Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Kennedy Disease

All Drugs and Chemicals

Antineoplastic Agents

Gallium 68 PSMA-11

Androgens

Taxane

Radiopharmaceuticals

Participants will receive 7.4 GBq (200 mCi) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT may be used.

For participants randomized to the ARDT arm, the change of ARDT treatment will be administered per the physician's orders. Best supportive care, including ADT may be used.

administered intravenously once every 6 weeks (1 cycle) for 6 cycles

[177Lu]Lu-PSMA-617

administered orally on a continuous basis, as per package insert and guidelines

ARDT

single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 259 MBq (3 - 7 mCi).

[68Ga]Ga-PSMA-11

Best supportive/best standard of care as defined by the local investigator

Best supportive care

Novartis Pharmaceuticals

The purpose of this study is to evaluate the efficacy of \[177Lu\]Lu-PSMA-617 over a change of androgen receptor-directed therapy (ARDT) treatment in prolonging radiographic progression free survival (rPFS) in Chinese metastatic castration-resistant prostate cancer patients, who were previously treated with another ARDT as last treatment and who have not been exposed to a taxane-containing regimen in castrate resistant prostate cancer (CRPC) or hormone-sensitive prostate cancer (HSPC) settings and who are considered appropriate for delaying taxane-based chemotherapy. The primary endpoint of rPFS will be assessed via blinded independent centralized review of radiographic images provided by the treating physician and as outlined in Prostate Cancer Working Group 3 (PCWG3) guidelines.

The study contains a screening period to assess the eligibility of participants, only participants fulfilling the \[68Ga\]Ga-PSMA-11 PET scan interpretation criteria for eligibility and meeting all other inclusion/exclusion criteria will be enrolled. In the randomization period, approximately 60 participants will be randomized 1:1 to receive \[177Lu\]Lu-PSMA-617 treatment or a change of approved ARDT treatment. Randomization will be stratified by symptomatology i.e., Asymptomatic or mildly symptomatic vs. symptomatic.

Participants randomized to \[177Lu\]Lu-PSMA-617 treatment group will receive 7.4 GBq (200 mCi) ± 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks (± 1 week) for 6 cycles. For participants randomized to the ARDT treatment arm, the change of ARDT treatment for each participant will be selected by the treating physician prior to randomization and will be administered per the physician's orders. Supportive care will be allowed in both arms at the discretion of the investigator. ARDT must not be administrated concomitantly with \[177Lu\]Lu-PSMA-617.

Efficacy assessment will 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. Upon confirmation of rPFS by BIRC, participants randomized to ARDT arm will be allowed to crossover to \[177Lu\]Lu-PSMA-617 treatment if the crossover criteria are met. Post-treatment follow up period will have a 30-day safety follow up post EOT visit and long term survival follow up.

A Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in Taxane Treatment Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer

An Open-label, Multi-center, Randomized, Phase II Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in the Treatment of Taxane Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer

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 expert 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 is currently available according to the process described on www.clinicalstudydatarequest.com

Radiographic progression free survival (rPFS) is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death.

Overall survival (OS) is defined as the time from the date of enrollment to the date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date).

Progression Free Survival (PFS) is defined as the time from date of randomization to the date of first documented progression by investigator assessment (radiographic progression, clinical progression, PSA progression) or death from any cause, whichever occurs first.

PSA 50 response rate is the proportion of PSA responders, defined as a participant who has achieved PSA decrease of \>= 50% from baseline that is confirmed by a second consecutive PSA measurement \>= 4 weeks later. Determination of response status will be based on PCWG3 recommendations.

Time to a first symptomatic skeletal event (TTSSE) is 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.

Time to PSA Progression (TTPSAP) defined as time from randomization to PSA progression. PSA progression date is defined as the date of 1) \>= 25% increase and \>= 2 ng/mL above the nadir, confirmed by a second value \>= 3 weeks later if there is a PSA decline from baseline, or 2) \>= 25% increase and \>= 2ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline:

Time to chemotherapy (TTCT) defined as time from randomization to initiation of the first subsequent chemotherapy or death, whichever occurs first.

