anbenitamab (KN026) / Alphamab, CSPC Pharma - LARVOL DELTA

Spatial molecular analyses reveal key features associated with response to KN026 in advanced HER2-positive breast cancer. (PubMed, Br J Cancer) - "Both HER2 and ESR1 are determinant of KN026 efficacy in advanced HER2-positive breast cancer, implying the potential of KN026 combined with endocrine therapy in HER2- and ER-positive breast cancer."

Journal • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK12 • ER • HER-2 • TFAP2A

Spatial molecular analyses reveal key features associated with response to KN026 in advanced HER2-positive breast cancer (Nature) - "Compared to the tumor regions with non-objective response (OR), those with OR had high expression of CALML5, TFAP2B, and ERBB2, and relatively low expression of ESR1 in tumor cells at baseline. The expression of ESR1 had a tentative association with PI3K/AKT and NOTCH signaling pathways which were downstream or interactive pathways of HER2 target and also acted as interactive pathways of ER-mediated signaling. The co-expression of ERBB2 and CDK12 emerged as a distinctive signature of OR. KN026 treatment also reshaped intratumoral activated T- and B-cell subtypes in hot-tumor regions, regardless of myeloid-derived cells."

Preclinical • HER2 Positive Breast Cancer

Anbenitamab in combination with chemotherapy in patients with HER2-positive gastric or gastroesophageal junction carcinoma who failed previous therapy containing trastuzumab: a multicenter, phase II study (KC-WISE 01). (PubMed, Cancer Commun (Lond)) - No abstract available

Journal • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • HER-2

KN026 in combination with chemotherapy for previously treated HER2-positive gastric or gastroesophageal carcinomas (GC/GEJC): Interim analysis of KC-WISE (ESMO 2025) - P2/3 | "Treatment-related deaths were reported in 0 and 5 patients in the anbenitamab and control groups, respectively. Conclusions Compared with chemotherapy alone, anbenitamab plus chemotherapy demonstrated clinically meaningful superior PFS and OS in patients with HER2-positive GC/GEJ adenocarcinoma whose previous therapy containing trastuzumab had failed."

Combination therapy • Late-breaking abstract • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • HER-2

Anbenitamab Plus Chemotherapy Significantly Improves Survival in Previously Treated HER2-Positive Gastric or GEJ Cancer (HMPL Global) - "Interim Results From the Phase 3 TKC-WISE Trial...A total of 188 patients were randomized: 95 to the anbenitamab plus chemotherapy group and 93 to the chemotherapy-alone group. At interim analysis, the combination demonstrated a marked improvement in PFS (median, 7.1 vs 2.7 months; hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.39; P <.0001) and OS (median, 19.6 vs 11.5 months; HR, 0.29; 95% CI, 0.17 to 0.50; P <.00001). The objective response rate was substantially higher with anbenitamab plus chemotherapy (56%) compared with chemotherapy alone (11%), indicating robust tumor activity....Safety findings were consistent with known profiles of HER2-targeted therapy and cytotoxic agents."

P3 data • Gastric Cancer • Gastroesophageal Cancer • HER-2

NEW DRUG APPLICATION FOR KN026 (ANBENITAMAB INJECTION) ACCEPTED BY THE NMPA (HKEXnews) - "Its indication is for use in combination with chemotherapy for the treatment of patients with HER2-positive locally advanced, recurrent, or metastatic gastric or gastroesophageal junction cancer who have failed at least one prior systemic therapy....This new drug application is primarily based on a pivotal Phase II/III clinical trial (KC-WISE)."

China filing • Gastric Cancer • Gastroesophageal Cancer

KN026:…Events after the Reporting Period (PRNewswire-Asia) - "(i) In July 2025, the...IND application for a phase III clinical trial of KN026 as first-line treatment for HER2-positive GC/GEJ was accepted by the CDE; (ii) In July 2025, the first interim analysis results from the phase III clinical study of KN026 in combination with chemotherapy as second-line or above treatment of HER2-positive GC/GEJ were accepted by the 2025...ESMO Congress and will be presented during the Congress in October."

New P3 trial • P3 data • Gastric Cancer • Gastroesophageal Cancer

KN026:…Expected Milestones in 2025 (PRNewswire-Asia) - "(i) A New Drug Application (NDA) will be submitted in China for KN026 combined with chemotherapy as second-line or above treatment for HER2-positive GC/GEJ; (ii) Enrollment of all patients will be completed in the phase III clinical trial of KN026 combined with albumin-bound docetaxel HB1801 as neoadjuvant treatment of HER2-positive early or locally advanced BC."

China filing • Enrollment status • Gastric Cancer • Gastroesophageal Cancer • HER2 Positive Breast Cancer

Longitudinal tissue analysis and correlation of microenvironmental changes with combined immunotherapy and targeted therapy response in metastatic breast cancer. (ASCO 2025) - P2 | "Funded by Guangdong Science and Technology Department(2023B1212060013, 2022B1515020100, 2022A1515012238), the Natural Science Foundation of China (82273033, 82072924, 82072906) Clinical Trial Registration Number: NCT04521179 Background: The ability to interrogate changes within the tumor microenvironment before, during and following therapeutic intervention could yield important understanding of treatment response and causes for disease progression.Here we conducted a multicenter phase II clinical trial (NCT04521179) examining the effect of a novel CTLA-4/PD-L1 bispecific (KN046) antibody in combination with a a novel anti-HER2 bispecific (KN026) antibody in treatment resistant metastatic breast cancer... We identified that regulatory T cells are activated while effector T cells, natural killer cells, and dendritic cells were significantly depleted in non-responding tumors. The immune response in responsive patients was effectively enhanced, whereas in nonresponsive..."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD4 • CD8 • CTLA4

JSKN003 Combined Treatment of HER2-positive Gastric Cancer (clinicaltrials.gov) - P2 | N=153 | Not yet recruiting | Sponsor: Shanghai JMT-Bio Inc.

New P2 trial • Gastric Cancer • Oncology • Solid Tumor

Efficacy and Safety of KN026 in Combination With HB1801 in the First-line Treatment of Subjects With HER2-positive Recurrent or Metastatic Breast Cancer. (clinicaltrials.gov) - P3 | N=880 | Recruiting | Sponsor: Shanghai JMT-Bio Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jul 2026 ➔ Jul 2025

Enrollment open • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

A Phase III Study of KN026 in Combination With HB1801 ± Carboplatin as Neoadjuvant Treatment for Early or Locally Advanced HER2-Positive Breast Cancer (clinicaltrials.gov) - P3 | N=520 | Recruiting | Sponsor: Shanghai JMT-Bio Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A Pivotal Phase II/III Clinical Study of Anti-HER2 Bispecific Antibody KN026 Have Met the Primary Endpoint of PFS at Interim Analysis (PRNewswire) - P2/3 | N=286 | NCT05427383 | Sponsor: Shanghai JMT-Bio Inc. | "Alphamab Oncology...and CSPC Pharmaceutical Group...jointly announced that a phase II/III clinical trial of anti-HER2 bispecific antibody KN026 (Study ID: KN026-001) in combination with chemotherapy as second-line or above treatment of HER2-positive gastric cancer (GC) (including gastroesophageal junction cancer (GEJ)), has completed the first interim analysis and met the pre-specified primary endpoint of progression-free survival (PFS) as evaluated by an Independent Data Monitoring Committee (IDMC), with both statistical significance and clinical relevance....The interim PFS analysis results demonstrated that, compared to the current standard treatment, KN026 in combination with chemotherapy significantly improved PFS, reduced the risk of disease progression or death, and showed a trend toward OS benefit. Detailed data from this study will be presented at an upcoming international academic conference."

P2/3 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • HER-2

Safety and Efficacy of KN046 in combination with KN026 in Patients with advanced HER2-positive Breast Cancer: a Phase II Trial. (PubMed, Clin Cancer Res) - "The combination of KN046 and KN026, as a chemo free regimen, demonstrated favorable clinical efficacy with comparative toxicities in pre-treated patients with advanced HER2-positive breast cancer."

Journal • P2 data • Breast Cancer • Dermatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Pruritus • Solid Tumor • HER-2

Efficacy and safety of KN026, a bispecific anti-HER2 antibody, in combination with KN046, an anti-CTLA4/PD-L1 antibody, in patients with advanced HER2-positive nonbreast cancer: a combined analysis of a phase Ib and a phase II study. (PubMed, Signal Transduct Target Ther) - "In the other HER2-positive solid tumor subgroup (n = 34), the ORR was 52.9% (95%CI 35.1%,70.2%). Thus, KN026 plus KN04 exhibits promising efficacy and acceptable safety profiles in HER2-positive nonbreast cancer, as does the 1st-line treatment for GC."

Journal • P1 data • P2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD4 • CTLA4 • HER-2

KN026 Plus Docetaxel Demonstrates Efficacy in HER2+ Metastatic Breast Cancer (OncLive) - P2 | N=68 | NCT04165993 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "In the open-label, single-arm trial, among efficacy-evaluable patients (n = 55), the combination generated an objective response rate (ORR) of 76.4% (95% CI, 63.0%-86.8%), including 3 complete responses and 39 partial responses. The median duration of response (DOR) was not yet reached (NR; 95% CI, 20.7 months-NR). The 12-, 24-, and 30-month DOR rates were 85.2%, 59.3%, and 51.6%, respectively. Furthermore, the clinical benefit rate (CBR) was 85.5% (95% CI, 73.3%-93.5%)...At a median follow-up of 31.1 months (range, 0.8-41.4), among the safety-evaluable population, the median PFS was 27.7 months (95% CI, 18.0-NR); the 6-, 12-, 24-, and 30-month PFS rates were 87.4% (95% CI, 75.4%-93.8%), 76.3% (95% CI, 62.6%-85.5%), 54.2% (95% CI, 39.7%-66.6%), and 45.2% (95% CI, 30.9%-58.4%), respectively."

P2 data • Breast Cancer • HER2 Positive Breast Cancer

Exploring the role of bispecific and CAR-T cell therapies in gastric cancer: A systematic review and meta-analysis. (ASCO-GI 2025) - "Bispecific antibodies were MCLA-128 (25/138), catumaxomab (15/138), AK104 PD-1/CTLA-4 (16/138), ABL 001 DLL4VEGFA (19/138), and KN026 (25/138) while CART therapy was CT041 (38/138)... This analysis shows promising results in GC patients using bi-specific antibodies and CAR-T cell therapy. However, further clinical trials are needed to fully explore their potential."

CAR T-Cell Therapy • Retrospective data • Review • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CTLA4 • PD-1

Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial. (PubMed, Cancer Commun (Lond)) - "KN026 plus docetaxel showed promising efficacy and a manageable safety profile in first-line treatment of HER2-positive recurrent/metastatic breast cancer."

Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Antibodies to watch in 2025. (PubMed, MAbs) - "In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key..."

Journal • Review • Oncology

A Phase III Study of KN026 in Combination With HB1801 as Neoadjuvant Therapy for Early or Locally Advanced HER2-Positive Breast Cancer (clinicaltrials.gov) - P3 | N=520 | Not yet recruiting | Sponsor: Shanghai JMT-Bio Inc.

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

BOCOM International: Maintain "Neutral" rating on Alphamab-B (09966) and lower target price to HK$5 [Google translation] (iis.aastocks.com) - "Zhitong Finance APP learned that BoCom International released a research report saying that it has lowered the target price of Alphamab-B...to HK$5 and maintained a 'neutral' rating. The company's product sales are under short-term pressure, and the research and development of multiple assets in the HER2 channel are rapidly advancing. The bank predicts that KN026 and JSKN003 are expected to generate a combined peak sales of nearly 5 billion yuan in the country....However, considering the impact of industry compliance regulations on Envida sales and individual drugs under development, The launch pace has been delayed, the 2025 revenue forecast has been lowered to 450 million yuan, and the POS-adjusted peak sales of Envida and KN046 have been lowered to 1.1 billion and 500 million yuan."

Sales projection • Breast Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Disitamab vedotin combined with apatinib in gastric cancer: A case report and review of literature. (PubMed, World J Clin Oncol) - "Despite the unfavorable prognosis associated with advanced GC, the implementation of personalized treatment approaches may still prove beneficial for select patients. In patients with HER2-positive GC with extensive metastatic involvement, the use of the HER2-targeted combination with apatinib has demonstrated the potential to prolong both PFS and overall survival."

IO biomarker • Journal • Review • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • PD-L1

IND Application for a Phase III Clinical Study of KN026 Combined with Albumin-bound Docetaxel as Neoadjuvant Treatment for Breast Cancer was Approved (PRNewswire-Asia) - "Alphamab Oncology...and CSPC Pharmaceutical....jointly announced that an application for a phase III clinical study (Study ID: KN026-004) of the anti-HER2 bispecific antibody KN026 combined with albumin-bound Docetaxel HB1801 has been approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer....The approved study is a randomized, controlled, open-label, multicenter phase III clinical study aimed at comparing the efficacy and safety of KN026 combined with HB1801 versus trastuzumab combined with pertuzumab and docetaxel as neoadjuvant therapy in patients with HER2-positive early or locally advanced breast cancer. The primary endpoint is the tpCR rate as evaluated by a blinded independent review committee (BIRC)."

New P3 trial • HER2 Positive Breast Cancer

Efficacy and safety of KN026 in combination with chemotherapy in patients (pts) with unresectable or metastatic HER2 positive gastric or gastroesophageal cancers (GC/GEJC) after first-line treatment with a trastuzumab-containing regimen (ESMO 2024) - P2/3 | "Previous study demonstrated KN026 monotherapy had shown promising efficacy in pts with GC/GEJC. In this multicenter, open-label, phase II study, pts with HER2 positive GC/GEJC after first-line treatment with a trastuzumab-containing regimen were assigned to receive KN026 (30 mg/kg, D1, Q3W) + paclitaxel (175 mg/m2, D1, Q3W) or irinotecan (125 mg/m2, D1 and D8, Q3W) at investigators' discretion based on previous treatment. KN026 in combination with chemotherapy have promising anti-tumor efficacy in pts with HER2 positive GC/GEJC after first-line treatment, with a well-tolerated safety profile. Phase III study of KN026 in combination with chemotherapy is ongoing."

Clinical • Combination therapy • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • ERBB3 • HER-2

...In May, it announced that the clinical trial of KN046-303 had failed. [Google translation] (Sina Corp) - P3 | N=408 | NCT05149326 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "KN046 is expected to determine whether to submit NDA in 2024 based on the final analysis results of OS in first-line squamous NSCLC, and KN026 is expected to submit NDA in 2025. It is worth noting that in May this year, the company announced that the overall survival results of the KN046-303 trial did not reach the preset endpoint."

China filing • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor