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

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.

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/1.73m2, 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.