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

Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [177Lu]Lu-NNS309 and the safety 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).

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Triple Negative Breast Cancer; Non-small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma; HR+/HER2- Ductal and Lobular Breast Cancer
• Intervention / Treatment: Drug: [68Ga]Ga-NNS309; Drug: [177Lu]Lu-NNS309

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.

• Study Type: Interventional
• Enrollment (Estimated): 162
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Recruiting
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2N2
      • Recruiting
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2W 1T8
      • Recruiting
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Novartis Investigative Site
• France
  • Bron, France, 69677
    • Recruiting
    • Novartis Investigative Site
  • Villejuif, France, 94800
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
  • München, Germany, 80377
    • Recruiting
    • Novartis Investigative Site
  • Rostock, Germany, 18057
    • Recruiting
    • Novartis Investigative Site
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Recruiting
      • Novartis Investigative Site
• Israel
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20133
      • Recruiting
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Recruiting
      • Novartis Investigative Site
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Novartis Investigative Site
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Recruiting
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Recruiting
    • Novartis Investigative Site
  • Madrid, Spain, 28009
    • Recruiting
    • Novartis Investigative Site
• Switzerland
  • Geneva, Switzerland, 1211
    • Recruiting
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Recruiting
      • Uni of Alabama at Birmingham
      • Principal Investigator: Jonathan McConathy
      • Contact: Sebastian Eady; Email: smeady@uabmc.edu
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California LA
      • Principal Investigator: Jonathan W Goldman
      • Contact: Angela Lool; Email: alool@mednet.ucla.edu
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University Medical Center
      • Principal Investigator: Farshad Moradi
      • Contact: Maria Isabel Leonio; Email: ileonio@stanford.edu
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Jacksonville
      • Contact: Alberta Lalljie; Phone Number: 904-953-7648; Email: Lalljie.Albertha@mayo.edu
      • Principal Investigator: Ephraim Parent
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Shadi Abdar Esfahani
      • Contact: Jonathan Robert Kim; Email: jkim215@mgh.harvard.edu
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • BAMF Health
      • Principal Investigator: Brandon Mancini
      • Contact: Lisa Orange; Email: lisa.orange@bamfhealth.com
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic Rochester
      • Principal Investigator: Andrea Wahner Hendrickson
      • Contact: Lucas Hamann; Phone Number: 507-538-2155; Email: hamann.lucas@mayo.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Uni Of TX MD Anderson Cancer Cntr
      • Principal Investigator: Jordi Rodon
      • Contact: Denisse Harkins; Phone Number: 713-792-2921; Email: dvelazquez1@mdanderson.org
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington
      • Contact: Heather White; Email: hwhite@fredhutch.org
      • Principal Investigator: Amir Iravani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• (Dose escalation part only) 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 109/L, hemoglobin < 9 g/dL, or platelet count < 100 x 109/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-NNS309

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Patients will receive [68Ga]Ga-NNS309, and if eligible, [177Lu]Lu-NNS309	Drug: [68Ga]Ga-NNS309; Radioligand imaging agent; Drug: [177Lu]Lu-NNS309; Radioligand therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with dose limiting toxicities of [177Lu]Lu-NNS309	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 Grade 3 or higher.	From start of study treatment until 6 weeks or 4 weeks after, depending on dosing schedule
Incidence and severity of adverse events and serious adverse events of [177Lu]Lu-NNS309	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-NNS309	Dose modifications (dose interruptions and reductions) for [177Lu]Lu-NNS309 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-NNS309	Dose intensity for [177Lu]Lu-NNS309 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

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	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
Progression free survival (PFS)	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
Duration of Response (DOR)	DOR is the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines, or death due to any cause.	Up to approximately 42 months
Disease control rate (DCR)	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
Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID)	Urine elimination data for [177Lu]Lu-NNS309 will be assessed based on decay-corrected urine radioactivity concentration data. Urine elimination data will be expressed as percentage of injected dose (%ID).	Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.
Renal clearance of [177Lu]Lu-NNS309	Urine samples will be collected over specified time intervals and analyzed for radioactivity. Renal clearance of 177Lu-NNS309 will be summarized using descriptive statistics.	Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.
Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309	The distribution of adverse events will be done via the analysis of frequencies for TEAEs and TESAEs and through the monitoring of relevant clinical and laboratory safety parameters.	From Imaging visit until 3 days after 68Ga-NNS309 administration, assessed up to approximately 3 days.
Visual and quantitative assessment of [68Ga]Ga-NNS309 uptake in normal tissues and tumor lesions over time	After [68Ga]Ga-NNS309 administration, [68Ga]Ga-NNS309 PET/CT or PET/MRI will be performed. Standardized uptake values (SUVs) of [68Ga]Ga-NNS309 in normal tissues and tumor lesions over time will be summarized.	From 0 up to approximately 3 hrs after [68Ga]Ga-NNS309 dosing
Area Under the Curve (AUC) of [177Lu]Lu-NNS309	The [177Lu]Lu-NNS309 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.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Total body clearance of [177Lu]Lu-NNS309	The [177Lu]Lu-NNS309 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.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Observed maximum blood concentration (Cmax) of [177Lu]Lu-NNS309	The [177Lu]Lu-NNS309 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.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Observed maximum radioactivity concentration (Rmax) of [177Lu]Lu-NNS309	The [177Lu]Lu-NNS309 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Rmax will be determined by non-compartmental methods.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Volume of distribution (Vz) of [177Lu]Lu-NNS309 during the terminal phase	The [177Lu]Lu-NNS309 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.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Terminal elimination half-life (T1/2) of [177Lu]Lu-NNS309	The [177Lu]Lu-NNS309 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.	Samples collected pre infusion to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.
Absorbed dose of [177Lu]Lu-NNS309	Time activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%ID/g) as a function of time.	Samples collected 5 hours to 360 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2024
• Primary Completion (Estimated): January 15, 2031
• Study Completion (Estimated): January 16, 2031

Study Registration Dates

• First Submitted: August 16, 2024
• First Submitted That Met QC Criteria: August 16, 2024
• First Posted (Actual): August 20, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer; breast cancer; non-small cell lung cancer; pancreatic ductal adenocarcinoma; radioligand therapy (RLT); [177Lu]Lu-NNS309; [68Ga]Ga-NNS309
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms
• Other Study ID Numbers: CFXX489A12101; 2023-510356-23 (Other Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No