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

NCT06562192 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CFXX489A121012023-510356-23
• Study Type: interventional
• Target: 162
• Locations: 10 countries
• Sites: 31

Brief Summary

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).

Conditions

Pancreatic Ductal Adenocarcinoma; Non-small Cell Lung Cancer; HR+/HER2- Ductal and Lobular Breast Cancer; Triple Negative Breast Cancer; Colorectal Cancer

Keywords

pancreatic ductal adenocarcinoma; non-small cell lung cancer; breast cancer; colorectal cancer; radioligand therapy (RLT); [177Lu]Lu-NNS309; [68Ga]Ga-NNS309

Outcome Measures

Primary Outcomes (4)

• 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 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-NNS309

  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.

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients will receive \[68Ga\]Ga-NNS309, and if eligible, \[177Lu\]Lu-NNS309

Drug: [68Ga]Ga-NNS309; Drug: [177Lu]Lu-NNS309

Interventions

[68Ga]Ga-NNS309 DRUG

Radioligand imaging agent

Arm 1

[177Lu]Lu-NNS309 DRUG

Radioligand therapy

Arm 1

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (31)

Uni of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

RECRUITING

University of California LA

Los Angeles, California, 90095, United States

RECRUITING

Stanford University Medical Center

Palo Alto, California, 94304, United States

RECRUITING

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

BAMF Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

BAMF Health

Grand Rapids, Michigan, 49503, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

RECRUITING

University Of Washington

Seattle, Washington, 98109, United States

RECRUITING

Novartis Investigative Site

Brussels, 1000, Belgium

RECRUITING

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Novartis Investigative Site

Toronto, Ontario, M5G 2N2, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Novartis Investigative Site

Bron, 69677, France

RECRUITING

Novartis Investigative Site

Villejuif, 94800, France

RECRUITING

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

München, 80377, Germany

RECRUITING

Novartis Investigative Site

Rostock, 18057, Germany

RECRUITING

Novartis Investigative Site

Tel Aviv, 6423906, Israel

RECRUITING

Novartis Investigative Site

Milan, MI, 20133, Italy

RECRUITING

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

RECRUITING

Novartis Investigative Site

Nijmegen, Gelderland, 6500HB, Netherlands

RECRUITING

Novartis Investigative Site

Utrecht, 3584 CX, Netherlands

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28009, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28040, Spain

RECRUITING

Novartis Investigative Site

Geneva, 1211, Switzerland

RECRUITING

Novartis Investigative Site

Lausanne, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms; Colorectal Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

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: August 16, 2024
• First Posted: August 20, 2024
• Study Start: October 15, 2024
• Primary Completion (Estimated): January 15, 2031
• Study Completion (Estimated): January 16, 2031
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (10); BE (1); DE (4); IL (1); FR (2); IT (2); NL (2); ES (3); CH (2); CA (4)