BGB-15025 / BeOne Medicines - LARVOL DELTA

HPK1 inhibition enhances tumor-reactive TIL expansion from pMMR colorectal cancer liver metastases (ESMO-IO 2025) - "We previously showed that the HPK1 inhibitor (BGB-15025), that blocks negative TCR signaling, prevents loss of tumor-reactive TILs and enhances reactivity...The reactive LM was distinguished by higher CD8+ infiltration and fewer M2 macrophages.Conclusions iHPK1 enhanced anti-tumor functionality and tumor-reactive TIL yield in pMMR CRC LM. Particularly in right-sided and otherwhise immune-resistant tumors, potentially opening new therapeutic opportunities.Legal entity responsible for the study The authors."

IO biomarker • pMMR • Colorectal Cancer • Oncology • Solid Tumor • BRAF • CD4 • CD8 • IFNG • IL2 • KRAS • TNFA

A first-in-human, phase I study of BGB-15025 (hematopoietic progenitor kinase 1 [HPK1] inhibitor) as monotherapy and in combination (combo) with tislelizumab (TIS; anti-PD-1 antibody) in patients (pts) with advanced solid tumors (ST) (ESMO 2025) - P1 | "Immune-mediated AEs occurred in 13 (28.9%) pts. Conclusions These results show BGB-15025 in combo with TIS ± CT demonstrated antitumor activity and was generally tolerable in advanced ST."

Clinical • First-in-human • Metastases • Monotherapy • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastroesophageal Junction Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

Hematopoietic Progenitor Kinase-1 (HPK-1) Inhibition Improves the In Vitro Efficacy ofBispecific Antibodies in CLL (IWCLL 2025) - "Aims: This study aimed to explore the effectiveness of HPK-1 inhibition combined with CD20XCD3 bispecific antibodies as a treatment strategy for CLL. Peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with selective HPK-1 inhibitors, such as HY-138568 or BGB15025, and subsequently activated with anti-CD3/CD28 antibodies. PBMCs from CLL patients treated with HPK-1 inhibitors and activated with anti-CD3/CD28 beads showed a significant increase in CD69 and CD25 surface expression on CD8+ T cells, with no significant change in CD4+ T cells. Additionally, HPK-1 inhibitor pretreatment led to a notable increase in IFN-γ and granzyme B release in response to CD3/CD28 activation. The incubation of CLL patient PBMCs with CD20xCD3 bispecific antibodies, including mosunetuzumab, epcoritamab, and glofitamab, resulted in increased IFNγ secretion, particularly with glofitamab."

Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Lymphoma • CD4 • CD69 • CD8 • GZMB • IFNG • IL2RA

HPK1 INHIBITOR BGB-15025 INDUCES APOPTOSIS IN AML CELLS THROUGH CELL CYCLE PATHWAY AND MAPK/ERK SIGNALING AXIS. (EHA 2025) - P1 | "Background: (AML), a clonal hematopoietic stem cell disorder, exhibits suboptimal long-term outcomes despite achieving initial complete remission in 60-80% of patients receiving anthracycline/cytarabine induction. Preclinical findings indicate that the selective HPK1 inhibitor BGB-15025 mediates anti-leukemic activity via G0/G1 cell cycle arrest and MAPK/ERK pathway suppression, inducing apoptosis in AML progenitors. These data collectively support its potential as a translational therapeutic candidate for AML."

Acute Myelogenous Leukemia • Oncology • Solid Tumor • CCND1 • CDK4 • MAPK8

HEMATOPOIETIC PROGENITOR KINASE-1 (HPK-1) INHIBITION IMPROVES THE IN VITRO EFFICACY OF BISPECIFIC ANTIBODIES IN CLL (EHA 2025) - "Peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with selective HPK-1 inhibitors, such as HY-138568 or BGB15025, and subsequently activated with anti-CD3/CD28 antibodies...The incubation of CLL patient PBMCs with CD20xCD3 bispecific antibodies, including mosunetuzumab, epcoritamab, and glofitamab, resulted in increased IFN-γ secretion, particularly with glofitamab... This study highlights the promising potential of integrating HPK-1 inhibitors with bispecific antibodies to boost antitumor T-cell cytotoxicity in patient-derived CLL samples. Our findings may pave the way for the development of innovative combination therapies that utilize HPK-1 inhibition to enhance cellular therapies in CLL."

Preclinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • CD4 • CD69 • CD8 • GZMB • IFNG • IL2RA

A phase 2 study of the OX40 agonist BGB-A445, in combination with docetaxel or BGB-15025, an HPK1 inhibitor, in patients with NSCLC pretreated by anti-PD-(L)1 antibodies. (ASCO 2025) - P2 | "BGB-A445 plus docetaxel or BGB-15025 was generally well tolerated in pts with advanced NSCLC and showed limited antitumor activity. SafetyPts with multiple AEs are counted once. All AEs are n (%)."

Clinical • Combination therapy • IO biomarker • P2 data • Cardiovascular • Hypertension • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma

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

BGB-A317-15025-101: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=157 | Active, not recruiting | Sponsor: BeiGene | Trial completion date: Mar 2025 ➔ Oct 2026 | Trial primary completion date: Mar 2025 ➔ Oct 2025

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

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 of BGB-A445 in Combination With Other Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=35 | Completed | Sponsor: BeiGene | Active, not recruiting ➔ Completed

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

BGB-A317-15025-101: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=157 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | N=330 ➔ 157

Enrollment change • Enrollment closed • Esophageal Cancer • Gastric Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of BGB-A445 in Combination With Other Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: BeiGene | Recruiting ➔ Active, not recruiting | N=100 ➔ 35 | Trial completion date: May 2026 ➔ Dec 2024 | Trial primary completion date: Jan 2026 ➔ Dec 2024

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

BeiGene Enters Next Phase of Global Growth with Announcement of Second Quarter 2024 Financial Results and Corporate Updates (Businesswire) - "BGB-16673 (BTK CDAC): Anticipating first subject enrolled in Phase 3 program in fourth quarter of 2024 or first quarter of 2025....Multiple randomized 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....Pan-KRAS, MTA-cooperative PRMT5 inhibitors and EGFR CDAC targeted protein degrader on track to enter the clinic in the second half of 2024."

Clinical data • New P3 trial • New trial • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

EFFECT AND MECHANISM OF HPK1 INHIBITOR BGB-15025 ON ACUTE MYELOID LEUKEMIA (EHA 2024) - "BGB-15025 demonstrated inhibitory effects on the growth and induction of apoptosis in both AML cell linesand primary AML cells. In vitro experiments have shown significant cytotoxicity against AML cell lines, butfurther investigations are required to elucidate its mechanism of action. As an investigational drug currentlyundergoing phase I clinical trials, BGB-15025 has exhibited promising efficacy in the treatment of AML andholds immense potential as a therapeutic intervention for AML patients in the foreseeable future."

IO biomarker • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • ANXA5

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

A first‑in‑human phase 1a dose‑escalation study of BGB‑15025 (HPK1 inhibitor) as monotherapy and in combination with tislelizumab (TIS; anti‑PD‑1 antibody) in patients (pts) with advanced solid tumors. (ASCO 2024) - P1 | "Research Funding: Bei Gene, Ltd. . These preliminary results show BGB-15025 mono tx or combo tx with TIS was generally tolerable. The antitumor activity of BGB-15025 was improved when given in combination with TIS. Further investigation of BGB-15025 + TIS +/- chemotherapy is ongoing in the expansion phase."

Clinical • Combination therapy • Metastases • Monotherapy • P1 data • Cervical Cancer • Fatigue • Gastroenterology • Gastrointestinal Disorder • Head and Neck Cancer • Hepatology • Immunology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

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

BGB-A317-15025-101: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=330 | Recruiting | Sponsor: BeiGene | Trial completion date: Aug 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Global Oncology Innovator BeiGene Highlights New Data across Hematology and Solid Tumor Portfolio at 2024 ASCO Annual Meeting (BeiGene Press Release) - "Reflecting BeiGene’s growing solid tumor development program, TEVIMBRA (tislelizumab-jsgr) will be the subject of multiple presentations – as a monotherapy, in combination with chemotherapy agents, and as part of immunotherapy regimens across a range of tumor types. Key highlights include: New data from the Phase 3 RATIONALE-306 study evaluating TEVIMBRA plus chemotherapy in patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC); and Initial data from a first-in-human study evaluating HPK1 inhibitor BGB-15025 alone and in combination with TEVIMBRA."

P1 data • P3 data • Esophageal Cancer • Gastrointestinal Cancer • 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

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

BGB-A317-15025-101: BGB-15025 Alone and in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Participants With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=330 | Recruiting | Sponsor: BeiGene

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of BGB-A445 in Combination With Other Investigational Agents in Participants With Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: BeiGene | Not yet recruiting ➔ Recruiting

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

HPK1 Inhibition Enhances HXRT Anti-Tumor Immune Response by Regulating RGS16 to Restore Functionality in Tumor-Infiltrating Exhausted CD8+T Cells (ASTRO 2023) - "Thus, we demonstrate that HPK1 mediates HFRT-induced CD8+T cell exhaustion by regulating RGS16, and HPK1 is an attractive drug target for enhancing local and systemic radiotherapy."

IO biomarker • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD8