Kelun-Biotech Announces the Latest Clinical Study Results of SKB264 (MK-2870) for the Treatment of TNBC at 2023 SABCS

The 46th American San Antonio Breast Cancer Symposium (SABCS) will be held from December 5th to 9th, Central Standard Time (CST), and the latest clinical results evaluating Kelun-Biotech's TROP2 ADC SKB264 (also known as MK-2870) will be presented in the form of a poster spotlight presentationthe Phase II expansion study for patients with locally advanced or metastatic triple-negative breast cancer (TNBC).

Previously, Kelun-Biotech had presented efficacy and safety data of SKB264 from a Phase II expansion study in TNBC at 2022 SABCS, and this year we will present updated results including overall survival (OS) data.

The Phase II expansion study includes 59 patients with previously treated locally advanced or metastatic TNBC who received SKB264 monotherapy, with a median follow-up time of 22.8 months (data cutoff date: May 5, 2023).

Baseline characteristics:
Among the 59 enrolled patients, 89.8% (53 patients) had previously received three or more treatment regimens, 27.1% (16 patients) had previously received immunotherapy, about half had lung metastases, and one-third had liver metastases.

Efficacy:
Among the 59 treated patients with locally advanced or metastatic TNBC, the objective response rate (ORR) was 42.4%, with 3 patients achieving complete response (CR); the disease control rate (DCR) was 76.3%; the median duration of response (mDoR) was 11.5 months. In addition, median progression-free survival (mPFS) was 5.7 months, and the median overall survival (mOS) reached 16.8 months, with 12-month and 24-month OS rates of 65% and 39.5%, respectively. Nearly 40% of patients in the study treated with SKB264 were alive at two years.. In the subgroup of patients with high TROP2 expression (H-score>200, n=32), the ORR was 53.1%, mDoR was 11.1 months, mPFS was 5.8 months, mOS had not been reached, and the 12-month and 24-month OS rates were 65.3% and 57.3% respectively.

Safety:
Treatment-related adverse events (TRAEs) were mainly hematologic toxicity, which was clinically manageable. The most common treatment-related adverse events (TRAEs ≥10%) of Grade 3 or higher were neutrophil count decrease, white blood cell count decrease, anemia, and platelet count decrease. TRAEs led to dose reduction in 13.6% of patients. No interstitial lung disease (ILD) or diarrhea of Grade 3 or higher was observed. No deaths occurred due to TRAE.

The updated clinical data indicated that patients with locally advanced or metastatic TNBC who have received multiple prior treatments may achieve sustained responses and extended overall survival (OS) trends with SKB264 treatment, and with manageable safety. Notably, a better response trend was observed in patients with locally advanced or metastatic TNBC with higher TROP2 expression.

Currently, the Phase III registrational clinical study of SKB264 monotherapy in at least second-line locally advanced or metastatic TNBC has reached the primary endpoint of improvement in PFS and has been included for priority review by the CDE. It is expected that a m product will be launched as soon as possible to benefit more patients.

About SKB264 (MK-2870)
SKB264 is a representative innovative ADC targeting TROP2, developed by Kelun-Biotech 's internationally renowned ADC research and development platform—OptiDC. It consists of a humanized anti-TROP2 monoclonal antibody with high affinity and targeting, combined with the self-developed small toxin molecule T030 (a topoisomerase I inhibitor) through a stability-optimized CL2A linker. The drug-to-antibody ratio (DAR) averages as high as 7.4. The stability of SKB264 has been enhanced in two main ways, allowing more ADC to effectively reach tumor cells. Firstly, the antibody end of the linker uses a sulfonamide pyrimidine connector, which allows for irreversible coupling with the antibody. Secondly, T030 contains a methyl sulfone structure, which can securely bind with the toxin end of the linker. The linker of SKB264 is affected by both extracellular pH-sensitive cleavage and intracellular enzymatic cleavage within tumor cells, which leads to efficient release of the small toxin molecule to exert its anti-tumor effects. T030 activity is similar to that of DXd and also shows a “bystander effect”. In summary, SKB264 exerts its anti-tumor effect in three ways. Firstly, the pH-sensitive linker can cleave and release T030 in the acidic tumor microenvironment. Secondly, after being engulfed by tumor cells, SKB264 releases T030 via enzymatic cleavage. Thirdly, T030 can also penetrate the cell membrane to exert a "bystander effect" to kill surrounding tumor cells. With a high-affinity monoclonal antibody, highly active toxin molecule, good stability, and high DAR value, the overall design of SKB264 contributes to its robust anti-tumor activity which has been preliminarily demonstrated in clinical studies to date.

SKB264 has received 3 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer (TNBC), locally advanced or metastatic EGFR-mutated non-small cell lung cancer which has failed EGFR-TKI therapy, and locally advanced or metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer which has received at least second-line systemic therapy.

Based on preliminary clinical data, SKB264 is currently being evaluated in Phase Ⅱ and Phase Ⅲ clinical trials as either a single agent or combination therapy in multiple solid tumors.

Domestic development:
The Phase Ⅲ pivotal clinical study of SKB264 monotherapy in patients with advanced or metastatic TNBC who have failed at least second-line therapy has reached the primary endpoint and is expected to be the first domestic TROP2-ADC to be approved for marketing.
Clinical trial registration of SKB264 monotherapy in patients with TKI-resistant EGFR-mutated NSCLC are rapidly advancing.
Several Phase Ⅱ clinical studies in combination with pembrolizumab (KEYTRUDA?, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are advancing steadily.

Developments abroad:
Kelun-Biotech has granted MSD the exclusive right to develop, manufacture, and commercialize SKB264 (MK-2870) in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).

About Kelun-Biotech
Kelun-Biotech（6990.HK）is a holding subsidiary of Kelun Pharmaceutical (002422.SZ), which focuses on the R&D, manufacturing, commercialization and global collaboration of innovative biological drugs and small molecule drugs. The company focuses on major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, and in establishing a globalized drug development and industrialization platform to address the unmet medical needs in China and the rest of world. The Company is committed to becoming a leading global enterprise in the field of innovative drugs.

At present, the Company has 33 ongoing innovative projects in major disease areas such as solid tumors, autoimmune, inflammatory, and metabolic diseases, including 14 projects in the clinical stage with several global trials being conducted simultaneously in multiple countries, including China, Europe, and the United States. The company has established one of the world’s leading proprietary ADC platforms, OptiDC, and has four ADC projects in the clinical stage (two of which are in the Phase III or NDA stage) and several projects in the preclinical stage. For more information, please visit https://kelun-biotech.com/.