Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Cancer, Mesothelioma, Ovarian Cancer, Pancreatic Ductal Adenocarcinoma, Sarcoma
Conditions
Keywords
Fibroblast Activation Protein, Solid tumor malignancy, Gastric cancer, Esophageal cancer, Colorectal cancer, Ovarian cancer, Head and neck cancer, Theronostic, Radiopharmaceutical, Radiotherapy, Alpha Particle, Pb-203, Pb-212
Brief summary
Phase I/IIa image-guided, alpha-particle therapy study of \[203Pb\]Pb-PSV359 and \[212Pb\]Pb-PSV359 in patients with solid tumors that are known to be Fibroblast Activation Protein (FAP)-positive.
Detailed description
This is a prospective, multi-center open label dose finding, dose expansion study of \[212Pb\]Pb-PSV359 in subjects with a positive Fibroblast Activation Protein (FAP) imaging scan with imaging agent. FAP is specifically expressed on the surface of cancer-associated fibroblasts in some tumor tissues and therefore is an attractive target in the diagnosis and treatment of various cancers. Lead-212 (\[212Pb\]Pb-) based peptide-radiopharmaceuticals are an emerging class of targeted alpha-particle cancer therapies that have potential to improve delivery of a highly effective form of radiation. This study will be conducted in 2 parts: Part 1: Dose-escalation: \[212Pb\]Pb-PSV359 is administered in escalating doses to determine the Maximum Tolerated radioactivity (MTD) Dose and potential recommended Phase 2 dose (RP2D). Part 2: Dose-expansion: This part will enroll subjects in expansion cohorts based on the identified MTD and RP2D for the selection of \[212Pb\]Pb-PSV359 doses for further clinical development. A Dosimetry sub-set utilizing an imaging surrogate, \[203Pb\]Pb-PSV359, has been incorporated into the study in order to assess organ biodistribution and tumor uptake of the investigational products. This sub study will also estimate radiation dosimetry and correlate uptake of the investigation products with observed toxicities and efficacy.
Interventions
DRUG[203Pb]Pb-PSV359
\[203Pb\]Pb-PSV359 is administered by intravenous bolus injection for single-photon emission computed tomography imaging.
DRUG[212Pb]Pb-PSV359
\[212Pb\]Pb-PSV359 is administered by intravenous infusion for treatment of FAP expressing cancers.
Sponsors
Perspective Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Aged ≥ 18 years * Satisfactory organ function as determined by laboratory testing * Eastern Cooperative Oncology Group performance (ECOG) status of 0 to 1 * Life expectancy \> 3 months * Progressive disease despite standard therapy or for whom no standard therapy exists * Positive \[203Pb\]Pb-PSV359 SPECT/CT scan showing uptake of \[203Pb\]Pb-PSV359 in at least 1 known lesion on the 1-hour SPECT/ CT scan * Histological, pathological, and/or cytological confirmation of solid tumor malignancy that is locally advanced or metastatic
Exclusion criteria
* Known hypersensitivity to the active agent or any of the excipients * Active secondary malignancy * Pregnancy or breastfeeding a child * Known brain metastases * Known active or uncontrolled infections requiring ongoing antifungals or antibiotics in the 3 days prior to enrollment * Known medical condition which would make this protocol unreasonably hazardous for the patient * Existence of any medical or social issues likely to interfere with study conductor that may cause increased risk to the subject or to others, e.g., lack of ability to follow radiation safety precautions * Medical history of a condition resulting in a severe allergic reaction such as anaphylaxis or angioedema to known components of the investigational product or excipients * Major surgery within 21 days prior to the administration of \[212Pb\]Pb-PSV359; the subject must be sufficiently recovered and stable before treatment administration * Diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to enrollment into the study * Current abuse of alcohol or illicit drugs * Treatment with any live/attenuated vaccine in the 7 days prior to enrollment * Previous treatment with any systemic anticancer therapy within 4 weeks prior to treatment on study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of safety and tolerability of [203Pb]Pb-PSV359 | 30 days (±1day) post dose | Incidence and severity of treatment-related adverse events following a single administration of \[203Pb\]Pb-PSV359 is determined |
| Determination of safety and tolerability of [212Pb]Pb-PSV359 | Up to 3 years | Incidence and severity of treatment-related adverse events following a single and each repeated administration of \[212Pb\]Pb-PSV359 is determined |
| To determine the recommended phase 2 dose of [212Pb]Pb-PSV359 | Up to approximately 6 months | The recommended phase 2 dose as determined by cohort observations and review by the Safety Monitoring Committee |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of duration of response following treatment with [212Pb]Pb-PSV359 | Up to 3 years | Median duration of response for subjects receiving at least 1 administration of \[212Pb\]Pb-PSV359 is assessed by RECIST V1.1 criteria |
| Determination of progression free survival following treatment with [212Pb]Pb-PSV359 | Up to 3 years | Progression free survival for subjects receiving at least 1 administration of \[212Pb\]Pb-PSV359 is assessed by RECIST V1.1 criteria |
| Determination of pharmacokinetic properties of [203Pb]Pb-PSV359 and [212Pb]Pb-PSV359 | Up to approximately 3 yrs | Blood radioactivity pharmacokinetic parameter such as area under the plasma concentration versus time curve (AUC) is determined. |
| Estimation of biodistribution of 203Pb PSV 359 using SPECT/CT scans | Up to approximately 3 years | Activity in tumor(s) and organs as percentage of injected dose is assessed |
Countries
United States
Contacts
CONTACTClinicalTrials at Perspectivetherapeutics
Outcome results
None listed