Clinical trial NCT05977322: A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.
Official title: A Phase I, Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry and Preliminary Activity of [177Lu]Lu-FF58 in Patients With Selected Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Pancreatic Ductal Adenocarcinoma
Gastroesophageal Adenocarcinoma
Glioblastoma Multiforme
Keywords: pancreatic ductal adenocarcinoma
PDAC
pancreatic cancer
gastroesophageal adenocarcinoma
GEA
gastric cancer
gastric adenocarcinoma
esophageal cancer
esophageal adenocarcinoma
glioblastoma multiforme
GBM
advanced solid tumors
radioligand therapy
RLT
[177Lu]Lu-FF58
[68Ga]Ga-FF58
integrins
alpha-v beta-3 integrin
αvβ3
alpha-v beta-5 integrin
αvβ5
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-04
Enrollment: 24
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 the study is to test the safety and dosing of \[177Lu\]Lu-FF58, a radioligand therapy for patients with advanced or metastatic tumors that express proteins known as integrins: alpha-v beta-3 integrin (αvβ3) and alpha-v beta-5 integrin (αvβ5). The study will also further characterize the radioligand imaging agent \[68Ga\]Ga-FF58 including its ability to identify tumor lesions and its safety profile.

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 be screened with a \[68Ga\]Ga-FF58 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan to assess eligibility for treatment with \[177Lu\]Lu-FF58. In the escalation part, different doses of \[177Lu\]Lu-FF58 will be tested to identify the recommended dose. The expansion part of the study will examine the safety and preliminary efficacy of \[177Lu\]Lu-FF58 at the recommended dose determined during the escalation part. The end of study will occur when at least 80% of the patients 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, or the study is terminated early in which case all patients would also be followed up for safety.

Eligibility criteria: Key Inclusion criteria

* Age \>= 18 years old
* Patients with locally advanced unresectable or metastatic PDAC, locally advanced unresectable or metastatic GEA, or recurrent GBM
* To be treated with \[177Lu\]Lu-FF58, patients must have at least one measurable lesion that shows \[68Ga\]Ga-FF58 uptake on PET/CT or PET/MRI

Key Exclusion criteria

* Absolute neutrophil count (ANC) \< 1.5 x 109/L, hemoglobin \< 10 g/dL, or platelet count \< 100 x 109/L
* Prior external beam radiation therapy (EBRT) to \> 25% of the bone marrow
* Creatinine clearance \< 60 mL/min
* Unmanageable bladder outflow obstruction or urinary incontinence
* Non-GBM patients: Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require local CNS-directed therapy (such as radiotherapy or surgery), or increasing doses of corticosteroids within 1 week before \[177Lu\]Lu-FF58 administration

Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence and severity of dose limiting toxicities of 177Lu-FF58
timeFrame: From start of study treatment until 6 weeks after
measure: Incidence and severity of adverse events and serious adverse events of 177Lu-FF58
timeFrame: From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months
measure: Dose modifications for 177Lu-FF58
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
measure: Dose intensity for 177Lu-FF58
timeFrame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: From start of study treatment until date of progression, assessed up to approximately 34 months
measure: Duration of Response (DOR)
timeFrame: From start of study treatment until date of progression, assessed up to approximately 34 months
measure: Disease control rate (DCR)
timeFrame: From start of study treatment until date of progression, assessed up to approximately 34 months
measure: Progression free survival (PFS)
timeFrame: From start of study treatment until date of progression, assessed up to approximately 34 months
measure: Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 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). Cycle=6 weeks or 3 weeks depending on schedule.
measure: Total body clearance from 177Lu-FF58 blood radioactivity data
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 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). Cycle=6 weeks or 3 weeks depending on schedule.
measure: Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 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). Cycle=6 weeks or 3 weeks depending on schedule.
measure: Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 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). Cycle=6 weeks or 3 weeks depending on schedule.
measure: Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data
timeFrame: Cycle 1 Day 1 (Pre-infusion, end of infusion, Post-dose (10 minutes(min), 30 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). Cycle=6 weeks or 3 weeks depending on schedule.
measure: Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA)
timeFrame: Cycle 1: Pre-infusion,beginning of infusion to first SPECT/CT image acquisition,first SPECT/CT image acquisition and 6 hours(hr) post-end-of infusion(EOI),6-24hr post-EOI,24-48hr post-EOI,48-72hr post-EOI. Cycle= 6 weeks or 3 weeks depending on schedule.
measure: Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions
timeFrame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.
measure: Absorbed dose of 177Lu-FF58
timeFrame: Cycle 1 Day 1, Cycle 1 Day 2 (24 hours (hr)), Cycle 1 Day 3 (48 hr), Cycle 1 Day 4 (72 hr), Cycle 1 Day 8 (168 hr). Cycle = 6 weeks or 3 weeks depending on schedule.
measure: Incidence and severity of adverse events and serious adverse events of 68Ga-FF58
timeFrame: From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment
measure: Imaging properties: Visual and quantitative assessment (expressed as SUV) and tumor-to-background ratio (TBR) of 68Ga-FF58 uptake in organs and tumor lesions over time
timeFrame: From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration
Other outcomes:
Locations:
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Geneve 14
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: