177LuPSMA in Renal Cell Carcinoma

NCT06964958 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-216
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to evaluate the efficacy and safety of 177Lu-PSMA-617 as a systemic therapy in patients with PSMA-positive advanced clear cell renal cell carcinoma (ccRCC). The name of the study drug involved in this research study is:

• 177Lu-PSMA-617 (a type of radioligand therapy)

Conditions

Renal Cell Carcinoma; Advanced Clear Cell Renal Cell Carcinoma; Kidney Cancer

Keywords

Renal Cell Carcinoma; Advanced Clear Cell Renal Cell Carcinoma; Kidney Cancer; ccRCC; Prostate-specific membrane antigen; PSMA

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of participants who experienced complete response (CR) or partial response (PR) during treatment. Tumors will be assessed for response and progression by RECIST version 1.1 by central radiology review.

  Tumor assessment will be performed every 12 weeks on treatment. Treatment duration is 36 weeks.

Secondary Outcomes (3)

• Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  Adverse events are collected every study visit until the discontinuation of treatment plus 30 days. Treatment duration is 36 weeks.

• Median Disease-free Survival (DFS)

  Tumor assessment will be performed every 12 weeks on treatment. Treatment duration is 36 weeks.

• Median Overall Survival (OS)

  Survival follow-up will be every 6 months until 5 years after discontinuing treatment. The treatment duration is 36 weeks.

Study Arms (1)

Experimental: 177Lu-PSMA-617

EXPERIMENTAL

Enrolled participants will complete: * Baseline visit --Imaging every 12 weeks, or 2 cycles * Cycles 1 through 2: * Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * PSMA PET scan before Cycle 3 Day 1 * Cycles 3 through 6: --Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * End of treatment visit with assessments * Follow Up: every 6 months for up to 5 years * If no radiographic responses of Complete or Partial Response are seen in the first 9 participants enrolled, the trial will terminate. If 1 or more responses are seen in the first 9 participants, the study will enroll an additional 15 participants.

Drug: 177Lu-PSMA-617

Interventions

177Lu-PSMA-617 DRUG

A radioligand therapy, single-dose vial, via intravenous (into the vein) infusion per protocol.

Also known as: Pluvicto, Lutetium Lu 177 vipivotide tetraxetan

Experimental: 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:

• Histologically or cytologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component. Patients with sarcomatoid histology are eligible.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
• Age ≥18 years.
• Prior receipt of at least one immune checkpoint inhibitor and at least one tyrosine kinase inhibitor in the neoadjuvant, adjuvant or metastatic settings. Prior treatment with Ra-223 is permitted providing that the last dose was ≥90 days prior to study entry.
• Presence of ≥1 PSMA-avid lesion (with uptake \> liver) on baseline/screening 68Ga-PSMA-11 PSMA-PET/CT (within 28 days of planned C1D1), and the absence of any measurable PSMA-negative lesions (i.e. nodal, soft tissue or visceral lesions \>1cm) on baseline/screening 68Ga-PSMA-11 PSMA-PET. All patients considered for the study should have their PSMA-PET imaging reviewed in a multidisciplinary meeting with Medical Oncology and Nuclear Medicine to confirm eligibility.
• ECOG performance status ≤2.
• Adequate organ and marrow function as per the below table:
• System Laboratory Value
• Hematologic
• ANC ≥ 1.5×109/L
• Platelets ≥100×109/L
• Hemoglobin ≥9g/dL (≥90g/L), independent of transfusions
• Hepatic
• Total bilirubin ≤1.5 × ULN OR \<2 × ULN if known or suspected Gilbert's syndrome
• ALT and AST ≤3 × ULN OR ≤5 × ULN if liver metastases present

You may not qualify if:

• Prior PSMA-targeted therapy (eg. 177Lu-PSMA-617).
• Participants who have had radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
• Participants who have received anti-neoplastic intervention or experimental anti-neoplastic therapy within 14 days of planned cycle 1 day 1 of study therapy.
• Participants who are receiving any other investigational agents.
• Participants with untreated brain metastases. Participants with treated brain metastases are eligible if follow-up brain imaging at least 4 weeks after central nervous system (CNS)-directed therapy shows no evidence of progression and ongoing corticosteroids are not required. Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia. Sensory neuropathy grade ≤2 is acceptable.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-PSMA-617.
• Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Concurrent active malignancy whose natural history or treatment has the potential to interfere with safety or efficacy assessment of the investigational regimen. Patients with non-melanomatous skin cancer, superficial bladder cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject to be in remission, or any prior malignancy that was treated with curative intent (no evidence of disease for at least 3 years) are permitted to enroll.
• NB - participants who are found to have suspected prostate cancer on the basis of PSMA-PET/CT performed for screening (eg. PSMA avid disease in the prostate) are eligible to proceed on study on the basis of clinical judgement by the treating physician. Prostate (or other) biopsy is not required to confirm evidence of prostate cancer, if suspected, prior to proceeding with study therapy as long as the treating physician deems RCC to be a more pressing treatment priority.
• The participant has 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, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], 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).
• Females that are pregnant and/or lactating.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

Pluvicto

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Praful Ravi, MB BCHir, MRCP

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 11, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)