AstraZeneca presented B7-H4 targeted ADC AZD8205 at the 2024 ESMO Annual Meeting (puxitatug samrotecan) Dose escalation results from the BLUESTAR I/IIa trial in patients with advanced solid tumors expressing B7-H4,AZD8205 demonstrates consistent controllable safety with similar ADCs and preliminary efficacy in heavily pretreated patients with advanced or metastatic solid tumors.
Summary of AZD8205
As of February 23, 2024, 46 patients had received treatment with AZD8205, including 21 during the dose-escalation phase and 25 in the expansion cohort. The median age was 56 years (range: 24–88 years), and the median number of prior lines of therapy at baseline was 4 (range: 2–9). Any-grade treatment-emergent adverse events (TEAEs) occurred in 97.8% of patients, the most common being nausea (58.7%), neutropenia (56.5%), and anemia (50.0%). Grade ≥3 TEAEs occurred in 82.6% of patients, the most common being neutropenia (37.0%) and anemia (30.4%). Two patients (4.3%) discontinued treatment due to TEAEs. Dose-limiting toxicities were observed in two patients at the 3.2 mg/kg dose level (decreased neutrophil count [n=1] and decreased platelet count [n=1]). Among 43 patients treated at doses ≥1.6 mg/kg, confirmed partial responses were observed in 9 patients with ovarian, breast, or endometrial cancer (20.9%).
Currently, there are no B7-H4 ADC products on the market globally. Apart from AZD8205, which is in Phase 1/2 clinical trials, other drugs under research are in Phase 1.AZD8205 is an ADC drug targeting B7-H4 developed by AstraZeneca using proprietary Linker technology. It connects the B7-H4 monoclonal antibody INT016 with the novel topoisomerase 1 inhibitor (TOP1i) AZ'0132 via a cleavable Linker. In a triple-negative breast cancer mouse model, a single intravenous dose of AZD8205 achieved a 69% overall response rate, with 36% reaching complete remission. In tumor models with high B7-H4 expression and DNA damage repair deficiencies, AZD8205 demonstrated even stronger anti-tumor activity.
In a mouse model of triple-negative breast cancer, a single intravenous dose of AZD8205 was administered.A total relief rate of 69% was achieved, with 36% reaching complete relief. In tumor models with high B7-H4 expression and DNA damage repair defects, AZD8205 demonstrated stronger anti-tumor activity. Data published at the 2023 AACR showed that in PARP inhibitor-resistant or low B7-H4 expressing PDX models, the combination of AZD8205 and AZD5305 (a PARP1 selective inhibitor) once again proved to have higher anti-tumor activity than monotherapy. Additionally, the combination of AZD8205 with an anti-PD-L1 antibody also enhanced anti-tumor efficacy.- Hansoh Pharma & GSK HS-20089
HS20089 is an ADC drug targeting B7-H4 developed by Hansoh Pharma, with a payload of topoisomerase inhibitor and a DAR of 6.On October 20, 2023, GSK acquired the rights to HS-20089 (GSK5733584), a B7-H4 ADC drug developed by Hansoh Pharma, for markets outside Greater China, with an upfront payment of $85 million and milestone payments totaling $1.485 billion, bringing the total deal value to $1.535 billion.HS-20089 is currently undergoing Phase I (NCT05263479) clinical trials in China.Clinical Results of HS-20089 Presented at 2023 ESMOAt the 2023 ESMO Congress, Hansoh Pharma released for the first time HS-20089 (B7-H4 ADC) for the treatment of advanced solid tumors that have failed or are intolerant to standard treatments: a multicenter, open-label Phase I first-in-human study NCT05263479 clinical trial data results:- As of April 11, 2023, 44 patients (41 with breast cancer, 2 with ovarian cancer, and 1 with endometrial cancer) had received HS-20089 treatment. Among 33 evaluable patients, the partial response (PR) rate was 24.2% (8/33), and the disease control rate (DCR) was 63.6% (21/33); in the TNBC subgroup, the partial response (PR) rate was 37.5% (6/16).
- As of August 17, 2023, in the subgroup of 28 evaluable TNBC patients, the objective response rate (ORR) was 28.6%, and the disease control rate (DCR) was 75.0%. At the potential target doses (4.8 and 5.0 mg/kg), the ORR was 30.4% (7/23) and the DCR was 73.9% (17/23) among 23 evaluable TNBC patients.
SGN-B7H4V is a novel ADC product targeting B7-H4 developed by Seagen (now acquired by Pfizer). It is obtained by conjugating the antibody with the cytotoxic payload monomethyl auristatin E (MMAE) via a protease-cleavable MC-VC linker.On January 12, 2022, Seagen initiated a Phase I clinical trial (SGNB7H4V-001/ NCT05194072) to evaluate the efficacy and safety of SGN-B7H4V in patients with locally advanced unresectable or metastatic solid tumors.At the 2023 ESMO Congress,PublishedPreliminary Results of the First-in-Human Phase 1 Study of SGN-B7H4V in Patients with Advanced Solid Tumors (SGNB7H4V-001):As of March 10, 2023, a total of 75 patients with locally advanced unresectable or metastatic solid tumors expressing or not expressing B7-H4 were enrolled. Patients received SGN-B7H4V treatment on Day 1 and Day 8 of a 21-day cycle (2Q3W, 0.75, 1.0, 1.25, or 1.5 mg/kg), or on Day 1 and Day 15 of a 28-day cycle (2Q4W, 1.25, 1.5, 1.75, or 2.0 mg/kg). Objective responses were observed in evaluable patients with breast cancer (7/25), ovarian cancer (2/15), endometrial cancer (1 (complete response)/16), and biliary tract cancer (2/9). Overall adverse reactions were safe and controllable.XMT-1660 is a B7H4-targeted ADC developed by Mersana based on its Dolasynthen and DolaLock platforms and Synaffix's GlycoConnect, with a payload of Auristatin F-HPA (AF-HPA) and a DAR value of 6.XMT-1660 is currently undergoing Phase I clinical trials (MER-XMT-1660-1/ NCT05377996) to investigate the safety, tolerability, and anti-tumor activity of XMT-1660 in patients with solid tumors.In September 2022, XMT-1660 received FDA Fast Track designation for the treatment of patients with advanced or metastatic triple-negative breast cancer (TNBC).BG-C9074 is a B7-H4 ADC that BeiGene introduced from DualityBio in July 2023. Based on specific R&D progress, regulatory milestones, and commercialization achievements under the collaborative research project, DualityBio is entitled to receive up to $1.3 billion in additional payments as well as tiered royalties.BG-C9074 inPhase 1 Clinical Trial Registered on ClinicalTrialsBG-C9074 is currently undergoing Phase 1 clinical trials in the United States and Australia.Evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C9074 alone and in combination with tislelizumab in patients with advanced solid tumors.On July 30, 2024, BeiGene registered a Phase 1a/1b first-in-human study on the Drug Clinical Trial Registration and Information Disclosure Platform website for BG-C9074 monotherapy and its combination with tislelizumab in treating patients with advanced solid tumors.To promote communication and innovation in the antibody industry,October 16-17, 2024The 7th Golden Autumn October Antibody Industry Development ConferenceAs scheduled. The conference aims to provide researchers with an interactive platform, which will help promote the further development of the antibody industry.Time:October 16-17, 2024
Location: Shanghai(Hotel Directional Notice)
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