FAPi Radioligand Therapy for Solid Cancers

(FRONTIER Trial)

No longer recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain solid tumors that over-express FAP, a protein present in many cancers. The trial tests the safety of two drugs, [Ga-68]-PNT6555 and [Lu-177]-PNT6555, which are part of a radioligand therapy, to determine the appropriate dose for future studies. Individuals with advanced or metastatic cancers, such as pancreatic, colorectal, or melanoma, that do not respond to standard treatments might be suitable candidates. Participants should have a life expectancy of at least six months and no brain metastases. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In earlier studies, [Ga-68]-PNT6555 cleared quickly from normal tissues but remained longer in tumors, suggesting easier handling by the body. The researchers are focusing on safety and tolerance, but more detailed information from human studies is needed since testing is in the early stages.

For [Lu-177]-PNT6555, research has shown it was well tolerated at different doses, meaning participants experienced few or manageable side effects at those levels.

Both treatments are in early testing stages. Researchers are still assessing their safety, but early results suggest they are promising and could be well-tolerated in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about [Ga-68]-PNT6555 and [Lu-177]-PNT6555 because these treatments introduce a novel approach to targeting solid cancers. Unlike traditional chemotherapy or radiation therapy, which can affect both healthy and cancerous cells, these treatments use radioligands that specifically target cancer cells expressing fibroblast activation protein (FAP). This targeted mechanism allows for a more precise attack on tumors, potentially reducing side effects and improving outcomes. Additionally, the use of the radioactive isotopes Ga-68 and Lu-177 enables both imaging and therapeutic capabilities, offering a dual approach to cancer management that is not commonly available in current treatments.

What evidence suggests that this trial's treatments could be effective for solid cancers?

Research has shown that [Ga-68]-PNT6555 and [Lu-177]-PNT6555 are promising treatments for certain solid tumors. In this trial, participants will receive one of these treatments, which target a protein called fibroblast activation protein (FAP) found in many cancerous tumors. Lab studies demonstrated that [Lu-177]-PNT6555 effectively shrinks tumors. Both treatments are designed to attach to tumors and remain there longer while exiting other parts of the body quickly. This approach focuses the treatment on cancer cells and reduces side effects. Early studies in humans have shown that these treatments are well-tolerated, offering hope for people with FAP-positive tumors. ^{2 4 5 6 7}

Who Is on the Research Team?

Jessica Jensen

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS3161

FRONTIER: FAPi radioligand open-label, phase 1 study to ... PNT6555, a potent FAP-targeting compound with rapid clearance from normal tissues and prolonged tumor retention in preclinical models.

2. jnm.snmjournals.org jnm.snmjournals.org/content/65/supplement_2/241162

FRONTIER: FAPi Radioligand OpeN-label, phase 1 study to ... Results: Twenty participants received [Ga-68]-PNT6555 and 18 meet study criteria for FAP-positivity. Ten met all eligibility criteria and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10199876/

Fibroblast activation protein-targeted radionuclide therapy Patients with FAP-avid disease on [68Ga]Ga-PNT6555 PET/CT will be eligible to receive up to 6 cycles of [177Lu]Lu-PNT6555. FAP tracers with albumin-binding ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05432193

NCT05432193 | FAPi Radioligand OpeN-Label, Phase 1 ... 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 ...

5. researchgate.net researchgate.net/publication/376104834_Preclinical_Development_of_PNT6555_a_Boronic_Acid-Based_Fibroblast_Activation_Protein-a_FAP-Targeted_Radiotheranostic_for_Imaging_and_Treatment_of_FAP-Positive_Tumors

Preclinical Development of PNT6555, a Boronic Acid ... Furthermore, the chelates [ 177 Lu]-PNT6555, PNT6952, and PNT6522 exhibited significant antitumor effects in FAP-positive tumor models, with [ 177 Lu]-PNT6555 ...

6. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-06840

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate ... 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 ...

7. mdpi.com mdpi.com/1424-8247/16/6/798

Pyrrolidin-2-yl-boronic Acid-Based PET Tracers for ... Akin to the control tracer [68Ga]Ga-PNT6555, [68Ga]Ga-SB04028 exhibited a minimal uptake in most normal organs/tissues, but demonstrated superior tumor/ ...