CLINICAL TRIALS PROFILE FOR LUTETIUM LU-177 VIPIVOTIDE TETRAXETAN

All Clinical Trials for lutetium lu-177 vipivotide tetraxetan

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT05113537 ↗	Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer	Not yet recruiting	Eli Lilly and Company	Phase 1/Phase 2	2021-12-31	This phase I/II trial tests the safety, side effects, and best dose of abemaciclib and whether it works before 177Lu-PSMA-617 in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abemaciclib is in a class of medications called kinase inhibitors. It is highly selective inhibitors of cyclin-dependent kinase 4 and 6, which are proteins involved in cell differentiation and growth. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. Radioligand therapy uses a small molecule (in this case 177Lu-PSMA-617), which carries a radioactive component to destroys tumor cells. When 177Lu-PSMA-617 is injected into the body, it attaches to the prostate-specific membrane antigen (PSMA) receptor found on tumor cells. After 177Lu-PSMA-617 attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving abemaciclib before 177Lu-PSMA-617 may help 177Lu-PSMA-617 kill more tumor cells.
NCT05113537 ↗	Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer	Not yet recruiting	Prostate Cancer Foundation	Phase 1/Phase 2	2021-12-31	This phase I/II trial tests the safety, side effects, and best dose of abemaciclib and whether it works before 177Lu-PSMA-617 in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abemaciclib is in a class of medications called kinase inhibitors. It is highly selective inhibitors of cyclin-dependent kinase 4 and 6, which are proteins involved in cell differentiation and growth. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. Radioligand therapy uses a small molecule (in this case 177Lu-PSMA-617), which carries a radioactive component to destroys tumor cells. When 177Lu-PSMA-617 is injected into the body, it attaches to the prostate-specific membrane antigen (PSMA) receptor found on tumor cells. After 177Lu-PSMA-617 attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving abemaciclib before 177Lu-PSMA-617 may help 177Lu-PSMA-617 kill more tumor cells.
NCT05113537 ↗	Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer	Not yet recruiting	University of California, San Francisco	Phase 1/Phase 2	2021-12-31	This phase I/II trial tests the safety, side effects, and best dose of abemaciclib and whether it works before 177Lu-PSMA-617 in treating patients with castration resistant prostate cancer that has spread to other places in the body (metastatic). Abemaciclib is in a class of medications called kinase inhibitors. It is highly selective inhibitors of cyclin-dependent kinase 4 and 6, which are proteins involved in cell differentiation and growth. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. Radioligand therapy uses a small molecule (in this case 177Lu-PSMA-617), which carries a radioactive component to destroys tumor cells. When 177Lu-PSMA-617 is injected into the body, it attaches to the prostate-specific membrane antigen (PSMA) receptor found on tumor cells. After 177Lu-PSMA-617 attaches to the PSMA receptor, its radiation component destroys the tumor cell. Giving abemaciclib before 177Lu-PSMA-617 may help 177Lu-PSMA-617 kill more tumor cells.

Clinical Trial Conditions for lutetium lu-177 vipivotide tetraxetan

Condition Name

Condition Name for lutetium lu-177 vipivotide tetraxetan
Intervention	Trials
Metastatic Castration-resistant Prostate Cancer	2
Metastatic Castration-resistant Prostate Carcinoma	1
Metastatic Prostate Adenocarcinoma	1

Condition MeSH

Condition MeSH for lutetium lu-177 vipivotide tetraxetan
Intervention	Trials
Prostatic Neoplasms	5
Carcinoma	2
Carcinoma, Adenoid Cystic	1

Clinical Trial Locations for lutetium lu-177 vipivotide tetraxetan

Trials by Country

Trials by Country for lutetium lu-177 vipivotide tetraxetan
Location	Trials
Australia	2
United States	2
Singapore	1
Israel	1
Japan	1

Trials by US State

Trials by US State for lutetium lu-177 vipivotide tetraxetan
Location	Trials
Virginia	1
California	1

