Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors

A Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-DFC413 and Safety and Imaging Properties of [68Ga]Ga-NNS309 in Patients With Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [177Lu]Lu-DFC413 and safety and imaging properties of [68Ga]Ga-NNS309 in patients aged ≥ 18 years with solid tumors

Study Overview

• Status: Recruiting
• Conditions: Soft Tissue Sarcoma; Colorectal Cancer; Non-Small Cell Lung Cancer; Triple Negative Breast Cancer; Pancreatic Ductal Adenocarcinoma; HR+/HER2- Ductal and Lobular Breast Cancer
• Intervention / Treatment: Drug: 68Ga-NNS309; Drug: 177Lu-DFC413

Detailed Description

GCJ904A12101 is first-in-human (FIH), phase I, open label study that consists of a dose escalation part followed by a dose expansion part. In both parts of the study, patients will initially be imaged with a 68Ga-NNS309 positron emission tomography (PET)/ computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan and will be evaluated for eligibility for 177Lu-DFC413 treatment. Patients eligible for treatment will receive 177Lu-DFC413. In the escalation part, different doses of 177Lu-DFC413 will be tested to assess its safety, tolerability, and dosimetry and identify the recommended radioactive administered dose(s) (RD(s)) for further evaluation. The expansion will include arms based on tumor type. 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 long-term follow-up period.

• Study Type: Interventional
• Enrollment (Estimated): 180
• 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

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Novartis Investigative Site
• Denmark
  • Odense C, Denmark, 5000
    • Recruiting
    • Novartis Investigative Site
• France
  • Vandœuvre-lès-Nancy, France, 54511
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Novartis Investigative Site
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Novartis Investigative Site
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adults ≥ 18 years with one of the following indications:
• Locally advanced unresectable or metastatic PDAC, with disease progression following, or intolerance to cytotoxic therapy, 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 chemotherapy and targeted therapy, unless patient was ineligible to receive such therapy
• Locally advanced unresectable or metastatic HR+/HER2- ductal and lobular breast cancer with disease progression following, or intolerance to, hormone therapy and CDK inhibitor, and at least one additional line of therapy, unless patient was ineligible to receive such therapy
• Locally advanced unresectable or metastatic triple negative breast cancer (TNBC) with disease progression following, or intolerance to, at least two 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
• (Dose expansion only) Locally advanced unresectable or metastatic soft tissue sarcoma (excluding GIST and Kaposi) with disease progression following, or intolerance to, at least one line of systemic 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
• eGFR < 60 mL/min, calculated using CKD-EPI 2021 or measured
• Unmanageable urinary tract obstruction or urinary incontinence
• Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy
• Any prior radioligand therapy
• Radiation therapy within 4 weeks prior to the first dose of [177Lu]Lu-DFC413

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-NNS309 and only patients with tumor uptake will receive 177Lu-DFC413	Drug: 68Ga-NNS309; Diagnostic investigational radiopharmaceutical; Drug: 177Lu-DFC413; Therapeutic investigational radiopharmaceutical

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of dose limiting toxicities of 177Lu-DFC413	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.	Within first treatment cycle, up to maximum 6 weeks
Incidence and severity of adverse events and serious adverse events of 177Lu-DFC413	The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) and through the monitoring of relevant clinical and laboratory safety parameters.	From study treatment start up to approximately 42 months
Dose modifications for 177Lu-DFC413	Dose modifications (dose interruptions and reductions) for 177Lu-DFC413 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.	From study treatment start until last dose of study treatment, assessed up to approximately 24 weeks
Dose intensity for 177Lu-DFC413	Dose intensity for 177Lu-DFC413 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 study treatment start 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.	From study treatment start up to 6 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.	From study treatment start up to 6 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.	From study treatment start up to 6 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.	From study treatment start up to 6 months
Area Under the Curve (AUC) of 177Lu-DFC413	The 177Lu-DFC413 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.	Up to 8 days after first dose
Total body clearance of 177Lu-DFC413	The 177Lu-DFC413 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.	Up to 8 days after first dose
Observed maximum blood concentration (Cmax) of 177Lu-DFC413	The 177Lu-DFC413 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.	Up to 8 days after first dose
Observed maximum radioactivity concentration (Rmax) of 177Lu-DFC413	The 177Lu-DFC413 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.	Up to 8 days after first dose
Volume of distribution (Vz) of 177Lu-DFC413 during the terminal phase	The 177Lu-DFC413 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.	Up to 8 days after first dose
Terminal elimination half-life (T1/2) of 177Lu-DFC413	The 177Lu-DFC413 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.	Up to 8 days after first dose
Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID)	Urine elimination data for 177Lu-DFC413 will be assessed based on decay-corrected urine radioactivity concentration data. Urine elimination data will be expressed as percentage of injected dose (%ID).	Up to 3 days after first dose
Renal clearance of 177Lu-DFC413	Urine samples will be collected over specified time intervals and analyzed for radioactivity. Renal clearance of 177Lu-DCF413 will be summarized using descriptive statistics.	Up to 3 days after first dose
Absorbed dose of 177Lu-DFC413	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.	Up to 8 days after first dose
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.	Up to 3 days after administration
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.	Up to 3 days after administration

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2025
• Primary Completion (Estimated): May 9, 2029
• Study Completion (Estimated): May 9, 2029

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): December 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Breast cancer; CRC; PDAC; STS; Radioligand therapy (RLT)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Neoplasms by Histologic Type; 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; Neoplasms, Connective and Soft Tissue; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Sarcoma; Triple Negative Breast Neoplasms
• Other Study ID Numbers: CGCJ904A12101; 2025-521702-18 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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 https://www.clinicalstudydatarequest.com/.

Drug and device information, study documents

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