Prostate Cancer > Abemaciclib

Abemaciclib + Radioligand Therapy for Prostate Cancer

(UPLIFT Trial)

Recruiting in Palo Alto (17 mi)

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.

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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.

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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.

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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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

University of California, San Francisco San Francisco, CA

Who Is Running the Clinical Trial?

University of California, San Francisco Lead Sponsor

Vadim S Koshkin Lead Sponsor

Eli Lilly and Company Industry Sponsor

Prostate Cancer Foundation Collaborator

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] Label="BACKGROUND">Prostate-specific membrane antigen (PSMA) is overexpressed in metastatic castration-resistant prostate cancer (mCRPC) and represents a target for imaging and therapy. We undertook a prospective trial of 177Lu-PSMA-617 radioligand therapy in men with high PSMA expression who progressed after standard therapies.

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] Label="BACKGROUND">Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer refractory to established therapies. While there is an increasing body of survival and other data from retrospective analyses and prospective trials, there is no clear understanding of how best to predict therapy response and survival outcomes.

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

Radionuclide Treatment Yields Responses in mCRPC. [2020] In a phase II, single-arm prospective trial, a novel, targeted radionuclide called Lutetium-177 PSMA-617 extended survival and improved quality of life in men with metastatic, castration-resistant prostate cancer whose disease advanced despite standard therapy.

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] Label="BACKGROUND">Previously, results from the TheraP trial showed that treatment with lutetium-177 [177Lu]Lu-PSMA-617 improved frequency of prostate-specific antigen (PSA) response rate and progression-free survival compared with cabazitaxel in men with metastatic castration-resistant prostate cancer. In this study, we aimed to analyse gallium-68 [68Ga]Ga-PSMA-11 PET (PSMA-PET) and 2-[18F]fluoro-2-deoxy-D-glucose PET (FDG-PET) imaging parameters as predictive and prognostic biomarkers in this patient population.

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] We report our initial clinical experience with β -emitting (177)Lu-PSMA-I&T ((177)Lu labeled prostate specific membrane antigen ligand for imaging and therapy) for systemic treatment of metastatic castration resistant prostate cancer.

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

Clinical Trials of Prostate-Specific Membrane Antigen Radiopharmaceutical Therapy. [2023] Prostate-specific membrane antigen (PSMA) theranostics has been a momentous triumph for nuclear medicine. The recent approvals of PSMA-targeted imaging agents (68Ga-PSMA-11, 18F-DCFPyL) and radiopharmaceutical therapy (177Lu-PSMA-617) have paved the way for theranostics as a viable care strategy for men with metastatic castration-resistant prostate cancer. The imaging clinical trials OSPREY, CONDOR, and those conducted at the University of California (Los Angeles and San Francisco), as well as the randomized phase 3 therapy trial VISION, have been the fruitful beginnings for PSMA theranostics. There are currently several ongoing clinical trials to expand the reach of PSMA theranostics to the earlier phases of prostate cancer and to optimize its utility in combination therapeutic regimens. We provide a brief narrative review of the many PSMA-directed radiopharmaceutical therapy clinical trials with the β-emitter 177Lu-PSMA-617 and the α-emitter 225Ac-PSMA-617 in prostate cancer.

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] Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

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] Label="BACKGROUND">Progressive metastatic castration-resistant prostate cancer is a highly lethal disorder and new effective therapeutic agents that improve patient outcomes are urgently needed. Lutetium-177 [177Lu]-PSMA-617, a radiolabelled small molecule, binds with high affinity to prostate-specific membrane antigen (PSMA) enabling beta particle therapy targeted to metastatic castration-resistant prostate cancer. We aimed to investigate the safety, efficacy, and effect on quality of life of [177Lu]-PSMA-617 in men with metastatic castration-resistant prostate cancer who progressed after standard treatments.

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] Prostate cancer is the most common cancer to affect men in the United States and the second most common cancer in men worldwide. Prostate-specific membrane antigen (PSMA)-based positron emission tomography (PET) imaging has become increasingly popular as a novel molecular imaging technique capable of improving the clinical management of patients with prostate cancer. To date, several 68Ga and 18F-labeled PSMA-targeted molecules have shown promising results in imaging patients with recurrent prostate cancer using PET/computed tomography (PET/CT). Studies of involving PSMA-targeted radiopharmaceuticals also suggest a higher sensitivity and specificity, along with an improved detection rate over conventional imaging (CT scan and methylene diphosphonate bone scintigraphy) and 11C/18F-choline PET/CT. In addition, PSMA-617 and PSMA I&T ligands can be labeled with α- and β-emitters (e.g., 225Ac, 90Y, and 177Lu) and serve as a theranostic tool for patients with metastatic prostate cancer. While the clinical impact of such concept remains to be verified, the preliminary results of PSMA molecular radiotherapy are very encouraging. Herein, we highlighted the current status of development and future perspectives of PSMA-targeted radiopharmaceuticals and their clinical applications.

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

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023] Label="BACKGROUND">Metastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.

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] Radiolabeled ligands targeting prostate-specific membrane antigen (PSMA) are currently being established. Prostate-specific membrane antigen radioligand therapy with Lu-PSMA-617 is a promising treatment in metastasized castration-resistant prostate cancer with high efficacy and safety and seems to prolong progression-free survival and overall survival. We present Ga-PSMA PET/CT images during and after 2 therapy courses, including each 4 cycles of Lu-PSMA-617, and prostate-specific antigen-level history of a 77-year-old heavily pretreated patient with metastasized castration-resistant prostate cancer.

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

Experimental 177Lu-PSMA-617 radioligand therapy in a patient with extended metastasized leiomyosarcoma. [2021] Systemic radionuclide therapy with 177Lu-PSMA-617 is a novel treatment option in patients with metastasized and castration-resistant prostate cancer 4. The molecular target of the 177Lu-PSMA-617 radioligand therapy is the prostate-specific membrane antigen (PSMA) highly expressed on prostate cancer cells. Beyond the enhanced accumulation of PSMA on prostate cancer cells, PSMA expression is also found on the molecular surface or in the tumor-associated neovasculature of various tumor tissues including sarcomas of the soft tissue 2. Thus, PSMA has theoretically been discussed as a possible future target for systemic radioligand therapy with 177Lu-PSMA-617 even in non-prostate malignancies 1.Here we report on a female patient with extended metastasized leiomyosarcoma experimentally treated with one application of 177Lu-PSMA-617 radioligand therapy.