Targeted radioligand [177Lu]Lu-DFC413 for advanced pancreatic, lung, breast, and colorectal cancers

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

This will test a new targeted radioactive medicine, [177Lu]Lu-DFC413 (with a PET tracer [68Ga]Ga-NNS309), to see if it is safe and shows activity in adults with advanced pancreatic, lung, breast, or colorectal cancer.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 7 sites (Montreal, Quebec and 6 other locations)
• Trial ID: NCT07261631 on ClinicalTrials.gov

What this trial studies

This first-in-human, open-label Phase I trial uses a dose-escalation part followed by a dose-expansion part to identify recommended radioactive dose(s) and gather early activity signals. Eligible patients are imaged with [68Ga]Ga-NNS309 PET/CT or PET/MRI to confirm tumor targeting and to support dosimetry before treatment. In escalation, small cohorts receive increasing radioactive doses of [177Lu]Lu-DFC413 to determine safety, tolerability, and organ radiation exposure; the expansion enrolls disease-specific cohorts at the selected dose(s). Patients are followed for adverse events, preliminary anti-tumor activity, and long-term outcomes.

Who should consider this trial

Good fit: Adults (≥18) with locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma, non-small cell lung cancer, HR+/HER2- or triple-negative breast cancer, or colorectal cancer who have progressed on or are intolerant of standard therapies and can undergo PET imaging and radioligand treatment are the intended candidates.

Not a fit: Patients with early-stage resectable disease, poor organ function, pregnancy, active infection, or tumors that do not show uptake on the [68Ga]Ga-NNS309 PET scan are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this approach could offer a new targeted radioligand option that delivers radiation directly to tumors and may shrink lesions or slow disease while limiting exposure to healthy tissue.

How similar studies have performed: Other Lu-177 radioligand therapies (for example PSMA-targeted agents in prostate cancer and Lutathera for neuroendocrine tumors) have demonstrated clinical benefit, but [177Lu]Lu-DFC413 is a novel first-in-human agent and its effectiveness across these solid tumors remains unproven.

Eligibility criteria

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.

Where this trial is running

Montreal, Quebec and 6 other locations

• Novartis Investigative Site — Montreal, Quebec, Canada (Recruiting)
• Novartis Investigative Site — Odense C, Denmark (Recruiting)
• Novartis Investigative Site — Vandœuvre-lès-Nancy, France (Recruiting)
• Novartis Investigative Site — Essen, Germany (Recruiting)
• Novartis Investigative Site — Haifa, Israel (Recruiting)
• Novartis Investigative Site — Tel Aviv, Israel (Recruiting)
• Novartis Investigative Site — Singapore, Singapore (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Pancreatic Ductal Adenocarcinoma; Non-Small Cell Lung Cancer; HR+/HER2- Ductal and Lobular Breast Cancer; Triple Negative Breast Cancer; Colorectal Cancer; Soft Tissue Sarcoma; PDAC; NSCLC