A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.
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ClinicalTrials.gov Identifier: NCT05977322 |
Recruitment Status :
Recruiting
First Posted : August 4, 2023
Last Update Posted : April 26, 2024
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Condition or disease | Intervention/treatment | Phase |
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Pancreatic Ductal Adenocarcinoma Gastroesophageal Adenocarcinoma Glioblastoma Multiforme | Drug: 68Ga-FF58 Drug: 177Lu-FF58 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 116 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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. |
Actual Study Start Date : | October 6, 2023 |
Estimated Primary Completion Date : | April 21, 2026 |
Estimated Study Completion Date : | April 21, 2026 |
Arm | Intervention/treatment |
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Experimental: Arm 1
Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.
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Drug: 68Ga-FF58
Kit for radiopharmaceutical preparation of 68Ga- FF58 solution for injection Drug: 177Lu-FF58 Solution for injection/infusion |
- Incidence and severity of dose limiting toxicities of 177Lu-FF58 [ Time Frame: From start of study treatment until 6 weeks after ]A dose limiting toxicity (DLT) is defined as any AE or abnormal laboratory value of CTCAE (v5.0) Grade 3 or higher that occurs within the DLT evaluation period (i.e., 6 weeks starting from the first administration of 177Lu-FF58) and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications.
- Incidence and severity of adverse events and serious adverse events of 177Lu-FF58 [ Time Frame: From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 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) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
- Dose modifications for 177Lu-FF58 [ Time Frame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks ]Dose modifications (dose interruptions and reductions) for 177Lu-FF58 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-FF58 [ Time Frame: From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks ]Dose intensity for 177Lu-FF58 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.
- Overall response rate (ORR) [ Time Frame: From start of study treatment until date of progression, assessed up to approximately 34 months ]ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI using FAS.
- Duration of Response (DOR) [ Time Frame: From start of study treatment until date of progression, assessed up to approximately 34 months ]DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause. Here, death due to any cause is considered as an event to be conservative and align with PFS event definition. DOR may be presented graphically if enough events are available for analysis, using Kaplan Meier plots for all patients who achieved a CR/PR in the study. The median DOR and corresponding 90% CI will be presented. Analysis will include responders with confirmed responses.
- Disease control rate (DCR) [ Time Frame: From start of study treatment until date of progression, assessed up to approximately 34 months ]DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients). It will be summarized along with the corresponding 90% exact CI, using FAS.
- Progression free survival (PFS) [ Time Frame: From start of study treatment until date of progression, assessed up to approximately 34 months ]PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines (non-GBM patients) or modified Response Assessment in Neuro- Oncology (mRANO) (GBM patients), or death due to any cause.
- Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data [ Time Frame: 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. ]Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity-based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. AUC from time zero to specified time point (mass x time x volume-1) will be listed and summarized using descriptive statistics.
- Total body clearance from 177Lu-FF58 blood radioactivity data [ Time Frame: 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. ]Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The total body clearance of drug from the plasma (volume x time-1) will be listed and summarized using descriptive statistics.
- Observed maximum plasma concentration (Cmax) from 177Lu-FF58 blood radioactivity data [ Time Frame: 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. ]Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Cmax will be listed and summarized using descriptive statistics.
- Volume of distribution during the terminal phase following intravenous elimination (Vz) from 177Lu-FF58 blood radioactivity data [ Time Frame: 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. ]Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. Vz will be listed and summarized using descriptive statistics.
- Terminal elimination half-life (T^1/2) from 177Lu-FF58 blood radioactivity data [ Time Frame: 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. ]Venous whole blood samples will be collected and analysed for radioactivity. Radioactivity based concentration units will be converted to mass-based concentration units using the specific activity of the dose at the time of manufacture (MBq/µg). Pharmacokinetics characterization will be performed on mass-based concentrations. The half-life will be listed and summarized using descriptive statistics.
- Urinary excretion of radioactivity expressed as a percentage of injected activity (%IA) [ Time Frame: 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. ]Urine samples will be collected over specified time intervals and analysed for radioactivity. The radioactivity excreted in each interval as a percentage of injected activity (%IA) will be listed and summarized using descriptive statistics.
- Time-activity curves (TACs) related to 177Lu-FF58 uptake in organs and tumor lesions [ Time Frame: 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. ]Time-activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%IA/g) as a function of time.
- Absorbed dose of 177Lu-FF58 [ Time Frame: 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. ]The absorbed dose in target organs will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
- Incidence and severity of adverse events and serious adverse events of 68Ga-FF58 [ Time Frame: From Imaging visit until 14 days after 68Ga-FF58 administration, or until first dose of study treatment ]The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
- 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 [ Time Frame: From Imaging until 1 hour (hr), 2 hr and 3 hr after 68Ga-FF58 administration ]After 68Ga-FF58 administration, 68Ga-FF58 PET/CT or PET/MRI will be performed. The statistical analyses of imaging properties of 68Ga-FF58 will be descriptive in nature and will include summaries and graphical presentations of data. No formal testing will be performed.
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05977322
Contact: Novartis Pharmaceuticals | 1-888-669-6682 | novartis.email@novartis.com | |
Contact: Novartis Pharmaceuticals | +41613241111 | novartis.email@novartis.com |
Israel | |
Novartis Investigative Site | Recruiting |
Tel Aviv, Israel, 6423906 | |
Netherlands | |
Novartis Investigative Site | Recruiting |
Nijmegen, Netherland, Netherlands, 6525 GA | |
Spain | |
Novartis Investigative Site | Recruiting |
Hospitalet de LLobregat, Catalunya, Spain, 08907 | |
Novartis Investigative Site | Recruiting |
Madrid, Spain, 28034 | |
Switzerland | |
Novartis Investigative Site | Recruiting |
Geneve 14, Switzerland, CH 1211 |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT05977322 |
Other Study ID Numbers: |
CAAA604A12101 2002-502367-37-00 ( Other Identifier: EU CTIS ) |
First Posted: | August 4, 2023 Key Record Dates |
Last Update Posted: | April 26, 2024 |
Last Verified: | April 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Adenocarcinoma Glioblastoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms |
Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue |