A Prospective, Open Label, Multicenter, Single Arm, Phase 2 Study of 177Lu-PSMA-617 in the Treatment of Participants With Progressive PSMA- Positive Metastatic Castration-resistant Prostate Cancer (mCRPC) in Japan
Overview
- Phase
- Phase 2
- Intervention
- 177Lu-PSMA-617
- Conditions
- Prostate Cancer
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 87
- Locations
- 9
- Primary Endpoint
- Part 2 (Post-taxane part) and Part 3 (Pre-taxane part): Overall Response Rate (ORR) based on local assessment
- Status
- Active, Not Recruiting
- Last Updated
- last month
Overview
Brief Summary
The purpose of this study is to assess the efficacy, tolerability, safety, pharmacokinetic (PK) and dosimetry of 177Lu-PSMA-617, in participants with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) in Japan. Furthermore, the safety, PK and dosimetry of 68Ga-PSMA-11 (PSMA imaging agent) are assessed in the same study.
Another purpose of this study is to provide humanistic perspective access to study treatment (68Ga-PSMA-11 and 177Lu-PSMA-617) for the eligible patients with PSMA-positive mCRPC until marketed products are available in Japan.
Furthermore, if data availability PK and dose rate of 177 Lu-PSMA-617 will be evaluated to refine discharge criteria in Japan.
After obtaining manufacturing and marketing approval in Japan, this clinical trial will continue as a post marketing trial.
Detailed Description
This study is an open label, multicenter, single arm, phase II study to evaluate the efficacy, tolerability, safety, PK and dosimetry of 177Lu-PSMA-617 in participants with progressive PSMA-positive mCRPC in Japan. Furthermore, the safety, PK, and dosimetry of 68Ga-PSMA-11 (PSMA imaging agent) are also evaluated in this study. This study consists of two populations: 1. Post-taxane population: The post-taxane population will include men with PSMA-positive mCRPC who received at least one ARDT (for example enzalutamide, abiraterone etc.) and were previously treated with at least one, but no more than two taxane regimens. Participants treated with only 1 prior taxane regimen are eligible if the participant's physician deems the participants unsuitable to receive a second taxane regimen. 2. Pre-taxane population; The pre-taxane population will include men with PSMA-positive mCRPC who were previously treated with one ARDT as last treatment and have not been exposed to a taxane-containing regimen in the CRPC or HSPC settings and for whom it is considered appropriate to delay taxane-based chemotherapy. This is a 4-part study: Part 1 (a safety run-in part), Part 2 (post-taxane part), Part 3 (pre-taxane part) and Part 4 (expanded trial part). 1. Part 1 (safety run-in part) will confirm the tolerability and safety of recommended regimen, once every 6-weeks, 7.4 GBq of the 177Lu-PSMA-617. Minimum of 3 participants as 177Lu-PSMA-617 tolerability evaluable participants will be enrolled. Dosimetry and PK assessments of 177Lu-PSMA-617 are mandatory for participants enrolled in this part. 2. Part 2 (post-taxane part) will evaluate the efficacy, safety, PK and dosimetry of 177Lu-PSMA-617 plus BSC/BSoC, as well as safety, PK, and dosimetry of 68Ga-PSMA-11 in post-taxane participants with PSMA-positive mCRPC. 3. Part 3 (pre-taxane part) will evaluate the efficacy, safety, PK and dosimetry of 177Lu-PSMA-617, as well as safety, PK, and dosimetry of 68Ga-PSMA-11 in taxane naïve participants with PSMA-positive mCRPC 4. Part 4 (expanded trial part) will provide humanistic perspective access of study treatment (68Ga-PSMA-11 and 177Lu-PSMA-617) for the Japanese post-taxane participants with PSMA-positive mCRPC until marketed products are available in Japan. Additional safety and efficacy of 68Ga-PSMA-11 and of 177Lu-PSMA-617 will be evaluated. Additionally, PK and dose rate will be evaluated (PK is optional and dose rate is mandatory in Part 4). Approximately 80 eligible participants will be enrolled in Part 4 and approximately 10 evaluable participants PK data will be collected. This study will consist of 3 periods: screening period, treatment period, and long term follow up. The long-term follow-up ends after participant transitions to a post marketing trial.
Investigators
Eligibility Criteria
Inclusion Criteria
- •ECOG performance status:
- •Post-taxane population only: 0 to
- •Pre-taxane population only: 0 to
- •Participants must have a previous histological, pathological, and/or cytological confirmation of prostate cancer.
- •Part 1/2/3 only; Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the sponsor's central reader, before the enrollment to 177Lu-PSMA-617 treatment period.
- •Participants must have a positive 68Ga-PSMA-11 PET/CT scan, as determined by the local investigator, before the enrollment to 177Lu-PSMA-617 treatment period.
- •Participants must have a castrate level of serum/plasma testosterone (\<50 ng/dL or \<1.7 nmol/L).
- •Post-taxane population only: Participants must have received at least one ARDT (for example enzalutamide, abiraterone, apalutamide, or darolutamide, etc.) in either the hormone-sensitive/castrate-resistant or non-metastatic/metastatic prostate cancer setting.
- •Pre-taxane population only: Participants must have progressed only once on prior second generation ARDT (abiraterone, enzalutamide, darolutamide, or apalutamide) and be a candidate for change in ARDT as assessed by the treating physician.
- •first generation androgen receptor inhibitor therapy (e.g. bicalutamide) is allowed but not considered as prior ARDT therapy
Exclusion Criteria
- •Previous treatment with any of the following within 6 months of the enrollment: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation. Previous PSMA-targeted therapy is not allowed.
- •Post-taxane population: Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\], ARDT is not included) within 28 days prior to day of the enrollment.
- •Pre-taxane population: Prior treatment with PARP inhibitor, cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy \[including monoclonal antibodies\]) \[Note: Taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting is allowed if 12 months have elapsed since completion of this adjuvant or neoadjuvant therapy\]
- •Known hypersensitivity to the components of 177Lu-PSMA-617, 68Ga-PSMA-11 or excipients or to drugs of similar classes.
- •Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitors, biological, AKT inhibitors or investigational therapy.
- •Participants with a history of CNS metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic, and not receiving corticosteroids for the purposes of maintaining neurologic integrity.
- •Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
Arms & Interventions
177Lu-PSMA-617
PSMA positivity will be confirmed by PET/CT scan after administration of 68Ga-PSMA-11. All eligible participants will receive recommended dose of 177Lu-PSMA-617 via intravenous injection every 6 weeks (+/- 1 week) for a maximum of 6 cycles.
Intervention: 177Lu-PSMA-617
177Lu-PSMA-617
PSMA positivity will be confirmed by PET/CT scan after administration of 68Ga-PSMA-11. All eligible participants will receive recommended dose of 177Lu-PSMA-617 via intravenous injection every 6 weeks (+/- 1 week) for a maximum of 6 cycles.
Intervention: 68Ga-PSMA-11
177Lu-PSMA-617
PSMA positivity will be confirmed by PET/CT scan after administration of 68Ga-PSMA-11. All eligible participants will receive recommended dose of 177Lu-PSMA-617 via intravenous injection every 6 weeks (+/- 1 week) for a maximum of 6 cycles.
Intervention: Best supportive/best standard of care
Outcomes
Primary Outcomes
Part 2 (Post-taxane part) and Part 3 (Pre-taxane part): Overall Response Rate (ORR) based on local assessment
Time Frame: From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years
Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) according to PCWG3 modified RECIST 1.1.
