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
Overview
- Phase
- Phase 1
- Intervention
- 177Lu-DFC413
- Conditions
- Not specified
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 180
- Locations
- 7
- Primary Endpoint
- Incidence and severity of dose limiting toxicities of 177Lu-DFC413
- Status
- Recruiting
- Last Updated
- 4 days ago
Overview
Brief Summary
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
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.
Investigators
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.
Arms & Interventions
Arm 1
Patients will receive 68Ga-NNS309 and only patients with tumor uptake will receive 177Lu-DFC413
Intervention: 177Lu-DFC413
Arm 1
Patients will receive 68Ga-NNS309 and only patients with tumor uptake will receive 177Lu-DFC413
Intervention: 68Ga-NNS309
Outcomes
Primary Outcomes
Incidence and severity of dose limiting toxicities of 177Lu-DFC413
Time Frame: Within first treatment cycle, up to maximum 6 weeks
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.
Incidence and severity of adverse events and serious adverse events of 177Lu-DFC413
Time Frame: From study treatment start up to approximately 42 months
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.
Dose modifications for 177Lu-DFC413
Time Frame: From study treatment start until last dose of study treatment, assessed up to approximately 24 weeks
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.
Dose intensity for 177Lu-DFC413
Time Frame: From study treatment start until last dose of study treatment, assessed up to approximately 24 weeks
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.
Secondary Outcomes
- Overall response rate (ORR)(From study treatment start up to 6 months)
- Duration of Response (DOR)(From study treatment start up to 6 months)
- Disease control rate (DCR)(From study treatment start up to 6 months)
- Observed maximum blood concentration (Cmax) of 177Lu-DFC413(Up to 8 days after first dose)
- Progression free survival (PFS)(From study treatment start up to 6 months)
- Area Under the Curve (AUC) of 177Lu-DFC413(Up to 8 days after first dose)
- Total body clearance of 177Lu-DFC413(Up to 8 days after first dose)
- Observed maximum radioactivity concentration (Rmax) of 177Lu-DFC413(Up to 8 days after first dose)
- Volume of distribution (Vz) of 177Lu-DFC413 during the terminal phase(Up to 8 days after first dose)
- Absorbed dose of 177Lu-DFC413(Up to 8 days after first dose)
- Terminal elimination half-life (T1/2) of 177Lu-DFC413(Up to 8 days after first dose)
- Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID)(Up to 3 days after first dose)
- Renal clearance of 177Lu-DFC413(Up to 3 days after first dose)
- Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309(Up to 3 days after administration)
- Visual and quantitative assessment of [68Ga]Ga-NNS309 uptake in normal tissues and tumor lesions over time(Up to 3 days after administration)