FAPi Radioligand Therapy for Solid Cancers

(FRONTIER Trial)

Recruiting at 3 trial locations

Overseen By Richard Cioci

Age: 18+

Sex: Any

Trial Phase: Phase 1

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

Disqualifiers: Metastatic brain disease, Kidney dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on systemic anti-cancer therapy, you must stop it at least 4 weeks before starting the study treatment. Hormone maintenance therapy might be allowed if you are on a stable dose with approval from the medical monitor.

What data supports the effectiveness of the treatment [Ga-68]-PNT6555, [Lu-177]-PNT6555 for solid cancers?

Research shows that PNT6555, when used in a similar form, has shown significant antitumor activity and improved survival in preclinical studies for FAP-positive tumors, suggesting its potential effectiveness in treating solid cancers. ^{1 2 3 4 5}

Is FAPi Radioligand Therapy generally safe for humans?

FAPi Radioligand Therapy, including treatments like [Lu-177]-PNT6555, has shown to be well-tolerated in studies, with low rates of serious side effects. In clinical trials, patients experienced some manageable side effects, but overall, the treatment was considered safe for use in humans. ^{2 3 4 6 7}

How is the FAPi Radioligand Therapy for Solid Cancers unique compared to other treatments?

The FAPi Radioligand Therapy using [Ga-68]-PNT6555 and [Lu-177]-PNT6555 is unique because it targets fibroblast activation protein (FAP), which is overexpressed in many solid tumors, allowing for precise delivery of radiation to cancer cells. This approach improves tumor retention and selectivity, potentially leading to better outcomes and fewer side effects compared to traditional therapies. ^{2 3 4 8 9}

What is the purpose of this trial?

This trial is testing two new drugs on patients with specific solid tumors that have high levels of a protein called FAP. The goal is to see if these drugs are safe and to find the best dose for future studies. The drugs work by targeting the FAP protein on the cancer cells.

Research Team

Jessica Jensen

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

Adults with advanced solid tumors (like pancreatic, colorectal, or skin cancer) that resist standard treatments can join this trial. They must have a life expectancy of at least 6 months and be in fairly good health otherwise (ECOG 0-1). Participants need to use two forms of birth control and cannot be pregnant. Those with brain metastases, recent other cancer therapies, severe medical conditions, or certain blood disorders are excluded.

Inclusion Criteria

I am over 18 years old.

My advanced cancer has not responded to standard treatments or I cannot receive them.

I am willing and able to follow the study's treatment and visit schedule.

Exclusion Criteria

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 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)

I have lasting side effects from cancer treatment, but not severe nerve damage, hair loss, hormone issues treated with medication, or anemia (in the US).

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive [Lu-177]-PNT6555 for dose escalation to evaluate safety, tolerability, and dosimetry

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Preliminary efficacy of [Lu-177]-PNT6555 based on tumor response and biomarker changes

Up to approximately 3 years

Treatment Details

Interventions

• [Ga-68]-PNT6555
• [Lu-177]-PNT6555

Trial Overview [Ga-68]-PNT6555 and [Lu-177]-PNT6555 are being tested for safety and dosage in patients whose tumors over-express FAP. This early-phase study will help find the right dose for Phase 2 trials by gradually increasing amounts given to new groups of patients as safety is confirmed.

Participant Groups

Group I: Dose escalation Experimental Treatment 2 Interventions

Up to 30 patients with FAP-avid solid tumors.

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

5

Recruited

670+

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

POINT Biopharma

Lead Sponsor

Trials

6

Recruited

720+

Findings from Research

In a study involving 9 patients with advanced solid tumors, 90Y-FAPI-46 radioligand therapy was found to be well tolerated, with a low incidence of serious adverse events, indicating its safety for use in heavily pretreated patients.

The therapy demonstrated sufficient tumor uptake in 78% of patients and showed signs of tumor response in 50%, suggesting potential efficacy, although further research is needed to confirm these findings in larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Clinical Experience with 90Y-FAPI-46 Radioligand Therapy for Advanced-Stage Solid Tumors: A Case Series of 9 Patients. Ferdinandus, J., Costa, PF., Kessler, L., et al.[2022]

The FAPI tetramer demonstrated significantly higher tumor uptake and longer retention in cancerous tissues compared to FAPI dimers and monomers, indicating its potential for improved diagnostic and therapeutic applications in cancer treatment.

In radioligand therapy studies, the 177Lu-labeled FAPI tetramer showed remarkable tumor suppression in mice, suggesting its efficacy as a promising radiopharmaceutical for targeted cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy. Pang, Y., Zhao, L., Fang, J., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of 90Y-FAPI-46 Radioligand Therapy in Patients with Advanced Sarcoma and Other Cancer Entities. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Preclinical Development of PNT6555, a Boronic Acid-Based, Fibroblast Activation Protein-α (FAP)-Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Novel Generation of FAP Inhibitor-Based Homodimers for Improved Application in Radiotheranostics. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic potential of [177Lu]Lu-DOTAGA-FAPi dimers in metastatic breast cancer patients with limited treatment options: efficacy and safety assessment. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

The inferior performance of [68Ga]Ga-FAPI-04 PET/CT as a diagnostic and theranostic biomarker in [177Lu]Lu-DOTATATE refractory well-differentiated neuroendocrine tumors. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Initial Clinical Experience with 90Y-FAPI-46 Radioligand Therapy for Advanced-Stage Solid Tumors: A Case Series of 9 Patients. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluating the Combined Anticancer Response of Checkpoint Inhibitor Immunotherapy and FAP-Targeted Molecular Radiotherapy in Murine Models of Melanoma and Lung Cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Development of FAPI Tetramers to Improve Tumor Uptake and Efficacy of FAPI Radioligand Therapy. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

86Y-Labeled Albumin-Binding Fibroblast Activation Protein Inhibitor for Late-Time-Point Cancer Diagnosis. [2022]