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

NCT06376253 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CGIZ943A121012023-507674-41-00
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Ovarian Cancer; Lung Cancer

Keywords

ovarian cancer; non-squamous non-small cell lung cancer (non sq. NSCLC); advanced solid tumors; radioligand therapy (RLT); [177Lu]Lu-EVS459; [68Ga]Ga-EVS459; folate receptor (FR)

Outcome Measures

Primary Outcomes (4)

• Number of participants with dose limiting toxicities of [177Lu]Lu-EVS459

  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

  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

  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

  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 Outcomes (15)

• Overall response rate (ORR)

  Up to approximately 42 months

• Duration of Response (DOR)

  Up to approximately 42 months

• Disease control rate (DCR)

  Up to approximately 42 months

• Progression free survival (PFS)

  Up to approximately 42 months

• Area Under the Curve (AUC) of [177Lu]Lu-EVS459

  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.

Study Arms (1)

Arm1

EXPERIMENTAL

Patients will receive \[68Ga\]Ga-EVS459 and, if eligible, \[177Lu\]Lu-EVS459

Drug: [68Ga]Ga-EVS459; Drug: [177Lu]Lu-EVS459

Interventions

[68Ga]Ga-EVS459 DRUG

Radioligand imaging agent

Arm1

[177Lu]Lu-EVS459 DRUG

Radioligand therapy

Arm1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (1)

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Lung Neoplasms

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2024
• First Posted: April 19, 2024
• Study Start: September 8, 2024
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: August 7, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)