izalontamab brengitecan (BL-B01D1) / Sichuan Biokin Pharmaceutical, BMS, Systimmune - LARVOL DELTA

Phase 1 Global Study of Iza-Bren in Patients With Metastatic EGFR-mutated NSCLC: Results of the Randomized Dose Expansion Cohort (IASLC-WCLC 2026) - P1 | "The median number of prior line of therapy was 2 (range 1-7); all pts had progressed on a third generation EGFR inhibitor, 64% progressed on platinum-based chemotherapy and 18% progressed on amivantamab. Primary G-CSF prophylaxis was associated with an improved safety profile. The totality of the safety, efficacy and PK data support 2.5 mg/kg D1D8 Q3W as the RP3D in the global registrational study (IZABRIGHT-Lung01) in EGFR-mutated NSCLC after progression on a third generation EGFR inhibitor (NCT05983432)."

Clinical • Metastases • P1 data • Febrile Neutropenia • Inflammation • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pneumonia • Solid Tumor • Thrombocytopenia • EGFR

Safety and antitumor activity of the first-in-class EGFR-HER3 bispecific antibody-drug conjugate iza-bren (BL-B01D1) in patients with pretreated locally advanced or metastatic breast cancer: a phase 1b study. (PubMed, Ann Oncol) - "Iza-bren exhibited a generally tolerable safety profile and demonstrated clinically meaningful antitumor activity across three major subtypes of heavily pretreated metastatic breast cancer."

Clinical • Journal • P1 data • Breast Cancer • Cerebral Hemorrhage • CNS Disorders • Febrile Neutropenia • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Interstitial Lung Disease • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Triple Negative Breast Cancer • EGFR • ERBB3 • HER-2

PANKU-Breast01: Randomized Phase III Study of Izalontamab Brengitecan (iza-bren) in Previously Treated Unresectable Locally Advanced or Metastatic (LA/M) Hormone Receptor-Positive/HER2-negative (HR+/HER2-) Breast Cancer (BC) (ESMO 2026) - No abstract available

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

PANKU-Lung01: Randomized Phase III Study of Izalontamab Brengitecan (iza-bren) in EGFR-Mutant Non-squamous Non‑Small Cell Lung Cancer (NSCLC) After Progression on a Third Generation EGFR TKI (ESMO 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

Achievement of a milestone in the global Phase III registration trial IZABRIGHT-Lung02 has triggered a USD 250 million near-term milestone payment to SystImmune, Inc. under its collaboration with Bristol Myers Squibb (AllSci Corp) - "The payment represents the second USD 250 million tranche under the agreement, alongside an USD 800 million upfront payment received after the deal was signed in December 2023. IZABRIGHT-Lung02 is a BMS-led global registrational Phase III study evaluating izalontamab brengitecan (iza-bren), an EGFRxHER3 bispecific antibody-drug conjugate (ADC), in previously untreated patients with locally advanced or metastatic EGFR-mutant non-small cell lung cancer (NSCLC)....Biokin did not disclose the specific milestone event that triggered the payment, and the announcement included no clinical efficacy or safety data."

Financing • Non Small Cell Lung Cancer

Upcoming treatments (EADV 2026) - "Cytokines are small, low-molecular-weight proteins (~5–25 kDa) that serve as critical chemical messengers for cell-to-cell communication within the immune system. Produced by a wide range of cells, including immune cells (such as T cells, B cells, macrophages, and natural killer cells) and non-immune cells (such as endothelial, fibroblast, and epithelial cells), they regulate immunity, inflammation, and hematopoiesis.Key Approved Monoclonal AntibodiesPembrolizumab (Keytruda): Blockade of the PD-1 immune checkpoint for multiple solid tumors including melanoma and non-small cell lung cancer.Trastuzumab (Herceptin): Targeting of the HER2 receptor in HER2-positive breast cancers.Lecanemab (Leqembi): Clearance of brain amyloid-beta plaques for early-stage Alzheimer's disease.Blinatumomab (Blincyto): Bispecific T-cell engager utilized for B-cell precursor acute lymphoblastic leukemia.Emerging Formats and Pipeline DrugsBispecific and Multispecific Antibodies: Engineered to..."

