biological products, immunotherapy, cytotoxic chemotherapy, other systemic radioisotopes (e.g. radium-223), poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or hemi-body radiotherapy treatment is not to be administered during the study treatment period. ARDT is not to be administered concomitantly with 177Lu-PSMA-617. After implementation of Protocol Amendment v4, crossover will be allowed regardless of radiographic progression.
Treatment period • 177Lu-PSMA-617 treatment arm Participants randomized to the investigational arm receive 7.4 GBq +/- 10% of 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT, could be used.
After the last day of study treatment, the participants have to have an End of Treatment (EOT) visit and enter the Post-treatment Follow-up.
- ARDT treatment arm For participants randomized to the ARDT treatment arm, the change of ARDT treatment for each participant is selected by the treating physician prior to randomization and is administered per the physician's orders. Best supportive care, including ADT, could be used. After, the participants have to have an End of Treatment (EOT) and enter the Post-treatment Follow-up.
In absence of safety concerns, every effort should be made to keep the participant on the randomized treatment until BICR-determined radiographic progression (up to implementation of Protocol Amendment v4).
End of Treatment
Randomized treatment may be discontinued if:
- The participant, sponsor or investigator chooses to discontinue treatment
- Toxicity
- Completion of the 6 cycles of 177Lu-PSMA-617
- Serious non-compliance to the protocol
- Disease progression (determined by BICR up to implementation of Protocol Amendment v4)
- Upon implementation of Protocol Amendment v4, participants with ongoing treatment with ARDT will discontinue study drug and either crossover or receive SOC per their treating physician off trial PSA progression is strongly discouraged as a criterion for initiation of a new neoplastic therapy prior to BICR-determined progression. PCWG3 guidelines should be followed to guide discontinuation of treatment End of Treatment visit must be performed ≤ 7 days after the last day of study treatment period. EOT is to occur before the participant enters the post-treatment Follow-up period of the study and before the initiation of any subsequent anticancer treatment, .
If a participant withdraws consent for the treatment period of the study, an EOT must be done and the participant will enter the Post-treatment Follow-up unless he specifically withdraws post-treatment Follow-up.
Crossover period Upon confirmation of rPFS by BICR, participants randomized to the ARDT arm could either be allowed to crossover to receive 177Lu-PSMA-617 within 28 days of central confirmation of radiographic progression or could continue to receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up.
In order for a participant randomized to the ARDT arm to cross over to receive 177Lu-PSMA-617, he must meet the following criteria:
- Confirmed radiographical progression as assessed by BICR. (After implementation of Protocol Amendment v4, radiographic progression is not required.)
- No intervening antineoplastic therapy is administered after the randomized treatment
- Any unresolved toxicity from prior therapy has to be controlled and can be no greater than CTCAE grade 2 or baseline at the time of registration for crossover.
- ECOG performance status 0-1 at the time of registration for crossover
- Adequate organ function at the time of registration for crossover
- Agreement to continue with the study visit schedule
A participant, who is deemed to have disease progression per investigator assessment, but not by BICR, is not eligible to cross over at that time. Such participant should continue to receive randomized study treatment until progression determined by BICR up to implementation of Protocol Amendment v4.
If crossover to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as for participants who were initially randomized to receive 177Lu-PSMA-617 as described above.
After the last day of study treatment period of 177Lu-PSMA-617 or upon second radiographic progression (rPFS2), the participants must have a second End of Treatment (EOT2) visit performed ≤ 7 days and enter the Post-treatment Follow-up. The participant can receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up.
Post-treatment Follow-up period:
- 30-day Safety Follow-up: All randomized and/or treated participants are to have a safety follow-up conducted approximately 30 days after the EOT visit.
- Long term follow-up:
Long term follow-up starts after the 30 Days Safety follow-up and lasts until the patient expires, is lost to follow-up or withdraws consent.
