Abemaciclib + Radioligand Therapy for Prostate Cancer

(UPLIFT Trial)

Overseen By UCSF Genitourinary Medical Oncology Recruitment

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, San Francisco

Must not be taking: CDK4/6 inhibitors

Disqualifiers: Small cell carcinoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 34

Duration: 24 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and evaluate the effectiveness of combining abemaciclib with radioligand therapy for treating prostate cancer that has spread and resists standard hormone treatments. Abemaciclib, a medication that prevents cancer cell multiplication, is administered before radioligand therapy, which uses a radioactive component to destroy cancer cells. Men with prostate cancer that has become resistant to hormone therapy and has metastasized may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's effects in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that abemaciclib is FDA-approved for treating certain types of breast cancer, indicating its general safety for other uses. Common side effects include diarrhea, tiredness, and nausea, but these are usually manageable.

For the radioligand therapy, 177Lu-PSMA-617 has been tested in prostate cancer patients. Specifically, the VISION trial demonstrated its effectiveness, with mostly mild to moderate side effects, such as dry mouth and tiredness.

While both treatments have been studied separately, their combined use is still under investigation. As this trial is in its early stages, the safety of the combination is still being explored. However, existing data on each treatment alone provides some reassurance about their safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Abemaciclib combined with Lutetium Lu 177-PSMA-617 for prostate cancer because this combination targets the disease in a unique way. Unlike standard treatments such as hormone therapy or chemotherapy, which focus on suppressing or killing cancer cells broadly, this therapy specifically targets prostate-specific membrane antigens (PSMA) on cancer cells. Abemaciclib is a CDK4/6 inhibitor that disrupts cancer cell growth, while Lutetium Lu 177-PSMA-617 is a radioligand therapy that delivers targeted radiation to PSMA-expressing cells. This dual approach not only increases precision in targeting cancer cells but also aims to reduce damage to healthy tissues, potentially improving outcomes and minimizing side effects.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will evaluate the combination of abemaciclib and 177Lu-PSMA-617 for prostate cancer. Research has shown that abemaciclib, a type of drug, stops cancer cells from growing by targeting certain proteins. Studies on 177Lu-PSMA-617, a form of targeted radiation therapy, have indicated it can effectively kill prostate cancer cells by attaching to a protein commonly found on these cells and delivering radiation directly to them. In this trial, using abemaciclib may increase cancer cells' sensitivity to the radiation from 177Lu-PSMA-617, potentially leading to better results. Early findings suggest this combination might outperform either treatment alone for prostate cancer that has spread and is resistant to standard treatments. ^{1 2 3 4 6}

Who Is on the Research Team?

Vadim S Koshkin, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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.

Patients must have life expectancy of > 6 months.

My cancer is of the adenocarcinoma type.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Lutetium Lu 177-PSMA-617

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.

How Is the Trial Designed?

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.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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 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]

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]

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]

[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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05113537

NCT05113537 | Abemaciclib Before 177Lu-PSMA-617 for ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10166155/

PSMA-Targeted Radiopharmaceuticals in Prostate Cancer This review summarizes the current and future role of radiopharmaceutical therapies in the management of patients with advanced prostate cancer.

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-11123

Abemaciclib before 177Lu-PSMA-617 for the Treatment of ... 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 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11655789/

The therapeutic use of 177 Lu-PSMA-617 radioligand ... This review paper aims to highlight the key phase III randomized controlled trials related to 177 Lu-PSMA-617 in all stages of prostate cancer.

5. withpower.com withpower.com/trial/phase-2-carcinoma-11-2021-041d8

Abemaciclib + Radioligand Therapy for Prostate Cancer 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.

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/lutetium-lu-177-vipivotide-tetraxetan?pn=1

Clinical Trials Using Lutetium Lu 177 Vipivotide Tetraxetan Review the clinical trials studying lutetium lu 177 vipivotide tetraxetan on this list and use the filters to refine the results by age and location.