Acute Lymphocytic Leukemia • Alzheimer's Disease • Breast Cancer • Chronic Spontaneous Urticaria • CNS Disorders • Dermatology • Hematological Malignancies • HER2 Breast Cancer • HER2 Positive Breast Cancer • Immunology • Leukemia • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Pruritus • Solid Tumor • Urticaria • HAVCR2 • HER-2 • LAG3 • TIGIT

Phase I global study of Iza-Bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and other solid tumors (ESMO 2025) - "# Non-evaluable: pts who discontinued or died without post-baseline tumor assessment Conclusions Iza-bren has demonstrated encouraging efficacy with an acceptable safety profile in multiple tumor types, including NSCLC and BC in this first report of a global population, consistent with the strong efficacy previously reported in Chinese pts. A global registrational study of first line TNBC is ongoing, while studies in other tumor types are planned."

Clinical • Metastases • P1 data • Breast Cancer • Esophageal Adenocarcinoma • Esophageal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • CSF3

BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic urothelial carcinoma (UC) (ESMO 2024) - P2 | "In patients with heavily pretreated UC, BL-B01D1 demonstrated manageable safety with encouraging antitumor activity. Further evaluation of BL-B01D1 in this patient population is ongoing."

Clinical • Metastases • Oncology • Solid Tumor • Urethral Cancer • Urothelial Cancer

Phase II study of iza-bren (BL-B01D1) in combination with serplulimab in patients with small cell lung cancer (SCLC) (ELCC 2026) - P2 | "In stage II, treatment-naive pts were treated with iza-bren at 2.5 or 2.75 mg/kg D1D8 Q3W plus serplulimab or plus serplulimab and anlotinib. Legal entity responsible for the study Baili-Bio (Chengdu) Pharmaceutical Co., Ltd. Funding Baili-Bio (Chengdu) Pharmaceutical Co., Ltd."

Clinical • Combination therapy • P2 data • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study. (ASCO 2023) - P1 | "BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced solid tumors, especially in pts with EGFRm NSCLC. The safety profile showed adequate safety and tolerability. Clinical trial information: NCT05194982."

Clinical • Metastases • P1 data • Alopecia • Anemia • Febrile Neutropenia • Head and Neck Cancer • Hematological Disorders • Infectious Disease • Leukopenia • Lung Cancer • Nasopharyngeal Carcinoma • Neuroendocrine Tumor • Neutropenia • Non Small Cell Lung Cancer • Novel Coronavirus Disease • Oncology • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thrombocytopenia • PD-1

BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with non-small cell lung cancer: Updated results from first-in-human phase I study (ESMO 2023) - P1 | "Conclusions BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced NSCLC, especially in pts with EGFRmut. The observed toxicity is deemed acceptable."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase I/II Study of Iza-Bren (BL-B01D1) as Monotherapy in Patients With Locally Advanced or Metastatic EGFR Mutated NSCLC (IASLC-WCLC 2025) - P3 | "Conclusions : In previously treated EGFRmt NSCLC pts, iza-bren demonstrated promising efficacy with a manageable safety profile. Phase 3 registrational study of iza-bren as monotherapy in EGFRmt NSCLC after progression on a third generation TKI is ongoing in China (NCT06382116)."

Clinical • Metastases • Monotherapy • P1/2 data • Alopecia • Anemia • Dental Disorders • Immunology • Interstitial Lung Disease • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis • Thrombocytopenia • EGFR

A Study Comparing BL-B01D1 in Combination With Osimertinib Versus Osimertinib Alone in Patients With Locally Advanced, Unresectable EGFR-mutated Non-small Cell Lung Cancer(Stage III) Whose Disease Has Not Progressed Following Definitive Platinum-based Chemoradiation Therapy(PANKU-Lung08) (clinicaltrials.gov) - P3 | N=418 | Recruiting | Sponsor: Sichuan Baili Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

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

Antibody-Drug Conjugates in the Treatment of Esophageal Cancer. (PubMed, Curr Treat Options Oncol) - "For HER2-negative gastroesophageal adenocarcinoma, trophoblast cell-surface antigen 2 represents a promising target given its high prevalence of moderate to strong expression in nearly 80% of cases, and sacituzumab tirumotecan is currently under phase III investigation in this setting...For Nectin-4-expressing tumors, enfortumab vedotin may be considered as a later-line alternative despite modest activity. Notably, the bispecific ADC targeting both epidermal growth factor receptor and human epidermal growth factor receptor 3, BL-B01D1, has demonstrated compelling efficacy in immunotherapy-refractory esophageal squamous cell carcinoma, and I consider it a breakthrough option in this subtype. For claudin-18.2-positive gastroesophageal junction adenocarcinoma, several ADCs including CMG901, IBI343, and tecotabart vedotin represent promising later-line choices. I emphasize that patient selection should be guided by validated predictive biomarkers, and treatment decisions..."

Biomarker • IO biomarker • Journal • Review • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Interstitial Lung Disease • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • CLDN18 • ERBB3 • HER-2 • NECTIN4

Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic breast cancer (BC) (ESMO-BC 2025) - P1 | "In heavily pre-treated locally advanced or metastatic HER2- BC, iza-bren has demonstrated encouraging efficacy with a manageable safety profile, including in pts with HER2 zero expression."

Clinical • Metastases • P1 data • Breast Cancer • Oncology • Solid Tumor • HER-2

Phase I study of iza-bren (BL-B01D1), an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic small cell lung cancer (SCLC). (ASCO 2025) - P1, P3 | "In SCLC pts, iza-bren has demonstrated an encouraging efficacy with a manageable safety profile. Notably, the high confirmed response rate of 75% in pts with limited prior treatment underscores its potential as a novel therapeutic option for SCLC, a disease with limited therapeutic advancements over decades. The phase III study of iza-bren in SCLC pts who received 1 prior line of PD(L)-1 and PBC combination treatment is ongoing (NCT06500026)."

Clinical • Metastases • P1 data • Anemia • Dental Disorders • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Leukopenia • Lung Cancer • Neutropenia • Oncology • Respiratory Diseases • Small Cell Lung Cancer • Solid Tumor • Stomatitis • Thrombocytopenia

Izalontamab brengitecan (iza-bren) versus chemotherapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC): A multicenter, randomized, open-label, phase III study. (ASCO 2026) - P3 | " Pts with recurrent or metastatic ESCC who had progressed after first-line treatment with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy were randomized (1:1) to receive iza-bren (2.5 mg/kg at D1D8 Q3W) or physician's choice of chemotherapy (irinotecan, paclitaxel, or docetaxel Q3W). The study met both dual primary endpoints at prespecified interim analysis. Iza-bren demonstrated statistically significant and clinically meaningful improvements in OS and PFS compared with chemotherapy in pts with recurrent or metastatic ESCC who had progressed after first line PD-1/PD-L1 inhibitor plus platinum-based chemotherapy. The safety profile was manageable."

Clinical • Metastases • P3 data • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Izalontamab brengitecan, an EGFR and HER3 bispecific antibody-drug conjugate, versus chemotherapy in heavily pretreated recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 study in China. (PubMed, Lancet) - P3 | "Iza-bren significantly improved the ORR compared with chemotherapy in individuals with heavily pretreated recurrent or metastatic nasopharyngeal carcinoma, with a manageable safety profile. These findings suggest iza-bren might represent a new therapeutic standard for this population. Further analysis will help to fully understand the benefit of this new therapy."

Journal • P3 data • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

BL-B01D1-LUNG-101: Evaluate BL-B01D1 in Patients With Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) and Other Solid Tumors (clinicaltrials.gov) - P1 | N=540 | Recruiting | Sponsor: SystImmune Inc. | Trial completion date: Mar 2028 ➔ Jul 2030 | Trial primary completion date: Dec 2026 ➔ Apr 2030

Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Endometrial Cancer • Esophageal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Prostate Adenocarcinoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRCA • HER-2

Phase II Study of Iza-Bren (BL-B01D1) Combo With Osimertinib in EGFR Mutated Locally Advanced or Metastatic NSCLC Patients (IASLC-WCLC 2025) - "No new safety signals were observed. Conclusions : iza-bren in combination with Osi has demonstrated promising activity with a manageable safety profile in first-line EGFRmt NSCLC pts."

Clinical • Metastases • P2 data • Alopecia • Anemia • Dental Disorders • Immunology • Interstitial Lung Disease • Leukopenia • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis • Thrombocytopenia • EGFR

A Study of BL-B01D1 With or Without PD-1 Monoclonal Antibody in Patients With High-Risk Locally Advanced Nasopharyngeal Carcinoma (clinicaltrials.gov) - P2 | N=60 | Not yet recruiting | Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.

New P2 trial • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor

Trial in progress: A phase 2/3 trial of iza-bren (BMS986507/BL-B01D1), an EGFRxHER3 antibody-drug conjugate, vs standard-of-care chemotherapy in patients with previously untreated, locally advanced, recurrent inoperable, or metastatic triple negative breast cancer ineligible for anti-PD-(L)1 treatment (IZABRIGHT-Breast01) (SABCS 2025) - P2/3 | " IZABRIGHT-Breast01 (NCT06926868) is an open-label, randomized phase 2/3 trial evaluating the efficacy and safety of iza-bren vs chemotherapy of investigator's choice (paclitaxel, nab-paclitaxel, capecitabine, or carboplatin plus gemcitabine) in patients with previously untreated, locally advanced, recurrent inoperable or metastatic TNBC or estrogen receptor (ER)-low, HER2-negative BC who are ineligible for approved anti-programmed death-1/programmed death ligand 1 (PD-[L]1)-based treatment combinations or endocrine therapy-based treatments, respectively. The key secondary endpoint is overall survival. Other secondary endpoints include investigator-assessed PFS, objective response, disease control rate, duration of response, time to response, time to subsequent treatment, PFS after next line of treatment, safety, and health-related quality of life."

Clinical • Metastases • P2/3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • ER • HER-2 • PGR

A bispecific antibody-drug conjugate targeting EGFR and HER3 in metastatic esophageal squamous cell carcinoma: a phase 1b trial. (PubMed, Nat Med) - P1 | "BL-B01D1 is a first-in-class antibody-drug conjugate consisting of an EGFR-HER3 bispecific antibody bound to a topoisomerase I inhibitor (Ed-04) payload via a cleavable linker...A further phase 3 clinical trial has already been initiated. ClinicalTrials.gov registration: NCT05262491 ."

Journal • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Interstitial Lung Disease • Leukopenia • Neutropenia • Oncology • Pulmonary Disease • Respiratory Diseases • Squamous Cell Carcinoma • Thrombocytopenia • EGFR • ERBB3

Phase II Study of Izalontamab Brengitecan (Iza-bren) plus Osimertinib in Patients with EGFR Mutant Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Izalontamab brengitecan (iza-bren) versus physician's choice of chemotherapy in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC): A randomized phase III study. (ASCO 2026) - P3 | "Patients were randomized 1:1 to receive iza-bren (2.5 mg/kg D1D8 Q3W) or treatment of physician's choice (TPC) (eribulin, capecitabine, gemcitabine, or vinorelbine). This pre-planned interim analysis met both dual-primary endpoints of PFS by BICR and OS. Iza-bren demonstrated a statistically significant and clinically meaningful improvement in both PFS and OS compared with chemotherapy, with a manageable safety profile in heavily pre-treated TNBC patients, supporting iza-bren as a new standard of care in this population."

Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2