RECRUITING

A Study of 177Lu-FAP-2286 in Advanced Solid Tumors

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Conditions

Solid Tumor177Lu-FAP-228668Ga-FAP-2286TheranosticFAP-2286Fibroblast Activation Protein (FAP)Dosimetrycancer-associated fibroblasts (CAF)Peptide-Targeted Radioligand Therapy (PTRT)Peptide Receptor Radionuclide Therapy (PRRT)Targeted radioligand therapy (TRT)Targeted radionuclide therapyLutetium-177Gallium-68

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Fibroblast activation protein (FAP) is a cell surface protein that is highly expressed on the surface of cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers, whereas limited expression of FAP is observed in normal tissues. In some cancers of mesenchymal origin, notably sarcoma and mesothelioma, FAP expression has also been observed on the tumor cells themselves. Given the restricted expression profile, FAP is a promising target for peptide-targeted radionuclide imaging and therapeutic agents. Phase 1 of this study is designed to evaluate the safety and establish the recommended intravenous (IV) Phase 2 dose (RP2D) for \[177Lu\]Lu FAP 2286 monotherapy in participants with FAP expressing solid tumors. Phase 2 is designed to evaluate the safety and efficacy of \[177Lu\]Lu FAP 2286 as monotherapy in participants with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and breast cancer (BC) and in combination with chemotherapy in participants with untreated PDAC or relapsed NSCLC. Participants in both Phase 1 and 2 will be selected for treatment with \[177Lu\]Lu FAP 2286 based on \[68Ga\]Ga FAP 2286 imaging for determining tumor FAP expression.

Official Title

LuMIERE: A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FAP-2286 in Patients With an Advanced Solid Tumor

Quick Facts

Study Start:2021-07-30
Study Completion:2028-06-30
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04939610

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.
  2. 2. Be ≥ 18 years of age at the time the ICF is signed.
  3. 3. Have consented to submission of fresh or archival tumor tissue, if available.
  4. 4. Have adequate organ function confirmed by the following laboratory values obtained within the Screening Period prior to administration of \[68Ga\]Ga FAP 2286 and prior to first cycle of chemotherapy in the combination groups:
  5. 5. Have an Eastern Oncology Group (ECOG) performance status of 0 or 1.
  6. 6. Have a life expectancy of ≥ 6 months.
  7. 7. Have measurable disease per RECIST v1.1 meeting the following criteria:
  8. 1. At least 1 lesion of ≥ 10 mm in the longest diameter for a non lymph node or ≥ 15 mm in the short axis diameter for a lymph node that is serially measurable according to RECIST v1.1 using conventional CT and/or MRI.
  9. 8. Have a histologically and/or cytologically confirmed advanced/metastatic solid tumor not amenable to treatment with curative intent:
  10. 9. Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below:
  11. * Participants must have progressed on at least one line of hormone-based therapy (either alone or in combination) and at least one, but not more than two lines of chemotherapy (including cytotoxic, targeted and/or anti-drug conjugate therapies) for metastatic disease.
  12. * Participants must have progressed on at least two lines of cytotoxic chemotherapy (including cytotoxic, anti-drug conjugate, targeted therapies and/or IO) for metastatic disease.
  1. 1. Active malignancy except for the specific cancer under investigation in this study, ie, participant known to have potentially fatal cancer present for which he/she may be (but not necessarily) currently receiving treatment with the following exceptions:
  2. 1. History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment;
  3. 2. Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and
  4. 3. Prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen.
  5. 2. Symptomatic and/or untreated CNS metastases or leptomeningeal disease or with primary tumor of CNS origin.
  6. 3. Received anticancer treatment with chemotherapy, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs ≤ 14 days prior (≤ 28 days prior in case of checkpoint inhibitor therapy and other antibody therapies) to the administration of \[177Lu\]Lu FAP 2286.
  7. 4. Received prior radiopharmaceutical therapy (eg, radium 223 223Ra-dichloride, \[177Lu\]Lu-DOTA-TATE, \[177Lu\]Lu-prostate-specific membrane antigen (PSMA)-617, actinium 225 \[225Ac\]Ac PSMA-617, etc.) or prior EBRT to more than 25% of the bone marrow or received any prior EBRT directly to kidney, or received any EBRT within 2 weeks prior to administration of \[177Lu\]Lu FAP 2286.
  8. * Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed before injection/infusion of \[68Ga\]Ga-FAP-2286 or \[177Lu\]Lu FAP 2286.
  9. 5. Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.
  10. 1. Clinically significant and/or uncontrolled cardiac disease such as congestive heart failure requiring treatment (New York Heart Association \> Class 2), uncontrolled hypertension, clinically significant arrhythmia, or congenital prolonged QT syndrome;
  11. 2. Corrected QT interval (Fridericia's formula) \> 450 msec for males or \> 470 msec for females at Screening; or
  12. 3. Acute coronary syndrome or acute myocardial infarction ≤ 6 months prior to administration of \[177Lu\]Lu FAP 2286.
  13. 9. Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the investigator, could prevent adhering to radiation safety instructions.
  14. 10. Severe chronic or active HIV infection:
  15. 14. The following are exclusion criteria, as applicable:
  16. 15. Significant weight loss (\> 10% of body weight) within 28 days prior to providing informed consent for this study.
  17. 16. Presence of any other condition that may increase the risk associated with study participation or interfere with the interpretation of study results, and, in the opinion of the investigator, would make the participant inappropriate for entry into the study.
  18. 17. Inability to complete the needed investigational and standard imaging examinations due to any reason (e.g., severe claustrophobia, inability to lie still for the entire imaging time).
  19. 18. Participants with known hypersensitivity to the active agent or excipients. 19. Severe chronic or active infections (including active tuberculosis, HBV, or HCV infection) requiring systemic antibacterial, antifungal or antiviral therapy within 2 weeks before enrollment.

Contacts and Locations

Study Contact

Novartis Pharmaceuticals
CONTACT
1-888-689-6682
novartis.email@novartis.com
Novartis Pharmaceuticals
CONTACT
+41613241111
novartis.email@novartis.com

Principal Investigator

Novartis Pharmaceuticals
STUDY_DIRECTOR
Novartis Pharmaceuticals

Study Locations (Sites)

UAB Comprehensive Cancer Center
Birmingham, Alabama, 35233
United States
UCSF Medical Center
San Francisco, California, 94158
United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
United States
Mayo Clinic
Rochester, Minnesota, 55905
United States
Columbia University Medical Center
New York, New York, 10032
United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

  • Novartis Pharmaceuticals, STUDY_DIRECTOR, Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-07-30
Study Completion Date2028-06-30

Study Record Updates

Study Start Date2021-07-30
Study Completion Date2028-06-30

Terms related to this study

Keywords Provided by Researchers

  • 177Lu-FAP-2286
  • 68Ga-FAP-2286
  • Theranostic
  • FAP-2286
  • Fibroblast Activation Protein (FAP)
  • Dosimetry
  • cancer-associated fibroblasts (CAF)
  • Peptide-Targeted Radioligand Therapy (PTRT)
  • Peptide Receptor Radionuclide Therapy (PRRT)
  • Targeted radioligand therapy (TRT)
  • Targeted radionuclide therapy
  • Lutetium-177
  • Gallium-68

Additional Relevant MeSH Terms

  • Solid Tumor