Abemaciclib Before 177Lu-PSMA-617 for the Treatment of Metastatic Castrate Resistant Prostate Cancer

NCT05113537 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 215510NCI-2021-11123
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Castration-Resistant Prostate Carcinoma; Metastatic Castration-resistant Prostate Carcinoma; Metastatic Castration-resistant Prostate Cancer; Metastatic Prostate Adenocarcinoma; Stage IV Prostate Cancer AJCC v8; Stage IVA Prostate Cancer AJCC v8; Stage IVB Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Recommended phase 2 dose (Part A)

  If two or more patients in a cohort experience a dose-limiting toxicity (DLT), then the maximum tolerated dose (MTD)has been exceeded. The previous dose level will be considered the MTD and the recommended phase 2 dose. Per Investigator discretion, the recommended phase 2 dose/schedule of abemaciclib followed by 177Lu-PSMA-617 may be established in the absence of reaching MTD, based on the cumulative safety data of the treatment regimen.

  6 weeks

• Proportion of participants with DLTs (Part A)

  Any non-hematologic, treatment-related adverse event (TRAE) Grade 3+, except of Grade 3 nausea,vomiting,diarrhea,constipation,fever,fatigue,skin rash,alopecia or non-clinically significant laboratory that resolves to Grade \<3 within 72 hours;Grade 4 thrombocytopenia lasting \>7 days;Grade 3+ thrombocytopenia with bleeding/requirement for platelet transfusion;Grade 4 neutropenia lasting \>7 days; Grade 3+ neutropenic fever;Grade 4+ anemia;TRAE requiring treatment discontinuation/delay of \>42 days;Failure to receive at least 66% of abemaciclib doses due to toxicity;Death not clearly due to underlying disease/extraneous causes;Hy's law;Grade 3+ nausea/vomiting/diarrhea \>72 hours;Grade 3+ fatigue \>7 days;Grade 3+ electrolyte abnormality \>72 hours, unless patient has clinical symptoms;All AEs of specified grades should count as DLTs except those that are clearly due to progression/extraneous causes.

  6 weeks

• Change in maximum standardized uptake value (SUVmax) across three lesions on gallium Ga 68 gozetotide (68Ga-PSMA-11) positron emission tomography (PET) scan (Part B)

  The uptake in the three lesions with the highest SUVmax on the initial scan will be compared to SUVmax measurements in the same lesions on the PSMA PET scan following 14 days of priming treatment with abemaciclib

  Up to 24 weeks

Secondary Outcomes (7)

• PSA50 response rate (Part B)

  Up to 24 weeks

• Proportion of participants with TRAEs (Part B)

  Up to 30 days after last dose of study drug, approximately 28 weeks

• Radiographic progression free survival (Part B)

  Up to 2 years

• Objective response rate (Part B)

  Up to 24 weeks

• Disease control rate (Part B)

  Up to 24 weeks

Study Arms (2)

Part A: Abemaciclib, 177Lu-PSMA-617

EXPERIMENTAL

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.

Drug: Abemaciclib; Drug: Lutetium Lu 177-PSMA-617

Part B: Recommended Phase 2 dose of Abemaciclib, 177Lu-PSMA-617

EXPERIMENTAL

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.

Drug: Abemaciclib; Drug: Lutetium Lu 177-PSMA-617

Interventions

Abemaciclib DRUG

Given Orally

Also known as: Abemaciclib Oral, LY-2835219, Verzenio

Part A: Abemaciclib, 177Lu-PSMA-617; Part B: Recommended Phase 2 dose of Abemaciclib, 177Lu-PSMA-617

Lutetium Lu 177-PSMA-617 DRUG

Given IV

Also known as: 177Lu-labeled PSMA-617, Lutetium Lu 177 Vipivotide Tetraxetan

Part A: Abemaciclib, 177Lu-PSMA-617; Part B: Recommended Phase 2 dose of Abemaciclib, 177Lu-PSMA-617

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed prostate cancer. Either fresh biopsy or archival tissue can be used for confirmation.
• Age \>= 18 years.
• Patients must have metastatic castration resistant prostate cancer (mCRPC) with progression based on Prostate Cancer Working Group 3 (PCWG3) criteria.
• Patients must have adenocarcinoma histology.
• Prior treatment with at least one novel hormonal agents (NHA) such as abiraterone acetate, enzalutamide, apalutamide, darolutamide etc.
• Patients must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\< 50 ng/dL or \< 1.7 nmol/L)
• Patients must have a 68Ga-PSMA-11 PET scan with at least one PSMA-positive lesions (maximum standardized uptake value \[SUVmax\] greater than SUVmax of liver) as determined by nuclear medicine review prior to start of lead-in treatment with abemaciclib
• Patients must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2
• Patients must have life expectancy of \> 6 months
• Patients must have adequate organ function as outlined below and bone marrow reserve
• White blood cell (WBC) \> 2.5
• Absolute neutrophil count (ANC) \> 1.5
• Hemoglobin (Hgb) \>= 8.0 \[Note- Participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion\]
• Platelets (Plt) \>= 100 x 10\^9/Liter (100,000/Microliter)
• Total bilirubin =\< 1.5 x the institutional upper limit of normal (ULN). For patients with known Gilbert's Syndrome =\< 2 ULN and direct bilirubin within normal limits is permitted

You may not qualify if:

• Patients with small cell or neuroendocrine carcinoma histology.
• Patients with a super scan seen in the baseline bone scan. Super scan refers to a bone scan with diffusely increased skeletal radioisotope uptake relative to soft tissue
• Patients with prior treatment with CDK4/6 inhibitors
• Patients with prior treatment with PSMA-targeted radioligand therapy. Patients with previous treatment with PSMA targeting therapies (Such as Chimeric antigen receptor T cells (CAR-T) or Bi-specific T-cell engagers (BiTEs) are eligible.
• Patients treated with Radium-223 within 6 weeks prior to study entry.
• Any systemic anti-cancer therapy within 3 weeks of study entry
• Patients who have experienced significant radiation-related adverse events (AEs) from prior radiation treatment (\>= grade 3) or have experienced persistent radiation-related AEs that have not resolved by the time of study randomization
• Patients with a history of central nervous system (CNS) metastases are ineligible unless they have received prior therapy (surgery, radiation therapy (RT), gamma knife) are asymptomatic, and not receiving corticosteroids for this indication. Head imaging is not required
• Patients with symptoms of cord compression or impending cord compression
• Patients with concurrent serious medical conditions as determined by primary investigator
• Patients with other significant malignancies that are expected to alter life expectancy or interfere with disease assessment. Patients with adequately treated skin cancer, non-muscle-invasive bladder cancer and patients with prior history of malignancy who have been disease free for more than 2 years are eligible. Patients with history of in-situ/early stage melanoma will not be excluded
• Patients who have not recovered from adverse events due to prior anti-cancer therapy to =\< grade 1 or baseline (other than alopecia or peripheral neuropathy)
• Patients with serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)
• The patient has active systemic bacterial infection (requiring intravenous (IV) antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C (for example, hepatitis B surface antigen positive). Screening is not required for enrollment
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Sponsors & Collaborators

• Vadim S Koshkin: lead
• Prostate Cancer Foundation: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abemaciclib; Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Vadim S Koshkin, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Genitourinary Medical Oncology Recruitment

CONTACT

877-827-3222; GUTrials@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investiator

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 9, 2021
• Study Start: July 8, 2022
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)