Phase 1 Multicenter Study of Safety, Tolerability, and Dosimetry of ^177Lu‑Vipivotide Tetratetan Radioligand Therapy in Metastatic Triple‑Negative Breast Cancer
- Trial ID
- 2025-524027-49-00
- Protocol
- 25-246
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to establish the recommended phase 2 dose (RP2D) regimen for intravenous administration of lutetium‑177 vipivotide tetraxetan (Pluvicto) in women with metastatic triple‑negative breast cancer by evaluating safety and tolerability, thereby providing the dose‑selection basis for subsequent therapeutic studies.
Participants
The sponsor did not provide information on the total number of participants. The trial population consists of adult female patients (≥ 18 years) with a histologically confirmed diagnosis of metastatic triple negative breast cancer that is HER‑2 negative (IHC 0‑1+ or FISH negative) and estrogen/progesterone receptor <1 %. Eligible individuals must have locally recurrent or metastatic disease, have received at least two prior systemic therapy lines with documented progression or intolerance, and exhibit a positive PSMA expression on PET/CT (≥ one PSMA‑positive lesion with uptake greater than blood pool). Additional health requirements include an ECOG performance status of 0‑2, a life expectancy of at least 24 weeks, and adequate bone‑marrow and organ function (platelets ≥ 100 ×10⁹/L, WBC ≥ 2.5 ×10⁹/L, neutrophils ≥ 1.0 ×10⁹/L, hemoglobin ≥ 9 g/dL, eGFR ≥ 50 mL/min/1.73 m², total bilirubin < 1.5 × ULN, AST/ALT < 3 × ULN, albumin ≥ 30 g/L). Participants must have measurable disease per RECIST v1.1 on recent imaging and must be able to comply with required lifestyle restrictions following administration of the investigational product.
Plans and Procedures
The study is an open‑label, multicentric, phase I trial evaluating the safety, tolerability and radiation dosimetry of intravenous administration of Pluvicto® in women with metastatic triple‑negative breast cancer. The design is a single‑arm, non‑randomized, uncontrolled investigation with an estimated recruitment period from 30 June 2026 to 30 September 2029. After providing informed consent, participants undergo a screening visit to confirm eligibility criteria, including laboratory assessments, imaging, and PSMA PET/CT confirmation of disease expression. Eligible subjects receive a single dose of the investigational radiopharmaceutical, followed by scheduled follow‑up visits at approximately weeks 1, 4, 8, 12, and 24 to monitor adverse events, laboratory parameters, and dosimetry outcomes. The end‑of‑study visit occurs at week 24 or earlier if discontinuation criteria are met. Participant involvement therefore extends up to 24 weeks post‑treatment. Early termination may occur due to dose‑limiting toxicities, emergence of serious adverse events, protocol non‑compliance, withdrawal of consent, or investigator determination of unacceptable risk. Primary endpoints focus on the incidence of dose‑limiting toxicities and the frequency of treatment‑emergent adverse events.
Treatment
The investigational product is Pluvicto, a solution for injection/infusion supplied at a concentration of 1 000 MBq/mL. The active moiety is lutetium‑177‑vipivotide tetraxetan. It is administered intravenously (IV) as a single infusion; the administered activity is expressed in gigabecquerels (GBq) according to the protocol‑defined dosing schedule.
The auxiliary radiopharmaceutical preparation kit, identified as gozetotide (Locametz 25 µg kit), is provided as a solution for injection. Each kit delivers a fixed activity of 259 MBq and is used to prepare the radioligand that is subsequently administered to participants via IV injection.
Dosing occurs on the designated treatment day of each study cycle, with the infusion performed under controlled conditions to ensure accurate delivery of the prescribed radioactivity. Compliance with the infusion schedule and dose administration is monitored through infusion logs, radiation safety checks, and verification of the administered activity against the prepared dose. Vital signs and relevant safety parameters are recorded before, during, and after the infusion to assess tolerability.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Patient is female and ≥ 18 years old.
- Patient is willing to provide signed and dated written informed consent form (ICF) prior to any study-specific procedures.
- Patient is willing to comply with required lifestyle restrictions following administration of the IMP per local regulations.
- Patient must have a life expectancy of at least 24 weeks from study entry in the assessment of the investigator.
- Patient must have a histologically confirmed diagnosis of TNBC. Patient must demonstrate HER-2 negative (IHC 0, 1+, or fluorescence in situ hybridization (FISH) negative and ER< 1%, and PR < 1%, per ASCO/CAP criteria).
- Patient must have locally recurrent or metastatic breast cancer and undergone ≥ 2 lines of therapy treatment and had progression or was intolerant of the latest treatment. Additionally, the available/suitable ADCs must have been applied if possible/applicable based on previous toxicities.
- Patient must exhibit an ECOG performance status of 0-2.
- Patient must have presence of disease target or non-target lesions (per RECIST v1.1) on CT/MRI and/or full body 99mTc bone scan performed within 6 weeks prior to screening.
- Patient must have a positive disease expression of PSMA as confirmed on PSMA PET/CT scan. Note: Positive disease is defined as having at least 1 PSMA-positive lesion of any size with higher uptake than bloodpool using semiquantitative assessment (SUV measurement). The lesion can be bone, lymph node or viscera. Further details regarding the interpretation of the diagnostic images can be found in the Image Acquisition Guidelines (Fendler et al., 2023).
