Abemaciclib + Radioligand Therapy for Prostate Cancer

(UPLIFT Trial)

Overseen by Vadim S Koshkin, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Small cell carcinoma, CNS metastases, others

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests if taking abemaciclib before using 177Lu-PSMA-617 can better treat prostate cancer that has spread and doesn't respond to usual treatments. Abemaciclib slows down cancer growth, and 177Lu-PSMA-617 uses radiation to kill the cancer cells. 177Lu-PSMA-617 targets a specific protein in prostate cancer cells and has shown promising results in treating advanced prostate cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a requirement for a 21-day washout period (time without taking certain medications) after your last chemotherapy dose before starting the trial treatment.

What data supports the effectiveness of the treatment Abemaciclib + Radioligand Therapy for Prostate Cancer?

Research shows that Lutetium-177 PSMA-617, a part of the treatment, has extended survival and improved quality of life in men with advanced prostate cancer that did not respond to standard treatments. ^{1 2 3 4 5}

Is the combination of Abemaciclib and Lutetium Lu 177-PSMA-617 safe for humans?

Lutetium Lu 177-PSMA-617 has been shown to be safe in patients with advanced prostate cancer, with ongoing studies to further evaluate its safety in combination therapies. While specific safety data for the combination with Abemaciclib is not available, Lutetium Lu 177-PSMA-617 alone has demonstrated promising safety results in clinical trials. ^{1 6 7 8 9}

What makes the Abemaciclib + Radioligand Therapy treatment unique for prostate cancer?

This treatment combines Abemaciclib, a drug that blocks proteins involved in cell division, with Lutetium Lu 177-PSMA-617, a radioligand therapy that targets and delivers radiation to prostate cancer cells. This combination is unique because it targets cancer cells in two different ways, potentially improving effectiveness for patients with advanced prostate cancer. ^{1 2 10 11 12}

Research Team

Vadim S Koshkin, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Men aged 18+ with metastatic castration resistant prostate cancer that has progressed despite previous taxane-based chemotherapy can join. They must have adequate organ function, no small cell/neuroendocrine carcinoma, and not be on recent anti-cancer therapy or have serious concurrent conditions. HIV-positive individuals on effective treatment are eligible.

Inclusion Criteria

Patients must have the ability to understand a written informed consent document, and the willingness to sign it.

I am 18 years old or older.

Patients must have life expectancy of > 6 months.

Exclusion Criteria

I do not have any active infections requiring IV antibiotics or known viral infections like HIV or active hepatitis B or C.

You are not currently taking any experimental drugs for treatment.

I have had radiation treatment to my lungs or liver.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive abemaciclib orally twice daily on days 1-14 and lutetium Lu 177 vipivotide tetraxetan intravenously on day 15. Treatment repeats every 6 weeks for up to 4 cycles.

24 weeks

4 cycles, each with 1 in-person visit for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

2 years

Follow-up at 30 days, then every 3 months

Treatment Details

Interventions

• Abemaciclib (Kinase Inhibitor)
• Lutetium Lu 177-PSMA-617 (Radioligand Therapy)

Trial Overview The trial is testing the safety and effectiveness of abemaciclib followed by radioligand therapy with 177Lu-PSMA-617 in men with advanced prostate cancer. Abemaciclib is a kinase inhibitor aiming to stop cancer growth, while 177Lu-PSMA-617 targets and kills tumor cells.

Participant Groups

Group I: Part B: Recommended Phase 2 dose of Abemaciclib, 177Lu-PSMA-617 Experimental Treatment 2 Interventions

Patients receive the recommended phase 2 dose of abemaciclib lead-in on days 1-14 and lutetium Lu 177 vipivotide tetraxetan IV over 30 minutes on day 15. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Group II: Part A: Abemaciclib, 177Lu-PSMA-617 Experimental Treatment 2 Interventions

Patients receive abemaciclib lead-in on days 1-14 and lutetium Lu 177 vipivotide tetraxetan IV over 30 minutes on day 15. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Vadim S Koshkin

Lead Sponsor

Trials

1

Recruited

30+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Findings from Research

In a study of men with metastatic castration-resistant prostate cancer (mCRPC) who were screened for 177Lu-PSMA-617 therapy, 24% were found to have low PSMA expression or discordant FDG-avid disease, leading to a poor prognosis with a median overall survival of only 2.5 months.

The findings suggest that patients with low PSMA expression or discordant disease after standard treatments have limited treatment options and short survival, highlighting the potential need for alternative therapies like 177Lu-PSMA-617 for those who qualify.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy. Thang, SP., Violet, J., Sandhu, S., et al.[2021]

Lutetium-177 PSMA radioligand therapy shows a significant response rate in treating metastatic castration-resistant prostate cancer, with 56% of patients experiencing a PSA decline of 50% or more, indicating its efficacy as a treatment option.

The therapy has a low toxicity profile, with serious adverse events occurring in a small percentage of patients, and is particularly effective in those with lymph node metastases and lower baseline PSA levels, suggesting these factors can help predict better survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer. Meyrick, D., Gallyamov, M., Sabarimurugan, S., et al.[2021]

In a phase II trial involving men with metastatic, castration-resistant prostate cancer, Lutetium-177 PSMA-617 was shown to extend survival and enhance quality of life for patients whose disease progressed despite standard treatments.

This study highlights the potential of targeted radionuclide therapy as an effective option for patients with advanced prostate cancer, suggesting a promising new avenue for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radionuclide Treatment Yields Responses in mCRPC. [2020]

In a study involving 200 men with metastatic castration-resistant prostate cancer, a higher PSMA-PET SUVmean (≥10) was found to significantly predict a better response to treatment with lutetium-177 [177Lu]Lu-PSMA-617 compared to cabazitaxel, with an odds ratio of 12.19, indicating a strong association between high PSMA uptake and treatment efficacy.

