tifcemalimab (TAB004) / Shanghai Junshi Biosci - LARVOL DELTA

A Phase I Clinical Study of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined With Toripalimab Injection in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | N=198 ➔ 31 | Recruiting ➔ Terminated; The trial was stopped early on the initiative of the sponsor on the basis of a change in the research and development strategy without safety concerns

Enrollment change • Trial termination • Cervical Cancer • Colorectal Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Liver Cancer • Microsatellite Instability • Oncology • Solid Tumor • Squamous Cell Carcinoma

JS004 Combined With Toripalimab and With Standard Chemotherapy Treat Patients With Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=119 | Completed | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Anti-Btla Antibody Tifcemalimab As a Single Agent or in Combination with Toripalimab in Relapsed/Refractory Lymphomas (ASH 2023) - P1 | "Tifcemalimab alone or in combination with toripalimab were well tolerated in all doses evaluated. The combination regimen showed favorable safety and durable efficacy in lymphoma patients with heavily pretreatment, providing evidence for future investigation."

Combination therapy • IO biomarker • Anemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • Oncology • BTLA

Review of design strategies for active targeted drug delivery systems for pancreatic cancer. (PubMed, Eur J Pharm Biopharm) - "The text introduces current pancreatic cancer treatment drugs, including gemcitabine, tegafur, and albumin-bound paclitaxel. The review offers a concise overview of the antibodies and ligands employed in active targeted drug delivery systems for PC, including hRS7, αTROP2, MF-T, TAB004, HzMUC1, as well as ligands such as EGF, GE11 peptide, Tf, tTR14, XQ-2d, cNGQ, α5β1-targeted peptide, IGF1, and SDC1. The therapeutic effects and prospects of combining active targeting strategies with photothermal therapy, immunotherapy, and gene editing technology are discussed in this paper."

Journal • Review • Oncology • Pancreatic Cancer • Solid Tumor • CA 19-9 • EGFR • GPC1 • IGF1 • MSLN • SDC1

A Randomized Study of JS004 and Toripalimab Combined With Chemotherapy vs Toripalimab Combined With Chemotherapy vs Chemotherapy Alone as Neoadjuvant Therapy for Stage II-III Triple-negative Breast Cancer (TNBC) (ChiCTR) - P2 | N=125 | Not yet recruiting | Sponsor: Shengjing Hospital of China Medical University; Shengjing Hospital of China Medical University

New P2 trial • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Perioperative study of BTLA combined with PD-1 and chemotherapy as bispecific immunosuppressants for resectable thoracic esophageal squamous cell carcinoma (BT-NICE trial): A prospective, single group, phase II study (ESMO 2025) - P2 | "Background Tifcemalimab, the world's first-in-class humanized IgG4 monoclonal antibody against B and T lymphocyte attenuator (BTLA), has shown preliminary anti-tumor activities in combination with Toripalimab (anti-PD-1). No treatment-related surgical delay or death occurred in 30 days. Conclusions BTLA inhibitor in combination chemotherapy with PD-1 inhibitor is feasible and effective in pts with locally advanced resectable ESCC, and might be a promising approach for neoadjuvant treatment."

Clinical • P2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • BTLA

Evaluating the Preliminary Efficacy and Safety of JS207 in NSCLC After Progression Following Platinum-based Chemotherapy and Immunotherapy (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Prospective，Single Arm, Multicenter Clinical Study of BTLA Monoclonal Antibody JS004 (B/T Lymphocyte Attenuator Factor Monoclonal Antibody) in Combination With Toripalimab in Patients With Unresectable or Advanced Renal Cell Carcinoma Who Had Failed Previous Immunotherapy (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: RenJi Hospital | Trial completion date: Dec 2026 ➔ Dec 2027 | Initiation date: Dec 2024 ➔ Oct 2025 | Trial primary completion date: Mar 2026 ➔ Oct 2026

Trial completion date • Trial initiation date • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Tifcemalimab Plus Toripalimab and Chemotherapy as a First-Line Therapy in ES-SCLC: A Phase Ib/II Study (IASLC-WCLC 2025) - P1/2 | "Methods : Patients with ES-SCLC who had not received systemic anti-tumor therapy were administrated with tifcemalimab 200 mg in combination with toripalimab 240 mg and etoposide 100 mg/m 2 plus carboplatin AUC 5 or cisplatin 75 mg/m 2 intravenously every 3 weeks until disease progression, intolerable toxicity, or completion of 2-year of tifcemalimab and toripalimab. TEAE leading to death occurred in 1 (2.3%) patient, which was not considered related to any treatment. Conclusions : Tifcemalimab in combination with toripalimab and chemotherapy showed promising antitumor activities with a manageable safety profile as a first-line treatment for patients with ES-SCLC."

Clinical • P1/2 data • Lung Cancer • Small Cell Lung Cancer • Solid Tumor • BTLA

A Randomized Study of JS004 and Toripalimab Combined With Chemotherapy vs Toripalimab Combined With Chemotherapy vs Chemotherapy Alone as Neoadjuvant Therapy for Stage II-III Triple-negative Breast Cancer (TNBC). (clinicaltrials.gov) - P2 | N=125 | Not yet recruiting | Sponsor: Shengjing Hospital

New P2 trial • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Evaluating the Preliminary Efficacy and Safety of JS207 in NSCLC After Progression Following Platinum-based Chemotherapy and Immunotherapy (clinicaltrials.gov) - P2 | N=72 | Not yet recruiting | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | N=42 ➔ 72 | Trial completion date: Sep 2026 ➔ Jun 2026 | Trial primary completion date: Sep 2026 ➔ Jun 2026

Enrollment change • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety, Tolerability and Pharmacokinetics of a Recombinant Humanized mAb Specific to B-and T-Lymphocyte Attenuator (BTLA) for Injection in Subjects With Advanced Malignancies (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Recruiting ➔ Completed | N=200 ➔ 47

Enrollment change • Trial completion • Oncology • Solid Tumor

Tifcemalimab as monotherapy or in combination with toripalimab in patients with relapsed/refractory lymphoma: a Phase I trial. (PubMed, Nat Commun) - P1 | "Grade 3/4 treatment-related adverse events occurred in 3 patients (12·0%) in Part A and 15 patients (32·6%) in Part B. No fatal adverse events were observed. Tifcemalimab with or without toripalimab demonstrated a favorable safety profile in lymphoma patients."

Journal • Monotherapy • P1 data • Classical Hodgkin Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • BTLA

Phase I/II Study of Tifcemalimab, an Anti-B and T-lymphocyte Attenuator Antibody, in Combination with Toripalimab in Previously Treated Advanced Lung Cancer. (PubMed, Clin Cancer Res) - "Tifcemalimab plus toripalimab showed promising antitumor activities with acceptable safety, especially, in advanced refractory SCLC."

Journal • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ALK • BTLA • EGFR

Tifcemalimab as monotherapy or in combination with toripalimab in patients with relapsed/refractory lymphoma: a Phase I trial (Nature) - P1 | N=71 | NCT04477772 | Sponsor: Jazz Pharmaceuticals | "No dose-limiting toxicities were observed, and MTD was not reached. The RP2D for tifcemalimab was 200 mg. Adverse events were predominantly Grade 1/2. Grade 3/4 treatment-related adverse events occurred in 3 patients (12·0%) in Part A and 15 patients (32·6%) in Part B. No fatal adverse events were observed. Tifcemalimab with or without toripalimab demonstrated a favorable safety profile in lymphoma patients."

P1 data • Lymphoma

Perioperative the BTLA inhibitor (tifcemalimab) combined with toripalimab and chemotherapy for resectable locally advanced thoracic esophageal squamous cell carcinoma trial (BT-NICE trial): a prospective, single-arm, exploratory study. (PubMed, Front Immunol) - "Patients with pathologically confirmed cT1b-3N1-3M0 or cT2-3N0M0 thoracic ESCC were treated with neoadjuvant tifcemalimab (200mg, iv, d1) in combination with toripalimab (240mg, iv, d1) and chemotherapy (paclitaxel 135-175 mg/m2, d1 + cisplatin 75 mg/m2, d1) every 3 weeks for 2 cycles. This study is the world's first prospective clinical trial to evaluate the safety and efficacy of the BTLA inhibitor in combination with PD-1 and chemotherapy as neoadjuvant/adjuvant therapy for locally advanced thoracic ESCC. We predicted that perioperative combination immunotherapy as a potentially preferred and effective treatment strategy may lead to better survival outcomes."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • BTLA

JS004 Combined With Toripalimab and With Standard Chemotherapy Treat Patients With Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=119 | Active, not recruiting | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Recruiting ➔ Active, not recruiting | N=240 ➔ 119 | Trial completion date: Nov 2024 ➔ Nov 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Phase I/II study of tifcemalimab combined with toripalimab in patients with previously treated advanced lung cancer (JSMO 2025) - No abstract available

Clinical • Metastases • P1/2 data • Lung Cancer • Oncology • Solid Tumor

Study of JS004 Combined With Toripalimab for Advanced Lung Cancer (clinicaltrials.gov) - P1/2 | N=67 | Completed | Sponsor: Shanghai Junshi Bioscience Co., Ltd. | Recruiting ➔ Completed | Trial primary completion date: Aug 2023 ➔ Oct 2024

Trial completion • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Phase II Clinical Study Evaluating the First-Line Treatment of Advanced HCC with JS004 in Combination with Toripalimab and Bevacizumab (ChiCTR) - P2 | N=39 | Sponsor: Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor • PD-L1

Phase II Clinical Study of Toripalimab + JS004 in Combination with Docetaxel for Advanced Non-Squamous NSCLC After Failure of Prior Platinum-based Chemotherapy and Immunotherapy (ChiCTR) - P2 | N=30 | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

Exploratory clinical study of Low-dose radiotherapy combined with concurrent Chemotherapy, Toripalimab and Tifcemalimab in first-line treatment of Extensive-Stage Small Cell Lung Cancer (ChiCTR) - P1 | N=12 | Sponsor: West China Hospital of Sichuan University; West China Hospital of Sichuan University

New P1 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Low-dose Radiotherapy Combined with Concurrent Chemotherapy, Toripalimab and Tifcemalimab in the Treatment of ES-SCLC (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Sichuan University

New P1 trial • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Prospective，Single Arm, Multicenter Clinical Study of BTLA Monoclonal Antibody JS004 (B/T Lymphocyte Attenuator Factor Monoclonal Antibody) in Combination With Toripalimab in Patients With Unresectable or Advanced Renal Cell Carcinoma Who Had Failed Previous Immunotherapy (clinicaltrials.gov) - P2 | N=31 | Not yet recruiting | Sponsor: RenJi Hospital

Combination therapy • Metastases • New P2 trial • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Tifcemalimab combined with toripalimab and docetaxel as 2nd line treatment for immunotherapy-treated squamous cell non-small cell lung cancer (Sq-NSCLC) patients: A phase Ib/II study (ESMO Asia 2024) - P1/2 | "The 6- month and 9-month OS rates were 85.3% and 70.1%, respectively. Conclusions Tifcemalimab in combination with toripalimab and docetaxel showed a promising antitumor activity with a manageable safety profile as a 2 nd line treatment for immunotherapy-treated Sq-NSCLC patients."

Clinical • P1/2 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BTLA