Beigene Initiates Phase 1 Trial of BG-C9074 Monotherapy and in Combo with Tislelizumab

 Beigene has registered a Phase 1 clinical trial (NCT06233942) of BG-C9074, an anti-B7H4 antibody-drug conjugate (ADC), as monotherapy or in combination with tislelizumab: enrolling approximately 150 patients with pretreated solid tumors. The study (still no IND application submission in China yet) is estimated to start in May 2024, which is in line with the target for 2024 H1.

BG-C9074

According to the Beigene slide deck, BG-C9074, a novel B7-H4-targeted ADC with a drug-to-antibody ratio (DAR) of 6, is designed to balance efficacy and toxicity, utilizing DualityBio ADC technology. 

BG-C9074

The efficacy of BG-C9074 was evaluated in a B7-H4 low/heterogeneous PDX model, as measured by tumor volume reduction. The 10 mpk dose resulted in a greater degree of tumor shrinkage compared to the 3 mpk dose.

B7-H4 low/heterogeneous PDX model

In addition to BG-C9074, Beigene plans to initiate another ADC targeting B7-H3 with stable DAR8 and a strong bystander effect.

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AZD8205

AZD8205, developed by AstraZeneca, is another TOP1i-based ADC targeting B7-H4 with a DAR of 8. It is currently in a Phase 1/2 clinical study.

AZD8205

XMT-1660

XMT-1660 is another DAR-6 Dolasynthen-based ADC developed by Mersana Therapeutics which is currently in the phase 1 tudy.

XMT-1660

SGN-B7H4V

SGN-B7H4V, a novel MMAE-based ADC directed to B7-H4 with a DAR of ~4, developed by Seagen (now a Pfizer company), has reported the results of its first-in-human study: "Confirmed objective responses (starting at 0.75 mg/kg) were observed in evaluable patients with breast (7/25 patients), ovarian (2/15 patients), endometrial (1 [complete response]/16 patients), and biliary tract cancers (2/9 patients). In 2Q3W (n=35), 3 patients (8.6%) had dose-limiting toxicities (DLTs) (1 in 1.25 mpk and 2 in 1.5 mpk). In 2Q4W (n=40), 2 of 39 DLT-evaluable patients (5.1%) had DLTs (1.5 mpk and 2.0 mpk)"

HS-20089

HS-20089 is a novel B7-H4 targeted ADC with a TOPOi payload (DAR=6), developed by Hansoh and licensed to GSK with an $85 million upfront payment. The results of the phase 1 study have been reported at the same time to SGN-B7H4V. "Three DLTs were observed in 2 pts (both in 7.2 mg/kg Q3W). Of 33 response-evaluable pts, 8 partial responses (PRs) were observed in pts treated with HS-20089 (response rate: 24.2%), including 3 confirmed PRs and 5 PRs awaiting confirmation. The disease control rate was 63.6%. In the subset of 16 triple-negative breast cancer (TNBC) pts, 6 PRs were observed (response rate: 37.5%), including 2 confirmed PRs and 4 PRs awaiting confirmation. At potential target therapeutic dose (4.8 and 5.8 mg/kg), 5 PRs of 12 pts were observed (response rate: 41.7%) in TNBC. The patient achieving PR with the longest treatment duration of 403 days remains on treatment in 0.7 mg/kg cohort." A phase 2 study (NCT06014190) of HS-20089 was initiated in patients with ovarian cancer and endometrial cancer.