In long term follow-up safety and efficacy information is collected:
- Safety: all medically significant adverse events (all SAEs) deemed to be related to 177Lu-PSMA-617. This includes potential late onset radiation toxicity. For participants who receive 177Lu-PSMA-617 in the 177Lu-PSMA-617 arm or in crossover, the following adverse events is captured beyond the 30 day safety period regardless of relationship to study treatment and whether new anticancer therapy has been initiated: hematologic toxicities with primary focus on myelosuppression and thrombocytopenia (including need for transfusion or use of growth factors), renal failure, xerostomia, xerophthalmia, secondary malignancies. After implementation of Protocol Amendment v4, 177Lu-PSMA-617 exposed participants will be discontinued from the trial once enrolled in the Long-term Safety study.
- Efficacy: Tumor assessments must be performed every 8 weeks after first dose of study treatment for the first 24 weeks (week 9, 17, 25) and then every 12 weeks (week 37, 49, etc.) until confirmation of radiographic progression by BICR regardless of whether treatment has been discontinued or new anticancer therapy initiated. After implementation of Protocol Amendment v4, tumor assessments need to continue only for patients actively treated with 177Lu-PSMA-617 as crossover therapy.
The long-term follow-up period also includes the collection of survival information and other assessments.
Other: Other data collected during long-term follow-up includes short physical exam, blood sampling for hematology, chemistry testing, coagulation, DNA and tumor samples for biomarkers. The visits are carried out every 12 weeks (± 28 days) .
Participants who receive 177Lu-PSMA-617 and remain in follow-up on the trial at the sponsor's completion of the study will be asked to join a separate study of long-term safety for a duration of up to 10 years from start of 177Lu-PSMA-617 treatment.
If the participant withdraws consent for the collection of blood samples, PROs, and imaging assessments during the long-term follow-up, information on survival subsequent therapy, and related SAEs is collected.
- Conditions
- Prostatic Neoplasms
- Being tested
- 177Lu-PSMA-617, 68Ga-PSMA-11, ARDT
- Keywords
- 177Lu-PSMA-617, Androgen receptor-directed therapy, ARDT, Metastatic castrate resistant prostate cancer, mCRPC, Radiographic progression free survival, rPFS, Castrate resistant prostate cancer, CRPC, Prostate-specific membrane antigen, PSMA
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-PSMA-617Drug
administered intravenously once every 6 weeks (1 cycle) for 6 cycles
68Ga-PSMA-11Drug
single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi).
ARDTDrug
Also called Comparator
administered orally on a continuous basis, as per package insert and guidelines
| Study group | Role | What they receive |
|---|---|---|
| 177Lu-PSMA-617 | Experimental | Participants received 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT could be used. Receives: Drug: 177Lu-PSMA-617; Drug: 68Ga-PSMA-11 |
| Androgen receptor-directed therapy (ARDT) | Active comparator | For participants randomized to the ARDT arm, abiraterone or enzalutamide was administered per the physician's orders. Best supportive care, including Androgen deprivation therapy (ADT) could be used. Receives: Drug: 68Ga-PSMA-11; Drug: ARDT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Radiographic Progression Free Survival (rPFS)
rPFS is defined as the time to radiographic progression by Prostate cancer working Group 3 (PCWG3)-modified RECIST v1.1 as assessed by Blinded independent central (BICR) review or death.
Measured: median FU (randomization to event or censoring) 3.65 months (range 0-12.3)
Secondary outcomes (12)
Overall Survival (OS) (Key Secondary Endpoint)
OS is defined as time to death for any cause.
Measured: approx. 26.9 months from randomization to cut-off
Radiographic Progression Free Survival 2 (rPFS2) by Blinded Independent Central Review (BICR)
rPFS2 by BICR is defined as time from the date of crossover (ARDT to 177Lu-PSMA-617) to the date of radiographic disease progression by BICR or death from any cause for participants who crossover from ARDT arm to Lu-PSMA treatment.
