Chia Tai broadens its biparatopic breast cancer approach

AstraZeneca and Daiichi’s Enhertu has already scuppered one western HER2 x HER2 ADC, Zymeworks’ zanidatamab zovodotin, but in China it’s another story. OncologyPipeline shows several similarly acting projects in development here including Chia Tai’s TQB2102, which will soon begin a new phase 3 breast cancer trial, a recent clinicaltrials.gov listing reveals.

True, the setting is neoadjuvant disease, where Enhertu isn’t yet approved either in the US or in China – but it could be soon, after a recent positive result in the Destiny-Breast11 trial. However, other studies being carried out by Chia Tai do clash with Enhertu’s approved uses.

The company has Chinese phase 3s ongoing in second-line breast cancer, including both HER2-positive and HER2-low. Enhertu got the go ahead in China in the former in February 2023, and in the latter in July the same year.

Notably, Chia Tai is testing TQB2102 against Roche’s HER2-targeting ADC Kadcyla in HER2-positive disease, and against chemo in HER2-low.

TQB2102 phase 3s in breast cancer

Note: all Chinese trials. Source: OncologyPipeline & clinicaltrials.gov.

CSPC and Alphamab are taking a similar approach with their HER2 x HER2 ADC contender anbenitamab repodatecan, which is also in Chinese phase 3s for second-line HER2-positive and HER2-low breast cancers.

All of these studies started after Enhertu’s Chinese breast cancer approvals. It’s possible that the Astra/Daiichi drug wasn’t being used widely in China at the time, but that could be changing, with Enhertu being added to the country’s state-run insurance list from January 2025.

One question for these developers could be whether Enhertu’s availability could hurt recruitment, something that will be relevant for the studies that started this year, or are about to begin.

Biparatopic

By hitting two different HER2 epitopes, biparatopic ADCs are designed to improve binding and internalisation, which could reduce toxicity and increase efficacy.

However, it’s still unclear whether the biparatopic approach really has an edge. Jazz’s HER2 x HER2 MAb Ziihera was FDA approved last year in the niche use of biliary tract cancer; that drug was licensed from Zymeworks and uses the same antibody as the now discontinued zanidatamab zovodotin. Jazz is also taking aim at breast cancer but appears to have accepted reality, with its phase 3 trial focusing on post-Enhertu patients.

Perhaps biparatopic ADCs will prove more efficacious than biparatopic MAbs – something the Chinese groups below will be banking on. But some are going further than others, with Hangzhou DAC’s DXC018 and Phrontline Biopharma’s TJ106 also employing dual payloads. Both assets are preclinical, but this is a hot new area of research, with much of the work being carried out in China.

HER2 x HER2 ADCs in development

Source: OncologyPipeline.