Flexible Dosing of 177Lu-PSMA-617 for Advanced Prostate Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Jeremie Calais

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Prior 177Lu-PSMA-617, Low GFR, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

In advanced metastatic castration resistant prostate cancer (mCRPC) progressing after chemotherapy and androgen receptor (AR)-targeted therapy 177Lu-PSMA-617 is an effective treatment. 177Lu-PSMA-617 RLT is administered with a fixed schedule: 6 treatment cycles, administered every 6 weeks. However, the optimum number of cycles of 177Lu-PSMA in patients who show good response remains unknown. Some patients may benefit from more than 6 cycles of therapy. Additionally, some patients experience a complete or almost complete response before the last cycle. It is unclear whether these patients benefit from the subsequent remaining treatment cycle(s). A treatment holiday period would spare these patients some exposure to the therapy agent and avoid potentially unnecessary toxicity when treatment efficacy is already maximal and additional treatment effect cannot be expected. This randomized phase 2 study compares a group of patients treated with LuPSMA on a flexible and extended dosing schedule including "treatment holiday" periods (investigational arm, up to 12 cycles, as described below) to a control group treated with a fixed dosing schedule of 6 treatments cycles maximum administered every 6 weeks. The flexible dosing schedule in the investigational arm will be based on single photon emission computed tomography (SPECT)/computed tomography (CT) response assessments obtained 24h after injection of LuPSMA therapy cycle. The response assessment during treatment holiday period will be based on positron emission tomography/computed tomography (PET/CT) every 12 weeks. Single-time point SPECT/CT dosimetry protocol at every cycle will be performed and will allow to determine the number of cycles that subjects may receive under the study without exceeding the kidney dose threshold.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, there must be at least 6 weeks between your last myelosuppressive therapy and the first cycle of the trial treatment.

What data supports the effectiveness of the drug Lutetium Lu 177 Vipivotide Tetraxetan for advanced prostate cancer?

The drug Lutetium Lu 177 Vipivotide Tetraxetan has been shown to improve overall survival in patients with advanced prostate cancer, as demonstrated in the VISION trial. Patients receiving this drug lived a median of 15.3 months compared to 11.3 months for those receiving standard care alone. ^{1 2 3 4 5}

Is Lutetium Lu 177 vipivotide tetraxetan safe for humans?

Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto, has been approved for treating advanced prostate cancer, and its safety was evaluated in a large clinical trial. While it showed a significant improvement in survival, like any treatment, it may have side effects, and its safety profile was considered acceptable for the approved use. ^{1 2 3 4 5}

What makes the drug Lutetium Lu 177 Vipivotide Tetraxetan unique for advanced prostate cancer?

Lutetium Lu 177 Vipivotide Tetraxetan is unique because it is a radioligand therapy that specifically targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor while sparing healthy tissue. This targeted approach is different from traditional chemotherapy and has shown to improve survival in patients with advanced prostate cancer who have already undergone other treatments. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for individuals with metastatic castration-resistant prostate cancer, which continues to grow despite low testosterone levels from traditional hormone therapy. Participants should have PSMA receptors on tumor cells and be suitable for a flexible treatment schedule.

Inclusion Criteria

White blood cell (WBC) ≥ 1500/ul

Absolute neutrophil count (ANC) ≥ 1000 mm^3

Patients must have the ability to understand and sign an approved informed consent form (ICF)

Exclusion Criteria

It has been less than 6 weeks since my last strong cancer treatment.

My kidney function is low, with a GFR under 30 ml/min.

I have previously received 177Lu-PSMA-617 therapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 intravenously every 6 weeks for up to 12 cycles, with potential treatment holiday periods based on response assessments

Up to 72 weeks

1 visit every 6 weeks

Treatment Holiday

Participants may have treatment holiday periods based on response assessments, monitored with PSMA PET/CT every 12 weeks

Variable, based on response

1 visit every 12 weeks during holiday

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

24 months

1 visit every 3 months

Treatment Details

Interventions

• Lutetium Lu 177 Vipivotide Tetraxetan (Radiopharmaceutical)

Trial Overview The study is testing a new dosing schedule of the drug 177Lu-PSMA-617 over 12 cycles versus the standard 6 cycles. It includes imaging techniques like PET scans and CTs to monitor progress, along with 'treatment holiday' periods.

Participant Groups

Group I: Arm I (177Lu-PSMA-617) Experimental Treatment 7 Interventions

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Group II: Arm II (177Lu-PSMA-617) Active Control 7 Interventions

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Lutetium Lu 177 Vipivotide Tetraxetan is already approved in United States, European Union for the following indications:

🇺🇸 Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer (mCRPC) in adults who have been treated with androgen receptor inhibitors and taxane-based chemotherapy

🇪🇺 Approved in European Union as Pluvicto for:

• Treatment of adult patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitors and taxane-based chemotherapy

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

UCLA / Jonsson Comprehensive Cancer Center Los Angeles, CA

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center Lead Sponsor

Novartis Pharmaceuticals Industry Sponsor

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. [2022] Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™, formerly known as 177Lu-PSMA-617) is a radioligand therapeutic agent that is being developed by Advanced Accelerator Applications (a subsidiary of Novartis) for the treatment of prostate-specific membrane antigen (PSMA)-expressing metastatic prostate cancer. The active part of the radiopharmaceutical is lutetium-177, which is linked to a ligand that binds to prostate-specific membrane antigen (PSMA), a transmembrane enzyme overexpressed in primary and metastatic prostate cancers. Based on efficacy results from the phase 3 VISION trial, lutetium Lu 177 vipivotide tetraxetan was approved in the USA on 23 March 2022 for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy. Regulatory review in the EU and other countries is underway. This article summarizes the milestones in the development of Lutetium Lu 177 vipivotide tetraxetan leading to this first approval as a therapeutic radioligand for mCRPC.

2. England pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. [2023] Label="INTRODUCTION"> 177Lu-vipivotide tetraxetan is a radiopharmaceutical that selectively targets prostate-specific membrane antigen (PSMA) and delivers beta-radiations to kill prostate cancer cells.

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023] On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC; n = 551) or BSoC alone (n = 280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and one or two prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS), with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (HR: 0.62; 95% confidence interval: 0.52-0.74; P

4. United States pubmed.ncbi.nlm.nih.gov

New Drug for Metastatic Castration-Resistant Prostate Cancer. [2022] Pluvicto (lutetium Lu 177 vipivotide tetraxetan) has been approved for the treatment of adult patients with prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer who have received androgen receptor pathway inhibition and taxane-based chemotherapy.

5. England pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. [2023] Label="BACKGROUND">In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results.

6. Switzerland pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. [2022] In March 2022, [177Lu]Lu-PSMA-617 (PluvictoTM) was approved by the FDA for the treatment of prostate cancer patients. Until now, the approval has been limited to patients with PSMA-positive metastatic castration-resistant prostate cancer who have previously received other therapy options (such as inhibition of the androgen receptor pathway and taxane-based chemotherapy). [177Lu]Lu-PSMA-617, which combines a PSMA-specific peptidomimetic with a therapeutical radionuclide, is used in a radioligand therapy that selectively delivers ionizing radiation to tumor cells, causing their death, while sparing the surrounding healthy tissue. In numerous clinical trials, the efficacy of [177Lu]Lu-PSMA-617 was demonstrated.