Measured: From date of crossover until second radiographic progression or death, whichever comes first, assessed up to approx. 32 months
Progression Free Survival (PFS) by Investigator's Assessment
PFS is defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic, clinical, or PSA progression) or death from any cause, whichever occurs first
Measured: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed upFrom date of randomization until date of death from any cause, assessed up to approx. 32 months
Second Progression Free Survival (PFS2) by Investigator's Assessment
PFS2 defined as time from date of randomization to the first documented progression by investigator's assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first, on next-line of therapy. Next-line therapy was defined as the first new (systemic) anti-neoplastic therapy initiated after discontinuation of study treatment regardless of end of treatment (EoT) reason.
Measured: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to approx. 32 months
PSA50 Response
PSA50 response was defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second Prostate specific antigen (PSA) measurement ≥ 4 weeks.
Measured: Weeks 12, 24, 48 and anytime during randomized phase
Time to First Symptomatic Skeletal Event (TTSE)
Time to SSE (TTSSE) defined as date of randomization to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first
Measured: From date of randomization till EOT or death, whichever happens first, assessed up to approx. 32 months
Time to Radiographic Soft Tissue Progression (TTSTP) Per BICR
TTSTP defined as time from randomization to radiographic soft tissue progression per Prostate cancer working Group 3 (PCWG3)-modified RECIST v1.1 (Soft Tissue Rules of Prostate Cancer Working Group modified Response Evaluation Criteria in Solid Tumors Version 1.1) as assessed by Blinded Independent Central Review (BICR).
Measured: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to approx. 32 months
Time to Chemotherapy (TTCT)
TTCT defined as time from randomization to initiation of the first subsequent chemotherapy or death, whichever occurs first. Since participants in ARPI arm were allowed to crossover to [177Lu]Lu-PSMA-617 (AAA617) arm upon confirmation of rPD by BICR, TTCT was delayed for participants who had crossed over.
Measured: From date of randomization until date of subsequent chemotherapy or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis)
European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D- 5L)
EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
Measured: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
The FACT-P total score determines the level of prostate cancer specific health related quality of life (HRQoL). The higher the FACT-P score, the better the QoL. FACT-P assesses symptoms/problems related to prostate carcinoma and its treatment. It is a combination of the FACT- General + the Prostate Cancer Subscale (PCS). The FACTGeneral (FACT-G) is a 27 item Quality of Life (QoL) measure that provides a total score as well as subscale scores: Physical (0-28), Functional (0-28), Social (0-28), and Emotional Well-being (0-24). The total score range is between 1-108, higher scores indicates better for total score and subscale scores. PCS is a 12-item prostate cancer subscale that asks about symptoms and problems specific to prostate cancer (Range 0-48, higher scores better). The FACT-P total score is the sum of all 5 subscale scores of the FACT-P questionnaire and ranges from 0-156. Higher scores indicate higher degree of functioning and better quality of life.
Measured: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months
Brief Pain Inventory - Short Form (BPI-SF) Questionnaire
The BPI-SF is a publicly available instrument to assess the pain and includes severity and interference scores. BPI-SF is an 11-item selfreport questionnaire that is designed to assess the severity and impact of pain on daily functions of a participant. Pain severity score is a mean value for BPI-SF questions 3, 4, 5 and 6 (questions inquiring about the extent of pain, where the extent is ranked from 0 [no pain] to 10 [pain as bad as you can imagine]). Pain severity progression is defined as an increase in score of 30% or greater from baseline without decrease in analgesic use.
Measured: From screening up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months (estimated final OS analysis)
Number of Participants With Treatment Emergent Adverse Events
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters. Treatment emergent adverse events falling into the category of myelosuppression, renal toxicity or second malignancy will be recorded beyond 30 day safety observation period.
Measured: From randomization till 30 day safety follow-up, assessed up to 43 months (estimated final OS analysis).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2020
- Study start15 Jun 2021
- Primary completion2 Oct 2022
- Study completion9 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Prostatic NeoplasmsStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients randomized to ARDT treatment had an option to crossover to 177Lu-PSMA-617 treatment after central confirmation of radiographic progression.
