There is no doubt that ADCs are becoming more and more important in the field of tumor treatment, and in the past they have focused on Her2 targets, and as the technology matures, more targets are being developed into ADC products, and Trop2 is also a potential target. At present, only one Trop-2 ADC has been approved for marketing worldwide, namely Gilead's gosatuzumab. The fastest progress among domestic enterprises is Kellenbotel's SKB264 (August 14, 2023, successful phase III study of triple-negative breast cancer), which is comparable to the development progress of AstraZeneca/Daiichi Sankyo Dato-DXd (September 22, 2023, successful TROPION-Breast01 breast cancer phase III study). Recently, Hansen Pharmaceutical, a blockbuster transformation enterprise of Haosen Pharmaceutical, has also carried out clinical research on Trop2 ADC, and the track has attracted more attention.
——Trop2 ADC Track News——
On September 25, Hansen Pharmaceutical issued an announcement that the Trop-2 targeted ADC drug HS-20105, independently developed by its subsidiary Hansen Biotech and Hengbang Pharmaceutical, has been approved for clinical trial and is intended for the treatment of advanced solid tumors, and the specific indications will be determined after clinical trials.
HS-20105 is an antibody-drug conjugate (ADC) formed by humanized anti-Trop-2 monoclonal antibodies of the IgG1 subtype after a protease-cleaved linker-conjugated DNA topoisomerase I inhibitor.
Hansen Pharmaceutical is a leading innovation-driven pharmaceutical company in China, with subsidiaries such as Haosen Pharmaceutical, Changzhou Hengbang Pharmaceutical, and Hansen Biopharmaceutical, which are committed to improving human health and quality of life through continuous innovation, focusing on anti-tumor, anti-infection, central nervous system diseases, metabolic diseases and autoimmune diseases. The company has been ranked among the top 100 global pharmaceutical enterprises and the top three industrial enterprises with the best pharmaceutical R&D product line in China for many consecutive years, and is a national key high-tech enterprise and a national technological innovation demonstration enterprise, and was listed on the Hong Kong Stock Exchange in June 2019 (03692. HK）。
From the technical fields that Hansen Pharmaceutical is good at displayed on its official website, it is enough to see some shadows of Haosen and Hengrui, and the research and development of innovative drugs still need to focus on professional expertise and continuous technology accumulation. Let's take a look at the fast-paced TROP 2 ADC SKB264 from Kolumbert.
——SKB264——
SKB264 is an antibody-drug conjugate (ADC) targeting TROP2 developed by Colonbot, which has been awarded three breakthrough therapy designations (BTDs) by CDE. They are:
- Locally advanced or metastatic triple-negative breast cancer (TNBC)
- Locally advanced or metastatic EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) that has failed EGFR-TKI therapy
- Locally advanced or metastatic hormone receptor-positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) breast cancer who have received at least second-line systemic chemotherapy
First, let's look at the TNBC data:
On December 6, 2022, Colombertai published the latest efficacy and safety data of the Phase II Expansion Study of TROP2-ADC SKB264 (MK-2870) in patients with locally advanced or metastatic triple-negative breast cancer (TNBC) in the form of posters at the 45th San Antonio Breast Cancer Symposium (SABCS). The simple organization is as follows:
- Test methods: A total of 59 treated patients with locally advanced or metastatic triple-negative breast cancer received SKB264 monotherapy every two weeks;
- Data follow-up: median follow-up 12.8 months as of October 10, 2022;
- Efficacy data: Among the 55 patients who could be evaluated for efficacy (21 in the 4 mg/kg group and 34 in the 5 mg/kg group), the confirmed ORR was 40% and the DCR was 80%; The ORR confirmed by patients with high expression of TROP2 was 55.2%, and the ORR confirmed by the high expression of TROP2 in the 5mg/kg dose group was as high as 62.5%. mDoR was 11.5 months, mPFS was 5.7 months, mOS was 14.6 months, and the 12-month OS rate was 66.4%;
- Safety data: 57.6% of patients reported grade ≥ 3 treatment-related adverse events (TRAEs). The most common ≥ grade 3 TRAEs (≥10%) are low neutrophil count, low white blood cell count, anemia, and low platelet count. TRAEs resulted in a dose reduction in 10.2% of patients. No deaths due to TRAE occurred and no interstitial lung disease (ILD) was observed.
