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

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

Alphamab Oncology announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to the combination therapy of KN026 plus KN046 for the treatment of gastric cancer, including cancer of the gastroesophageal junction (Alphamab Press Release) - "Alphamab Oncology...announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to KN026 (anti-HER2 bispecific antibody) in combination with KN046 (PD-L1/CTLA-4 bispecific antibody)...for the treatment of HER2-positive or low expressing gastric or gastroesophageal junction cancer."

Orphan drug • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Phase 2 Trial of KN026+KN046±XELOX in HER2-positive Locally Advanced GC (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: Peking University | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Peking University | Active, not recruiting ➔ Completed

Trial completion • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

KN026-CHN-001: Trial of KN026 in Patients With HER2-positive Advanced Malignant Breast Cancer and Gastric Cancer (clinicaltrials.gov) - P1 | N=63 | Completed | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Active, not recruiting ➔ Completed

Metastases • Monotherapy • Trial completion • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

KN026-202: KN026 in Patients With HER2 Expressing Gastric/Gastroesophageal Junction Cancer (clinicaltrials.gov) - P2 | N=45 | Completed | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Unknown status ➔ Completed

Metastases • Trial completion • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2

Two and a half years follow-up data of HER2-targeted bispecific antibody KN026 combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer. (SABCS 2023) - "Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab and pertuzumab. KN026 in combination with docetaxel is well tolerated and has shown promising clinical benefit as 1L treatment for HER2-positive BC. After 2.5 years follow-up, mPFS was 27.7 mons and the 24-months OS rate was 84.2%, which is very promising. No new safety signals were observed."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Alphamab Oncology Presented Clinical Data of KN026 Combined with Docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer (Alphamab Press Release) - P2 | N=68 | NCT04165993 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "Alphamab Oncology...announced that a two-and-a-half-year follow-up update of the Phase II clinical study of KN026 combined with docetaxel chemotherapy in first-line treatment of HER2-positive recurrent/metastatic breast cancer patients (Study No. KN026-201) at the 2023 SAN Antonio Breast Cancer Conference (SABCS 2023)....The median follow-up was 30.6 mos (95%CI: 29.11, 31.77). Among 55 evaluable subjects, the objective response rate (ORR) was 76.4% (95% CI:62.98,86.77). Median DoR follow-up time was 28.1 months (95% CI: 26.28, 29.08), and DoR was not reached (95% CI: 20.73, NE). Median progression-free survival (mPFS) was 27.7 months (95% CI:17.97, NE), and median overall survival (mOS) was not reached."

P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

KN026 was Granted Breakthrough Therapy Designation by CDE (PRNewswire-Asia) - "Alphamab Oncology...and CSPC Pharmaceutical Group...jointly announced, that the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) granted a Breakthrough Therapy designation to KN026 (HER2 bispecific antibody) combined with chemotherapy for the treatment of HER2-positive gastric cancer (including gastroesophageal junction cancer)."

Non-US regulatory • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma

Two-year follow-up data on the efficacy and safety of KN026, a HER2-targeted bispecific antibody combined with docetaxel as first-line treatment for HER2-positive recurrent/metastatic breast cancer (ESMO 2023) - P2 | "Fully humanized, IgG1-like antibody binds to two distinct HER2 epitopes, the same domains as trastuzumab and pertuzumab. After 2 years follow-up, mPFS was 25.4m and the 30-m OS rate was 83.7%, which is very promising. Robustness of efficacy and safety results will be further confirmed in an ongoing randomized phase 3 clinical trial with PTH as control."

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

KN026 in combination with docetaxel as neoadjuvant treatment for HER2+ early or locally advanced breast cancer (BC): A single-arm, multicenter, phase II study (ESMO 2023) - P2 | "Background Trastuzumab (H) plus Pertuzumab (P) combined with cytotoxic agents has been the SOC for Her2+BC across perioperative to late stage. Conclusions KN026 plus docetaxel as neoadjuvant treatment has shown promising clinical benefit and acceptable safety for pts with HER2+ early or LABC. Further validation in a large-scale randomized controlled trial is warranted."

Clinical • Combination therapy • Metastases • P2 data • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Alphamab Oncology updated data from two studies of KN026 in combination with docetaxel for HER2-positive breast cancer at ESMO (PRNewswire-Asia) - P2 | N=30 | NCT04881929 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "KN026-208 (NCT04881929) is a phase II, open label, multi-center clinical study, evaluating the efficacy, safety, and tolerability of KN026 in combination with docetaxel as neoadjuvant treatment for HER2-positive early or locally advanced breast cancer....From August 9th, 2021, to July 29th, 2022, a total of 30 patients (pts) were enrolled from 5 sites. As of Nov 21st, 2022, the study completed the primary outcome. 28 pts completed the surgery followed by pathological evaluation, and 2 pts discontinued from the study earlier due to AEs. In FAS, tpCR rate was 56.7% (17/30, 95% CI: 37.43%-74.54%), posterior probability for tpCR>40% was 96.7%; bpCR rate was 60% (18/30, 95% CI:40.60%-77.34%); ORR was 90.0% (27/30, 95% CI: 73.47%-97.89%); confirmed ORR was 86.7% (26/30, 95% CI:69.28%-96.24%)."

P2 data • HER2 Positive Breast Cancer