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

Recruiting now · Phase 1/Phase 2

Conditions studied: Solid Tumor

In brief

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.

Key facts

Study ID

NCT04939610

Run by

Novartis Pharmaceuticals

People needed

222

Starts

2021-07-30

Expected to finish

2028-06-30

Last updated by the study team

2026-07-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Eligible participants must meet the following inclusion criteria. The criteria below apply to participants enrolling in Phase 1 and Phase 2, unless otherwise specified.
• Have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved Informed Consent Form (ICF) prior to any study-specific evaluation.
• Be ≥ 18 years of age at the time the ICF is signed.
• Have consented to submission of fresh or archival tumor tissue, if available.
• 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:
• a. Bone Marrow Function (independent of transfusion or growth factor support within 21 days prior to planned first administration of [177Lu]Lu FAP 2286): i. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; ii. Platelets > 100 × 109/L; and iii.Hemoglobin ≥ 9 g/dL. b. Hepatic Function: i. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × institutional upper limit of normal (ULN); if liver metastases, then ≤ 5 × the institutional ULN; ii. Serum Bilirubin ≤ 1.5 × institutional ULN or if known Gilbert's syndrome then ≤ 3 × institutional ULN; iii. Serum albumin ≥ 30 g/L (3 g/dL) and iv. INR ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT)≤1.5 x ULN. This applies to participants who are not receiving therapeutic anticoagulation, participants receiving therapeutic anticoagulation should be on a stable dose.
• c. Renal Function: i. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min using the Cockcroft Gault formula.
• Have an Eastern Oncology Group (ECOG) performance status of 0 or 1.
• Have a life expectancy of ≥ 6 months.
• Have measurable disease per RECIST v1.1 meeting the following criteria:
• 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.
• Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation must show subsequent evidence of substantial size increase to be deemed a target lesion.
• For Phase 1 only:
• Have a histologically and/or cytologically confirmed advanced/metastatic solid tumor not amenable to treatment with curative intent:
• a. Tumor must be refractory to or have progressed following prior treatment and have no satisfactory alternative treatment options.
• For Phase 2 only:
• Have cytologically or histologically and radiologically confirmed recurrent or metastatic disease as outlined below:
• a. Pancreatic Cancer monotherapy group: i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded) ii. Participants must have progressed after at least 1, but no more than two prior chemotherapy regimens for locally advanced unresectable or metastatic disease.
• Criteria b through h removed during Protocol amendment 7. i. Pancreatic Cancer combination group (with mFOLFIRINOX) i. Pancreatic ductal adenocarcinoma (ductal adenocarcinoma and related subtypes eligible; endocrine and neuroendocrine tumors excluded); ii. Participants have not received prior systemic therapy for metastatic disease.
• j. Non-small cell lung cancer monotherapy group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harboring mutations amenable to targeted therapy treatment, are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1st or 2nd line are also eligible to participate to the study.
• iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible. Participants with NSCLC and targeted therapy treatment options are eligible for the clinical trial as long as they meet these criteria.
• iv. Participants with recurrent disease > 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint inhibitor (given either together or sequentially to treat the recurrence), are eligible v. Participants must have received platinum-based chemotherapy for advanced or metastatic disease and immune checkpoint inhibitor either together (in the same line of treatment) or sequentially (two different lines of treatment) and then progressed.
• k. Non small cell lung cancer combination group i. Non-small cell lung cancer (adenocarcinoma and squamous eligible; endocrine, neuroendocrine and small cell tumors are excluded) ii. Participants must have progressed after at least 1 but not more than 2 prior systemic regimens including chemotherapy and immunotherapy. Participants with NSCLC and targeted therapy treatment options, are eligible for the clinical trial as long as they meet these criteria (progression after 1 or 2 prior therapies). Note: Participants with NSCLC harboring mutations amenable to targeted therapy treatment, are eligible if received targeted therapy as single agent or in combination in 1st or 2nd line of treatment; participants not eligible to receive such therapies in 1st or 2nd line are also eligible to participate to the study.
• iii. Participants who have received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and an immune checkpoint inhibitor and developed recurrent or metastatic disease while on or within 12 months of completing therapy are eligible iv. Participants with recurrent disease > 12 months after adjuvant or neoadjuvant platinum-based chemotherapy, who also subsequently progressed during or after a platinum-doublet regimen and an immune checkpoint inhibitor (given either together or sequentially to treat the recurrence), are eligible v. Participants must not have received prior taxane therapy either as monotherapy or in combination.
• l. Breast cancer monotherapy group i. HR positive HER2 negative

Where it is running

• UAB Comprehensive Cancer Center — Birmingham, Alabama, United States (enrolling)
• City of Hope — Duarte, California, United States (enrolling)
• Hoag Hospital Irvine — Irvine, California, United States (enrolling)
• University of California Los Angeles (UCLA) — Los Angeles, California, United States (enrolling)
• UCSF Medical Center — San Francisco, California, United States (enrolling)
• Mayo Clinic — Jacksonville, Florida, United States (enrolling)
• University of Miami Hospital and Clinics — Miami, Florida, United States (enrolling)
• University of Chicago Medical Center — Chicago, Illinois, United States (enrolling)
• University of Iowa Hospitals and Clinics — Iowa City, Iowa, United States (enrolling)
• Karmanos Cancer Institute — Detroit, Michigan, United States (enrolling)
• Mayo Clinic — Rochester, Minnesota, United States (enrolling)
• Saint Louis University Hospital — St Louis, Missouri, United States (enrolling)
• Columbia University Medical Center — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• UNC Hospitals — Chapel Hill, North Carolina, United States (enrolling)
• Oregon Health and Science University — Portland, Oregon, United States (enrolling)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (enrolling)
• University of Texas MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• Univ of Utah, Huntsman Cancer Institute — Salt Lake City, Utah, United States (enrolling)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (enrolling)
• Novartis Investigative Site — Adelaide, South Australia, Australia (enrolling)
• Novartis Investigative Site — Melbourne, Victoria, Australia (enrolling)
• Novartis Investigative Site — Melbourne, Victoria, Australia (enrolling)
• Novartis Investigator Site — Murdoch, Western Australia, Australia (enrolling)
• Novartis Investigating Site — London, Ontario, Canada (enrolling)

Full record on ClinicalTrials.gov

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