NCT05670106

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)

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 62 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: Male
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was 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 were 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.

Detailed description

This was a 2-part study: 1. Main part: Thirty participants with at least 1 measurable lesion by PCWG3-modified RECIST v1.1 criteria were enrolled in the main part. The primary endpoint of confirmed overall response rate (ORR) was analyzed with participants in this part and was 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 enrolled additional 30 participants with or without measurable lesions following the main part. The secondary endpoints were analyzed with all participants in both main part and extension part. Screening and enrollment period: Written informed consent form (ICF) was obtained prior to any screening procedures. All screening procedures described in the Assessment Schedule were completed within 28 days prior to enrollment, except for radiographic imaging assessment, which was done within 21 days prior to enrollment. The participants were assessed for eligibility and underwent 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 were enrolled. Following completion of all required screening procedures and verifying participant eligibility, the participant was enrolled. \[177Lu\]Lu-PSMA-617 was 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) could be delayed by up to an additional 3 days only for unexpected scheduling delays. Participants received 7.4 Gigabecquerel (GBq) (200 Millicuries (mCi)) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for a planned 6 cycles. BSC/BSoC coud be used, including available care for the eligible participants according to best institutional practice. ARPIs (e.,g., abiraterone, etc.) were allowed. BSC/BSoC for each participant was selected at the discretion of the Investigator prior to \[177Lu\]Lu-PSMA-617 administration, and could be modified over time as needed. BSC/BSoC was administered per the physician's orders according to clinical best practice. Radiographic imaging (CT with contrast/Magnetic Resonance Imaging (MRI) and bone scan) was 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 have to have an EOT visit performed ≤ 7 days and enter into the Post-treatment Follow-up period. If a participant withdrew consent for the treatment period of the study, an EOT is supposed to be done and the participant would enter into the Post-treatment Follow-up unless he specifically withdrew consent for post-treatment follow-up. Post-treatment Follow-up period: 1. 30-day Safety Follow-up. All treated participants are to have a safety follow-up conducted approximately 30 days after EOT visit. 2. Long term Follow-up. The long-term follow-up would start after the 30-day Safety follow-up and would last until study completion. If a participant in the long-term follow-up period discontinued treatment for reasons other than BICR-determined radiographic progression, his tumor assessments were required to 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 also includes 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 are supposed to 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 allows the data collection on medically significant long-term toxicities, such as long-term radiotoxicity. If the participant withdrew 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 are to be collected. PK/dosimetry assessments: Both PK and dosimetry of \[68Ga\]Ga-PSMA-11 was to 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 could be evaluated in any participant regardless of his PSMA status. Both PK and dosimetry of \[177Lu\]Lu-PSMA-617 are to be evaluated in at least 10 and up to 12 participants (at least 6 participants in main part). Participants who took part in PK and dosimetry evaluation of \[177Lu\]Lu-PSMA-617 were to take part in the efficacy and safety evaluation together with the other participants. The treatment and assessment procedure followed the same as above.

Conditions

• Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Interventions

Type	Name	Description
DRUG	[177Lu]Lu-PSMA-617	Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles.
OTHER	Best supportive/best standard of care (BS/BSOC)	Best supportive/best standard of care as defined by the local investigator
DRUG	68Ga-PSMA-11	Administered single intravenous dose of approximately 150 MBq. Administered dose could not be lower than 111 MBq or higher than 259 MBq (3 - 7 mCi).

Timeline

• Start date: 2023-05-16
• Primary completion: 2024-05-17
• Completion: 2026-06-30
• First posted: 2023-01-04
• Last updated: 2026-02-13

Locations

17 sites across 1 country: China