177Lu-LNC1004 / Dongcheng Pharma - LARVOL DELTA

Treatment Outcome and Predictive Factors for Radioligand Therapy with 177Lu-LNC1004 in Patients with End-Stage Metastatic Cancers (SNMMI 2025) - "The 177Lu-LNC1004 was given six weekly with a median administered activity of 3.1GBq/cycle up to four cycles. Using the RECIST, disease control was confirmed in 13 patients [13/28, 46%], with 4 and 9 demonstrating partial response and stable disease, respectively. Evaluable patients with SUVmax ≤ 15 in targeted lesions had better DCR than that of patients with SUVmax > 15 (P=0.022)."

Biomarker • Clinical • IO biomarker • Metastases • Oncology • Solid Tumor

Sequential 177Lu/225Ac-LNC1004 targeted radionuclide therapy with anti-PD-L1 immune checkpoint blockade synergistically enhance anti-tumor efficacy in pancreatic adenocarcinoma (SNMMI 2025) - "On Panc02-tumor bearing mice, 177Lu-LNC1004 demonstrated sustained tumor uptake for more than 72 h and high tumor-to-background ratio, even given the moderate FAP expression level of Panc02 tumor. In terms of therapeutic efficacy, by combining the α-PD-L1 ICB with 18.5 or 30 MBq 177Lu-LNC1004, the tumor growths were further suppressed compared to radionuclide therapy alone. Most excitingly, the combination therapy of 30 MBq 177Lu-LNC1004 and α-PD-L1 mAb cleared tumor volume during 40 days of observation."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Endocrine Cancer • Neuroendocrine Tumor • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • FAP

Study of 177Lu-LNC1004 injection for patients wiht radioactive iodine refractory differentiated thyroid cancer (ChiCTR) - P1 | N=20 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

New P1 trial • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • FAP

Evaluation of the efficacy and safety of 177Lu-LNC1004 injection in advanced gastrointestinal cancer patients with fibroblast activation protein (FAP) positivity (ChiCTR) - P1 | N=6 | Recruiting | Sponsor: Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

New P1 trial • Gastrointestinal Cancer • Gastrointestinal Disorder • Oncology • Solid Tumor • FAP

Study of 177Lu-LNC1004 Injection in FAP-positive Radioiodine-refractory Differentiated Thyroid Cancer (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: Peking Union Medical College Hospital

New P1 trial • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma

177Lu-LNC1004 Radioligand Therapy in Patients with End-stage Metastatic Cancers: A Single-Center, Single-Arm, Phase II Study. (PubMed, Clin Cancer Res) - "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."

Journal • P2 data • Hematological Disorders • Hepatology • Leukopenia • Neutropenia • Oncology • Thrombocytopenia • FAP

INDIGO-FAPI: Cutting Edge Imaging With PET-FAPI for Earlier Pancreatic Cancer Diagnosis (clinicaltrials.gov) - P2 | N=35 | Not yet recruiting | Sponsor: Institut Curie

New P2 trial • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Initial Clinical Experience with 177Lu-EB-FAPI Radioligand Therapy in Patients with End-StageMetastatic Cancers (EANM 2024) - "FAP-targeted radioligand therapy with 177Lu-EBFAPI was well tolerated, with a low rate of attributable adverse events. We observed signs of tumor response, but further studies are warranted to determine efficacy and the toxicity profile in a larger cohort."

Clinical • Metastases • Anemia • Breast Cancer • Colorectal Cancer • Endocrine Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Disorders • Kidney Cancer • Leukopenia • Lung Cancer • Nasopharyngeal Carcinoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Thrombocytopenia • Thyroid Gland Carcinoma • FAP

Combination of Fibroblast Activation Protein (FAP)-targeted Radioligand Therapy with Anti-PD-L1 immunotherapy and Anti-VEGF Therapy (EANM 2024) - "The mice were randomly grouped (n = 8/group) to receive control, monotherapy or combinational therapy treated using 18.5 MBq 177Lu-3BP-3940 with anti-VEGF; 177Lu-LNC1004 with anti-PD-L1; 177Lu-DOTA-2P[FAPI]2 with anti-PD-L1 and monitored for body weight and tumour size... Combining FAP-targeted RLT with anti-PD-L1 and anti-VEGF therapies demonstrated significant promise in FAP-positive tumour-bearing mouse models. With the development of novel compounds for FAP-targeted theranostics, investigating complementary treatment strategies is poised for a new clinical regimen for cancer management."

Oncology • Solid Tumor • CAFs • FAP

Investigating the Efficacy and Mechanism of FAP-targeted Radioligand Therapy Combined with Immune Checkpoint Blockade: A Translational Study (EANM 2024) - P1 | "In conclusion, our preclinical data suggested that 177Lu-LNC1004 can amplify the antitumor efficacy of ICB. Furthermore, preliminary clinical data indicated that 177Lu-LNC1004 is a safe and well-tolerated therapeutic regimen with encouraging antitumor activity. Our data foster further exploration of the synergy between 177Lu-LNC1004 and immunotherapy in patients with advanced and refractory disease, particularly in those with FAP-positive tumors."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Oncology • CD8 • FAP

Diagnosis of Metastatic Tumors on 68Ga-FAPI PET-CT and Radioligand Therapy with 177Lu-EB-FAPI (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Peking Union Medical College Hospital | Trial completion date: Apr 2023 ➔ Apr 2025 | Trial primary completion date: Jan 2023 ➔ Jan 2025

Metastases • Trial completion date • Trial primary completion date • Oncology

Antitumor Efficacy and Potential Mechanism of FAP-targeted Radioligand Therapy Combined with Immune Checkpoint Blockade: From Bench to Bedside (SNMMI 2024) - P1 | "In conclusion, our preclinical data suggested that 177Lu-LNC1004 can amplify the antitumor efficacy of ICB. Furthermore, preliminary clinical data indicated that 177Lu-LNC1004 is a safe and well-tolerated therapeutic regimen with encouraging antitumor activity. Our data foster further exploration of the synergy between 177Lu-LNC1004 and immunotherapy in patients with advanced and refractory disease, particularly in those with FAP-positive tumors."

Checkpoint block • Checkpoint inhibition • Clinical • IO biomarker • Oncology • CD8 • FAP

Initial Clinical Experience with 177Lu-EB-FAPI Radioligand Therapy in Patients with End-Stage Metastatic Cancers (SNMMI 2024) - "FAP-targeted radioligand therapy with 177Lu-EB-FAPI was well tolerated, with a low rate of attributable adverse events. We observed signs of tumor response, but further studies are warranted to determine efficacy and the toxicity profile in a larger cohort."

Clinical • Metastases • Anemia • Breast Cancer • Colorectal Cancer • Endocrine Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Disorders • Kidney Cancer • Leukopenia • Lung Cancer • Nasopharyngeal Carcinoma • Oncology • Prostate Cancer • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Thrombocytopenia • Thyroid Gland Carcinoma • FAP

Development of dual targeting heterodimer 177Lu-LNC1009 for cancer theranostics (SNMMI 2024) - "For the comparison, SPECT images of 177Lu-DOTA-NC1007, 177Lu-EB-RGD, and 177Lu-LNC1004 (177Lu-EB-FAPI) were also performed in U87MG tumor model...SPECT imaging of 177Lu-LNC1009 showed significantly improved tumor uptake and retention than those of 177Lu-DOTA-FAPI-RGD... 177Lu-LNC1009 was successfully synthesized and radiolabeled with high radiochemical purity and stability. With significantly improved absolute tumor uptake and decreased normal organ uptake, 177Lu-LNC1009 has the potential to enhance therapy effect that promises clinical translation for the treatment of many types of solid tumors that are FAP+/αvβ3-, FAP-/αvβ3+, or FAP+/αvβ3+."