- Masking
- None (open label)
- Enrolment
- 469 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04689828
- Sponsor's protocol ID
- CAAA617B12302
- Other IDs
- 2023-507772-50-00, 2023
- Acronym
- PSMAfore
- Status last verified
- Oct 2026
- First submitted
- 9 Dec 2020
- Last updated
- 4 Nov 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Fizazi K, Chi KN, Shore ND, Herrmann K, de Bono JS, Castellano D, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Fleming M, Haas T, Ghebremariam S, Kreisl TN, Rajagopalan S, Sartor O, Morris MJ; PSMAfore Investigators. Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2025 Nov;36(11):1319-1330. doi: 10.1016/j.annonc.2025.07.003. Epub 2025 Jul 17.
PubMed 40680993Fizazi K, Morris MJ, Shore ND, Chi KN, Crosby M, de Bono JS, Herrmann K, Roubaud G, Nagarajah J, Fleming M, Lewis B, Nordquist L, Carnahan N, Ghebremariam S, Hertelendi M, Castellano D, Sartor O. Health-related quality of life, pain, and symptomatic skeletal events with [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): an open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Jul;26(7):948-959. doi: 10.1016/S1470-2045(25)00189-5. Epub 2025 May 26.
PubMed 40441170Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, Chi KN, Crosby M, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Studentova H, Nagarajah J, Mellado B, Montesa-Pino A, Kpamegan E, Ghebremariam S, Kreisl TN, Wilke C, Lehnhoff K, Sartor O, Fizazi K; PSMAfore Investigators. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024 Sep 28;404(10459):1227-1239. doi: 10.1016/S0140-6736(24)01653-2. Epub 2024 Sep 15.
PubMed 39293462
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PSMAfore: A Phase III, Open-label, Multi-Center, Randomized Study Comparing 177Lu-PSMA-617 vs. a Change of Androgen Receptor-Directed Therapy in the Treatment of Taxane Naïve Men With Progressive Metastatic Castrate Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT04689828
- Acronym / sponsor ID
- PSMAfore / CAAA617B12302
- Conditions
- Prostatic Neoplasms
- Keywords
- 177Lu-PSMA-617, Androgen receptor-directed therapy, ARDT, Metastatic castrate resistant prostate cancer, mCRPC, Radiographic progression free survival, rPFS, Castrate resistant prostate cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 469 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2021 (actual)
- Primary completion
- 2 Oct 2022 (actual)
- Study completion
- 9 Sep 2026 (actual)
- First posted
- 30 Dec 2020 (actual)
- Results
- Posted 9 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether 177Lu-PSMA-617 improves the Radiographic progression-free survival (rPFS) or Overall Survival (OS) compared to a change in Androgen receptor-directed therapy (ARDT) in metastatic castrate resistant prostate cancer (mCRPC) participants that were previously treated with an alternate ARDT and not exposed to a taxane-containing regimen in the CRPC or mHSPC settings.
469 participants were randomized (235 in the 177Lu-PSMA-617 group and 234 in the ARDT group.
Detailed description
This is a phase III, open label, multicenter randomized study evaluating the superiority of 177Lu-PSMA-617 over a change of ARDT treatment in prolonging rPFS. The primary endpoint of rPFS is to assess via blinded independent centralized review (BICR) of radiographic images provided by the treating physician and as outlined in PCWG3 modified RECIST v 1.1 Guidelines.
The study also evaluates whether 177Lu-PSMA-617 improves the overall survival (OS) in participants with progressive PSMA-positive mCRPC compared to participants treated with a change in ARDT treatment. OS is defined as the time from randomization to death due to any cause.
Treatment duration: approximately 43 months.
Screening period At screening, the participants are assessed for eligibility and undergo a 68Ga-PSMA-11 positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria are randomized.
