alcestobart (LBL-007) / Leads Biolabs - LARVOL DELTA

Novel anti-LAG-3 antibody LBL-007 with anti-PD-1 blockade enhances antitumor immunity by promoting T cell-induced apoptosis. (PubMed, Sci Rep) - "The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell apoptosis compared with monotherapy in human LAG-3 transgenic mice subjected to transplantation with colorectal tumor cells. Taken together, the combination of LBL-007 and anti-PD-1 antibodies plays an enhanced antitumor role by improving T cell viability and activity as well as by promoting T cell-induced apoptosis, thereby suggesting this combination as a potential effective strategy for cancer immunotherapy."

IO biomarker • Journal • Colorectal Cancer • Melanoma • Oncology • Solid Tumor • Transplantation • IL10 • IL2 • LAG3

A Phase 2 Multicenter Umbrella Trial Assessing Tislelizumab ± Anti-TIGIT or Anti-LAG-3 mAb ± Chemotherapy in Resectable NSCLC (IASLC-WCLC 2025) - P2 | "Patients with PD-L1 TC ≥50% were assigned to Substudy 1 and randomized to TIS (anti-PD-1; Arm 1A), TIS plus ociperlimab (anti-TIGIT; Arm 1B), or TIS plus LBL-007 (anti-LAG-3; Arm 1C); patients with PD-L1 TC <50% were assigned to Substudy 2 and randomized to TIS and chemotherapy (Arm 2A) or TIS plus LBL-007 and chemotherapy (Arm 2C). Conclusions : Neoadjuvant TIS as monotherapy or TIS-based immunotherapy combinations in PD-L1 TC ≥50% NSCLC had promising MPR/pCR; the addition of other immunotherapy to neoadjuvant TIS and chemotherapy in PD-L1 TC <50% did not provide additional efficacy benefit. Treatment guided by histology and PD-L1 expression is suggested for future exploration."

Clinical • IO biomarker • P2 data • Anemia • Hematological Disorders • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • ALK • EGFR • TIGIT

A Study to Assess LBL-007 in Combination With Toripalimab and Axitinib Tablets Subjects With Advanced Melanoma (clinicaltrials.gov) - P1 | N=79 | Completed | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor

A Trial of LBL-024 Monotherapy, LBL-024 Combined With LBL-007 or Toripalimab in Patients With Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Melanoma • Oncology • Solid Tumor

A Trial of LBL-024 Monotherapy, LBL-024 Combined With LBL-007 or Toripalimab in Patients With Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=200 | Not yet recruiting | Sponsor: Nanjing Leads Biolabs Co.,Ltd

Monotherapy • New P1/2 trial • Melanoma • Oncology • Solid Tumor

BGB-HNSCC-201: A Study of Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=160 | Active, not recruiting | Sponsor: BeiGene | Trial completion date: Jan 2027 ➔ May 2026 | Trial primary completion date: Jan 2027 ➔ Jun 2025

Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Updated efficacy, safety and biomarker analysis of a phase 2 study of LBL-007 (alcestobart, an anti-LAG-3 mAb) combined with tislelizumab (an anti–PD-1 mAb) and chemotherapy in previously untreated recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). (ASCO 2025) - P1/2, P3 | " Untreated R/M NPC patients received gemcitabine at 1 g/m² on days 1 and 8, cisplatin at 80 mg/m² on day 1 (GP) in combination with LBL-007 600 mg and tislelizumab 200 mg on day 1 of every 3 weeks, the chemotherapy was up to 6 cycles, followed by LBL-007 and tislelizumab on day 1 of every 3 weeks as maintenance therapy. LBL-007/tislelizumab combined with GP chemotherapy has shown encouraging ORR, PFS and DoR in R/M NPC as first-line treatment with favorable safety profiles. These findings support a pivotal phase III study comparing LBL-007/tislelizumab plus GP with tislelizumab plus GP in R/M NPC in 1L setting. The correlation between higher LAG-3 expression and improved efficacy was observed, which warranted further validation in larger population."

