Clinical trial NCT06562192: Phase I Study of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers
Official title: Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-08-20
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).

Detailed description: The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a \[68Ga\]Ga-NNS309 positron emission tomography (PET)/ computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan and will be evaluated for eligibility for \[177Lu\]Lu-NNS309 treatment. In the escalation part, different doses of \[177Lu\]Lu-NNS309 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of \[177Lu\]Lu-NNS309 at the RD(s) determined during the escalation part. 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 36-month long-term follow-up period.

Eligibility criteria: Inclusion Criteria:

* 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

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
* 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

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number of patients with dose limiting toxicities of [177Lu]Lu-NNS309
timeFrame: From start of study treatment until 6 weeks or 4 weeks after, depending on dosing schedule
measure: Incidence and severity of adverse events and serious adverse events of [177Lu]Lu-NNS309
timeFrame: From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months
measure: Dose modifications for [177Lu]Lu-NNS309
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
measure: Dose intensity for [177Lu]Lu-NNS309
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to approximately 42 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 42 months
measure: Disease control rate (DCR)
timeFrame: Up to approximately 42 months
measure: Progression free survival (PFS)
timeFrame: Up to approximately 42 months
measure: Area Under the Curve (AUC) of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Total body clearance of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Observed maximum blood concentration (Cmax) of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Observed maximum radioactivity concentration (Rmax) of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Volume of distribution (Vz) of [177Lu]Lu-NNS309 during the terminal phase
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Terminal elimination half-life (T1/2) of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post dose (30 minutes (min), 1 hours (hr), 2hr, 4hr, 6hr, 12hr)), Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID)
timeFrame: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.
measure: Renal clearance of [177Lu]Lu-NNS309
timeFrame: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.
measure: Absorbed dose of [177Lu]Lu-NNS309
timeFrame: Cycle 1 Day 1, Cycle 1 Day 2 (24hr), Cycle 1 Day 3 (48hr), Cycle 1 Day 4 (72hr), Cycle 1 Day 8 (168hr). The duration of a cycle is 4 weeks or 6 weeks.
measure: Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309
timeFrame: From Imaging visit until 3 days after 68Ga-NNS309 administration, assessed up to approximately 3 days.
measure: Visual and quantitative assessment of [68Ga]Ga-NNS309 uptake in normal tissues and tumor lesions over time
timeFrame: From 0 up to approximately 3 hrs after [68Ga]Ga-NNS309 dosing
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: BAMF Health
state: Michigan
city: Houston
country: United States
facility: Uni Of TX MD Anderson Cancer Cntr
state: Texas
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
Study officials:
References: