P2, N=10, Not yet recruiting, Ankara University

FAP-directed RLT using 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated with an acceptable toxicity profile. Nearly half of patients achieved disease control, which was associated with prolonged PFS and OS.

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2025 --> Dec 2025 | Trial primary completion date: Apr 2025 --> Dec 2025

Increased FAP expression in the TME as a result of radiotherapy can be exploited to target agonist 4-1BB immunotherapy to malignant tumor lesions using an FAP-4-1BBL antibody fusion protein.

P2/3, N=109, Recruiting, KU Leuven | Not yet recruiting --> Recruiting

The safety profile of FAP-IL2v in combination with pembrolizumab was manageable and consistent with the known safety profile. However, further exploration of FAP-IL2v and pembrolizumab was precluded in melanoma patients with prior CPI due to the lack of clinical activity.

P=N/A, N=30, Recruiting, Ziv Hospital

P2/3, N=109, Not yet recruiting, KU Leuven

Specifically, FAPI-Cy7-Cl exhibited superior imaging performance in both estrogen receptor α positive breast cancer (MCF-7) and triple-negative breast cancer (TNBC) (MDA-MB-231) subtypes in mouse models. Notably, in the MDA-MB-231 tumor-bearing model, the tumor-to-liver ratio (T/L) of FAPI-Cy7-Cl increased rapidly after 2 h postinjection, reaching nearly 4.5 at 48 h, making it an optimal imaging probe for guiding TNBC surgery resection.

P1/2, N=54, Completed, Hoffmann-La Roche | Active, not recruiting --> Completed | N=80 --> 54

The novel OncoFAP-GlyPro-MMAF and the previously described OncoFAP-GlyPro-MMAE were compared in a head-to-head therapeutic experiment in mice bearing FAP-positive tumors. Surprisingly, the MMAF conjugate mediated potent antitumor activity, despite its poor cellular permeability.

P2, N=35, Not yet recruiting, Institut Curie

P=N/A, N=10, Completed, I-MED Radiology Network | Recruiting --> Completed

In this work, a workflow to select binding affinities for bispecific antibodies that integrates preclinical in vitro data, mathematical modeling and simulation, and knowledge on target expression in the patient population, is provided. The early implementation of this approach can increase the probability of success with cancer immunotherapy in clinical development.

The safety profile of FAP-IL2v in combination with cetuximab was acceptable and pharmacodynamic markers support the proposed mode-of-action of this combination, but the overall low antitumor activity does not warrant further clinical exploration in HNSCC. [Part C of Study BP29842 (NCT02627274).].

P2, N=28, Completed, The First Affiliated Hospital of Xiamen University | Recruiting --> Completed | Phase classification: P1 --> P2 | N=20 --> 28 | Trial completion date: Jun 2025 --> Oct 2024 | Trial primary completion date: Dec 2024 --> Sep 2024

FAP-IL2v plus atezolizumab is clinically active and has manageable safety in patients with recurrent and/or metastatic cervical SCC.

P=N/A, N=30, Completed, Sichuan Provincial People's Hospital

P=N/A, N=50, Not yet recruiting, Mercy Radiology, Epsom, Auckland

177Lu-OncoFAP and 177Lu-FAP-2286 were included in the biodistribution study as controls. OncoFAP-23 presents enhanced tumor uptake and tumor retention and low accumulation in healthy organs, findings that correspond to a strongly improved in vivo antitumor efficacy. The data presented in this work support the clinical development of 177Lu-OncoFAP-23 for the treatment of FAP-positive solid tumors.

P1, N=160, Recruiting, Boehringer Ingelheim | Trial completion date: Jan 2027 --> Nov 2028 | Trial primary completion date: Apr 2026 --> Aug 2027

And [18F]FAPI-42 PET/CT offers synergistic value when used in combination with [18F]FDG PET/CT. Notably, the nomogram generated from the model incorporating [18F]FAPI-42 PET/CT, [18F]FDG PET/CT parameters, gene mutation, and type of targeted therapy could yield more precise predictions of the response of recurrent metastatic GISTs.

P1/2, N=222, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

P1, N=186, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P1, N=36, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting

P1, N=30, Active, not recruiting, Akamis Bio | Recruiting --> Active, not recruiting | Phase classification: P1a/1b --> P1 | Trial completion date: Jul 2024 --> Dec 2024 | Trial primary completion date: May 2024 --> Aug 2024

The superior affinity and faster tumor accumulation of eFAP-6 over FAPI-46 makes it a suitable compound for radionuclide imaging. After further optimization, the eFAP series has great potential for various oncological interventions, including fluorescent-guided surgery and effective targeted radionuclide theranostics.

This head-to-head study demonstrated heterogeneous FAP expression in intracranial tumors. The FAP expression volume percentage in tumor parenchyma may therefore offer benefit with respect to differentiating between intracranial tumor types.

We examine the development and clinical applications of FAP inhibitors (FAPIs) and peptides, providing insights into their diagnostic accuracy, initial therapeutic efficacy, and clinical impact across diverse cancer types, as well as the synthesis of novel FAP-targeted ligands. This review aims to showcase the promising outcomes and challenges in integrating FAP-targeted approaches into cancer management.

P=N/A, N=30, Completed, Sichuan Provincial People's Hospital | Recruiting --> Completed

This was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell inactivation. In conclusion, our data supported the efficacy of immunotherapy combined with 177Lu-LNC1004 for cancer patients with FAP-positive tumors.

This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of 177Lu-FAPI-46 with Pazopanib.

In patients with low-grade and NA sarcomas, 68Ga-FAPI PET demonstrates uptake, detection rates, and accuracy superior to those of 18F-FDG PET. 68Ga-FAPI PET criteria identified eligibility for FAP-RPT in about half of sarcoma patients.

P2; FAP-IL2v plus atezolizumab demonstrated clinical activity and was tolerable in patients with previously treated esophageal SCC.

In this investigation, PT-100 (also referred to as Talabostat, Val-boroPro, and BXCL701), an orally administered and nonselective dipeptidyl peptidase inhibitor, not only augmented the effectiveness of anti-PD-1 therapy but also significantly improved T immune cell infiltration and reversed the immunosuppressive tumor microenvironment...The results further suggested that PT-100 dramatically reduced the ratio of tumor-associated macrophages. These findings provide a promising combination strategy for immunotherapy in lung cancer.

FAP-IL2v had a manageable safety profile and showed initial signs of antitumor activity in advanced/metastatic solid tumors.

P1/2, N=80, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Jul 2025 --> Dec 2024 | Trial primary completion date: Jul 2025 --> Dec 2024

P2, N=15, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

As we continue to deepen our understanding of this novel imaging technique, it is hoped that FAPI PET imaging will play an increasingly important role in the fight against cancer. However, as with any new technology, further research is needed to fully understand the potential and limitations of FAPI PET imaging in the clinical setting.

P1, N=46, Terminated, Molecular Partners AG | N=78 --> 46 | Recruiting --> Terminated; After completion of the dose-escalation part of the study, the safety profile of MP0317 in monotherapy is considered adequately characterized in the dose-escalation part of the study.

P1/2, N=222, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting

P1, N=80, Completed, Hoffmann-La Roche | Recruiting --> Completed