TROP2 gets more crowded

The crowded anti-TROP2 pipeline hasn’t stopped more companies taking a punt on this mechanism. The latest to do so is Jiangsu Hansoh, which is set to begin a clinical trial next year of its ADC HS-20105. 

In other popular areas for development, PentixaPharm and GluBio Therapeutics are progressing with a radiopharmaceutical and protein degrader respectively. Meanwhile, Zhejiang Doer Biologics is taking a triplet approach with DR30206, and Johnson & Johnson has moved forward with a mystery bispecific. 

TROP2 too

According to OncologyPipeline there are 22 TROP2-targeting agents in clinical development, most of which are ADCs. 

Gilead’s Trodelvy is already approved in third-line triple-negative breast and urothelial cancers, while AstraZeneca and Daiichi are planning to file datopotamab deruxtecan soon in second-line lung and breast cancers. Other late-stage rivals include Merck & Co and Kelun with sacituzumab tirumotecan.

Still, the shine has come off TROP2 somewhat since Gilead paid $21bn for Trodelvy’s developer, Immunomedics. Trodelvy itself has underwhelmed, while in lung cancer datopotamab looks likely to be limited to patients with non-squamous histology.

Like Trodelvy, datopotamab deruxtecan and sacituzumab tirumotecan, Hansoh’s HS-20105 uses a topoisomerase I inhibitor payload, though the company doesn't specify which one. Hansoh recently hooked GSK as a partner for another asset, the B7-H4-targeting HS-20089. However, with B7-H4 much less crowded than TROP2, the Chinese group will need to show something special to tempt another big pharma into HS-20105.

Triple whammy

Zhejiang Doer Biologics, meanwhile, appears to be one of two companies targeting PD-L1, VEGF and TGF-β with one molecule. However, each component will be familiar to oncology watchers, with PD-(L)1 and VEGF inhibitors already well established, and TGF-β on shaky ground after the failure of Merck KGaA/GSK’s anti-PD-L1/TGF-β fusion protein bintrafusp alfa.

Various companies are evaluating projects against anti-PD-(L)1 plus either VEGF or TGF-β. One of the most advanced is Summit Therapeutics, which believes that its anti-PD-1/VEGF bispecific ivonescimab could produce efficacy greater than the sum of its parts. The group licensed this project, currently in phase 3, from China’s Akeso for $500m up front in late 2022. 

Zhejiang Doer Biologics’ contender, DR30206, is set to go into the clinic this week, joining Biotheus’s PM8003, an anti-PD-L1/TGF-β/VEGF trispecific already in a Chinese phase 1/2 trial.

Mystery bispecific

Not many details are available about J&J’s JNJ-87801493, but it appears to have originated from a collaboration with Xencor that began two years ago; Xencor said in its third-quarter earnings release than J&J had submitted a clinical trial application for a CD28 bispecific antibody targeted against a B-cell tumour target. 

The project is designed to activate T cells through the CD28 co-stimulatory receptor, and is being tested in combinations with T-cell engagers. The companies are developing a similarly acting asset against an unnamed prostate cancer target.

Recently disclosed first-in-human studies*

Note: *projects newly listed on the clinicaltrials.gov database between 15 and 23 Nov 2023.