Randomization period The participants are randomized 1:1 to receive 177Lu-PSMA-617 or a change of the ARDT treatment. The ARDT change includes approved Androgen Receptor (AR) axis targeted therapy (abiraterone or enzalutamide). Supportive care is allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT). Investigational agents, biological products, immunotherapy, cytotoxic chemotherapy, other systemic radioisotopes (e.g. radium-223), poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors or hemi-body radiotherapy treatment is not to be administered during the study treatment period. ARDT is not to be administered concomitantly with 177Lu-PSMA-617. After implementation of Protocol Amendment v4, crossover will be allowed regardless of radiographic progression.
Treatment period • 177Lu-PSMA-617 treatment arm Participants randomized to the investigational arm receive 7.4 GBq +/- 10% of 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT, could be used.
After the last day of study treatment, the participants have to have an End of Treatment (EOT) visit and enter the Post-treatment Follow-up.
- ARDT treatment arm For participants randomized to the ARDT treatment arm, the change of ARDT treatment for each participant is selected by the treating physician prior to randomization and is administered per the physician's orders. Best supportive care, including ADT, could be used. After, the participants have to have an End of Treatment (EOT) and enter the Post-treatment Follow-up.
In absence of safety concerns, every effort should be made to keep the participant on the randomized treatment until BICR-determined radiographic progression (up to implementation of Protocol Amendment v4).
End of Treatment
Randomized treatment may be discontinued if:
- The participant, sponsor or investigator chooses to discontinue treatment
- Toxicity
- Completion of the 6 cycles of 177Lu-PSMA-617
- Serious non-compliance to the protocol
- Disease progression (determined by BICR up to implementation of Protocol Amendment v4)
- Upon implementation of Protocol Amendment v4, participants with ongoing treatment with ARDT will discontinue study drug and either crossover or receive SOC per their treating physician off trial PSA progression is strongly discouraged as a criterion for initiation of a new neoplastic therapy prior to BICR-determined progression. PCWG3 guidelines should be followed to guide discontinuation of treatment End of Treatment visit must be performed ≤ 7 days after the last day of study treatment period. EOT is to occur before the participant enters the post-treatment Follow-up period of the study and before the initiation of any subsequent anticancer treatment, .
If a participant withdraws consent for the treatment period of the study, an EOT must be done and the participant will enter the Post-treatment Follow-up unless he specifically withdraws post-treatment Follow-up.
Crossover period Upon confirmation of rPFS by BICR, participants randomized to the ARDT arm could either be allowed to crossover to receive 177Lu-PSMA-617 within 28 days of central confirmation of radiographic progression or could continue to receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up.
In order for a participant randomized to the ARDT arm to cross over to receive 177Lu-PSMA-617, he must meet the following criteria:
- Confirmed radiographical progression as assessed by BICR. (After implementation of Protocol Amendment v4, radiographic progression is not required.)
- No intervening antineoplastic therapy is administered after the randomized treatment
- Any unresolved toxicity from prior therapy has to be controlled and can be no greater than CTCAE grade 2 or baseline at the time of registration for crossover.
- ECOG performance status 0-1 at the time of registration for crossover
- Adequate organ function at the time of registration for crossover
- Agreement to continue with the study visit schedule
A participant, who is deemed to have disease progression per investigator assessment, but not by BICR, is not eligible to cross over at that time. Such participant should continue to receive randomized study treatment until progression determined by BICR up to implementation of Protocol Amendment v4.
If crossover to 177Lu-PSMA-617 is selected, then 177Lu-PSMA-617 will be administered with the same dose/schedule as for participants who were initially randomized to receive 177Lu-PSMA-617 as described above.
After the last day of study treatment period of 177Lu-PSMA-617 or upon second radiographic progression (rPFS2), the participants must have a second End of Treatment (EOT2) visit performed ≤ 7 days and enter the Post-treatment Follow-up. The participant can receive any other therapy per the discretion of the treating physician in the Post-treatment Follow-up.
Post-treatment Follow-up period:
- 30-day Safety Follow-up: All randomized and/or treated participants are to have a safety follow-up conducted approximately 30 days after the EOT visit.
- Long term follow-up:
Long term follow-up starts after the 30 Days Safety follow-up and lasts until the patient expires, is lost to follow-up or withdraws consent.
In long term follow-up safety and efficacy information is collected:
- Safety: all medically significant adverse events (all SAEs) deemed to be related to 177Lu-PSMA-617. This includes potential late onset radiation toxicity. For participants who receive 177Lu-PSMA-617 in the 177Lu-PSMA-617 arm or in crossover, the following adverse events is captured beyond the 30 day safety period regardless of relationship to study treatment and whether new anticancer therapy has been initiated: hematologic toxicities with primary focus on myelosuppression and thrombocytopenia (including need for transfusion or use of growth factors), renal failure, xerostomia, xerophthalmia, secondary malignancies. After implementation of Protocol Amendment v4, 177Lu-PSMA-617 exposed participants will be discontinued from the trial once enrolled in the Long-term Safety study.
- Efficacy: Tumor assessments must be performed every 8 weeks after first dose of study treatment for the first 24 weeks (week 9, 17, 25) and then every 12 weeks (week 37, 49, etc.) until confirmation of radiographic progression by BICR regardless of whether treatment has been discontinued or new anticancer therapy initiated. After implementation of Protocol Amendment v4, tumor assessments need to continue only for patients actively treated with 177Lu-PSMA-617 as crossover therapy.
The long-term follow-up period also includes the collection of survival information and other assessments.
Other: Other data collected during long-term follow-up includes short physical exam, blood sampling for hematology, chemistry testing, coagulation, DNA and tumor samples for biomarkers. The visits are carried out every 12 weeks (± 28 days) .
Participants who receive 177Lu-PSMA-617 and remain in follow-up on the trial at the sponsor's completion of the study will be asked to join a separate study of long-term safety for a duration of up to 10 years from start of 177Lu-PSMA-617 treatment.
If the participant withdraws consent for the collection of blood samples, PROs, and imaging assessments during the long-term follow-up, information on survival subsequent therapy, and related SAEs is collected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients randomized to ARDT treatment had an option to crossover to 177Lu-PSMA-617 treatment after central confirmation of radiographic progression.
| Arm | Type | Receives |
|---|---|---|
| 177Lu-PSMA-617 | Experimental | Drug: 177Lu-PSMA-617, Drug: 68Ga-PSMA-11Participants received 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT could be used. |
| Androgen receptor-directed therapy (ARDT) | Active comparator | Drug: 68Ga-PSMA-11, Drug: ARDTFor participants randomized to the ARDT arm, abiraterone or enzalutamide was administered per the physician's orders. Best supportive care, including Androgen deprivation therapy (ADT) could be used. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Signed informed consent must be obtained prior to participation in the study.
- Participants must be adults >= 18 years of age.
- Participants must have an ECOG performance status of 0 to 1.
- Participants must have histological pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- Participants must be 68Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader.
Key exclusion criteria (24 listed)
- 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.
- 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. Prior treatment with sipuleucel-T is allowed].
- Any investigational agents within 28 days prior to day of randomization.
- Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 177Lu-PSMA-617administered intravenously once every 6 weeks (1 cycle) for 6 cycles | Drug | 177Lu-PSMA-617 |
| 68Ga-PSMA-11single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi). | Drug | 177Lu-PSMA-617, Androgen receptor-directed therapy (ARDT) |
| ARDTAlso: Comparatoradministered orally on a continuous basis, as per package insert and guidelines | Drug | Androgen receptor-directed therapy (ARDT) |
Primary outcome
Radiographic Progression Free Survival (rPFS)
Time frame: median FU (randomization to event or censoring) 3.65 months (range 0-12.3)
rPFS is defined as the time to radiographic progression by Prostate cancer working Group 3 (PCWG3)-modified RECIST v1.1 as assessed by Blinded independent central (BICR) review or death.
