AAA614 / Clovis, 3B Pharma, Novartis - LARVOL DELTA

Preclinical evaluation, and clinical translation of 68Ga/177Lu-JH04, a novel FAP-targeting radiolabeled agent (AACR 2025) - "The objective of this study is to evaluate the specificity, biodistribution, pharmacokinetics, and dosimetry of 68Ga/177Lu-JH04 through preclinical and preliminary clinical investigations, and to compare these findings with those of 68Ga/177Lu-FAP-2286. The FAP-positive cell line HT1080-FAP was employed in in vitro and in vivo studies. 68Ga/177Lu-JH04, novel FAP-targeting agent with excellent binding affinity, high tumor uptake, prolonged retention, and robust tumor-suppressive effects. These promising results encourage us to conduct further clinical research."

Preclinical • Oncology • FAP

FAUNUS: 177Lu-FAP-2286 Treatment in Urethelial Neoplasms: Utility and Safety as a Novel Treatment. (clinicaltrials.gov) - P2 | N=10 | Not yet recruiting | Sponsor: Ankara University

New P2 trial • Oncology

177Lu-FAP-2286 Therapy in a Case of Squamous Lung Cancer. (PubMed, Clin Nucl Med) - "Radiological remission was observed on follow-up FAP imaging 7 months later with squamous cell carcinoma antigen decreased to normal level. No other abnormality monitored by routine laboratory examination was noted."

Journal • Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Comprehensive Preclinical Study and Administration Protocol for 177Lu-FAP-2286: Validation, Tumor Uptake, and Dosimetry Investigations (EANM 2024) - "The validation of production and quality control processes for 177Lu-FAP-2286, along with the comprehensive preclinical studies and dosimetry investigations, demonstrate the potential for effective clinical translation. The use of lysine and arginine for kidney blockage, in combination with furosemide, shows promise in minimizing background activity in normal organs."

Preclinical • Oncology

Development of Multivalent OncoFAP Derivatives for the Tumor-Targeted Delivery of Theranostic Radionuclides (EANM 2024) - "When compared to 177Lu-FAP-2286, the most advanced FAP-targeted RLT in clinical development, 177Lu-TriOncoFAP exhibited a ~2.7-fold higher overall uptake in tumors, with a ~1.8-fold lower kidney uptake... The data presented in this work strongly supports the clinical development of 177Lu-TriOncoFAP. We are launching a Phase I clinical trial to define the 177Lu-TriOncoFAP maximum tolerated dose, evaluating its safety profile, and collecting preliminary signs of efficacy. The compound will be given as single agent or in combination with L19-IL2 in patients with multiple types of FAP-positive tumors."

Oncology • Solid Tumor • FAP • IL2

Initial experience with 177Lu-FAP-2286 peptide targeted radionuclide therapy in advanced solid tumors (EANM 2024) - " Treatment protocol: Patients were pre-medicated with I.V. ondansetron, pantoprazole & Dexamethasone. 177Lu-FAP-2286 PTRT seems to be a viable therapeutic option for FAP-positive tumors. However, due to variability in objective response, use in combination with single-agent chemo or immunotherapeutic agent is to be explored for better results."

Metastases • Endometrial Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Triple Negative Breast Cancer • FAP • PD-L1

Preclinical Evaluation of 177Lu-OncoFAP-23, a Multivalent FAP-Targeted Radiopharmaceutical Therapeutic for Solid Tumors. (PubMed, J Nucl Med) - "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."

Journal • Preclinical • Oncology • Solid Tumor • FAP

A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE) (clinicaltrials.gov) - P1/2 | N=222 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor • FAP

Efficacy and Safety Evaluation of 177Lu-FAP-2286 in the Treatment of Advanced Lung Cancer. (PubMed, Clin Nucl Med) - "177Lu-FAP-2286 has the potential to be a viable PTRT option for patients with advanced lung cancer."

Clinical • Journal • Metastases • Lung Cancer • Metabolic Disorders • Oncology • Pain • Pulmonary Disease • Solid Tumor

Feasibility and therapeutic potential of [177Lu]Lu-FAPI-2286 in patients with advanced metastatic sarcoma. (PubMed, Eur J Nucl Med Mol Imaging) - "[177Lu]Lu-FAPI-2286 PTRT, utilized for diverse cancer types, exhibited favorable tolerability in sarcoma patients, with minimal side effects, long-lasting retention of the radiopeptide within the tumor, and promising therapeutic effects. Preliminary findings of this prospective study need to be confirmed through further clinical trials."

Journal • Metastases • Oncology • Pain • Sarcoma • Solid Tumor

Comparison of 68Ga-FAP-2286 and 18F-FDG PET/CT in the diagnosis of advanced lung cancer. (PubMed, Front Oncol) - "However, the detection sensitivity for primary tumors using both modalities was comparable [100% (13/13) for both]. Compared to 18F-FDG PET/CT, 68Ga-FAP-2286 PET/CT demonstrated better lesion detection capabilities for lung cancer, particularly in lymph nodes and bone metastases, providing compelling imaging evidence for the efficacy of 177Lu-FAP-2286 treatment."

FDG PET • Journal • Metastases • Lung Cancer • Oncology • Solid Tumor

Development of Multivalent OncoFAP Derivatives for the Tumor-Targeted Delivery of Theranostic Radionuclides (SNMMI 2024) - "When compared to 177Lu-FAP-2286, the most advanced FAP-targeted RLT in clinical development, 177Lu-TriOncoFAP exhibited a ~2... The data presented in this work strongly supports the clinical development of 177Lu-TriOncoFAP. We have recently completed GMP central labeling set-up. Philogen is launching a Phase I clinical trial to define the 177Lu-TriOncoFAP maximum tolerated dose, evaluating its safety profile, and collecting preliminary signs of efficacy."

Hepatology • Oncology • Solid Tumor • FAP • IL2

177Lu-FAP-2286 Therapy in a Patient With Metastatic Rhabdoid Meningioma. (PubMed, Clin Nucl Med) - "Herein, we reported a patient of rhabdoid meningioma with multiple liver, pancreas, and bone metastases, who received 177Lu-FAP-2286 therapy. After 1 treatment cycle, 68Ga-FAP-2286 PET/CT revealed partial remission of the lesions."

Journal • Metastases • Brain Cancer • CNS Tumor • Meningioma • Oncology • Pancreatic Cancer • Solid Tumor

Metastatic Lung Adenocarcinoma Received Combined 177Lu-FAP-2286 Radiation Therapy and Targeted Therapy. (PubMed, Clin Nucl Med) - "After 1 treatment cycle, improvement of symptoms and radiological remission was observed. Moreover, the patient did not report any adverse effects."

Journal • Metastases • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

177Lu-FAP-2286 Therapy in a Metastatic Bone Malignant Solitary Fibrous Tumor. (PubMed, Clin Nucl Med) - "After 1 treatment cycle, 68Ga-FAP-2286 PET/CT revealed remission of the lesions. Moreover, the patient did not report any adverse effects."

Journal • Metastases • Oncology

A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE) (clinicaltrials.gov) - P1/2 | N=222 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor • FAP

177Lu-FAP-2286 Therapy in a Case of Recurrent Bladder Cancer With Multiple Metastatic Lesions. (PubMed, Clin Nucl Med) - "Encouragingly, radiological remission and alleviation of his symptom were noted. In addition, the patient did not have any adverse effects."

Journal • Metastases • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE) (clinicaltrials.gov) - P1/2 | N=300 | Recruiting | Sponsor: Clovis Oncology, Inc. | N=170 ➔ 300

Enrollment change • Metastases • Oncology • Solid Tumor

Fibroblast activation protein (FAP)-targeted radiotherapy increases tumor CD8+ T cell infiltration and enhances response to PD-1 immune checkpoint blockade (AACR 2023) - "FAP-targeted radiopharmaceutical enhances PD-1-antibody-mediated TGI by increasing recruitment of tumor-infiltrating CD8+ T cells, which is enhanced and maintained in the presence of anti-PD-1. These findings provide a rationale for clinical studies of combined 177Lu-FAP-2286 radiotherapy and immune checkpoint blockade in FAP-positive tumors."

Checkpoint block • Checkpoint inhibition • IO biomarker • Fibrosarcoma • Oncology • Sarcoma • Solid Tumor • CD8 • CD86 • FAP

Comparative biodistribution and radiotherapeutic efficacy of the fibroblast activation protein (FAP)-targeting agents FAP-2286 and FAPI-46 (AACR 2022) - P1/2 | "In preclinical studies, the radiotherapeutic 177Lu-FAP-2286 showed longer tumor retention, resulting in greater tumor inhibition than 177Lu-FAPI-46. The phase 1/2 LuMIERE clinical trial (NCT04939610) will evaluate FAP-2286 as a therapeutic (177Lu-FAP-2286) and imaging (68Ga-FAP-2286) agent in multiple indications."

Clinical • Oncology • FAP

Clovis Oncology Files for Chapter 11 Protection and Enters into Agreement to Sell FAP-2286 (Businesswire) - "Clovis Oncology, Inc....announced that it and certain of its subsidiaries (collectively, the 'Debtors') have voluntarily initiated a Chapter 11 proceeding in the United States Bankruptcy Court for the District of Delaware ('Bankruptcy Court') and will seek to sell their assets through a court supervised sales process....Funding during the Chapter 11 proceeding, Clovis has received a commitment of up to $75 million in a multi-draw DIP financing facility....Prior to the Chapter 11 filing, and subject to Bankruptcy Court approval, the Company entered into a 'stalking horse' purchase and assignment agreement with Novartis Innovative Therapies AG ('Novartis') to acquire substantially all of the rights of the Company to its pipeline clinical candidate, FAP-2286, as a therapeutic agent for an upfront payment of $50 million and up to an additional $333.75 million upon the successful achievement of specified development and regulatory milestones and $297 million in later sales milestones."

Licensing / partnership • Oncology

LuMIERE: A phase 1/2 study investigating safety, pharmacokinetics, dosimetry, and preliminary antitumor activity of 177Lu-FAP-2286 in patients with advanced or metastatic solid tumors (AACR 2022) - P1/2 | "Secondary objectives include the assessment of radiation dosimetry, pharmacokinetics, and preliminary efficacy of 177Lu-FAP-2286 and the evaluation of safety and tumor uptake of 68Ga-FAP-2286. Phase 2 will evaluate the efficacy, safety, and dosimetry of 177Lu-FAP-2286 in patients with select FAP-expressing solid tumors."

Clinical • P1/2 data • PK/PD data • Oncology • Solid Tumor • CAFs • FAP

Clovis Oncology Highlights Updated LuMIERE Phase 1 Data of Targeted Radiotherapy Candidate FAP-2286 at the 35th Annual EANM Congress (Businesswire) - P1 | N=170 | LuMIERE (NCT04939610) | Sponsor: Clovis Oncology, Inc | "Updated LuMIERE Phase 1 data demonstrated a manageable safety profile with some preliminary evidence of anti-tumor activity. Eleven patients treated to date with 177Lu-FAP-2286 up to 7.4 GBq/dose. No serious adverse events, treatment discontinuations, or deaths related to 177Lu-FAP-2286 observed. Confirmed partial response (PR) in one patient who completed the maximum six administrations of 177Lu-FAP-2286 in the 3.7 GBq dose cohort. Patient continues without disease progression or subsequent anti-cancer therapy more than twelve months after first dose. Stable disease (SD) in one heavily pretreated patient who completed four administrations of 177Lu-FAP-2286 in the 5.55 GBq dose cohort...FAP-2286 has shown high tumor uptake and good prolonged retention across a range of solid tumors...'We anticipate additional clinical data from the LuMIERE study to be presented at a medical conference in the first quarter of 2023'."

P1 data • P1/2 data • Oncology • Solid Tumor

Clovis Oncology and Isotopia Announce Lutetium-177 Clinical Supply Agreement (Businesswire) - "Clovis Oncology, Inc...announced the signing of a clinical supply agreement that provides Clovis Oncology with Isotopia’s lutetium-177 (177Lu) n.c.a. for use in the clinical development of FAP-2286, Clovis’ fibroblast activation protein (FAP)-targeting therapeutic candidate. FAP-2286 is the first peptide-targeted radionuclide therapeutic (PTRT) candidate directed against fibroblast activation protein undergoing clinical testing and is currently being investigated in the Phase 1/2 LuMIERE study for patients with advanced solid tumors....In June 2022, the first presentation of initial data from the Clovis-sponsored Phase 1/2 LuMIERE study of FAP-2286 in advanced solid tumors took place at SNMMI and the Company plans to present a further interim data update during the EANM Congress in October 2022."

Licensing / partnership • P1/2 data • Oncology • Solid Tumor

177Lu-FAP-2286: “Treatment-emergent adverse events (TEAEs) were generally mild to moderate across patients receiving 3.7 or 5.55 GBq of 177Lu-FAP-2286”; Solid tumor (Clovis Oncology) - Corporate Presentation

P1 data • Oncology • Solid Tumor