Biomarker • Clinical • IO biomarker • Metastases • P2 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • LAG3

A Phase Ib/II Clinical Study of LBL-007 in Combination With Toripalimab in Treatment of Advanced Malignant Tumors (clinicaltrials.gov) - P1/2 | N=80 | Completed | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Recruiting ➔ Completed | N=200 ➔ 80

Enrollment change • Trial completion • Oncology • Solid Tumor

BGB-A317-LBL-007-202: A Study to Evaluate LBL-007 in Combination With Tislelizumab Plus Chemotherapy in Participants With Unresectable Locally Advanced or Metastatic Esophageal Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=118 | Active, not recruiting | Sponsor: BeiGene | Trial completion date: Sep 2025 ➔ May 2026

Trial completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

A novel fully human LAG-3 monoclonal antibody LBL-007 combined with PD-1 antibody inhibits proliferation, migration and invasion of tumor cells via blocking NF-κB pathway (PubMed, Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi) - "Treatment with the NF-κB signaling pathway agonist TNF-α reversed the suppressive effects of LBL-007 and BE0188 on tumor cell proliferation, invasion, migration, and NF-κB signaling. Conclusion LBL-007 and anti-PD-1 antibody synergistically inhibit the invasion, migration, and proliferation of A549 and MGC803 tumor cells by blocking the NF-κB signaling pathway."

IO biomarker • Journal • Oncology • LAG3 • MMP2 • MMP9 • NFKBIA • TNFA

Liberty-201: A Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=113 | Active, not recruiting | Sponsor: BeiGene | Trial completion date: Apr 2026 ➔ Dec 2026 | Trial primary completion date: Apr 2026 ➔ May 2025

Mismatch repair • pMMR • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor • PD-L1

BGB-LC-201: A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: BeiGene | Trial completion date: Jul 2025 ➔ Oct 2025 | Trial primary completion date: Jul 2025 ➔ Oct 2025

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=430 | Enrolling by invitation | Sponsor: BeiGene | N=300 ➔ 430

Enrollment change • Oncology • Solid Tumor

2025 ASCO: Encouraging Clinical Data from Leads Biolabs' Innovative Bispecific Antibody LBL-024 against PD-L1 and 4-1BB Selected for Oral Presentation (Leads Biolabs Press Release) - "Nanjing Leads Biolabs Co., Ltd...announced that two of its innovative oncology assets, LBL-024 and LBL-007, have been selected for oral and poster presentations, respectively, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, to be held in Chicago from May 30 to June 3. The selection highlights the strong clinical potential and innovation of Leads Biolabs’ immuno-oncology pipeline."

Clinical data • Nasopharyngeal Carcinoma • Neuroendocrine Tumor

BGB-LC-202: Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=121 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed | Trial completion date: Dec 2026 ➔ Jan 2025 | Trial primary completion date: Dec 2026 ➔ Jan 2025

Monotherapy • Trial completion • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Anti-LAG-3 antibody LBL-007 plus anti-PD-1 antibody toripalimab in advanced nasopharyngeal carcinoma and other solid tumors: an open-label, multicenter, phase Ib/II trial. (PubMed, J Hematol Oncol) - "LBL-007 plus toripalimab exhibited a manageable safety profile in patients with advanced solid tumors and demonstrated promising antitumor activity in NPC, especially in immunotherapy-naive patients. These findings warrant further validation in future studies."

IO biomarker • Journal • P1/2 data • Cardiovascular • Fatigue • Heart Failure • Hematological Disorders • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • PD-L1

BGB-900-102: Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=114 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed

Trial completion • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

BGB-LC-201: A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=400 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Study to Assess LBL-007 in Combination With Toripalimab and Axitinib Tablets Subjects With Advanced Melanoma (clinicaltrials.gov) - P1 | N=88 | Recruiting | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

BGB-900-102: Study of BGB-A425 and LBL-007 in Combination With Tislelizumab in Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=114 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | N=358 ➔ 114

Enrollment change • Enrollment closed • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • PD-L1

Liberty-201: A Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Fluoropyrimidine Versus Bevacizumab Plus Fluoropyrimidine in Participants With Unresectable or Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=113 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | N=226 ➔ 113 | Trial completion date: Apr 2028 ➔ Apr 2026 | Trial primary completion date: Apr 2028 ➔ Apr 2026

Enrollment change • Enrollment closed • Mismatch repair • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Oncology • Solid Tumor • PD-L1

Phase Ib/II Clinical Study of LBL-007 in Treatment of Advanced Malignant Tumors (clinicaltrials.gov) - P1/2 | N=200 | Recruiting | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Trial completion date: Mar 2025 ➔ Aug 2025 | Trial primary completion date: Dec 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

BGB-HNSCC-201: Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=160 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

BGB-LC-202: Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations in Participants With Resectable Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=121 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

LBL-007-CN-004: A Phase Ib/II Clinical Trial of LBL-007 Combined With Tislelizumab in the Treatment of Malignant Tumors (clinicaltrials.gov) - P1/2 | N=490 | Recruiting | Sponsor: Nanjing Leads Biolabs Co.,Ltd | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Oct 2025

Combination therapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor