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)

NCT05432193 | Terminated Phase 1 FDA Drug

• 1 other identifier: PNT6555-01
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 4

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Treatment emergent adverse events

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

  From first dose of study drug through end of treatment (~24 weeks)

Secondary Outcomes (5)

• Adverse events for [Ga-68]-PNT6555

  From first dose of imaging study drug through 7 days post dose

• Biodistribution and radiation dosimetry of [Lu-177]-PNT6555 to normal organs.

  From first dose of study drug through end of treatment (~24 weeks)

• Biodistribution and radiation dosimetry of [Ga-68]-PNT6555 to normal organs.

  From first dose of imaging study drug through 7 days post dose

• Detection of [Ga-68]-PNT6555 in tumor lesions

  From first dose of imaging study drug through 7 days post dose

• Uptake of [Ga-68]-PNT6555 in tumor lesions

  From first dose of imaging study drug through 7 days post dose

Other Outcomes (5)

• Preliminary efficacy of [Lu-177]-PNT6555 based on tumor response.

  From first dose of study drug until disease progression (up to approximately 3 years)

• Preliminary efficacy of [Lu-177]-PNT6555 based on change in biomarkers.

  From first dose of study drug through end of treatment (~24 weeks)

• Tumor immune response to administration of [Lu-177]-PNT6555.

  From first dose of study drug through end of treatment (~24 weeks)

Study Arms (1)

Dose escalation

EXPERIMENTAL

Up to 30 patients with FAP-avid solid tumors.

Drug: [Ga-68]-PNT6555; Drug: [Lu-177]-PNT6555

Interventions

[Ga-68]-PNT6555 DRUG

\[Ga-68\]-PNT6555 IV administered as imaging agent for PET/CT

Dose escalation

[Lu-177]-PNT6555 DRUG

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.

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company: lead

Study Sites (4)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University Health Network - Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Centre hospitalier de l'Université de Montréal

Montreal, Quebec, H2X 3E4, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Esophageal Neoplasms; Melanoma; Sarcoma; Squamous Cell Carcinoma of Head and Neck; Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma

Study Officials

• Jessica Jensen

  Eli Lilly and Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 27, 2022
• Study Start: July 13, 2022
• Primary Completion: November 10, 2023
• Study Completion: October 2, 2024
• Last Updated: June 25, 2025

Record last verified: 2025-06

Locations

US (1); CA (3)