FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)
Study Details
Study Description
Brief Summary
This Phase 1 study will evaluate the safety and tolerability of [Ga-68]-PNT6555 and [Lu-177]-PNT6555 in subjects with select solid tumors that have FAP over-expression, in order to determine a recommended Phase 2 dose.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Dose escalation Up to 30 patients with FAP-avid solid tumors. |
Drug: [Ga-68]-PNT6555
[Ga-68]-PNT6555 IV administered as imaging agent for PET/CT
Drug: [Lu-177]-PNT6555
Patients with FAP-avid disease as determined by the [Ga-68]-PNT6555 screening PET/CT will receive [Lu-177]-PNT6555 at a fixed dose level for up to 6 doses at an interval of 6 weeks between each dose.
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Outcome Measures
Primary Outcome Measures
- Treatment emergent adverse events [From first dose of study drug through end of treatment (~24 weeks)]
Occurrence of Treatment emergent adverse events as per CTCAE v5.0
Secondary Outcome Measures
- Adverse events for [Ga-68]-PNT6555 [From first dose of imaging study drug through 7 days post dose]
Occurrence of adverse events for [Ga-68]-PNT6555 as per CTCAE v5.0
- Biodistribution and radiation dosimetry of [Lu-177]-PNT6555 to normal organs. [From first dose of study drug through end of treatment (~24 weeks)]
Absorbed dose estimates (Gy) in normal organs for [Lu-177]-PNT6555
- Biodistribution and radiation dosimetry of [Ga-68]-PNT6555 to normal organs. [From first dose of imaging study drug through 7 days post dose]
Absorbed dose estimates (Gy) in normal organs for [Ga-68]-PNT6555
- Detection of [Ga-68]-PNT6555 in tumor lesions [From first dose of imaging study drug through 7 days post dose]
Anatomic distribution of [Ga-68]-PNT6555
- Uptake of [Ga-68]-PNT6555 in tumor lesions [From first dose of imaging study drug through 7 days post dose]
Maximum and average standardized uptake values of [Ga-68]-PNT6555 in tumor lesions
Other Outcome Measures
- Preliminary efficacy of [Lu-177]-PNT6555 based on tumor response. [From first dose of study drug until disease progression (up to approximately 3 years)]
Objective response rate (ORR) based on RECIST 1.1
- Preliminary efficacy of [Lu-177]-PNT6555 based on change in biomarkers. [From first dose of study drug through end of treatment (~24 weeks)]
CA 19-9, CEA
- Tumor immune response to administration of [Lu-177]-PNT6555. [From first dose of study drug through end of treatment (~24 weeks)]
Circulating T cell changes: CD8 and CD4, PD-1, and Ki67
- Radiation dosimetry of [Lu-177]-PNT6555 to tumor lesions. [From first dose of study drug through end of treatment (~24 weeks)]
Absorbed dose estimates (Gy) in tumor lesions for [Lu-177]-PNT6555
- Uptake of the [Ga-68]-PNT6555 imaging agent and optimal scanning specifications for future studies [From first dose of imaging study drug through two hours post dose]
[Ga-68]-PNT6555 SUV at 60, 90, and 120 min of tumor lesions and normal organs
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male and female patients 18 - 80 years of age
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Females of childbearing potential and males and their female partner(s) of childbearing potential must use two acceptable forms of contraception, one being a barrier method, during the study and also for 31 weeks (females) or 18 weeks (males) after last study drug administration.
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Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
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The patient has read, understood, and signed the written informed consent form(s)
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Advanced or metastatic solid tumor that is refractory to standard treatment, for which no standard treatment is available, or it is contraindicated, or the patient refuses standard therapy:
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Adenocarcinoma of the Pancreas
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High grade Soft Tissue Sarcoma (excluding Chordoma)
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Esophageal Cancer (Squamous Cell Carcinoma or Adenocarcinoma, excluding Gastroesophageal Junction Cancer)
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Colorectal Cancer
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Melanoma Skin Cancer
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Laboratory values at initial screening and also within three days prior to dosing of [Lu-177]-PNT6555:
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Platelets greater than 120,000/ mm^3 at dosing. Transfusions allowed, but not for first dose
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Neutrophils greater than 1500cells/mm^3
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Hemoglobin greater than 8.5g/dL
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Liver Chemistries:
- ALT and AST < 2.5 x ULN or < 5 x ULN for patients with liver metastases ii. Bilirubin < 2 mcg/Liter; patients with Gilbert's syndrome are permitted e. Normal PT(secs) and aPTT(sec); normal INR (ratio). Patients taking anticoagulants must be in therapeutic range
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Glomerular filtration rate defined as creatinine clearance >70 ml/min/1.73 m2 OR Serum Creatinine <1.5 x ULN.
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Life expectancy of at least 6 months per investigator judgement
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Eastern Cooperative Oncology Group (ECOG) 0 to 1
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Patients must have previously received treatment for their underlying disease and have no potentially curative options available
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Positive [Ga-68]-PNT6555 PET/CT scan, defined as at least 50% of lesions with an SUVmax of 1.5 times or greater the SUVmean of the liver
Exclusion criteria
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Patient has metastatic brain disease
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Women who are pregnant, lactating, or planning to attempt to become pregnant during the study or within 31 weeks after last administration of study drug
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Males with female partners who are pregnant, lactating or planning to attempt to become pregnant during this study or within 18 weeks after last administration of study drug
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Subject has received prior hemi- or total- body radiation
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Subject has received whole brain radiation
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History of any grade 4 myelosuppression, or grade 3 myelosuppression requiring more than 6 weeks recovery
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History of any kidney dysfunction (e.g., acute kidney failure, acute tubular necrosis (ATN)) for any reason
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Secondary malignancy that may interfere with the safety assessments of this study
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Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities
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Patient has received any other investigational agents within 4 weeks of starting the study treatment
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Patient has received systemic anti-cancer therapy within 4 weeks of starting the study treatment; hormone maintenance therapy may be permitted with approval by the medical monitor if the patient is on a stable dose (preferred duration of a stable dose will be 4 weeks)
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Patient has undergone surgery within 4 weeks of starting the study treatment; exceptions are permitted with approval by Medical Monitor
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Previous radioligand therapy
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Previous Adoptive T-Cell Therapy (e.g. CAR-T therapy, TCR therapy, etc.)
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | University Health Network - Princess Margaret Cancer Centre | Toronto | Ontario | Canada | M5G 2M9 |
Sponsors and Collaborators
- POINT Biopharma
Investigators
- Study Director: Jessica Jensen, POINT Biopharma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- PNT6555-01