Part 1 (safety run-in part): Dose Limiting Toxicity (DLT) during 1 cycle (6 weeks)
Time Frame: Cycle 2 Day 1 (Day 42)
A Dose Limiting Toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to 177Lu-PSMA-617 while fulfilling one of the criteria as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Secondary Outcomes
- Part 2 and Part 3 (main part): Percentage of Participants with Biochemical Response as measured by Prostate Specific Antigen (PSA)(From Baseline till 30 days safety follow-up, assessed up to 2 years)
- Part 2 and Part 3 (main part): Change from Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) Questionnaire(From Baseline up till end of treatment visit, an average of 13 months)
- Part 2 and Part 3 (main part): Absorbed dose and Effective whole-body dose of 177Lu-PSMA-617(177Lu-PSMA-617 SPECT/CT imaging acquired at Day 1, 2, 3 and 8 of Cycle 1)
- Part 2 and Part 3 (main part): Change from Baseline in European Quality of Life (EuroQol) - 5 Domain 5 Level scale (EQ-5D- 5L)(From Baseline up till end of treatment visit, an average of 13 months)
- Part 2 and Part 3 (main part): Overall Survival (OS)(From date of the first administration of 177Lu-PSMA-617 until date of death from any cause, assessed up to 2 years)
- Part 2 and Part 3 (main part): Disease Control Rate (DCR) as per central and local review(From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part3 (main part): Time to first symptomatic skeletal event (SSE) of 177Lu-PSMA-617(From the date of the first administration of 177Lu-PSMA-617 until the date of SSE or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part 3 (main part): Progression Free Survival (PFS)(From the date of the first administration of 177Lu-PSMA-617 until the date of progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part 3 (main part): Change from Baseline in Brief Pain Inventory - Short Form (BPISF) Questionnaire: Pain Interference Score(From Baseline up till end of treatment visit, an average of 13 months)
- Part 2 and Part 3 (main part): Radiographic Progression-Free-Survival (rPFS) based on local assessment(From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part 3 (main part): Duration of Response (DOR) based on local imaging(From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to 2 years)
- Part 2 and Part 3 (main part): Overall Response Rate (ORR) based on central review(From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part 3 (main part): Percentage of Participants with treatment emergent adverse events(From Baseline till 30 days safety follow-up, assessed up to 2 years)
- Part 2 and Part 3 (main part): Absorbed dose and Effective whole-body dose 68Ga-PSMA-11(68Ga-PSMA-11 PET imaging acquired at Day 1 (0, 20, 40 , 60, 90, 180 and 255 minutes post infusion))
- Part 2 and Part 3 (main part): Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): Total systemic clearance for intravenous administration (CL) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 4 (expanded trial part): Radiographic Progression-Free-Survival (rPFS) based on local assessment(From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 2 and Part 3 (main part): Change from Baseline in Brief Pain Inventory - Short Form (BPISF) Questionnaire: Pain Severity Score(From Baseline up till end of treatment visit, an average of 13 months)
- Part 2 and Part 3 (main part): Time of maximum observed drug concentration occurrence (Tmax) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main part): Observed maximum plasma concentration (Cmax) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): AUC(0-t) divided by the dose administered (AUC(0- t)/D) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): Terminal elimination half-life (T1/2) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main study): volume of distribution during the terminal phase following intravenous elimination (Vz) of 68Ga-PSMA-11(Cycle 1 Day 1 (0.083, 0.25, 0.5, 0.75, 1.42, 2.92 and 4.08 hours post infusion))
- Part 2 and Part 3 (main part): Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main part): Time of maximum observed drug concentration occurrence (Tmax) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main part): Observed maximum plasma concentration (Cmax) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): Area Under the plasma concentration-time Curve from the time 0 to the last observed quantifiable concentration (AUC(0-t)) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): AUC(0-t) divided by the dose administered (AUC(0- t)/D) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): Terminal elimination half-life (T^1/2) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): Area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUCinf) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): Total systemic clearance for intravenous administration (CL) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 2 and Part 3 (main study): volume of distribution during the terminal phase following intravenous elimination (Vz) of 177Lu-PSMA-617(Cycle 1 Day 1 (0, 0.33, 1, 2 and 4 hours post infusion), Cycle 1 Day 2 (24 hours post infusion), Cycle 1 Day 3 (48 hours post infusion), Cycle 1 Day 4 (72 hours post infusion), Cycle 1 Day 6 (120 hours post infusion))
- Part 4 (expanded trial part): Overall Response Rate (ORR) based on local assessment(From date of the first administration of 177Lu-PSMA-617 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 2 years)
- Part 4 (expanded trial part): Overall Survival (OS)(From date of the first administration of 177Lu-PSMA-617 until date of death from any cause, assessed up to 2 years)
- Part 4 (expanded trial part): Progression Free Survival (PFS)(From the date of the first administration of 177Lu-PSMA-617 until the date of progression or date of death from any cause, whichever comes first, assessed up to 2 years)