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

NCT04939610 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: CO-2286-114CAAA614A121012023-508995-12-00
• Study Type: interventional
• Target: 222
• Locations: 6 countries
• Sites: 40

Brief Summary

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.

Conditions

Solid Tumor

Keywords

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

Outcome Measures

Primary Outcomes (7)

• Phase 1: Dose-limiting toxicity (DLTs)

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D

  From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)

• Phase 1: recommended Phase 2 dose (RP2D)

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D

  From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)

• Phase 1: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [177Lu]Lu FAP 2286

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D

  From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)

• Phase 2: Objective Response Rate (ORR)

  Objective response is defined as a best confirmed response of CR or PR by RECIST v1.1 as assessed by the investigator. A confirmed CR or PR is a response that is maintained and documented on a subsequent tumor assessment no less than 28 days after the initial response. For Phase 2, ORR defined as the frequency and percentage of participants with a best confirmed response of CR or PR will be analyzed.

  From date of first [177Lu]Lu FAP 2286 treatment until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to 59 months

• Phase 2: Dose-limiting toxicity (DLTs)

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose escalation for combination therapy)

  Assessed within 4 weeks of first Lu-FAP2286 treatment

• Phase 2: recommended Phase 2 dose (RP2D)

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose escalation for combination therapy)

  From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)

• Phase 2: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of [177Lu]Lu FAP 2286

  To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D in combination with mFOLFIRINOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose escalation for combination therapy)

  From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years)

Secondary Outcomes (17)

• Phase 1: Absorbed dose (Gy) estimated in organs and tumor lesions

  From first dose of study drug until disease progression or end of treatment (up to approximately 9 months)

• Phase 1: Maximum standardized uptake value (SUVmax) in tumor lesions

  Taken within 2 hours after 68Ga-FAP-2286 IV administration

• Phase 1: Comparison of SUVmax in tumor lesions

  From time of screening FDG PET/CT to 68Ga-FAP-2286 PET/CT (up to approximately 1 month)

• Phase 1: Concentration of [177Lu]Lu FAP 2286 at the end of infusion (Ceoi)

  From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)

• Phase 1: Cmax of [177Lu]Lu FAP 2286

  From first dose of study drug to end of Cycle 6 with (each cycle ~ 6 weeks) (Total Time Frame estimated up to approximately 9 months)

Study Arms (2)

Phase 1: Dose Escalation

EXPERIMENTAL

Up to 30 patients with solid tumors.

Drug: 68Ga-FAP-2286; Drug: 177Lu-FAP-2286

Phase 2: Specific Solid Tumors

EXPERIMENTAL

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

Drug: 68Ga-FAP-2286; Drug: 177Lu-FAP-2286

Interventions

68Ga-FAP-2286 DRUG

68Ga-FAP-2286 IV administered as imaging agent for PET scan.

Phase 1: Dose Escalation; Phase 2: Specific Solid Tumors

177Lu-FAP-2286 DRUG

Phase 1: Patients with positive uptake of 68Ga-FAP- 2286 will receive a fixed dose of 177Lu-FAP-2286 IV administered every 6 weeks for a maximum of 6 doses. Doses range between 3.7 and 9.25 GBq (100-250 mCi). Phase 2: Monotherapy: Patients with positive uptake of 68Ga FAP 2286 will receive a fixed dose of 177Lu FAP 2286 IV administered at the RP2D determined in Phase 1 dose escalation in every 4 weeks. Combination therapy: Patients with positive uptake of 68Ga FAP 2286 will receive 177Lu-FAP-2286 based on dose escalation (starting with dose level 1) followed by dose expansion at selected dose.

Phase 1: Dose Escalation; Phase 2: Specific Solid Tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• Participants who meet any of the following criteria will be excluded from the study. The criteria below apply to participants enrolling in Phase 1 or Phase 2.
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• 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:
• History of second malignancy that has been successfully treated, with no evidence of active cancer for 3 years prior to enrollment;
• Surgically cured low-risk tumors, such as early-stage cervical or endometrial cancer, any cancer in situ, or non-melanoma skin cancers; and
• 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.
• Symptomatic and/or untreated CNS metastases or leptomeningeal disease or with primary tumor of CNS origin.
• a. Participants with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable for at least 4 weeks and have completed RT\> 2 weeks prior to treatment. Participants may be on corticosteroids if on a stable dose equivalent to prednisone 10 mg daily or less.
• 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.
• 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.
• 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.
• Ongoing adverse effects from anticancer treatment NCI-CTCAE v5.0 (or higher) Grade 1, with the exception for alopecia and vitiligo.
• 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;
• Corrected QT interval (Fridericia's formula) \> 450 msec for males or \> 470 msec for females at Screening; or
• Acute coronary syndrome or acute myocardial infarction ≤ 6 months prior to administration of \[177Lu\]Lu FAP 2286.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (40)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

Hoag Hospital Irvine

Irvine, California, 92618, United States

RECRUITING

University of California Los Angeles (UCLA)

Los Angeles, California, 90095, United States

RECRUITING

UCSF Medical Center

San Francisco, California, 94158, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Saint Louis University Hospital

St Louis, Missouri, 63110-2539, United States

RECRUITING

Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

UNC Hospitals

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Univ of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109-1023, United States

RECRUITING

Novartis Investigative Site

Adelaide, South Australia, 5000, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

RECRUITING

Novartis Investigator Site

Murdoch, Western Australia, 6150, Australia

RECRUITING

Novartis Investigating Site

London, Ontario, N6A 5W9, Canada

RECRUITING

London Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Novartis Investigator Site

Montpellier, Cedex 5, 34298, France

RECRUITING

Novartis Investigator Site

Bordeaux, 33000, France

RECRUITING

Novartis Investigator Site

Clermont-Ferrand, 63011, France

RECRUITING

Novartis Investigating Site

Marseille, 13385, France

RECRUITING

Novartis Investigator Site

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Novartis Investigative Site

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Novartis Investigating Site

Milan, 20141, Italy

RECRUITING

Novartis Investigator Site

Naples, 80131, Italy

RECRUITING

Novartis Investigative Site

A Coruña, 15006, Spain

RECRUITING

Novartis Investigating Site

Badalona, 08916, Spain

RECRUITING

Novartis Investigating Site

Madrid, 28040, Spain

RECRUITING

Novartis Investigating Site

Madrid, 28041, Spain

RECRUITING

Novartis Investigating Site

Madrid, 28050, Spain

RECRUITING

Related Publications (1)

• Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.

  PMID: 38753757 DERIVED

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-689-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 25, 2021
• Study Start: July 30, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (3); US (20); AU (4); FR (5); IT (3); ES (5)