Clinical Trial Progress for lutetium lu-177 vipivotide tetraxetan

Clinical Trial Phase

Clinical Trial Phase for lutetium lu-177 vipivotide tetraxetan
Clinical Trial Phase	Trials
Phase 4	1
Phase 3	1
Phase 2	3

Clinical Trial Status

Clinical Trial Status for lutetium lu-177 vipivotide tetraxetan
Clinical Trial Phase	Trials
Not yet recruiting	5
Recruiting	1

Clinical Trial Sponsors for lutetium lu-177 vipivotide tetraxetan

Sponsor Name

Sponsor Name for lutetium lu-177 vipivotide tetraxetan
Sponsor	Trials
Novartis Pharmaceuticals	3
OncoC4, Inc.	1
Maria Sklodowska-Curie National Research Institute of Oncology	1

Sponsor Type

Sponsor Type for lutetium lu-177 vipivotide tetraxetan
Sponsor	Trials
Industry	5
Other	4

Lutetium Lu-177 Vipivotide Tetraxetan: Clinical Trials Update, Market Analysis, and Projections

Introduction

Lutetium Lu-177 vipivotide tetraxetan, also known as Pluvicto, has revolutionized the treatment landscape for prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC). Here, we delve into the latest clinical trial updates, market analysis, and future projections for this groundbreaking radioligand therapy.

Clinical Trials Update

PSMAfore Trial

The PSMAfore trial, a phase III study, has been a significant milestone in the clinical development of lutetium Lu-177 vipivotide tetraxetan. Presented at the European Society for Medical Oncology (ESMO) Congress 2023, the trial demonstrated a 59% reduction in the risk of radiographic disease progression compared to a change in androgen receptor pathway inhibitor (ARPI) therapy. The trial met its primary endpoint of radiographic progression-free survival, with a median time to radiographic disease progression of 12.0 months for patients receiving lutetium Lu-177 vipivotide tetraxetan, compared to 5.6 months for those on ARPI therapy[1].

VISION Trial and Real-World Experience

The VISION trial, which led to the FDA approval of lutetium Lu-177 vipivotide tetraxetan in March 2022, has shown that the benefits observed in clinical trials are translating well into real-world practice. According to Dr. George from Duke University, the treatment has been manageable with a favorable toxicity profile, allowing most patients to complete the full 6 cycles of treatment over 9 months. This has resulted in substantial treatment breaks for patients, a significant improvement in a disease state where continuous treatment was previously the norm[2].

Ongoing and Future Studies

The PSMAddition trial, currently ongoing, is exploring the use of lutetium Lu-177 vipivotide tetraxetan in the metastatic hormone-sensitive setting, combining it with standard-of-care hormonal therapy. This study aims to assess potential synergies between radioligand therapy and hormonal treatments, which could open new avenues for treatment in earlier stages of the disease[2].

Market Analysis

FDA Approval and Global Accessibility

Lutetium Lu-177 vipivotide tetraxetan received FDA approval in March 2022 and subsequent approvals from the European Medicines Agency (EMA) in December 2022. Initially, access was limited to higher-volume academic centers due to supply constraints, but over the past year, availability has expanded to community centers, significantly increasing patient access[2].

Market Impact

The integration of lutetium Lu-177 vipivotide tetraxetan into clinical practice has been a game-changer for mCRPC treatment. It has not only improved radiographic progression-free survival and overall survival but also enhanced quality of life for patients. The manageable toxicity profile and the ability to complete full treatment cycles have made it a preferred option in the refractory population[2].

Projections and Future Directions

Expanded Treatment Paradigms

The success of lutetium Lu-177 vipivotide tetraxetan is expected to drive further research into radioligand therapies. Studies like the PSMAddition trial will help determine the potential of combining these therapies with other treatments, such as hormonal therapies, in earlier disease stages. This could lead to a broader range of treatment options and improved outcomes for patients with prostate cancer[2].

Increased Accessibility

As production and distribution improve, lutetium Lu-177 vipivotide tetraxetan is likely to become more widely available, reaching a larger patient population. This increased accessibility, coupled with growing physician experience, will further solidify its position in the treatment paradigm for mCRPC[2].

Ongoing Research and Development

A new study (NCT06531499) is assessing the dosimetry, safety, and tolerability of extended cycles (up to 12 cycles) of lutetium Lu-177 vipivotide tetraxetan in taxane-naïve patients with PSMA-positive mCRPC. This research aims to optimize treatment regimens and further enhance patient outcomes[3].

Quality of Life and Patient Outcomes

Radiographic Progression-Free Survival

The significant reduction in radiographic disease progression, as seen in the PSMAfore trial, translates into improved patient outcomes. Patients on lutetium Lu-177 vipivotide tetraxetan maintained their quality of life for longer periods, with a delay in worsening pain and better preservation of functional scores compared to those on ARPI therapy[1].

Overall Survival

While the overall survival data from the PSMAfore trial is still maturing, the crossover-adjusted analysis suggests a potential benefit. The unadjusted intent-to-treat analysis was confounded by the high crossover rate, but future interim analyses are expected to provide clearer insights into the overall survival benefit[1].

Adverse Events and Tolerability

Common Adverse Events

The most frequently reported adverse events associated with lutetium Lu-177 vipivotide tetraxetan are generally mild to moderate, including dry mouth, asthenia, nausea, anemia, and fatigue. These side effects are manageable, allowing most patients to complete the full treatment course without significant complications[1].

Key Takeaways

• Clinical Efficacy: Lutetium Lu-177 vipivotide tetraxetan has demonstrated significant clinical benefits in radiographic progression-free survival and quality of life in patients with PSMA-positive mCRPC.
• Market Expansion: The drug's availability has expanded beyond academic centers to community settings, increasing patient access.
• Future Directions: Ongoing studies are exploring its use in earlier disease stages and in combination with other therapies, potentially opening new treatment avenues.
• Patient Outcomes: The treatment has shown improved patient outcomes, including delayed disease progression and better quality of life.
• Tolerability: The adverse event profile is manageable, allowing for completion of full treatment cycles.

FAQs

Q: What is lutetium Lu-177 vipivotide tetraxetan used for?

A: Lutetium Lu-177 vipivotide tetraxetan is used for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy[5].

Q: What were the key findings of the PSMAfore trial?

A: The PSMAfore trial showed a 59% reduction in the risk of radiographic disease progression and improved quality of life for patients receiving lutetium Lu-177 vipivotide tetraxetan compared to those on ARPI therapy[1].

Q: How has the real-world experience been with lutetium Lu-177 vipivotide tetraxetan?

A: Real-world experience has mirrored clinical trial results, with the treatment being manageable and effective, allowing patients to complete full treatment cycles and experience substantial treatment breaks[2].

Q: What ongoing studies are significant for lutetium Lu-177 vipivotide tetraxetan?

A: The PSMAddition trial is exploring its use in the metastatic hormone-sensitive setting, and another study (NCT06531499) is assessing the safety and tolerability of extended treatment cycles[2][3].

Q: What are the common adverse events associated with lutetium Lu-177 vipivotide tetraxetan?

A: Common adverse events include dry mouth, asthenia, nausea, anemia, and fatigue, which are generally mild to moderate and manageable[1].

Sources

1. ASCO Post: PSMAfore: Lutetium Lu-177 Vipivotide Tetraxetan in Metastatic Prostate Cancer.
2. OncLive: Integration of Lutetium Lu 177 Vipivotide Tetraxetan Highlights Potential of Radioligands in Prostate Cancer.
3. Novartis Clinical Trials: A Study of Radiation Dosimetry, Safety, and Tolerability of Extended Cycles of (177Lu) Vipivotide Tetraxetan.
4. JAMA Network Open: Lu-177 PSMA in Survival of Metastatic Castration-Resistant Prostate Cancer.
5. DrugBank: Lutetium Lu-177 vipivotide tetraxetan.