Beijing, China, July xx, 2022 -- Biocytogen subsidiary Eucure Biopharma announced that the first patient has been dosed in a phase II clinical trial (No. YH003006) evaluating YH003, an internally developed CD40 monoclonal antibody (mAb), in combination with Pembrolizumab (PD-1 mAb) and albumin-bound paclitaxel as a first-line treatment for patients with unresectable/metastatic mucosal melanoma.
The trial, which is being conducted in China, is a multi-center, single-arm, open-label phase II clinical study. Each subject will receive 0.3 mg/kg YH003, 200 mg Pembrolizumab and 200mg/m2 albumin-bound paclitaxel intravenously every three weeks. The primary endpoint is the antitumor efficacy according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Safety and tolerability of the combination therapy will be assessed.
"Mucosal melanoma is a subtype of melanoma with high malignancy and more aggressive condition. At present, there is no effective standard treatment and the prognosis is very poor," said Professor Zhang Xiaoshi, the Principal Investigator of this study at Sun Yat-sen University Cancer Center. "In previous clinical trials of melanoma in Europe and the United States, most patients with mucosal melanoma were not included or limited, resulting in the current lack of high-level evidence-based medical evidence to support the use of immunotherapy for mucosal melanoma. In Europe and the United States, skin type of melanoma is more common, mucosal type is less, while in China and East Asia, the incidence rate of mucosal melanoma is very high. Worldwide, there is a lack of effective drugs for the treatment of mucosal melanoma, and in China due to the large number of patients, the unmet medical needs are even greater ".
Dr. Rong Chen, Deputy General Manager of Biocytogen, CEO and CMO of Eucure Biopharma, said: "In previous phase I clinical trials, YH003 showed very good tolerability and safety profiles, and demonstrated encouraging antitumor activities against malignant melanoma, pancreatic cancer and some other tumors. We expect that the combination of YH003, PD-1 mAb and chemotherapy may be used in more difficult tumor conditions, so that to benefit patients worldwide."
YH003 is a humanized IgG2 agonist antibody targeting the CD40 receptor. YH003 promotes the activation of antigen-presenting cells and positively regulates the effector activity of anti-tumor T cells. CD40 is essential for the initiation and expansion of immune response. Studies to date have shown that the activation of CD40 is one of the most critical regulatory points in tumor immunotherapy in addition to PD-1. Targeting CD40 has the potential to transform cold tumors that lack immune cell infiltration into hot tumors that have a good response to tumor immunotherapy, but the toxicity of this target has challenged the immunotherapy field over the past two decades.
However, by using syngeneic tumor models built on Biocytogen’s humanized CD40 mice, YH003 mAb was quickly screened out that completely inhibited tumor growth and had no side effects such as hepatotoxicity in mice. YH003 has good specificity and human monkey cross recognition, and the IgG2 subtype design avoids ADCC effects, which extends the half-life of YH003 in vivo, and increases the therapeutic window. Whether used alone or in combination with anti-PD-1 mAb, YH003 showed strong antitumor activities against a variety of tumor models in mice, and pharmacodynamic studies demonstrated that YH003 significantly increased the proportion of anti-tumor-infiltrating T cells. In preclinical head-to-head safety studies of YH003 and selicrelumab in the same animal model, high-dose YH003 showed no signs of transaminase increase, indicating that YH003 had no or little toxicity in the liver, while selecrelumb exhibited elevated transaminase and characteristic cytokine-related toxicity. Cyno safety evaluation tests indicated that YH003 also demonstrated good safety even at a very high dose.
The phase I dose escalation study (protocol number: YH003002) carried out in Australia indicated that YH003 combined with PD-1 mAb (toripalimab) had excellent safety and antitumor activity in patients with advanced solid tumors. As of April 3, 2022, a total of 26 subjects have been enrolled, all of whom are advanced solid tumor patients who have progressed or are intolerant to the standard treatment. Patients have received 3-line (median) treatment (range 1 – 7), and 11 of the 26 enrolled patients have received immunotherapy (PD-1, PD-L1 or PD-1/CTLA-4 bispecific antibody, etc.). YH003 did not reach the maximum tolerable dose when escalating from 0.03mg/kg to 3.0 mg/kg. Two cases had grade 3 AEs related to YH003, which were neutropenia and elevated transaminase, respectively. No > level 4 AE occurred. Only one DLT event was observed in all subjects during the study, and no drug-related SAE occurred. Among the 19 subjects who could be evaluated by imaging, 3 were PRs (ORR=15.8%) and 4 were SD (DCR=36.8%). These first-in-human clinical studies further confirmed that YH003 had no elevated transaminase and liver toxicity, and no adverse reactions related to cytokine release.
Multiple international multicenter phase II clinical studies of YH003 are currently ongoing. The efficacy and safety of YH003 combined with PD-1 mAb will be evaluated in the treatment of PD-(L)1 resistant unresectable / metastatic melanoma patients as well as YH003 combined with PD-1 mAb in the second-line treatment of unresectable / metastatic pancreatic ductal adenocarcinoma (PDAC) patients, and YH003 combined with PD-1 monoclonal antibody and chemotherapy in the first-line treatment of unresectable / metastatic PDAC patients.
About Eucure Biopharma
As a wholly owned subsidiary of Biocytogen, Eucure Biopharma undertakes the mission of clinical development for Biocytogen’s R&D pipelines. Relying on a strong clinical development team and extensive clinical development experience, Eucure Biopharma focuses on antibody drug therapy for oncology and other indications. The company has established a product pipeline for more than 10 targets, with two products in launched phase II multi-regional clinical trials (MRCT) and two in phase I. For details, please visit: www.eucure com。
Biocytogen Pharmaceuticals (Beijing) Co., Ltd. is a global biotechnology company that drives the research and development of novel antibody-based drugs with innovative technologies. Using its proprietary RenMabTM /RenLite® mice platforms for fully human monoclonal and bispecific antibody development, Biocytogen has integrated its in vivo drug efficacy screening platforms and strong clinical development expertise to streamline the entire drug development process. Biocytogen is undertaking a large-scale project to develop antibody drugs for more than 1000 targets, known as Project Integrum, and has entered ongoing collaborations with dozens of partners worldwide to produce a variety of first-in-class and/or best-in-class antibody drugs. The company's pipeline includes 12 core products, among which two products are in phase II multi-regional clinical trials and two products are in phase I. Headquartered in Beijing, Biocytogen has branches in Haimen Jiangsu, Shanghai, Boston, USA and Heidelberg, Germany.