erfonrilimab (KN046) / Alphamab - LARVOL DELTA

Efficacy and safety of surufatinib (S) plus KN046 (K) and chemotherapy in first line (1L) advanced pancreatic cancer (PC): A single-arm, phase 1b/2 trial. (ASCO 2025) - P1/2 | "Clinical Trial Registration Number: NCT05832892 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • P1/2 data • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

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

TATE and KN046 in MCRC (clinicaltrials.gov) - P2 | N=42 | Terminated | Sponsor: Zhejiang Raygene Pharmaceuticals Co., Ltd

New P2 trial • Colorectal Cancer • Hepatology • Oncology • Solid Tumor

The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial. (PubMed, Nat Commun) - P2 | "Circulating tumor DNA status before the third cycle of treatment was associated with prognosis. In conclusion, First-line KN046 plus lenvatinib shows promising efficacy for advanced unresectable or metastatic HCC."

IO biomarker • Journal • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor • CTLA4

The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial (Nature, Nat Commun) - P2 | N=55 | NCT04542837 | "The results meet the pre-specified primary endpoints. No DLT was observed in the safety run-in period. The incidence of serious adverse events and grade ≥3 treatment-related adverse events (TRAEs) was 30.9% and 47.3%, respectively. Grade ≥3 immunotherapy-related adverse events occurred in 3 (5.5%) participants. Five (9.1%) participants discontinued treatment due to TRAEs, all of which were grade 1-2. The ORR was 45.5% (95% CI, 31.97-59.45). The median progression-free survival was 11.0 (95% CI, 8.21-15.24) months. The median overall survival (OS) was 16.4 (95% CI, 11.20-not estimable) months, and 12-month OS rate was 60.0% (95% CI, 45.87-71.55)."

P2 data • Hepatocellular Cancer

The anti-PD-L1/CTLA-4 bispecific antibody KN046 plus lenvatinib in advanced unresectable or metastatic hepatocellular carcinoma: a phase II trial (Nature, Nat Commun) - P2 | N=55 | NCT04542837 | "The results meet the pre-specified primary endpoints. No DLT was observed in the safety run-in period. The incidence of serious adverse events and grade ≥3 treatment-related adverse events (TRAEs) was 30.9% and 47.3%, respectively. Grade ≥3 immunotherapy-related adverse events occurred in 3 (5.5%) participants. Five (9.1%) participants discontinued treatment due to TRAEs, all of which were grade 1-2. The ORR was 45.5% (95% CI, 31.97-59.45). The median progression-free survival was 11.0 (95% CI, 8.21-15.24) months. The median overall survival (OS) was 16.4 (95% CI, 11.20-not estimable) months, and 12-month OS rate was 60.0% (95% CI, 45.87-71.55)."

P2 data • Hepatocellular Cancer

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

The efficacy and safety of KN046 combined with axitinib for previously untreated and checkpoint inhibitor treated advanced non-small cell lung cancer: A single-arm, open-label, multicenter phase II clinical trial (ESMO-IO 2024) - P2 | "24.7% pts had immune-related adverse events, 10.6% were grade ≥ 3.Conclusions KN046-axitinib combination showed encouraging efficacy and tolerability in advanced NSCLC pts. Further validation in a large-scale trial is warranted."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD80 • CD86

Alphamab Oncology Presented the Phase II Clinical Data of KN046 in Combination with Axitinib for the Treatment of Advanced NSCLC at ESMO IO Congress 2024 (PRNewswire-Asia) - P2 | N=54 | NCT05420220 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "As of September 1, 2024, 53 and 32 patients were treated in Cohort A and B, the median follow-up time was 14.6 months and 11.2 months, respectively. 95.3% patients had ECOG PS=1, 85.9% patients had stage IV disease, and 49.4% patients had squamous disease. By central lab testing, 67.1% and 24.7% patients had PD-L1 TPS≥1% and≥50%, respectively...In Cohort A, the ORR in PD-L1 TPS≥1% (N=44) and≥50% (N=15) patients were 56.8% (95% CI 41.0, 71.7) and 73.3% (95% CI 44.9, 92.2); confirmed ORR were 54.5% (95% CI 38.8, 69.6) and 66.7% (95% CI 38.4, 88.2). The DCR were 90.9% (95% CI 78.3,97.5) and 93.3% (95% CI 68.1, 99.8)...In Cohort B (N=32), the ORR and confirmed ORR were both 9.4% (95% CI 2.0, 25.0) and the DCR was 81.3% (95% CI 63.6, 92.8)...KN046-Axitinib combination showed encouraging efficacy and tolerability in advanced NSCLC patients."

P2 data • Non Small Cell Lung Cancer

68Ga-FAPI PET imaging assesses tumor immunity and guides TGF-β inhibition to sensitize metastatic colorectal cancer to immunotherapy (EANM 2024) - "Mouse cohorts of metastatic CRC were treated with TGF-βR inhibitor combined with KN046 which blocks PD-L1 and CTLA4, followed with 68Ga-FAPI and 18F-FDG micro-PET/CT imaging to assess tumor responses... 68Ga-FAPI PET/CT imaging is powerful in assessing tumor immunity and response to immunotherapy in metastatic CRC. This study supports future clinical application of 68Ga-FAPI PET/CT to guide CRC patients for precise TGF-β inhibition plus immunotherapy, recommending 68Ga-FAPI and 18F-FDG dual PET/CT for CRC management."

Metastases • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAFs • TGFB1

Antibodies to watch in 2024. (PubMed, MAbs) - "In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi))...These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa)...Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates..."

Journal • Infectious Disease • Novel Coronavirus Disease • Oncology • Respiratory Diseases

...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

First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial. (PubMed, Cancer Immunol Immunother) - "The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients."

Journal • Metastases • P1 data • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Disorder • Hematological Disorders • Leukopenia • Neutropenia • Oncology • Pneumonia • Squamous Cell Carcinoma

Surufatinib Combined With KN046 and AG Regimen Chemotherapy as First-Line Treatment for Unresectable Advanced Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=41 | Recruiting | Sponsor: Shanghai Zhongshan Hospital | Trial primary completion date: Jun 2024 ➔ Nov 2024

Combination therapy • Metastases • Trial primary completion date • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • PD-L1

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

Study of KN046 in Subjects With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=54 | Recruiting | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Enrolling by invitation ➔ Recruiting | Trial completion date: Mar 2024 ➔ Dec 2027 | Trial primary completion date: Mar 2023 ➔ May 2027

Combination therapy • Enrollment status • Metastases • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • PD-L1

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

Alphamab Oncology Reports Full Year 2023 Financial Results and Business Highlights (PRNewswire-Asia) - "Expected Milestones in 2024: (i) Perform final OS analysis of the phase III clinical trial of KN046 in combination with chemotherapy as the first-line treatment for sq NSCLC; (ii) Perform final OS analysis of the phase III clinical trial of KN046 in combination with chemotherapy as the first-line treatment for advanced pancreatic cancer; (iii) The relevant data from the phase II clinical trial of KN046 in combination with axitinib in the treatment for advanced NSCLC will be read out and expected to be presented at the ESMO Congress in October 2024."

P2 data • P3 data • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

KN046, a bispecific antibody against PD-L1 and CTLA-4, plus chemotherapy as first-line treatment for metastatic NSCLC: A multicenter phase 2 trial. (PubMed, Cell Rep Med) - P2 | "In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. These findings indicate that first-line treatment with KN046 and chemotherapy is effective and tolerable in metastatic NSCLC patients, warranting further investigation in a larger phase 3 trial. The trial is registered at ClinicalTrials.gov (NCT04054531)."

Journal • Metastases • P2 data • Anorexia • Dermatology • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pruritus • Solid Tumor • PD-L1

The Results of Phase II Clinical Study of KN046 Plus Chemotherapy as First-line Treatment for Metastatic NSCLC were Published in Cell Reports Medicine (PRNewswire-Asia) - P2 | N=50 | NCT04054531 | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | "Alphamab Oncology...announced that the phase II clinical research results of anti- PD-L1/CTLA-4 bispecific antibody KN046 plus chemotherapy as first-line treatment for metastatic...NSCLC were published online in the renowned journal Cell Reports Medicine....The confirmed objective response rate (ORR) was 46.0% (95% CI:35.2%-57.0%) and median duration of response (DoR) was 8.1 (95% CI:4.14-13.90) months. Median progression-free survival (PFS) was 5.8 (95% CI: 5.26-7.10) months, median overall survival (OS) was 26.6 (95%CI:16.92-NR) months, and the 12-month OS rate was 74.2% (95% CI:63.46%-82.18%). In the non-sq-NSCLC cohort, the confirmed ORR was 43.1%, median DoR was 9.7months, median PFS was 5.8 months, and median OS was 27.2 months; In the sq-NSCLC cohort, the confirmed ORR was 50.0%, median DoR was 7.3months, median PFS was 5.7 months, and median OS was 26.6 months."

P2 data • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer

The Study of KN046 in Combination With Lenvatinib in Advanced Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=55 | Completed | Sponsor: Peking University Cancer Hospital & Institute | Recruiting ➔ Completed | Trial completion date: May 2023 ➔ Mar 2024

Combination therapy • Metastases • Trial completion • Trial completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

ENREACH-Thymic: KN046 (a Humanized PD-L1/CTLA4 Bispecific Single Domain Fc Fusion Protein Antibody) in Subjects With Thymic Carcinoma (clinicaltrials.gov) - P2 | N=95 | Terminated | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | The overall safety of KN046 is good, and no new safety signals have been found. The decision to terminate this study was made due to the adjustment of the sponsor's development strategy.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Oncology • Solid Tumor • Thymic Carcinoma • Thymus Cancer

ENREACH-PDAC-01: KN046 in Subjects With Advanced Pancreatic Ductal Adenocarcinoma. (clinicaltrials.gov) - P3 | N=408 | Recruiting | Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd | Active, not recruiting ➔ Recruiting

Enrollment open • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma