A Phase I Study of [177Lu]Lu-FF58 in Patients With Advanced Solid Tumors.

NCT05977322 | Terminated Phase 1 FDA Drug

• 2 other identifiers: CAAA604A121012020-502367-37-00
• Study Type: interventional
• Target: 24
• Locations: 4 countries
• Sites: 5

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.

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

Outcome Measures

Primary Outcomes (4)

• Incidence and severity of dose limiting toxicities of 177Lu-FF58

  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.

  From start of study treatment until 6 weeks after

• Incidence and severity of adverse events and serious adverse events of 177Lu-FF58

  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.

  From start of study treatment until 180 days after the last dose of study treatment, assessed up to approximately 15 months

• Dose modifications for 177Lu-FF58

  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.

  From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks

• Dose intensity for 177Lu-FF58

  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.

  From start of study treatment until last dose of study treatment, assessed up to approximately 36 weeks

Secondary Outcomes (14)

• Overall response rate (ORR)

  From start of study treatment until date of progression, assessed up to approximately 34 months

• Duration of Response (DOR)

  From start of study treatment until date of progression, assessed up to approximately 34 months

• Disease control rate (DCR)

  From start of study treatment until date of progression, assessed up to approximately 34 months

• Progression free survival (PFS)

  From start of study treatment until date of progression, assessed up to approximately 34 months

• Area Under the Curve (AUC) from 177Lu-FF58 blood radioactivity data

  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.

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients will receive 68Ga-FF58 and only patients with tumor uptake of 68Ga-FF58 will receive 177Lu-FF58.

Drug: 68Ga-FF58; Drug: 177Lu-FF58

Interventions

68Ga-FF58 DRUG

Kit for radiopharmaceutical preparation of 68Ga- FF58 solution for injection

Arm 1

177Lu-FF58 DRUG

Solution for injection/infusion

Arm 1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Tel Aviv, 6423906, Israel

Location

Novartis Investigative Site

Nijmegen, 6500HB, Netherlands

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28034, Spain

Location

Novartis Investigative Site

Geneva, CH 1211, Switzerland

Location

Related Links

• CAAA604A12101 Clinical Trial Results
• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Glioblastoma; Pancreatic Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Adenocarcinoma Of Esophagus

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2023
• First Posted: August 4, 2023
• Study Start: October 6, 2023
• Primary Completion: December 13, 2024
• Study Completion: December 13, 2024
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); CH (1); IL (1); ES (2)