Oncology • Solid Tumor • FAP

Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade. (PubMed, Signal Transduct Target Ther) - "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."

Checkpoint block • Checkpoint inhibition • IO biomarker • Journal • Oncology • CD8 • FAP

The Safety and Dosimetry Study of 177Lu-LNC1004 Injection (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Yantai LNC Biotechnology Singapore PTE. LTD. | Not yet recruiting ➔ Recruiting | Initiation date: May 2023 ➔ Oct 2023

Enrollment open • Metastases • Trial initiation date • Oncology • Solid Tumor

Fibroblast Activation Protein-Targeted Radioligand Therapy with 177Lu-EB-FAPI for Metastatic Radioiodine Refractory Thyroid Cancer: First-in-Human, Dose-Escalation Study. (PubMed, Clin Cancer Res) - "FAP-targeted radioligand therapy with 177Lu-LNC1004 at 3.33 GBq/cycle was well tolerated in patients with advanced mRAIR-TC, with high radiation dose delivery to the tumor lesions, encouraging therapeutic efficacy, and acceptable side effects."

Journal • Metastases • P1 data • Endocrine Cancer • Hematological Disorders • Oncology • Solid Tumor • Thrombocytopenia • Thyroid Gland Carcinoma

CISPD-5: A Study to Evaluate the Safety and Efficacy of PRRT With 177Lu-EB-FAPI in Patients With Advanced Cholopancreatic Tumors (clinicaltrials.gov) - P1 | N=29 | Recruiting | Sponsor: Zhejiang University

Metastases • New P1 trial • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A subsidiary of Dongcheng Pharmaceutical (002675.SZ) was notified of the clinical trial approval of "177Lu-LNC1004 Injection" [Google translation] (Zhitong Finance) - "Zhitong Finance APP news, Dongcheng Pharmaceutical...announced that recently, the company's subsidiary company YANTAI LNC BIOTECHNOLOGY SINGAPORE PTE. LTD. HSA approved and issued the drug clinical trial authorization notice for 177Lu-LNC1004 injection, which will carry out Phase I clinical trial in Singapore in the near future."

New P1 trial • Oncology

The Safety and Dosimetry Study of 177Lu-LNC1004 Injection (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Yantai LNC Biotechnology Singapore PTE. LTD.

New P1 trial • Oncology • Solid Tumor • FAP

IND granted for FAP targeting therapeutic in SOFIE partnership (PRNewswire) - "SOFIE Biosciences (SOFIE)...will be supporting, through companion diagnostic [68Ga]FAPI-46 PET, Yantai LNC Biotechnology's recently FDA accepted clinical study....On Jan 6th, 2023 Yantai LNC Biotechnology received FDA clearance to proceed with a Phase 1 clinical study of 177Lu-LNC1004 injection, targeting fibroblast activation protein (FAP). The study accepted as part of the FDA IND review is a Phase I, open label study of the safety and dosimetry of a 4-dose regimen of escalating doses of 177Lu-LNC1004 injection in adult patients with advanced FAP-positive solid tumors....The study is expected to enroll up to 24 subjects in advanced solid tumors that show high level of FAP expression detected by [68Ga]FAPI-46 and will establish the recommended expansion phase dose with 177Lu-LNC1004. Site feasibility and selection is complete and the study is expected to launch in Singapore Q2 2023."

IND • New P1 trial • Oncology • Solid Tumor

177Lu-LNC1004 injection, a subsidiary of Dongcheng Pharmaceutical (002675.SZ), was approved by FDA [Google translation] (Zhitong Finance) - "Zhitong Finance APP news, Dongcheng Pharmaceutical (002675.SZ) announced that on January 6, 2023, Lannacheng Singapore, a subsidiary of the company, received the approval and issuance of the 177Lu drug by the US Food and Drug Administration ('FDA') - LNC1004 Injection’s Drug Clinical Trial Approval Notification ('SMP'), which will carry out phase I clinical trial in the near future."

IND • Oncology • Solid Tumor