177Lu-FAP-2286 for Solid Cancers

(LuMIERE Trial)

Recruiting in Palo Alto (17 mi)

+8 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Clovis Oncology, Inc.

Must not be taking: Radiopharmaceuticals, Anticancer drugs

Disqualifiers: Active malignancy, CNS metastases, Cardiac diseases, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new drug, [177Lu]Lu FAP 2286, which targets a specific protein on cancer cells and delivers radiation to kill them. It focuses on patients with certain types of cancer that have this protein. The goal is to see if the drug is safe and effective.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the study team to ensure they don't interfere with the trial treatments.

What data supports the effectiveness of the treatment 177Lu-FAP-2286 for solid cancers?

Research shows that 177Lu-FAP-2286 was well tolerated in patients with advanced adenocarcinomas, with significant uptake and long retention in tumors, leading to high absorbed doses in cancerous areas. Additionally, a case study of a patient with recurrent bladder cancer showed radiological remission and symptom relief after treatment with 177Lu-FAP-2286, without adverse effects. ^{1 2 3 4 5}

Is 177Lu-FAP-2286 safe for use in humans?

177Lu-FAP-2286 has been tested in humans with various cancers and was generally well tolerated. Most patients did not experience severe side effects, although a few had moderate issues like low blood cell counts and pain flare-ups. Overall, it appears to be relatively safe, but more studies are needed to confirm this. ^{1 2 3 4 6}

What makes the drug 177Lu-FAP-2286 unique for treating solid cancers?

177Lu-FAP-2286 is unique because it targets the fibroblast activation protein (FAP), which is highly expressed in many tumors but not in normal tissues, allowing for precise targeting of cancer cells. This drug is a type of peptide-targeted radionuclide therapy (PTRT) that combines a FAP-binding peptide with a radioactive component, lutetium-177, to deliver radiation directly to the tumor, potentially reducing side effects compared to traditional therapies. ^{1 3 4 6 7}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced solid tumors that have worsened after treatment or don't respond to it. They should be in good physical condition, not pregnant, and willing to use contraception. People with active secondary cancers, brain metastases, recent cancer treatments or surgeries, ongoing serious side effects from past treatments (except hair loss), severe urinary issues, known allergies to scan contrast media, infections needing antibiotics recently, significant heart problems are excluded.

Inclusion Criteria

Have a life expectancy of ≥ 6 months

My cancer has returned or spread and this is confirmed by tests.

Have measurable disease per RECIST v1.1 meeting specific criteria

Exclusion Criteria

Inability to complete needed investigational and standard imaging examinations

I have heart problems that affect my daily activities.

I have lost a lot of weight recently.

Treatment Details

Interventions

• 177Lu-FAP-2286 (Radioisotope Therapy)

Trial Overview The study tests the safety and ideal dose of a new drug called 177Lu-FAP-2286 in Phase 1 and its effectiveness at shrinking tumors in Phase 2. Patients must have specific FAP-expressing tumor types for Phase 2. The response rate will be measured using standard criteria.

Participant Groups

Group I: Phase 2: Specific Solid Tumors Experimental Treatment 2 Interventions

Up to 192 participants treated with \[177Lu\]Lu-FAP-2286 in tumor-specific participant groups in monotherapy and in combination with chemotherapy.

Group II: Phase 1: Dose Escalation Experimental Treatment 2 Interventions

Up to 30 patients with solid tumors.

Who Is Running the Clinical Trial?

Clovis Oncology, Inc.

Lead Sponsor

Trials

65

Recruited

11,100+

Patrick J. Mahaffy

Clovis Oncology, Inc.

Chief Executive Officer since 2009

BA from Haverford College, MBA from Columbia University

Lindsey Rolfe

Clovis Oncology, Inc.

Chief Medical Officer since 2015

Specialist accreditation in pharmaceutical medicine

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

A 34-year-old man with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) showed stable disease after receiving multiple cycles of 177 Lu-FAPI-46 radionuclide therapy, indicating its potential efficacy in treating advanced cases.

The therapy demonstrated significant radiotracer uptake in metastatic lesions, suggesting that 177 Lu-FAPI-46 could be a promising option for patients with refractory cancers, although further research is needed to enhance the targeting vector.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177 Lu-FAPI-46. Fu, H., Huang, J., Sun, L., et al.[2023]

The novel radiopharmaceutical agent 177Lu-DOTA-DG was successfully synthesized with a high radiochemical yield and demonstrated excellent stability in human serum for up to 120 hours, indicating its potential for safe use in cancer imaging and therapy.

In preclinical studies, 177Lu-DOTA-DG caused significantly more DNA damage in cancer cells compared to untreated cells, suggesting its efficacy as a targeted treatment for cancer tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. Zhang, J., Wang, Z., Liu, H., et al.[2019]

References

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

177 Lu-FAP-2286 Therapy in a Case of Recurrent Bladder Cancer With Multiple Metastatic Lesions. [2023]

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

FAP-Targeted Radionuclide Therapy of Advanced Radioiodine-Refractory Differentiated Thyroid Cancer With Multiple Cycles of 177 Lu-FAPI-46. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Fibroblast activation protein targeted radiotherapy induces an immunogenic tumor microenvironment and enhances the efficacy of PD-1 immune checkpoint inhibition. [2023]

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

Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177Lu-FAP-2286: First-in-Humans Results. [2022]

5. Greece pubmed.ncbi.nlm.nih.gov

In vivo and in vitro evaluation of 177Lu-labeled DOTA-2-deoxy-D-glucose in mice. A novel radiopharmaceutical agent for cells imaging and therapy. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

First-In-Human Results on the Biodistribution, Pharmacokinetics, and Dosimetry of [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2. [2021]

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

Albumin Binder-Conjugated Fibroblast Activation Protein Inhibitor Radiopharmaceuticals for Cancer Therapy. [2023]