12 secondary outcomes
Overall Survival (OS) (Key Secondary Endpoint)
Time frame: approx. 26.9 months from randomization to cut-off
Radiographic Progression Free Survival 2 (rPFS2) by Blinded Independent Central Review (BICR)
Time frame: From date of crossover until second radiographic progression or death, whichever comes first, assessed up to approx. 32 months
Progression Free Survival (PFS) by Investigator's Assessment
Time frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed upFrom date of randomization until date of death from any cause, assessed up to approx. 32 months
Second Progression Free Survival (PFS2) by Investigator's Assessment
Time frame: From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to approx. 32 months
PSA50 Response
Time frame: Weeks 12, 24, 48 and anytime during randomized phase
Time to First Symptomatic Skeletal Event (TTSE)
Time frame: From date of randomization till EOT or death, whichever happens first, assessed up to approx. 32 months
Time to Radiographic Soft Tissue Progression (TTSTP) Per BICR
Time frame: From date of randomization until date of soft tissue radiographic progression or date of death from any cause, whichever comes first, assessed up to approx. 32 months
Time to Chemotherapy (TTCT)
Time frame: From date of randomization until date of subsequent chemotherapy or date of death from any cause, whichever comes first, assessed up to 43 months (estimated final OS analysis)
European Quality of Life (EuroQol) - 5 Domain 5 Level Scale (EQ-5D- 5L)
Time frame: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months
Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire
Time frame: From randomization up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months
Brief Pain Inventory - Short Form (BPI-SF) Questionnaire
Time frame: From screening up till 30 day safety Follow-up or week 48 of long term Follow-up for patients prematurely discontinued, assessed up to 43 months (estimated final OS analysis)
Number of Participants With Treatment Emergent Adverse Events
Time frame: From randomization till 30 day safety follow-up, assessed up to 43 months (estimated final OS analysis).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40680993Fizazi K, Chi KN, Shore ND, Herrmann K, de Bono JS, Castellano D, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Fleming M, Haas T, Ghebremariam S, Kreisl TN, Rajagopalan S, Sartor O, Morris MJ; PSMAfore Investigators. Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Ann Oncol. 2025 Nov;36(11):1319-1330. doi: 10.1016/j.annonc.2025.07.003. Epub 2025 Jul 17.
- Derived from this study: PubMed 40441170Fizazi K, Morris MJ, Shore ND, Chi KN, Crosby M, de Bono JS, Herrmann K, Roubaud G, Nagarajah J, Fleming M, Lewis B, Nordquist L, Carnahan N, Ghebremariam S, Hertelendi M, Castellano D, Sartor O. Health-related quality of life, pain, and symptomatic skeletal events with [177Lu]Lu-PSMA-617 in patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): an open-label, randomised, phase 3 trial. Lancet Oncol. 2025 Jul;26(7):948-959. doi: 10.1016/S1470-2045(25)00189-5. Epub 2025 May 26.
- Derived from this study: PubMed 39293462Morris MJ, Castellano D, Herrmann K, de Bono JS, Shore ND, Chi KN, Crosby M, Piulats JM, Flechon A, Wei XX, Mahammedi H, Roubaud G, Studentova H, Nagarajah J, Mellado B, Montesa-Pino A, Kpamegan E, Ghebremariam S, Kreisl TN, Wilke C, Lehnhoff K, Sartor O, Fizazi K; PSMAfore Investigators. 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor therapy for taxane-naive patients with progressive metastatic castration-resistant prostate cancer (PSMAfore): a phase 3, randomised, controlled trial. Lancet. 2024 Sep 28;404(10459):1227-1239. doi: 10.1016/S0140-6736(24)01653-2. Epub 2024 Sep 15.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
72 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing 177Lu-PSMA-617, 68Ga-PSMA-11 and ARDT in people with Prostatic Neoplasms, run by Novartis Pharmaceuticals at 72 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 72 sites in United States, Spain, United Kingdom, France, Belgium and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiographic Progression Free Survival (rPFS) (time frame: median FU (randomization to event or censoring) 3.65 months (range 0-12.3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04689828, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.