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)

Sponsor

POINT Biopharma (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05432193

Collaborator

(none)

Enrollment

Location

Arm

52.6

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

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
Pancreatic Ductal Adenocarcinoma Colorectal Cancer Esophageal Cancer Melanoma (Skin) Soft Tissue Sarcoma	Drug: [Ga-68]-PNT6555 Drug: [Lu-177]-PNT6555	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 13, 2022

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

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

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female patients 18 - 80 years of age
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)
Colorectal Cancer
Melanoma Skin Cancer

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 8.5g/dL
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

Glomerular filtration rate defined as creatinine clearance >70 ml/min/1.73 m2 OR Serum Creatinine <1.5 x ULN.
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
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
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 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)
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.)