LBL-007 / Leads Biolabs, BeiGene - LARVOL DELTA

BGB-A317-290-LTE1: Study of Tislelizumab, Pamiparib, and Other Investigational Agents in Participants With Advanced Malignancies (clinicaltrials.gov) - P3 | N=300 | Enrolling by invitation | Sponsor: BeiGene | Trial completion date: Aug 2024 ➔ Dec 2026 | Trial primary completion date: Aug 2024 ➔ Dec 2026

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

BeiGene Reports First Quarter 2024 Financial Results and Business Updates (Businesswire) - "Gastrointestinal Cancers: Multiple tislelizumab combination cohorts with LBL-007 (anti-LAG3) and BGB-A445 (anti-OX40) reading out in 2024; Plan to submit a BLA with the NMPA for zanidatamab for the treatment of second-line biliary tract cancer; and CEA-ADC and FGFR2b-ADC on track to enter the clinic in the second half of 2024."

New trial • Non-US regulatory • P2 data • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

BeiGene Reports First Quarter 2024 Financial Results and Business Updates (Businesswire) - "Enrolled last subject in a Phase 3 clinical trial for ociperlimab (anti-TIGIT) for first-line PD-L1 high NSCLC; Multiple tislelizumab lung cancer combination cohorts with BGB-A445 (anti-OX40), LBL-007 (anti-LAG3) and BGB-15025 (HPK1 inhibitor) expected to read out in 2024; and Pan-KRAS and MTA-cooperative PRMT5 inhibitors and EGFR CDAC on track to enter the clinic in the second half of 2024."

Clinical data • New trial • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody tislelizumab with or without chemotherapy in patients with advanced nasopharyngeal cancer and other malignant tumors: A phase Ib/II dose escalation/expansion study. (ASCO 2024) - P1/2 | "Clinical Trial Registration Number: NCT05516914"

Clinical • Combination therapy • Metastases • P1/2 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

BGB-LC-201 (NCT05635708): A phase 2, open-label, multi-arm study of tislelizumab (TIS; anti-PD-1) in combination with investigational agents +/- chemotherapy as first-line treatment for patients with locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) (AACR 2024) - P2 | "This phase 2 study will determine whether adding investigational agents BGB-A445 (OX40 agonistic monoclonal antibody [mAb]), LBL-007 (anti-lymphocyte activation gene-3 mAb), or BGB-15025 (hematopoietic progenitor kinase 1 [HPK1] inhibitor) improves the therapeutic benefit of TIS (anti-PD-1 mAb) +/- chemo in patients with locally advanced, unresectable, or metastatic NSCLC. The umbrella design allows for the use of multiple investigational drugs, administered alone or in combination, in patients with untreated locally advanced, unresectable, or metastatic NSCLC without actionable driver mutations. Exploratory endpoints include overall survival, time to response, and relevant biomarker associations with response or resistance to study treatments. Enrollment is ongoing at 66 sites in China, Asia-Pacific, the United States, and the European Union."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Liberty-201: Maintenance fluoropyrimidine and bevacizumab with or without anti-lymphocyte activation gene-3 (LAG-3) antibody LBL-007 plus anti-programmed cell death protein-1 (PD-1) antibody tislelizumab (TIS) for patients (pts) with metastatic or unresectable microsatellite stable (MSS)/mismatch repair proficient (pMMR) colorectal cancer (CRC) (AACR 2024) - P1/2 | "Secondary endpoints include overall survival, PFS2, overall response rate, duration of response, safety, pharmacokinetics, and immunogenicity. Exploratory endpoints include potential biomarkers (including but not limited to PD-L1 and LAG-3)."

Clinical • IO biomarker • Metastases • Mismatch repair • Colorectal Cancer • Gastrointestinal Cancer • Microsatellite Instability • Oncology • Solid Tumor • MSI • PD-L1

BGB‑A317‑LBL‑007‑202: A phase 2, randomized, active-controlled, open-label study to evaluate the efficacy and safety of LBL‑007 (anti-LAG-3) in combination with tislelizumab (TIS; anti-PD-1) plus chemotherapy (chemo) as first-line (1L) treatment in patients with unresectable locally advanced/metastatic esophageal squamous cell carcinoma (ESCC) (AACR 2024) - P2 | "The chemo doublet will consist of either cisplatin (60-80 mg/m2 IV Q3W) + 5-fluorouracil (750-800 mg/m2 IV daily on Days 1-5 Q3W), or cisplatin + paclitaxel (175 mg/m2 IV Q3W), determined by the investigator before randomization. Exploratory endpoints include comparison of overall survival, assessment of predictive, prognostic, and pharmacodynamic biomarkers, pharmacokinetic evaluation of LBL-007 and TIS, and immunogenicity. The study is currently recruiting at approximately 46 sites across Asia, including Taiwan, mainland China, South Korea, and Thailand."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • LAG3

Translational assessment of triple combination with Tislelizumab (anti-PD-1), LBL-007 (anti-LAG-3) and Surzebiclimab (anti-TIM-3) highlights its strong anti-tumor activity and clinical potential in solid tumors such as HNSCC (AACR 2024) - P2 | "The concurrent blockade of PD-1/LAG-3/TIM-3 represents a promising strategy to enhance T cell function and anti-tumor activity. The results demonstrated the therapeutic potential of the triple combination. A Ph2 study evaluating Tisle in combination with LBL-007 and/or Surze in first-line treatment of recurrent or metastatic HNSCC (NCT05909904) is recruiting."

Clinical • IO biomarker • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IFNG

Anti-LAG-3 antibody LBL-007 in combination with anti-PD-1 antibody toripalimab, in patients with advanced malignant tumors: A phase Ib/II, open-label, multicenter, dose escalation/expansion study (AACR 2024) - P1/2 | "LBL-007 in combination with toripalimab is well tolerated in patients with advanced malignant tumors and has demonstrated encouraging preliminary efficacy in patients with advanced NPC with or without prior anti-PD-(L)1 therapy. Clinical trial information: NCT05102006."

Clinical • Combination therapy • Metastases • P1/2 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

BeiGene to Present Clinical and Preclinical Data from Broad Portfolio and Pipeline at AACR Annual Meeting 2024 (Businesswire) - "An additional clinical presentation includes the first data from a Phase 1a dose escalation study of BGB-10188, a phosphatidylinositol 3 kinase delta (PI3Kδ) inhibitor, plus tislelizumab in patients with solid tumors. BeiGene will also be presenting preclinical characterizations of several novel molecules from its internal discovery engine, including a CEA x 4-1BB bispecific antibody and a chimeric degradation activation compound (CDAC) targeting BTK, BGB-16673....An additional preclinical presentation highlights the therapeutic potential of the triple-combination of tislelizumab with anti-LAG-3 (LBL-007) and anti-TIM-3 (surzebiclimab)..."

Preclinical • Head and Neck Cancer • Hematological Malignancies • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

A Study of Tislelizumab in Combination With Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=400 | Recruiting | Sponsor: BeiGene | N=200 ➔ 400

Combination therapy • Enrollment change • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung 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: Apr 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Jul 2024

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

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: Apr 2024 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

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

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=226 | Recruiting | Sponsor: BeiGene | Phase classification: P1b/2 ➔ P1/2

Phase classification • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

BGB-HNSCC-201: Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: BeiGene

Combination therapy • Metastases • 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

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=120 | Recruiting | Sponsor: BeiGene | N=90 ➔ 120

Enrollment change • Monotherapy • 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

BGB-LC-202 (NCT05577702): Phase II Umbrella study of tislelizumab (TIS) monotherapy and TIS-based immunotherapy combinations +/- chemotherapy (CT) as neoadjuvant treatment in Chinese patients (pts) with resectable stage II to IIIA non-small cell lung cancer (NSCLC) (ESMO Asia 2023) - P2 | "Sixty pts in Substudy 1 (PD-L1 ≥50%) will be randomized 1:1:1 to TIS monotherapy (Arm 1A), TIS + ociperlimab (anti-T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains mAb) (Arm 1B), or TIS + LBL-007 (anti-LAG-3 mAb) (Arm 1C). Secondary endpoints include pathological complete response per BIPR, overall survival, event-free survival, and disease-free survival (both per investigator; RECIST v1.1), adverse events (per CTCAE v5.0), the proportion of pts who undergo surgical resection following treatment, and pharmacodynamic assessments of the investigational agents. Enrollment is ongoing."

Clinical • IO biomarker • Monotherapy • P2 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR

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=116 | Recruiting | Sponsor: BeiGene

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma

BGB-HNSCC-201 (NCT05909904): Phase 2, Open-Label, Multi-Arm, Global Study of Tislelizumab (TIS) + Investigational Agents as First-Line (1L) Treatment in Patients (Pts) With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (ESMO-IO 2023) - P2 | "Anti-programmed cell death-protein 1 (PD-1) therapy, either alone or in combination with chemotherapy (CT), extended overall survival (OS) vs cetuximab + CT in pts with programmed cell death-ligand 1 (PD-L1)-positive R/M HNSCC in the 1L setting; however, not all pts respond to single-agent anti-PD-1 therapy...This Phase 2 study will assess efficacy and safety of TIS in combination with investigational agents targeting the immune-checkpoint inhibitors TIM-3 (BGB-A425) and/or LAG-3 (LBL-007) as 1L treatment in pts with R/M HNSCC...Secondary endpoints include progression-free survival, duration of response, clinical benefit rate, and disease control rate (all per investigator; RECIST v1.1) as well as safety, OS, and immunogenicity to study drugs. Enrollment is ongoing and additional experimental arms may be added in the future."

Clinical • Metastases • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • HAVCR2 • LAG3

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=116 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma

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) - P1b/2 | N=226 | Recruiting | Sponsor: BeiGene | Trial completion date: Aug 2026 ➔ Apr 2028 | Trial primary completion date: Feb 2025 ➔ Apr 2028

Combination therapy • IO biomarker • Metastases • Mismatch repair • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

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=116 | Not yet recruiting | Sponsor: BeiGene

Combination therapy • Metastases • New P2 trial • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Oncology • Squamous Cell Carcinoma

A Study Investigating the Efficacy and Safety of LBL-007 Plus Tislelizumab in Combination With Bevacizumab Plus Capecitabine Versus Bevacizumab Plus Capecitabine in Participants With Unresectable or Metastatic Colorectal Cancer (clinicaltrials.gov) - P1b/2 | N=202 | Recruiting | Sponsor: BeiGene | Active, not recruiting ➔ Recruiting

Combination therapy • Enrollment open • IO biomarker • Metastases • Mismatch repair • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • PD-L1

Tislelizumab in Combination With Investigational Agents in Participants With Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov) - P2 | N=160 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

Enrollment open • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Chime Biologics Announces Strategic Cooperation with Leads Biolabs and BeiGene to Advance LBL-007 mAb Development and Manufacturing Globally (PRNewswire) - "Chime Biologics...announced that it has established 3-way strategic cooperation with Leads Biolabs and BeiGene to accelerate LBL-007 mAb development and manufacturing for speedy clinical advancement....Leads Biolabs has entrusted Chime Biologics with the file supporting work related to the production of LBL-007 project and clinical trial materials in mainland China....BeiGene is also entrusting Chime Biologics to provide support for clinical development and manufacturing of clinical trial materials in order to facilitate multiple clinical trials. The indications encompass colorectal cancer, non-small cell lung cancer, head and neck squamous cell carcinoma, as well as other solid tumors."

Licensing / partnership • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck