Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Micronutrients

Hematinics

All Drugs and Chemicals

Vitamins

Folic Acid

Vitamin B Complex

Folinic Acid

Folate

Vitamin B9

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

[68Ga]Ga-EVS459

[177Lu]Lu-EVS459

Novartis Pharmaceuticals

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).

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.

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

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

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.

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.

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.

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.

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.

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.

DOR is the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines.

DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease according to RECIST v1.1 guidelines.

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.

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.

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.

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.

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.

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.

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).

Urine samples will be collected over specified time intervals and analysed for radioactivity. Renal clearance of 177Lu-EVS459 will be summarized using descriptive statistics.

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

Lesion number will be assigned by dosimetry expert.

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.

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.

Spots Global Cancer Trial Database for folate receptor (fr)