Overall response rate (ORR)is defined as the proportion of participants with best overall response of complete response or partial response in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

Disease control rate (DCR) is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1

Time to response (TTR) is defined as the time from the date of randomization to the date of first documented response (CR or PR, which must be confirmed subsequently). CR and PR are based on tumor response data as per BICR and according to PCWG3-modified RECIST v1.1. Participants who did not achieve a confirmed CR or PR will be censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. FPFV to LPLV used for the analysis) when they did have a PFS event.

Duration of response (DOR) is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause.

Time to soft tissue progression (TTSTP) defined as time from randomization to radiographic soft tissue progression per PCWG3-modified RECIST v1.1 assessed by BICR.

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.

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.

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.

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs), through the monitoring of relevant clinical and laboratory safety parameters.

Patients will receive the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) may be used

Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles.

Best supportive/best standard of care (BS/BSOC)

68Ga-PSMA-11

The purpose of this study is to assess the efficacy, safety, tolerability, Pharmacokinetic(s) (PK) and dosimetry of \[177Lu\]Lu-PSMA-617 when administered in addition to Best Supportive/Best Standard of Care (BSC/BSoC) in Chinese participants with progressive PSMA-positive mCRPC who received at least 1 novel androgen receptor pathway inhibitor (ARPI) and were previously treated with 1 to 2 taxane regimens. Furthermore, the safety, PK, and dosimetry of \[68Ga\]Ga-PSMA-11 are assessed.

Data from this study will be used to bridge global pivotal phase III study (VISION, AAA617A12301) and to support China registration of \[177Lu\]Lu-PSMA-617 as a novel anticancer modality, namely radioligand therapy, in mCRPC.

This is a 2-part study:

1. Main part: Approximately 30 participants with at least 1 measurable lesion by PCWG3-modified RECIST v1.1 criteria will be enrolled in the main part. The primary endpoint of confirmed ORR will be analyzed with participants in this part, and will be assessed via independent centralized review of radiographic images provided by the Investigator and as outlined in PCWG3-modified RECIST v1.1 criteria.
2. Extension part: The extension part will enroll additional 30 participants with or without measurable lesions following the main part. The secondary endpoints will be analyzed with all participants in both main part and extension part.

Screening and enrollment period:

Written informed consent form (ICF) must be obtained prior to any screening procedures. All screening procedures described in the Assessment Schedule must be completed within 28 days prior to enrollment, except for radiographic imaging assessment, which must be done within 21 days prior to enrollment.

The participants will be assessed for eligibility and will undergo a mandatory \[68Ga\]Ga-PSMA-11 Positron Emission Tomography (PET)/Computed Tomography (CT) scan to evaluate Prostate-specific Membrane Antigen (PSMA) positivity for eligibility as assessed by central readers. Only participants with PSMA positive cancer and confirmed eligibility criteria will be enrolled.

Following completion of all required screening procedures and verifying participant eligibility, the participant will be enrolled. \[177Lu\]Lu-PSMA-617 will be ordered in parallel with interactive response technology (IRT) enrollment registration to allow at least 2 weeks to order and deliver \[177Lu\]Lu-PSMA-617.

Treatment period:

In principle, all participants should begin \[177Lu\]Lu-PSMA-617 dosing within 14 days after enrollment registration. However, Cycle 1 Day 1 (C1D1) can be delayed by up to an additional 3 days only for unexpected scheduling delays. Participants will receive 7.4 Gigabecquerel (GBq) (200 Millicuries (mCi)) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for a planned 6 cycles. BSC/BSoC may be used, including available care for the eligible participants according to best institutional practice. ARPIs (e.,g., abiraterone, etc.) are allowed. BSC/BSoC for each participant will be selected at the discretion of the Investigator prior to \[177Lu\]Lu-PSMA-617 administration, and can be modified over time as needed. BSC/BSoC will be administered per the physician's orders according to clinical best practice.

Radiographic imaging (CT with contrast/Magnetic Resonance Imaging (MRI) and bone scan) will be done at every 8 weeks (± 4 days) after first dose of \[177Lu\]Lu-PSMA-617 for the first 24 weeks (independent of dose delays), then every 12 weeks (± 4 days) thereafter and at End of Treatment (EOT) Visit (if not done within 28 days of EOT) until radiographic disease progression confirmed by central reader, death, withdrawal of consent, loss to follow-up, or subject/guardian's decision.

After the last day of study treatment period of \[177Lu\]Lu-PSMA-617 (i.e. after completion of 6 cycles of treatment OR treatment discontinuation for any reason) \[e.g. upon radiographic progression as confirmed by blinded independent centralized review\]), the participants must have an EOT visit performed ≤ 7 days and enter into the Post-treatment Follow-up period.

If a participant withdraws consent for the treatment period of the study, an EOT must be done and the participant will enter into the Post-treatment Follow-up unless he specifically withdraws consent for post-treatment Follow-up.

Post-treatment Follow-up period:

1. 30-day Safety Follow-up. All treated participants should have a safety follow-up conducted approximately 30 days after EOT visit.
2. Long term Follow-up. The long-term follow-up starts after the 30-day Safety follow-up and lasts until study completion. If a participant in the long term follow-up period discontinues treatment for reasons other than BICR-determined radiographic progression, his 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. The long-term follow-up period will also include the collection of survival and treatment updates, patient reported outcomes (PROs), serious adverse events (suspected to be related to study treatment), as well as blood sampling for hematology, chemistry testing, coagulation, and PSA. The visits will be carried out every 12 weeks (± 4 weeks) until death, lost to follow-up, withdrawal of consent, opposition to use data/biological samples or study completion, whichever occurs first. This follow-up will allow the data collection on medically significant long-term toxicities, such as long-term radiotoxicity.

If the participant withdraws consent for the collection of blood samples, PROs, and imaging assessments during the long-term follow-up, the information on survival, serious adverse events (SAEs) related to study treatment and post-treatment antineoplastic therapy will be collected.

PK/dosimetry assessments:

Both PK and dosimetry of \[68Ga\]Ga-PSMA-11 will be evaluated in at least 10 and up to 12 participants (at least 6 participants in main part). PK and dosimetry of \[68Ga\]Ga-PSMA-11 can be evaluated in any participant regardless of his PSMA status.

Both PK and dosimetry of \[177Lu\]Lu-PSMA-617 will be evaluated in at least 10 and up to 12 participants (at least 6 participants in main part).

Participants who take part in PK and dosimetry evaluation of \[177Lu\]Lu-PSMA-617 will also take part in the efficacy and safety evaluation together with the other participants. The treatment and assessment procedure follow the same as above.

A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC

A Prospective, Open-label, Multi-center, Single-arm, Phase II Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Confirmed Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR is based on PCWG3-modified RECIST v1.1 response for patients with measurable disease at baseline.

Radiographic progression free survival (rPFS) is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1 as assessed by blinded independent central review, or death

PSA response rate is the proportion of PSA responders, defined as a participant who has achieved PSA decrease of \>= 50% from baseline that is confirmed by a second consecutive PSA measurement \>= 4 weeks later. Determination of response status will be based on PCWG3 recommendations.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[177Lu\]Lu-PSMA-617 in at least 10 and up to 14 patients. Blood concentration of \[177Lu\]Lu-PSMA-617 will be summarized with descriptive statistics.

The quantity of ionizing radiation absorbed by organs and tissues will be summarized with descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. AUClast will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. Cmax will be listed and summarized using descriptive statistics.

Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of \[68Ga\]Ga-PSMA-11 in at least 10 and up to 14 patients. Blood concentration of \[68Ga\]Ga-PSMA-11 will be summarized with descriptive statistics.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Evaluating [177Lu]Lu-PSMA-617 vs. a Change of Androgen Receptor-directed Therapy in Taxane Treatment Naive Chinese Male Patients With Progressive Metastatic Castrate Resistant Prostate Cancer	NCT05658003	Metastatic Cast...	[177Lu]Lu-PSMA-... ARDT [68Ga]Ga-PSMA-1... Best supportive...	18 Years -	Novartis
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC	NCT05670106	Metastatic Cast...	[177Lu]Lu-PSMA-... Best supportive... 68Ga-PSMA-11	18 Years -	Novartis
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive mCRPC	NCT05670106	Metastatic Cast...	[177Lu]Lu-PSMA-... Best supportive... 68Ga-PSMA-11	18 Years -	Novartis

Spots Global Cancer Trial Database for chinese adult male population