Conversely, a high metabolic tumor volume (MTV ≥200 mL) on FDG-PET was associated with lower PSA response rates across both treatment groups, suggesting that patients with high tumor volumes may require more intensive treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. Buteau, JP., Martin, AJ., Emmett, L., et al.[2022]

In a study involving patients with metastatic castration-resistant prostate cancer who had previously failed other treatments, (177)Lu-PSMA-I&T therapy demonstrated a favorable safety profile, with no severe toxicities observed at higher doses, and manageable side effects like dry mouth and anemia.

The therapy showed promising efficacy, with 56% of patients achieving a prostate-specific antigen decrease of 30% or more, and 74% of patients experiencing stable or improved performance status, indicating potential benefits in managing this advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Radioligand Therapy with (177)Lu Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer. Heck, MM., Retz, M., D'Alessandria, C., et al.[2019]

PSMA-targeted imaging agents and radiopharmaceutical therapy have been approved, marking a significant advancement in treating metastatic castration-resistant prostate cancer, with trials like VISION demonstrating their efficacy.

Ongoing clinical trials aim to extend the use of PSMA theranostics to earlier stages of prostate cancer and explore combination therapies, indicating a promising future for this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trials of Prostate-Specific Membrane Antigen Radiopharmaceutical Therapy. Jadvar, H., Colletti, PM.[2023]

[177Lu]Lu-PSMA-617 has shown definitive safety and efficacy in treating metastatic castration-resistant prostate cancer in patients who have previously undergone at least one taxane treatment and one novel androgen-axis drug, indicating its potential as a standard therapy.

Ongoing phase 3 trials are evaluating the effectiveness of [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T in various clinical situations, highlighting the need for guidelines to optimize patient selection and manage potential side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT). Kratochwil, C., Fendler, WP., Eiber, M., et al.[2023]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

Prostate-specific membrane antigen (PSMA)-based PET imaging has shown higher sensitivity and specificity for detecting recurrent prostate cancer compared to traditional imaging methods, improving clinical management for patients.

PSMA-targeted radiopharmaceuticals, such as PSMA-617 and PSMA I&T, can be used for both imaging and therapy (theranostics) in metastatic prostate cancer, with preliminary results indicating promising outcomes for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-Specific Membrane Antigen-Targeted Radiopharmaceuticals in Diagnosis and Therapy of Prostate Cancer: Current Status and Future Perspectives. Lin, M., Ta, RT., Kairemo, K., et al.[2021]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of 177Lu-PSMA-617 to standard care significantly improved both imaging-based progression-free survival (8.7 months vs. 3.4 months) and overall survival (15.3 months vs. 11.3 months).

While 177Lu-PSMA-617 was associated with a higher incidence of grade 3 or above adverse events (52.7% vs. 38.0%), it did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, O., de Bono, J., Chi, KN., et al.[2023]

Lu-PSMA-617 radioligand therapy shows high efficacy and safety in treating metastasized castration-resistant prostate cancer, potentially prolonging both progression-free and overall survival.

The study includes detailed Ga-PSMA PET/CT imaging and prostate-specific antigen level tracking in a 77-year-old patient, demonstrating the therapy's impact over two treatment courses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Survival and Excellent Response to Repeated 177Lu-Prostate-Specific Membrane Antigen 617 Radioligand Therapy in a Patient With Advanced Metastatic Castration-Resistant Prostate Cancer. Roll, W., Bräuer, A., Weckesser, M., et al.[2021]

177Lu-PSMA-617 is a promising new treatment for patients with advanced prostate cancer, specifically targeting the prostate-specific membrane antigen (PSMA) found on cancer cells.

The therapy was also experimentally applied to a female patient with metastasized leiomyosarcoma, suggesting potential for PSMA-targeted treatment in other types of tumors beyond prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. Jüptner, M., Marx, M., Zuhayra, M., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Poor Outcomes for Patients with Metastatic Castration-resistant Prostate Cancer with Low Prostate-specific Membrane Antigen (PSMA) Expression Deemed Ineligible for 177Lu-labelled PSMA Radioligand Therapy. [2021]

2. France pubmed.ncbi.nlm.nih.gov

Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer. [2021]

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

Radionuclide Treatment Yields Responses in mCRPC. [2020]

4. England pubmed.ncbi.nlm.nih.gov

PSMA and FDG-PET as predictive and prognostic biomarkers in patients given [177Lu]Lu-PSMA-617 versus cabazitaxel for metastatic castration-resistant prostate cancer (TheraP): a biomarker analysis from a randomised, open-label, phase 2 trial. [2022]

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

Systemic Radioligand Therapy with (177)Lu Labeled Prostate Specific Membrane Antigen Ligand for Imaging and Therapy in Patients with Metastatic Castration Resistant Prostate Cancer. [2019]

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

Clinical Trials of Prostate-Specific Membrane Antigen Radiopharmaceutical Therapy. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

Joint EANM/SNMMI procedure guideline for the use of 177Lu-labeled PSMA-targeted radioligand-therapy (177Lu-PSMA-RLT). [2023]

8. England pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. [2021]

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

Prostate-Specific Membrane Antigen-Targeted Radiopharmaceuticals in Diagnosis and Therapy of Prostate Cancer: Current Status and Future Perspectives. [2021]

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

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]

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

Long-term Survival and Excellent Response to Repeated 177Lu-Prostate-Specific Membrane Antigen 617 Radioligand Therapy in a Patient With Advanced Metastatic Castration-Resistant Prostate Cancer. [2021]

12. Germany pubmed.ncbi.nlm.nih.gov

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021]