- Patient has at least 4 weeks or 5 half-lives (whichever is longer) elapsed between last anti-cancer treatment administration and the initiation of study treatment.
- Patient has all previous treatment-related toxicities to CTCAE version 6.0 grade of ≤3 resolved.
- Patient’s prior major surgery according to the European Surgical Association (ESA, Martin et al., 2020) must be at least 12 weeks away prior to study entry.
- Patient must have adequate bone marrow reserve and organ function as demonstrated by blood count, and serum biochemistry at baseline: − Platelets ≥ 100 × 10⁹/L − WBC ≥ 2.5 × 10⁹/L − Neutrophils ≥ 1.0 × 10⁹/L − Haemoglobin ≥ 9 g/dL − eGFR ≥ 50 ml/min/1,73 m² − Total bilirubin remains unchanged < 1.5 × ULN − AST/ALT < 3 × ULN − Albumin ≥ 30 g/L
Exclusion Criteria
- Patient is not willing to take adequately safe contraceptive measures.
- Patient has received an investigational drug in another trial within the last 30 days.
- Patient is simultaneously participating in another clinical interventional trial.
- Patient is institutionalised due to official or court order.
- Patient has known hypersensitivity to the therapeutic IMP or diagnostic AxMP or any of their constituents.
- Patient shows presence of PSMA-negative disease: PSMA-negative disease defined as any PSMA-negative (lower uptake than blood pool using semiquantitative assessment (SUV measurement)) but FDG-or CT-positive lymph node >1 cm in the short axis and/or a PSMA-negative bone metastasis which has a significant soft tissue component suggesting ongoing disease activity and/or a PSMA-negative solid organ metastasis >1 cm in the long axis. Further details are provided in the Image Acquisition Guidelines (Fendler et al., 2023).
- Patient has diffuse marrow infiltration of disease (‘superscan’ appearance on full body 99mTc bone scan). A superscan is defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake in relation to soft tissues along with absent or faint activity in the genitourinary tract and soft tissues due to diffuse bone/bone marrow metastases. Further details regarding this appearance are provided in the Image Acquisition Guidelines (Fendler et al., 2023)..
- Patient has symptomatic spinal cord compression, or clinical or radiological findings that are indicative of impending spinal cord compression.
- Patient has known history of hematological malignancy.
- Patient has known history of central nervous system (CNS) metastases. Exception: Patient with a history of CNS metastases who has received and completed therapy (e.g. surgery, radiotherapy), and is neurologically stable, asymptomatic and does not require corticosteroids or anti-convulsants to control neurological symptoms will be eligible. Discrete dural metastases are permitted but diffuse leptomeningeal disease is not. For patients with a history of CNS metastases, baseline imaging and subsequent radiological imaging for assessing treatment response must include MRI or ceCT evaluation of the brain.
- Patient has known history of other solid malignancy that may reduce life expectancy and/or may interfere with disease assessment. Exception: Patients with histopathologically confirmed prior malignancy that has been treated, and who have been disease-free for >3 years. Patients with treated non-melanoma skin cancer and non-muscle invasive bladder cancer will be eligible.
- Patient has an unresolved urinary tract obstruction defined as radiographic evidence of hydronephrosis with or without ureteric stent/nephrostomy. Exception: Where the clinical team judges that the patient’s hydronephrosis is not obstructing, and renal function meets the inclusion criteria, the patient may undergo 99mTc mercaptoacetyltriglycerine scanning during the screening period and if the result is non-obstructed, the patient can be eligible for the study.
- Patient has any uncontrolled significant medical, psychiatric, or surgical condition or laboratory finding, that would pose a risk to patient safety or interfere with study participation or interpretation of individual patient results. For cardiac conditions, this includes, but is not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, and myocardial infarction diagnosed within 6 months prior to enrolment.
- Patient has ongoing treatment with bisphosphonates for bone-targeted therapy. Exception: Patients will be eligible if they have received a stable dose of Zoledronic acid for at least 8 weeks prior to enrolment. These patients must have had renal function monitored since initiation of bisphosphonate therapy, with a stable pattern observed, and must have an eGFR ≥ 60 mL/min.
- Patient has severe urinary incontinence that would preclude safe disposal of radioactive urine.
- Patient has a single kidney or renal transplant or any concomitant nephrotoxic therapy that might put the patient at high risk of renal toxicity during the study in the judgement of the investigator.
- Patient has clinically significant abnormalities on a single 12-lead electrocardiogram (ECG) at screening.
- Patient received previously external beam irradiation to a field that includes more than 30% of the bone marrow or kidneys.
- Patient is a sponsor employees or investigator site personnel directly affiliated with this study, and their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
- Patient had previous treatment with any of the following: PSMA-targeted radionuclide therapy, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation.
- Patient has a bilateral hip replacement or any significant metallic implants or objects, which may in the opinion of the investigator, affect image quality and/or dosimetry calculations.
- Patient needs transfusion of blood products for the sole purpose of meeting the eligibility criteria for this clinical study.
- Patient is pregnant or breastfeeding.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Not Yet Recruiting | 30 Jun 2026 | 18 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Pluvicto 1 000 MBq/mL solution for injection/infusion | Test | SOLUTION FOR INJECTION/INFUSION | INJECTION | 00 | 48 | PRD10117050 |
Locametz 25 micrograms kit for radiopharmaceutical preparation | Other | KIT FOR RADIOPHARMACEUTICAL PREPARATION | INJECTION | 259 | 1 | PRD10117083 |