Clinical trial NCT06376253: A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
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)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-04-19
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with dose limiting toxicities of [177Lu]Lu-EVS459
timeFrame: From start of study treatment until 6 weeks after
measure: Incidence and severity of adverse events and serious adverse events of [177Lu]Lu- EVS459
timeFrame: From start of study treatment until completion of the 36 month follow up , assessed up to approximately 42 months
measure: Dose modifications for [177Lu]Lu- EVS459
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
measure: Dose intensity for [177Lu]Lu- EVS459
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to approximately 42 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 42 months
measure: Disease control rate (DCR)
timeFrame: Up to approximately 42 months
measure: Progression free survival (PFS)
timeFrame: Up to approximately 42 months
measure: Area Under the Curve (AUC) of [177Lu]Lu-EVS459
timeFrame: 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.
measure: Total body clearance of [177Lu[Lu-EVS459
timeFrame: 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.
measure: Observed maximum plasma concentration (Cmax) of [177Lu]Lu-EVS459
timeFrame: 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.
measure: Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-EVS459
timeFrame: 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.
measure: Terminal elimination half-life (T1/2) of [177Lu]Lu-EVS459
timeFrame: 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.
measure: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)
timeFrame: 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.
measure: Renal clearance of [177Lu]Lu- EVS459
timeFrame: 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.
measure: Absorbed dose of [177Lu]Lu- EVS459
timeFrame: 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.
measure: Time-activity curves (TACs) related to [177Lu]Lu-EVS459 uptake in organs and tumor lesions
timeFrame: 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.
measure: Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-EVS459
timeFrame: From Imaging visit until 14 days after 68Ga-EVS459 administration or until first dose of study treatment, assessed up to approximately 14 days
measure: Visual and quantitative assessment of [68Ga]Ga-EVS459 uptake in normal tissues and tumor lesions over time
timeFrame: From 0 up to approximately 3 hours after [68Ga]Ga-EVS459 dosing
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
Study officials:
References: