pulocimab (AK109) / Akesobio - LARVOL DELTA

Akeso, Inc…announced today that it has received clearance from the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) to initiate Phase II clinical trials for AK146D1, a first-in-class Trop2 /Nectin4 bispecific antibody-drug conjugate (ADC), and AK138D1, an innovative HER3-targeting ADC. (The Manila Times) - "The studies will evaluate these two novel ADC candidates in combination with the Company's pioneering immuno-oncology (IO) 2.0 bispecific antibodies, cadonilimab (PD-1/CTLA-4) and ivonescimab (PD-1/VEGF), as well as other proprietary high-potential anti-tumor assets, including AK117 (anti-CD47 monoclonal antibody) and AK109 (anti-VEGF monoclonal antibody), across a spectrum of advanced solid tumors....These Phase II studies will leverage the cadonilimab and ivonescimab as foundational backbone therapies, capitalizing on their validated clinical profiles in checkpoint blockades and dual VEGF/PD-1 inhibition."

New P2 trial • Solid Tumor

Efficacy and Safety of Cadonilimab Plus Pulocimab in NSCLC Patients Who Progressed Following Prior Immunotherapy: A Phase 1b/2 Study (IASLC-WCLC 2025) - P1/2 | "These findings suggest that this combination may overcome immunotherapy resistance and offer a potential new option for second-line treatment of NSCLC. A further phase III clinical trial is currently in planning."

Clinical • P1/2 data • Hypertension • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Renal Disease • Solid Tumor • Thrombocytopenia • CTLA4 • PD-1

Efficacy and safety of cadonilimab in combination with pulocimab and paclitaxel as second-line therapy in patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer who failed immunochemotherapy: A multicenter, double-blind, randomized trial. (ASCO 2024) - P1/2 | "The combination of cadonilimab with pulocimab and paclitaxel demonstrated manageable safety profile and encouraging efficacy as second-line therapy in pts with G/GEJ cancer progressed after immunochemotherapy. Incorporation of dual immunotherapy to VEGFR-2 targeting therapy could be a potential strategy to overcome immunotherapy resistance. Additional phase III study is warranted to confirm it."

Clinical • Combination therapy • Metastases • Gastric Cancer • Gastrointestinal Cancer • Infectious Disease • Novel Coronavirus Disease • Oncology • CTLA4

Cadonilimab(PD-1/CTLA-4) plus Pulocimab (VEGFR-2) Combination Therapy Shows Promising Results in IO-Resistant Non-Small Cell Lung Cancer in Oral Presentation at the 2025 WCLC (PRNewswire) - "As of January 13, 2025, with a median follow-up of 16.7 months, the cadonilimab-based combination achieved a median overall survival (mOS) of 15.6 months and a median progression-free survival (mPFS) of 5.8 months in IO-resistant NSCLC. In the squamous NSCLC (sqNSCLC) subgroup, mOS was 16.7 months, mPFS was 7.1 months, the disease control rate (DCR) reached 96.2%, and the objective response rate (ORR) was 11.5%. In the non-squamous NSCLC (nsq-NSCLC) subgroup, mOS was 12.8 months, mPFS was 5.5 months, DCR was 95.2%, and ORR was 14.3%."

P1/2 data • Non Small Cell Lung Cancer

AK109-102: A Study of AK109 Combined With AK104 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=198 | Recruiting | Sponsor: Akeso | Trial completion date: Dec 2024 ➔ Apr 2027 | Trial primary completion date: Dec 2024 ➔ Apr 2027

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

AK109-201: A Study of AK109 and AK104 in Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=138 | Recruiting | Sponsor: Akeso | N=87 ➔ 138 | Trial completion date: Jan 2024 ➔ Jan 2027 | Trial primary completion date: Jul 2023 ➔ Oct 2025

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P3 | N=506 | Recruiting | Sponsor: Akeso | Not yet recruiting ➔ Recruiting

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

A Study of AK109 Combined With AK104 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=198 | Recruiting | Sponsor: Akeso | Trial completion date: Mar 2024 ➔ Dec 2024 | Trial primary completion date: Feb 2023 ➔ Dec 2024

Metastases • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of AK104/Placebo Plus AK109/Placebo And Paclitaxel in Gastric or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P3 | N=506 | Not yet recruiting | Sponsor: Akeso

New P3 trial • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

First-in-human, phase I study of AK109, an anti-VEGFR2 antibody in patients with advanced or metastatic solid tumors. (PubMed, ESMO Open) - P1 | "AK109 showed manageable safety profile and promising antitumor activity, supporting further clinical development in a large population."

Journal • Metastases • P1 data • Cardiovascular • Hematological Disorders • Hypertension • Oncology • Renal Disease • Solid Tumor • Thrombocytopenia

A Study of Anti-VEGFR2 AK109 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Akeso | Recruiting ➔ Completed | N=24 ➔ 40 | Trial completion date: Dec 2021 ➔ Oct 2022

Enrollment change • Metastases • Trial completion • Trial completion date • Oncology • Solid Tumor

First-in-human, phase I study of AK109, an anti-VEGFR2 antibody, in patients (pts) with advanced or metastatic solid tumors. (ASCO 2022) - P1, P1/2 | "AK109 showed manageable safety and promising anti-tumor activity. Two phase II studies of AK109 combined with AK104 (anti PD-1/CTLA-4 bi-specific antibody) are ongoing to evaluate the efficacy of AK109 combined with AK104 in patients with multiple solid tumors (NCT05142423, NCT04982276)."

Clinical • P1 data • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Hypertension • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Renal Disease • Solid Tumor

A Study of AK109 Combined With AK104 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=198 | Recruiting | Sponsor: Akeso | Trial completion date: Oct 2023 ➔ Mar 2024 | Trial primary completion date: Aug 2022 ➔ Feb 2023

IO biomarker • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

A Study of AK109 and AK104 in Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1/2 | N=87 | Recruiting | Sponsor: Akeso | Trial completion date: Dec 2022 ➔ Jan 2024 | Trial primary completion date: Jun 2022 ➔ Jul 2023

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of AK109 Combined With AK104 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=198; Recruiting; Sponsor: Akeso

Clinical • IO biomarker • New P1/2 trial • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PD-L1

Akeso’s PD-1/CTLA-4 BsAb/VEGFR-2 mAb combo greenlit for Phase Ib/ II study in solid tumors (GBI Health) - "China-based Akeso Biopharma (9926.HK) announced receiving the go-ahead from the National Medical Products Administration (NMPA) to initiate an open, multi-center Phase Ib//II study for its cadonilimab (AK104), a novel programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4-targeted (CTLA-4) bispecific antibody (BsAb) in combination with its AK109, an anti-vascular endothelial growth factor receptor-2 (VEGFR-2) monoclonal antibody (mAb). The targeted indication is general advanced solid tumors."

New P1/2 trial • Oncology • Solid Tumor

A Study of AK109 and AK104 in Advanced Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma (clinicaltrials.gov) - P1/2; N=87; Recruiting; Sponsor: Akeso

New P1/2 trial • Esophageal Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Phase update (clinicaltrials.gov) - Preclinical➔P1, Oncology

Phase shift • Oncology

A Study of Anti-VEGFR2 AK109 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=24; Recruiting; Sponsor: Akeso

Clinical • New P1 trial • Oncology • Solid Tumor

Kangfang Bio (09926.HK) independently developed the drug AK109, the first patient with advanced solid tumor in China completed enrollment and administration (Eastmoney.com) - "Kangfang Bio-B (09926.HK) released an announcement that the company's self-developed VEGFR-2 new fully humanized monoclonal antibody drug AK109 has successfully completed the first advanced solid tumor patient in China's dose-climbing phase I clinical trial Enrollment and administration. The research was led by the First Affiliated Hospital of Zhejiang University School of Medicine and its professor of medical oncology, Professor Xu Nong , was the main researcher."

Enrollment closed • Oncology • Solid Tumor