Primary study data results
TNBC field, safety data is good.
EGFRm NSCLC Research Progress:
The SKB264-III.-09 study is a randomized, open-label, multicenter phase III. clinical study comparing the efficacy and safety of SKB264 monotherapy with pemetrexed combined with platinum in EGFR-TKI in locally advanced or metastatic NSCLC with EGFR-TKI mutations that have failed to treat. It was planned to enroll 356 patients with the primary endpoint of IRC-assessed progression-free survival (PFS). The leading research center in China is the Cancer Prevention and Treatment Center of Sun Yat-sen University. The clinical registration number is: CTR20231535. NCT05870319
——2023 ASCO Research Data Report——
The Phase II. Expansion Study Data of SKB264 in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) were included in the poster format at the 2023 ASCO Annual Meeting, releasing for the first time the study data of EGFR mutation and driver gene negative population.
Study Design:
- This is a phase 1/2, multicenter, dose-escalation/expansion study (NCT04152499) in patients with relapsed or refractory locally advanced/metastatic NSCLC and other tumor types
- All patients with NSCLC received SKB264 5 mg/kg IV Q2W
- The investigators performed RECIST 1.1-based tumor evaluation every 8 weeks
Of the 43 patients enrolled, about 50% (22 versus 21 patients) were EGFR mutant and EGFR wild-type NSCLC, of which 76.7% (33/43) had previously received two or more regimens for metastatic disease.
Research results:
- As of 9 February 2023, a total of 43 patients (63% male, 88% ECOG PS 1, median age 58 years [44-74]) were enrolled. The median follow-up was 11.5 months (mo; 95% CI, 10.4-12.2). The median duration of treatment was 5.7 months (range, 0.5-14.1).
- Among the 39 evaluable patients, the ORR was 44% (17/39, 15 confirmed, 2 TBD), the median DoR was 9.3 months (range, 1.3+ to 11.2+), and the 6-month DoR rate was 77%.
to time and duration of mitigation
Percentage change from baseline (%)
Further subgroup analyses:
- Patients with mEGFR had an ORR of 60%, a DCR of 100%, an mDoR of 9.3 months, an mPFS of 11.1 months, and a December OS rate of 80.7%.
- Patients with EGFR wild-type (who previously received a median of 2 treatments including anti-PD-1/L1) had an ORR of 26.3%, a DCR of 89.5% (17/19), an mDoR of 9.6 months, and a December OS rate of 60.6%.
Security data
- 67.4% (29/43) of patients had grade 3 treatment-related adverse events (TRAEs). The most common grade 3 TRAEs (occurring in 5% of patients) were decreased neutrophil count (32.6%), anemia (30.2%), decreased white blood cell count (WBC) (23.3%), stomatitis (9.3%), rash (7.0%), and decreased lymphocyte count (7.0%). Most hematologic toxicities occur within the first two months of treatment and resolve without transfusion with granulocyte colony-stimulating factor or erythropoietin. 23.3% (10/43) of participants experienced dose reduction due to TRAE. Neuropathy or drug-related ILD/pneumonia were not reported. No TRAE resulted in treatment interruption or death.
Conclusions:
- SKB264 at 5 mg/kg Q2W demonstrated encouraging antitumor activity and a manageable safety profile in patients with relapsed or refractory locally advanced/metastatic NSCLC. TRAE is predominantly hematologic toxicity.
（DOI: 10.1200/JCO.2023.41.16_suppl.9114IF: 45.3 Q1 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 9114-9114.）
In 2022, Kelun Pharmaceutical granted R&D, manufacturing and commercialization rights to two solid tumor ADC drugs (SKB264 targeting TROP2 and SKB315 targeting Claudin18.2) to Merck for global R&D. The down payment for the two drugs totaled $82 million, and the milestone payments totaled $2.264 billion. are all potential blockbuster target ADC tape products in the future, and Merck, as a dividend enjoyer in the era of pembrolizumab, also has to lay out the product pipeline in the post-PD-1 era. Compared with the total amount of transactions that have repeatedly created miracles in recent years, what is more valuable is the down payment and the setting of each node, do not see the total amount and be shocked, the sickle is too fast, often wielded, cut leeks. We still have to focus on the release of its research data and observe carefully.