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NCT06562192PHASE1Recruiting

Phase I Study of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers

Novartis Pharmaceuticals

Start Date

10/15/2024

Completion Date

1/16/2031

Summary

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-NNS309 and the safety, dosimetry and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC) and colorectal cancer (CRC).

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-NNS309 positron emission tomography (PET)/ computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan and will be evaluated for eligibility for \[177Lu\]Lu-NNS309 treatment. In the escalation part, different doses of \[177Lu\]Lu-NNS309 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-NNS309 at the RD(s) determined during the escalation part. The end of study will occur when all patients per disease group 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

Age Range: 18 years to 100 years

Inclusion Criteria: * Age ≥ 18 years old * Patients with one of the following indications: * Locally advanced unresectable or metastatic PDAC with disease progression following, or intolerance to cytotoxic chemotherapy, unless patient was ineligible to receive such therapy * Locally advanced unresectable or metastatic NSCLC without any actionable genomic alterations with disease progression following, or intolerance to chemotherapy and immunotherapy, unless patient was ineligible to receive such therapy, or locally advanced unresectable or metastatic NSCLC with an actionable genomic alteration with disease progression following, or intolerance to targeted therapy, unless patient was ineligible to receive such therapy * Locally advanced unresectable or metastatic HR+/HER2- ductal or lobular BC with disease progression following, or intolerance to, at least 2 lines of therapy, unless patient was ineligible to receive such therapy * Locally advanced unresectable or metastatic TNBC with disease progression following, or intolerance to, at least 2 lines of therapy, unless patient was ineligible to receive such therapy * Locally advanced or metastatic unresectable CRC with disease progression following, or intolerance to cytotoxic chemotherapy, unless patient was ineligible to receive such therapy. Patients with known microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status must also have had disease progression following, or intolerance to immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy * Patients must have lesions showing 68Ga-NNS309 uptake Exclusion Criteria: * Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L, hemoglobin \< 9 g/dL, or platelet count \< 100 x 10\^9/L * QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec * Calculated estimated glomerular filtration rate \< 60 mL/min/1.73m2 * Unmanageable urinary tract obstruction or urinary incontinence * Radiation therapy within 4 weeks prior to the first dose of \[177Lu\]Lu-NNS309 Other protocol-defined inclusion/exclusion criteria may apply.

Interventions

DRUG

[68Ga]Ga-NNS309

DRUG

[177Lu]Lu-NNS309

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Conditions

Pancreatic Ductal AdenocarcinomaNon-small Cell Lung CancerHR+/HER2- Ductal and Lobular Breast CancerTriple Negative Breast CancerColorectal Cancer

Locations

Uni of Alabama at Birmingham

Birmingham, Alabama 35249

United States

University of California LA

Los Angeles, California 90095

United States

Stanford University Medical Center

Palo Alto, California 94304

United States

Mayo Clinic Jacksonville

Jacksonville, Florida 32224

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

BAMF Health

Grand Rapids, Michigan 49503

United States

Mayo Clinic Rochester

Rochester, Minnesota 55905

United States

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas 77030

United States

University Of Washington

Seattle, Washington 98109

United States

Novartis Investigative Site

Brussels, 1000

Belgium

Novartis Investigative Site

Toronto, Ontario M5G 2M9

Canada

Novartis Investigative Site

Montreal, Quebec H2X 1R9

Canada

Novartis Investigative Site

Montreal, Quebec H3T 1E2

Canada

Novartis Investigative Site

Bron, 69677

France

Novartis Investigative Site

Villejuif, 94800

France

Novartis Investigative Site

Cologne, North Rhine-Westphalia 50937

Germany

Novartis Investigative Site

Essen, 45147

Germany

Novartis Investigative Site

München, 80377

Germany

Novartis Investigative Site

Rostock, 18057

Germany

Novartis Investigative Site

Tel Aviv, 6423906

Israel

Novartis Investigative Site

Milan, MI 20133

Italy

Novartis Investigative Site

Reggio Emilia, RE 42123

Italy

Novartis Investigative Site

Nijmegen, Gelderland 6500HB

Netherlands

Novartis Investigative Site

Utrecht, 3584 CX

Netherlands

Novartis Investigative Site

Barcelona, 08036

Spain

Novartis Investigative Site

Madrid, 28009

Spain

Novartis Investigative Site

Madrid, 28040

Spain

Novartis Investigative Site

Geneva, 1211

Switzerland

Novartis Investigative Site

Lausanne, 1011

Switzerland