Colorectal Cancer, Ewing Sarcoma, Gastric Cancer, Neuroendocrine Differentiated (NED) Prostate Cancer, NTSR1 Expressing Solid Tumours, Pancreatic Ductal Adenocarcinoma (PDAC), Squamous Cell Carcinoma of Head and Neck
Conditions
Keywords
Solid Tumor, FPI-2059, FPI-2058, Pancreas, Prostate, Neuroendocrine, Stomach cancer, Gastric, Ewing sarcoma, HNSCC, Squamous cell carcinoma, CRC, Colorectal, actinium, targeted alpha therapy, radiopharmaceuticals
Brief summary
This is a first-in-human Phase 1 clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and biodistribution of \[225Ac\]-FPI-2059 and \[111In\]-FPI-2058 in participants with neurotensin receptor 1 (NTSR1)-expressing solid tumours.
Detailed description
This is a first-in-human, Phase 1, non-randomized, multi-centre, open-label clinical trial designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics (PK) of \[225Ac\]-FPI-2059 and \[111In\]-FPI-2058, as well as the pharmacodynamics and preliminary anti-tumour activity of \[225Ac\]-FPI-2059 in participants with neurotensin receptor 1 (NTSR1)-expressing advanced, metastatic and/or recurrent solid tumours. The study will employ a 3+3 dose escalation design to identify the recommended phase 2 dose (RP2D) and regimen of \[225Ac\]-FPI-2059 administered intravenously every 56 days. After the RP2D for \[225Ac\]-FPI-2059 is determined, enrolment will continue into an expansion cohort, to confirm the safety and tolerability of the RP2D, as well as to identify any preliminary evidence of efficacy in selected NTSR1-expressing tumour types.
Interventions
DRUG[225]-FPI-2059
\[225Ac\]-FPI-2059 is a targeted alpha therapeutic that consists of an NTSR1-targeting small molecule that is linked to Ac-225, an alpha particle emitting radionuclide. Participants will be dosed through IV administration every 56 days up to four cycles. The dose depends on cohort assignment. In the Dose Expansion arm, \[225Ac\]-FPI-2059 will be administered at the RP2D as determined in Phase 1 Dose Escalation.
DRUG[111In]-FPI-2058
\[111In\]-FPI-2058 is an imaging agent that consists of an NTSR1-targeting small molecule linked to In-111.Participants will receive \[111In\]-FPI-2058 by IV Injection for imaging once during screening period. The dose is consistent across cohorts.
Sponsors
3B Pharmaceuticals GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Signed ICF prior to initiation of any study-specific procedures * Histologically and/or cytologically confirmed solid tumor that is metastatic or locally advanced, inoperable, or recurrent. Solid tumors indications may include PDAC, CRC, NED prostate cancer, gastric cancer, SCCHN, and Ewing sarcoma. * Disease that has progressed despite prior treatment, and for which additional effective standard therapy is not available or is contraindicated, not tolerable, or the patient refuses standard therapy * Measurable disease per RECIST v.1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Sufficient target expression in at least one measurable lesion as determined by imaging following injection of \[111In\]-FPI-2058 * Adequate organ function * Tumor tissue (either archival within the last 24 months or fresh biopsy) Key
Exclusion criteria
* Previous treatment with any radiopharmaceutical * Contraindications to or inability to perform the imaging procedures required in this study * Anti-cancer therapy, such as chemotherapy, immunotherapy, hormonal therapy, targeted therapy, or investigational agents within certain amount of time prior to administration of the first dose of \[111In\]-FPI-2058 * Radiation therapy (RT) within 28 days prior to the first dose of \[111In\]-FPI-2058 * Patients with known CNS metastatic disease * Concurrent severe and/or uncontrolled illness that would limit compliance with study requirements * Known or suspected allergies or contraindication to the investigational treatment * Received any type of vaccine within 30 days prior to the first dose of \[111In\]-FPI-2058
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Adverse Events to evaluate safety and tolerability of [225Ac]-FPI-2059 and [111In]-FPI-2058 | approximately 5 years post final administration |
| Maximum tolerated dose (MTD) of [225Ac]-FPI-2059 | 56 days post administration |
| Radiation dose of [111In]-FPI-2058 and [225Ac]-FPI-2059 to whole body, organs, and selected regions of interest | within 56 days of administration |
Secondary
| Measure | Time frame |
|---|---|
| Anti-tumor activity of [225Ac]-FPI-2059 regimen measured by response per RECIST v1.1 | approximately 5 years post final administration |
| Tumor uptake of [111In]-FPI-2058 by evaluating SPECT/CT and planar images | within 56 days of administration |
| Pharmacokinetics (PK) of [225Ac]-FPI-2059 and [111In]-FPI-2059 by measuring changes in clearance, AUC, Cmax, and half-life | approximately 36 days of final administration |
Countries
Australia, United States
Outcome results
None listed