On March 4, 2024, according to the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration, DB-1303 for injection of antibody drug conjugate (ADC) declared by Yingen Biotech is intended to be included in the breakthrough ** variety. For advanced, sexual, or metastatic HER2-expressing endometrial cancer that has progressed during or after prior immune checkpoint inhibitor (ICI).
About DB-1303
DB-1303 is composed of a humanized anti-HER2 IgG1 monoclonal antibody covalently linked to a proprietary DNA topoisomerase I inhibitor (P1003) via a maleimide tetrapeptide-based cleavable linker with a high drug-tologic antibody ratio.
In January 2023, DB-1303 was granted Fast Track Designation by the U.S. FDA for patients with advanced or metastatic endometrial cancer who are receiving or have received HER2 overexpression in the current standard regimen.
The safety, tolerability and efficacy of the drug were demonstrated in a Phase 1 2A clinical trial (NCT05150691). As of January 13, 2023, 85 patients have received 6 dose levels. 0 and 100 mg kg) and received a median of 7 prior **, including 32Nine percent of patients had received anti-HER2 ADCs**. The median** duration was 630 days. According to RECIST 11 standard, 23 patients had objective partial tumor remission, and the disease control rate (DCR) of all patients was 885%γ
DB-1303 is well tolerated in patients with advanced metastatic solid tumors who have undergone extensive pretreatment and has encouraging preliminary antitumor activity.
On December 21, 2023, DB-1303 was granted Breakthrough Designation by the U.S. FDA for patients with advanced endometrial cancer who have progressed on or after immune checkpoint inhibitors.
Based on Phase 1 2 clinical study data presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and the 2023 European Society of Oncology (ESGO) Annual Meeting, BNT323 DB-1303 has encouraging antitumor activity in patients with advanced endometrial cancer who have received a significant amount of pre-production**, with an unconfirmed overall response rate of 588%, and the unconfirmed disease control rate was 941%, 70 mg kg and 8The overall response rate (ORR) was 50 for patients at the 0 mg kg dose, respectively0% and 615%γ
In all patients with advanced metastatic solid tumors evaluated, BNT323 DB-1303 was well tolerated with a manageable safety profile.
When it comes to HER2-targeted ADCs, two drugs may first come to mind: T-DM1 and DS-8201 (Enhertu). These two drugs represent first-generation ADCs and second-generation ADCs, respectively. Among them, the DS-8201 established the transcendent status of ADC.
About DS-8201:
DS-8201 (trade name: Enhertu, generic name: Fam-trastuzumab deruxtecan) targets cancer cells by linking trastuzumab, a human HER2 antibody, to a novel topoisomerase inhibitor via a tetrapeptide linker and delivers the drug inside the cells.
In December 2021, DS-8201 was approved by the U.S. Food and Drug Administration (FDA) for patients with unresectable or metastatic HER2-positive breast cancer** who have received more than 2 prior HER2-targeted breast cancers.
On January 3, the official website of the Center for Drug Evaluation (CDE) of the State Food and Drug Administration of China announced that DS-8201 (trastuzumab, enhertu), jointly declared by AstraZeneca and Daiichi Sankyo, is intended to be included in the breakthrough ** variety, and the proposed indication is: patients with unresectable or metastatic non-small cell lung cancer** who have activated HER2 (ERBB2) mutations and have received at least one system** before.
The latest data from the Phase II clinical Destiny-LUNG02 study of DS-8201** in patients with previously treated HER2-mutant metastatic NSCLC cancer presented at the 2023 World Conference on Lung Cancer (WCLC) showed that trastuzumab 54 mg kg and 6The 4mg kg dose was clinically significant, durable in tumor remission with a manageable safety profile.
As of December 23, 2022, the study enrolled 152 patients at multiple sites in Asia, Europe, Oceania, and North America. 5.The median follow-up time in the 4 mg kg** group (n=102) was 115 months, 6The median follow-up time in the 4 mg kg** group (n=50) was 118 months.
The results showed that as assessed by blinded independent central review (BICR), 54 mg kg** group and 6The overall response rate (ORR) was 49 in the 4 mg kg** arm, respectively0% and 560%γThe disease control rate (DCR) was 93 in both groups1% and 920%γ5.The duration of response (DOR) was 16 in the 4 mg kg** group8 months, 6Median duration of response was not achieved in the 4 mg kg group. In addition, the median progression-free survival (MPFS) was 9 in both groups9 months and 154 months. 5.The median overall survival (OS) was 19 in the 4 mg kg group5 months, 6The 4 mg kg** group was not reached.
In summary, DB-1303 shows good early-stage antitumor activity in patients with advanced endometrial cancer. This breakthrough designation suggests that DB-1303 has the potential to be a new option for patients with HER2-expressing advanced endometrial cancer.
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Resources. 1. fda grants breakthrough therapy designation to bnt323/db-1303 in endometrial cancer (
2. abstract 2793: preclinical pharmacokinetics in cynomolgus monkeys and first in human dose prediction of db-1303, a her2-targeting antibody-drug conjugate | cancer research | american association for cancer research (
3. safety and efficacy of db-1303 in patients with advanced/metastatic solid tumors: a multicenter, open-label, first-in-human, phase 1/2a study. |journal of clinical oncology (