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

• Status: Not yet recruiting
• Trial end date: 2028-01-13
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Gallium 68 PSMA-11

Criteria

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed.

2. Participants must be Chinese male adults >= 18 years of age.

3. Participants must have histological, pathological, and/or cytological confirmation of prostate cancer.

4. Participants must be [68Ga]Ga-PSMA-11 PET/CT scan positive, and eligible as determined by the sponsor's central reader according to the VISION read rules.

5. Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dl, or < 1.7 nmol/L).

6. Participants must have received at least one ARPI (such as enzalutamide and/orabiraterone).

7. Participants must have been previously treated with at least 1, but no more than 2 previous taxane regimens.

• A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. If a participant has received only 1 taxane regimen, the participant is eligible if: the participants' physician deems him unsuitable to receive a second taxane regimen (e.g., frailty assessed by geriatric or health status evaluation or intolerance, etc.)

8. Documented progressive mCRPC, based on at least 1 of the following criteria:

• Serum/plasma PSA progression defined as 2 consecutive increases in PSA measured at least 1 week apart, the minimal start value is 2.0 ng/ml

• Soft-tissue progression defined based on 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)

9. Participants must have >= 1 metastatic lesion that is present on baseline CT, MRI or bone scan imaging obtained =< 21 days prior to enrollment via central reading.

• In main part: participant must have at least one measurable lesion by PCWG3-modified RECIST v1.1 via central reading

10. Participants must have adequate organ function:

• Bone marrow reserve:

• White blood cell (WBC) count >= 2.5 × 109/L OR absolute neutrophil count (ANC) >= 1.5 × 109/L

• Platelets >=100 × 109/L

• Hemoglobin >= 9 g/dL

• Hepatic:

• Total bilirubin =< 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome =< 3 × ULN is permitted

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 3.0 × ULN OR =< 5.0 × ULN for participants with liver metastases

• Renal:

• eGFR >= 50 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) equation

11. Albumin >3.0 g/dL.

Exclusion Criteria:

1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation.

2. Previous PSMA-targeted radioligand therapy.

3. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies], APRI is not included) within 28 days prior to day of enrollment.

4. Any investigational agents (e.g. poly adenosine diphosphate-ribosyl polymerase inhibitors [PARPi]) within 28 days prior to day of enrollment.

5. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.

6. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, or investigational therapy.

7. Transfusion for the sole purpose of making a subject eligible for study inclusion.

8. Participants with a history of central nervous system (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.

9. Symptomatic spinal cord compression, or clinical or radiologic findings indicative of impending cord compression.