A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers

July 7, 2026 updated by: Novartis Pharmaceuticals

A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [177Lu]Lu-EVS459 and the safety and imaging properties of [68Ga]Ga-EVS459 in patients aged ≥ 18 years with advanced high-grade serous ovarian cancer (OC) or locally advanced unresectable or metastatic non-squamous non-small cell lung carcinoma (non-sq. NSCLC).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a [68Ga]Ga EVS459 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan. In the escalation part, different doses of [177Lu]Lu-EVS459 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of [177Lu]Lu-EVS459 at the RD(s) determined during the escalation part. The end of study will occur when at least 80% of the patients in the expansion part have completed the follow-up for disease progression or discontinued from the study for any reason, and all patients have completed treatment and the 36-month long-term follow-up period.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Novartis Pharmaceuticals
  • Phone Number: +41613241111

Study Locations

  • Israel
      • Tel Aviv, Israel, 6423906
        • Novartis Investigative Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Age >= 18 years old
  • Patients with advanced high-grade serous ovarian cancer (OC) or locally advanced unresectable or metastatic non-squamous non-small cell lung cancer (non sq. NSCLC) with disease progression following, or intolerance to, at least 1 line of therapy

Key Exclusion Criteria:

  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L, hemoglobin < 10 g/dL, or platelet count < 100 x 10^9/L
  • QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
  • Creatinine clearance < 60 mL/min
  • Unmanageable urinary tract obstruction or urinary incontinence
  • Radiation therapy within 4 weeks prior to the first dose of [177Lu]Lu-EVS459

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm1
Patients will receive [68Ga]Ga-EVS459 and, if eligible, [177Lu]Lu-EVS459
Drug: [68Ga]Ga-EVS459
Radioligand imaging agent
Drug: [177Lu]Lu-EVS459
Radioligand therapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with dose limiting toxicities of [177Lu]Lu-EVS459
Time Frame: From start of study treatment until 6 weeks after
A dose limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory value of CTCAE (version 5.0) Grade 3 or higher that occurs within the DLT evaluation period and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with a few exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
From start of study treatment until 6 weeks after
Incidence and severity of adverse events and serious adverse events of [177Lu]Lu- EVS459
Time Frame: From start of study treatment until completion of the 36 month follow up , assessed up to approximately 42 months
The distribution of adverse events will be done via the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) and through the monitoring of relevant clinical and laboratory safety parameters.
From start of study treatment until completion of the 36 month follow up , assessed up to approximately 42 months
Dose modifications for [177Lu]Lu- EVS459
Time Frame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
Dose modifications (dose interruptions and reductions) for [177Lu]Lu-EVS459 will be assessed and summarized using descriptive statistics. The number of patients with dose modification will be summarized by treatment groups.
From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
Dose intensity for [177Lu]Lu- EVS459
Time Frame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
Dose intensity for [177Lu]Lu- EVS459 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.
From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: Up to approximately 42 months
ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.
Up to approximately 42 months
Duration of Response (DOR)
Time Frame: Up to approximately 42 months
DOR is the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines.
Up to approximately 42 months
Disease control rate (DCR)
Time Frame: Up to approximately 42 months
DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease according to RECIST v1.1 guidelines.
Up to approximately 42 months
Progression free survival (PFS)
Time Frame: Up to approximately 42 months
PFS is defined as the time from the date of start of treatment to the date of the first documented progression according to RECIST v1.1 guidelines or death due to any cause.
Up to approximately 42 months
Area Under the Curve (AUC) of [177Lu]Lu-EVS459
Time Frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
The [177Lu]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. AUC will be determined by non-compartmental methods.
Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Total body clearance of [177Lu[Lu-EVS459
Time Frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
The [177Lu]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Total body clearance will be determined by non-compartmental methods.
Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Observed maximum plasma concentration (Cmax) of [177Lu]Lu-EVS459
Time Frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
The [177Lu]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Cmax will be determined by non-compartmental methods.
Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-EVS459
Time Frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
The [177Lu]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Vz will be determined by non-compartmental methods.
Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Terminal elimination half-life (T1/2) of [177Lu]Lu-EVS459
Time Frame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
The [177Lu]Lu-EVS459 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. T1/2 will be determined by non-compartmental methods.
Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes and 30 minutes, 1, 2, 4, 6 and 12 hours), Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)
Time Frame: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition and 6 hours post-end-of infusion(EOI), 6-24 hours post-EOI, 24-48 hours post-EOI, 48-72 hours post-EOI. The duration of a cycle is 6 weeks.
Urine elimination data for [177Lu]Lu-EVS459 will be assessed based on decay-corrected urine radioactivity concentration data. Urine elimination data will be expressed as percentage of injected activity (%IA).
Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition and 6 hours post-end-of infusion(EOI), 6-24 hours post-EOI, 24-48 hours post-EOI, 48-72 hours post-EOI. The duration of a cycle is 6 weeks.
Renal clearance of [177Lu]Lu- EVS459
Time Frame: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition and 6 hours post-end-of infusion(EOI), 6-24 hours post-EOI, 24-48 hours post-EOI, 48-72 hours post-EOI. The duration of a cycle is 6 weeks.
Urine samples will be collected over specified time intervals and analysed for radioactivity. Renal clearance of 177Lu-EVS459 will be summarized using descriptive statistics.
Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition and 6 hours post-end-of infusion(EOI), 6-24 hours post-EOI, 24-48 hours post-EOI, 48-72 hours post-EOI. The duration of a cycle is 6 weeks.
Absorbed dose of [177Lu]Lu- EVS459
Time Frame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.

The absorbed dose in normal tissues and tumor lesions will be summarized with descriptive statistics.

Lesion number will be assigned by dosimetry expert.
Cycle 1 Day 1, Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Time-activity curves (TACs) related to [177Lu]Lu-EVS459 uptake in organs and tumor lesions
Time Frame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.
Cycle 1 Day 1, Cycle 1 Day 2 (24 hours), Cycle 1 Day 3 (48 hours), Cycle 1 Day 4 (72 hours), Cycle 1 Day 8 (168 hours). The duration of a cycle is 6 weeks.
Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-EVS459
Time Frame: From Imaging visit until 14 days after 68Ga-EVS459 administration or until first dose of study treatment, assessed up to approximately 14 days
The distribution of adverse events will be done via the analysis of frequencies for treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) and through the monitoring of relevant clinical and laboratory safety parameters.
From Imaging visit until 14 days after 68Ga-EVS459 administration or until first dose of study treatment, assessed up to approximately 14 days
Visual and quantitative assessment of [68Ga]Ga-EVS459 uptake in normal tissues and tumor lesions over time
Time Frame: From 0 up to approximately 3 hours after [68Ga]Ga-EVS459 dosing
After [68Ga]Ga-EVS459 administration, [68Ga]Ga-EVS459 PET/CT or PET/MRI will be performed. Standardized uptake values (SUVs) of [68Ga]Ga-EVS459 in normal tissues and tumor lesions over time will be summarized.
From 0 up to approximately 3 hours after [68Ga]Ga-EVS459 dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 8, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 10, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 10, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 16, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 19, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 9, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CGIZ943A12101
  • 2023-507674-41-00 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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