search
Back to results

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)

Primary Purpose

Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, Esophageal Cancer

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
[Ga-68]-PNT6555
[Lu-177]-PNT6555
Sponsored by
POINT Biopharma
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Ductal Adenocarcinoma focused on measuring radioligand therapy, FRONTIER, PNT6555, 177Lu-FAP, 68Ga-FAP, PDAC, CRC, Melanoma, STS, Esophageal cancer, fibroblast activation protein, FAP, FAPi, Lu-177, GA-68, HNSCC, Cholangiocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Male and female patients 18 - 80 years of age
  2. 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.
  3. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
  4. The patient has read, understood, and signed the written informed consent form(s)
  5. 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:

    • Adenocarcinoma of the Pancreas
    • High grade Soft Tissue Sarcoma (excluding Chordoma)
    • Esophageal Cancer (Squamous Cell Carcinoma or Adenocarcinoma, excluding Gastroesophageal Junction Cancer)
    • Colorectal Cancer
    • Melanoma Skin Cancer
  6. Laboratory values at initial screening and also within three days prior to dosing of [Lu-177]-PNT6555:

    1. Platelets greater than 120,000/ mm^3 at dosing. Transfusions allowed, but not for first dose
    2. Neutrophils greater than 1500cells/mm^3
    3. Hemoglobin greater than 8.5g/dL
    4. Liver Chemistries:

    i. 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

  7. Glomerular filtration rate defined as creatinine clearance >70 ml/min/1.73 m2 OR Serum Creatinine <1.5 x ULN.
  8. Life expectancy of at least 6 months per investigator judgement
  9. Eastern Cooperative Oncology Group (ECOG) 0 to 1
  10. Patients must have previously received treatment for their underlying disease and have no potentially curative options available
  11. 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

  1. Patient has metastatic brain disease
  2. 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
  3. 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
  4. Subject has received prior hemi- or total- body radiation
  5. Subject has received whole brain radiation
  6. History of any grade 4 myelosuppression, or grade 3 myelosuppression requiring more than 6 weeks recovery
  7. History of any kidney dysfunction (e.g., acute kidney failure, acute tubular necrosis (ATN)) for any reason
  8. Secondary malignancy that may interfere with the safety assessments of this study
  9. 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
  10. Patient has received any other investigational agents within 4 weeks of starting the study treatment
  11. 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)
  12. Patient has undergone surgery within 4 weeks of starting the study treatment; exceptions are permitted with approval by Medical Monitor
  13. Previous radioligand therapy
  14. Previous Adoptive T-Cell Therapy (e.g. CAR-T therapy, TCR therapy, etc.)

Sites / Locations

  • Memorial Sloan Kettering Cancer CenterRecruiting
  • University Health Network - Princess Margaret Cancer CentreRecruiting
  • CHUM - Centre hospitalier de l'Université de MontréalRecruiting
  • Jewish General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dose escalation

Arm Description

Up to 30 patients with FAP-avid solid tumors.

Outcomes

Primary Outcome Measures

Treatment emergent adverse events
Occurrence of Treatment emergent adverse events as per CTCAE v5.0

Secondary Outcome Measures

Adverse events for [Ga-68]-PNT6555
Occurrence of adverse events for [Ga-68]-PNT6555 as per CTCAE v5.0
Biodistribution and radiation dosimetry of [Lu-177]-PNT6555 to normal organs.
Absorbed dose estimates (Gy) in normal organs for [Lu-177]-PNT6555
Biodistribution and radiation dosimetry of [Ga-68]-PNT6555 to normal organs.
Absorbed dose estimates (Gy) in normal organs for [Ga-68]-PNT6555
Detection of [Ga-68]-PNT6555 in tumor lesions
Anatomic distribution of [Ga-68]-PNT6555
Uptake of [Ga-68]-PNT6555 in tumor lesions
Maximum and average standardized uptake values of [Ga-68]-PNT6555 in tumor lesions

Full Information

First Posted
June 8, 2022
Last Updated
August 24, 2023
Sponsor
POINT Biopharma
search

1. Study Identification

Unique Protocol Identification Number
NCT05432193
Brief Title
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)
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 13, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
POINT Biopharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, Esophageal Cancer, Melanoma (Skin), Soft Tissue Sarcoma, Head and Neck Squamous Cell Carcinoma, Cholangiocarcinoma
Keywords
radioligand therapy, FRONTIER, PNT6555, 177Lu-FAP, 68Ga-FAP, PDAC, CRC, Melanoma, STS, Esophageal cancer, fibroblast activation protein, FAP, FAPi, Lu-177, GA-68, HNSCC, Cholangiocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dose escalation
Arm Type
Experimental
Arm Description
Up to 30 patients with FAP-avid solid tumors.
Intervention Type
Drug
Intervention Name(s)
[Ga-68]-PNT6555
Intervention Description
[Ga-68]-PNT6555 IV administered as imaging agent for PET/CT
Intervention Type
Drug
Intervention Name(s)
[Lu-177]-PNT6555
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment emergent adverse events
Description
Occurrence of Treatment emergent adverse events as per CTCAE v5.0
Time Frame
From first dose of study drug through end of treatment (~24 weeks)
Secondary Outcome Measure Information:
Title
Adverse events for [Ga-68]-PNT6555
Description
Occurrence of adverse events for [Ga-68]-PNT6555 as per CTCAE v5.0
Time Frame
From first dose of imaging study drug through 7 days post dose
Title
Biodistribution and radiation dosimetry of [Lu-177]-PNT6555 to normal organs.
Description
Absorbed dose estimates (Gy) in normal organs for [Lu-177]-PNT6555
Time Frame
From first dose of study drug through end of treatment (~24 weeks)
Title
Biodistribution and radiation dosimetry of [Ga-68]-PNT6555 to normal organs.
Description
Absorbed dose estimates (Gy) in normal organs for [Ga-68]-PNT6555
Time Frame
From first dose of imaging study drug through 7 days post dose
Title
Detection of [Ga-68]-PNT6555 in tumor lesions
Description
Anatomic distribution of [Ga-68]-PNT6555
Time Frame
From first dose of imaging study drug through 7 days post dose
Title
Uptake of [Ga-68]-PNT6555 in tumor lesions
Description
Maximum and average standardized uptake values of [Ga-68]-PNT6555 in tumor lesions
Time Frame
From first dose of imaging study drug through 7 days post dose
Other Pre-specified Outcome Measures:
Title
Preliminary efficacy of [Lu-177]-PNT6555 based on tumor response.
Description
Objective response rate (ORR) based on RECIST 1.1
Time Frame
From first dose of study drug until disease progression (up to approximately 3 years)
Title
Preliminary efficacy of [Lu-177]-PNT6555 based on change in biomarkers.
Description
CA 19-9, CEA
Time Frame
From first dose of study drug through end of treatment (~24 weeks)
Title
Tumor immune response to administration of [Lu-177]-PNT6555.
Description
Circulating immune cell changes
Time Frame
From first dose of study drug through end of treatment (~24 weeks)
Title
Radiation dosimetry of [Lu-177]-PNT6555 to tumor lesions.
Description
Absorbed dose estimates (Gy) in tumor lesions for [Lu-177]-PNT6555
Time Frame
From first dose of study drug through end of treatment (~24 weeks)
Title
Uptake of the [Ga-68]-PNT6555 imaging agent and optimal scanning specifications for future studies
Description
[Ga-68]-PNT6555 SUV at 0 - 60, 60, 90, and 120 min of tumor lesions and normal organs
Time Frame
From first dose of imaging study drug through two hours post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult (>18 years) male and female patients 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. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations The patient has read, understood, and signed the written informed consent form(s) 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: Adenocarcinoma of the Pancreas High grade Soft Tissue Sarcoma (excluding Chordoma) Esophageal Cancer (Squamous Cell Carcinoma or Adenocarcinoma, excluding Gastroesophageal Junction Cancer at US sites only) Colorectal Cancer Melanoma Skin Cancer Head and Neck Squamous Cell Carcinoma (oral cavity, oropharynx, hypopharynx, nasopharynx, and larynx) (only at Canadian sites) Cholangiocarcinoma (only at Canadian sites) Laboratory values at initial screening and also within three days prior to dosing of [Lu-177]-PNT6555: Platelets greater than 120,000/ mm^3 at dosing. Transfusions allowed, but not for first dose Neutrophils greater than 1500cells/mm^3 Hemoglobin: Greater than 8.0 g/dL (only in Canada) Greater than 8.5 g/dL (only in US) Liver Chemistries: ALT and AST < 2.5 x ULN or < 5 x ULN for patients with liver metastases Bilirubin < 2 mg/dL (<34.2 µmol/L); patients with Gilbert's syndrome are permitted if bilirubin is < 3 mg/dL (< 51.3 µmol/L) (only in Canada). Total Bilirubin ≤ 1.5 x upper limit of normal (ULN); Total bilirubin ≤ 3 ULN is acceptable if a patient has Gilbert's provided that direct bilirubin ≤ 1.5 ULN (only in US) Normal PT(secs) and aPTT(sec); normal INR (ratio). Patients taking anticoagulants must be in therapeutic range Glomerular filtration rate defined as creatinine clearance >60 ml/min/1.73 m2 based on Cockcroft-Gault formula Life expectancy of at least 6 months per investigator judgement Eastern Cooperative Oncology Group (ECOG) 0 to 1 Patients must have previously received treatment for their underlying disease and have no potentially curative options available 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 Patient has metastatic brain disease 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 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 Subject has received prior hemi- or total- body radiation Subject has received whole brain radiation History of any grade 4 myelosuppression, or grade 3 myelosuppression requiring more than 6 weeks recovery History of any kidney dysfunction (e.g., acute kidney failure, acute tubular necrosis (ATN)) for any reason (only in US) Secondary malignancy that may interfere with the safety assessments of this study 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 a. Or the patient has persistent NCI-CTCAE version 5.0 Grade ≥ 2 toxicity due to prior cancer therapy. Permitted exceptions include Grade 2 neuropathy, alopecia, endocrinopathy with replacement therapy, and anemia (only in US) Patient has received any other investigational agents within 4 weeks of starting the study treatment Patient has received systemic anti-cancer therapy: Within 4 weeks or 5 half-lives, whichever is shorter 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) (only in Canada) 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) (only in US) Patient has undergone surgery within 4 weeks of starting the study treatment; exceptions are permitted with approval by Medical Monitor Previous radioligand therapy Previous Adoptive T-Cell Therapy (e.g. CAR-T therapy, TCR therapy, etc.) Prolonged QT, defined as QTc > 470 ms regardless of sex (only in US) In patients who have received prior EBRT, each case should be reviewed by the site Investigators to determine appropriateness of eligibility given potential increased risk for radiation toxicities. In patients who have received a prior course of radiation therapy adjacent to either kidney, the mean kidney dose from EBRT must be available to inform potential risk, otherwise the patient will be ineligible. Patients who have previously exceeded dose limits for critical organs from prior EBRT are ineligible (only in US)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Richard Cioci
Phone
+1-833-544-2637
Ext
202
Email
rcioci@pointbiopharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica Jensen
Organizational Affiliation
POINT Biopharma
Official's Role
Study Director
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
University Health Network - Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Name
CHUM - Centre hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 3E4
Country
Canada
Individual Site Status
Recruiting
Facility Name
Jewish General Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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)

We'll reach out to this number within 24 hrs